No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Coffee, tea, and caffeine consumption and prevention of late-life cognitive decline and dementia: A systematic review
Abstract
A prolonged preclinical phase of more than two decades before the onset of dementia suggested that initial brain changes of Alzheimer’s disease (AD) and the symptoms of advanced AD may represent a unique continuum. Given the very limited therapeutic value of drugs currently used in the treatment of AD and dementia, preventing or postponing the onset of AD and delaying or slowing its progression are becoming mandatory. Among possible reversible risk factors of dementia and AD, vascular, metabolic, and lifestyle-related factors were associated with the development of dementia and late-life cognitive disorders, opening new avenues for the prevention of these diseases. Among diet-associated factors, coffee is regularly consumed by millions of people around the world and owing to its caffeine content, it is the best known psychoactive stimulant resulting in heightened alertness and arousal and improvement of cognitive performance. Besides its short-term effect, some case-control and cross-sectional and longitudinal population-based studies evaluated the long-term effects on brain function and provided some evidence that coffee, tea, and caffeine consumption or higher plasma caffeine levels may be protective against cognitive impairment/decline and dementia. In particular, several cross-sectional and longitudinal population-based studies suggested a protective effect of coffee, tea, and caffeine use against late-life cognitive impairment/decline, although the association was not found in all cognitive domains investigated and there was a lack of a distinct dose-response association, with a stronger effect among women than men. The findings on the association of coffee, tea, and caffeine consumption or plasma caffeine levels with incident mild cognitive impairment and its progression to dementia were too limited to draw any conclusion. Furthermore, for dementia and AD prevention, some studies with baseline examination in midlife pointed to a lack of association, although other case-control and longitudinal population-based studies with briefer follow-up periods supported favourable effects of coffee, tea, and caffeine consumption against AD. Larger studies with longer follow-up periods should be encouraged, addressing other potential bias and confounding sources, so hopefully opening new ways for diet-related prevention of dementia and AD.
... Ao traçarmos uma relação causal, observa-se, claramente, que o avanço da medicina e o aumento global da expectativa de vida criam um ambiente propício para a senilidade; portanto, o fato de que o envelhecimento da população aumenta a prevalência de doenças que advém dessa condição, requer novos conhecimentos, tratamentos e medidas preventivas para que o impacto nas sociedades ao redor do mundo seja o menor possível e a expectativa de vida, junto ao bem-estar, estejam em pauta (Panza et al., 2015). Nesse sentido, sabemos que as síndromes demenciais tem um papel importante nesse cenário, mundialmente, a Doença de Alzheimer (DA) é responsável por 50-70% dos casos, seguida pela Doença de Parkinson (DP) (Londzin et al., 2021;Hong et al., 2020), além de outras doenças como a Demência Vascular. ...
... O café é uma das bebidas mais consumidas no mundo e suas propriedades psicoativas, resultam numa melhora temporária da cognição e ativa o estado de vigília. As propriedades antioxidantes e outros benefícios do café exercem efeitos sistêmicos e em diversas patologias, como no diabetes e no infarto agudo isquêmico e hemorrágico, além de evidências positivas na DP e na DA, em geral advindas da cafeína; não obstante, existem relatos sobre a participação de outras substâncias, comprovadas, também, por experimentos com a ingestão do café livre de cafeína (Carman et al., 2014;Panza et al., 2015). Porém, a expressão dos efeitos da cafeína -presente no café, na erva mate, na cola, no guaraná e em bebidas energéticas -em si, são dependentes de diversos fatores, sendo que a dose é um ponto crucial, já que os níveis delimitados seguros estão entre 400mg por dia, de acordo com a European Food Safety Authority (EFSA), considerando que em um copo de aproximadamente 473mL de café coado está presente, em média, 188mg de cafeína (Kolahdouzan & Hamadeh, 2017). ...
... Quanto as constatações em humanos, um estudo longitudinal acompanhou, durante 21 anos, 875 mulheres e 534 homens com mais de 50 anos, relatando que um consumo moderado, entre 3-5 copos por dia reduziu o risco de DA em 62%-64% em comparação com pessoas que ingeriram de zero a dois copos por dia (Eskelinen et al., 2009;Kolahdouzan & Hamadeh, 2017), outro estudo, realizado no Canadá, pela análise de 10.263 pessoas acima de 65 anos, confirmou a redução de 31% no risco de DA naqueles com a ingesta de café (Kolahdouzan & Hamadeh, 2017). Outra revisão analisou uma gama de estudos, com relações condizentes com as já citadas, entretanto, um estudo longitudinal, realizado durante 28 anos, com participantes entre 46-52 anos, com a ingestão média de 5.4 copos de café por dia, não confirmou o benefício da ingestão de café, durante a meia idade, no desenvolvimento de DA (Panza et al., 2015). Por fim, outro trabalho de revisão, pela análise de cinco estudos prospectivos relacionou as dosagem de três a quatro copos (aproximadamente 300mg) como a melhor dosagem com efeito protetor quanto ao desenvolvimento de DA, enquanto outros dois pequenos estudos relatam esse nível entre 62mg/dia e 200mg/dia (Carman et al., 2014). ...
Introdução: A prevalência da Doença de Alzheimer (DA) e da Doença de Parkinson (DP), tende a aumentar com o envelhecimento populacional. Até o momento, os esquemas terapêuticos para essas doenças não consegue alcançar a cura e geralmente não são atualizados, o que evidencia a necessidade de outras opções para a melhora da qualidade de vida desses pacientes. Dado que essas síndromes demenciais tem etiologia multifatorial, a dieta, por meio do café, tem mostrado evidências significativas na degeneração neuronal, que é um dos principais aspectos alterados no desenvolvimento dessas patologias. Metodologia: Trata-se de uma revisão integrativa, que buscou responder quais os possíveis efeitos da cafeína como fator protetor no desenvolvimento e na progressão da revisional e da DP, nas bases de dados: Biblioteca Virtual de Saúde (BVS), National Library of Medicine (PubMed MEDLINE) e Scientific Electronic Library Online (Scielo). Resultados e Discussão: A cafeína age no sistema nervoso central (SNC) pela mimetização aos receptores de adenosina, mais concentrada nos receptores A1R e A2aR. Como antagonista competitivo, a cafeína, eventualmente, poderia reduz os processos de formação das placas b-amiloides na DA e reduzir a neuroinflamação e neurodegeneração na DP, além de outros possíveis mecanismos. Conclusão: A delimitação de um consenso sobre a relação dose/efeito decorrente do uso da cafeína é de difícil estabelecimento e ainda não se observa um consenso, entretanto, é possível observar que um consumo entre 200mg a 511mg por dia poderia trazer efeitos benéficos tanto na DP, como na DA, superando os possíveis efeitos colaterais.
... In recent years, an increasing attention towards the beneficial impact of coffee also on some neuropsychiatric and neurological disorders has been noted, although epidemiological studies did not reach consensus regarding a protective effect of caffeine on the risk of cognitive impairment. While several findings have reported a coffee-related protection on cognition (Panza et al. 2015;Rom an et al. 2019), a detailed neuropsychological assessment was rarely carried out and a firm association has not been established yet, at least not for every cognitive domain (Panza et al. 2015). The same holds true for a consensus on a dose-response association with mood status or cognitive performance (Jarvis 1993;Johnson-Kozlow et al. 2002;Gelber et al. 2011;Lucas et al. 2011;Panza et al. 2015). ...
... In recent years, an increasing attention towards the beneficial impact of coffee also on some neuropsychiatric and neurological disorders has been noted, although epidemiological studies did not reach consensus regarding a protective effect of caffeine on the risk of cognitive impairment. While several findings have reported a coffee-related protection on cognition (Panza et al. 2015;Rom an et al. 2019), a detailed neuropsychological assessment was rarely carried out and a firm association has not been established yet, at least not for every cognitive domain (Panza et al. 2015). The same holds true for a consensus on a dose-response association with mood status or cognitive performance (Jarvis 1993;Johnson-Kozlow et al. 2002;Gelber et al. 2011;Lucas et al. 2011;Panza et al. 2015). ...
... While several findings have reported a coffee-related protection on cognition (Panza et al. 2015;Rom an et al. 2019), a detailed neuropsychological assessment was rarely carried out and a firm association has not been established yet, at least not for every cognitive domain (Panza et al. 2015). The same holds true for a consensus on a dose-response association with mood status or cognitive performance (Jarvis 1993;Johnson-Kozlow et al. 2002;Gelber et al. 2011;Lucas et al. 2011;Panza et al. 2015). ...
Coffee intake has been recently associated with better cognition and mood in mild vascular cognitive impairment (mVCI). As tobacco can reduce the caffeine half-life, we excluded smokers from the original sample. Hamilton Depression Rating Scale (HDRS), mini-mental state examination (MMSE), Stroop Colour-Word Interference Test (Stroop), activities of daily living (ADL0) and instrumental ADL were the outcome measures. Significant differences were observed in higher consumption groups (moderate intake for HDRS; high intake for MMSE and Stroop) compared to the other groups, as well as in age and education. With age, education and coffee used as independent predictors, and HDRS, Stroop and MMSE as dependent variables, a correlation was found between age and both MMSE and Stroop, as well as between education and MMSE and between HDRS and Stroop; coffee intake negatively correlated with HDRS and Stroop. Higher coffee consumption was associated with better psycho-cognitive status among non-smokers with mVCI.
... Further caffeine intake comes from tea, energy or sports drinks, and various chocolate products (Fitt et al., 2013). While many advocates for the neuroprotective and cognitive-enhancing effects of caffeine (McLellan et al., 2016;Panza et al., 2015), others proposed that the magnitude of these benefits are negligible, furthermore, a higher dose can have detrimental effects on physical and mental health (Nehlig, 2010(Nehlig, , 1999. As past literature tended to treat memory as a subset of cognitive functions, the specific effect of caffeine on memory has not been thoroughly discussed. ...
... Similar interactions between caffeine and sex, where a larger protective effect for females than males has been reported in a systematic review (Panza et al., 2015). However, Panza et al. (2015) focused on the role of habitual caffeine consumption in preventing cognitive decline and dementia, without detailing mechanisms underlying this sex effect. ...
... Similar interactions between caffeine and sex, where a larger protective effect for females than males has been reported in a systematic review (Panza et al., 2015). However, Panza et al. (2015) focused on the role of habitual caffeine consumption in preventing cognitive decline and dementia, without detailing mechanisms underlying this sex effect. Given the various metabolic pathways of caffeine, habitual consumption may participate in physiological processes that affect global cognition (de Mejia and Ramirez-Mares, 2014), but this does not translate to the effect of caffeine on memory tasks in the healthy population. ...
Caffeine is a widely used nootropic drug, but its effects on memory in healthy participants have not been sufficiently evaluated. Here we review evidence of the effects of caffeine on different types of memory, and the associated drug, experimental, and demographical factors. There is limited evidence that caffeine affects performance in memory tasks beyond improved reaction times. For drug factors, a dose-response relationship may exist but findings are inconsistent. Moreover, there is evidence that the source of caffeine can modulate its effects on memory. For experimental factors, past studies often lacked a baseline control for diet and sleep and none discussed the possible reversal of withdrawal effect due to pre-experimental fasting. For demographic factors, caffeine may interact with sex and age, and the direction of the effect may depend on the dose, individual tolerance, and metabolism at baseline. Future studies should incorporate these considerations, as well as providing continued evidence on the effect of caffeine in visuospatial, prospective, and implicit memory measures.
... Although people with MCI have a greater risk of dementia, many studies have reported that it is possible to prevent progression to dementia by controlling environmental factors such as dietary habits, exercise, and chronic disease management (Eshkoor et al., 2015;Jiang et al., 2017). Several studies have recently investigated the associations between cognitive function and dietary factors, including certain foods and nutrients (Panza et al., 2015;Jiang et al., 2017). Adequate consumption of omega-3 fatty acids (Cederholm et al., 2013), fruits and vegetables (Dong et al., 2016;Jiang et al., 2017), dairy products (Ogata et al., 2016), and moderate alcohol consumption (Xu et al., 2017) have been reported to have protective effects against disease. ...
... Adequate consumption of omega-3 fatty acids (Cederholm et al., 2013), fruits and vegetables (Dong et al., 2016;Jiang et al., 2017), dairy products (Ogata et al., 2016), and moderate alcohol consumption (Xu et al., 2017) have been reported to have protective effects against disease. However, the association between dietary factors and the risk of cognitive impairment and dementia remains unclear (Panza et al., 2015;Kesse-Guyot et al., 2016;Smith and Blumenthal, 2016). ...
... A recent systematic review of several cross-sectional studies and longitudinal population-based studies suggested that coffee and tea intake had a protective effect on cognitive impairment in older people. Although there were some limitations (such as using a dose-response analysis and cognitive domains), this review reported that this association was stronger in females than in males (Panza et al., 2015). Barbour et al. (2014) examined the effects of nut consumption on blood pressure, glucose regulation, endothelial vasodilator function, arterial compliance, inflammatory biomarkers, and cognitive function through several epidemiological or intervention studies. ...
The prevalence of age-related diseases such as dementia and cognitive disorders is rapidly increasing. This study aimed to identify the dietary patterns associated with mild cognitive impairment (MCI) in adults aged over 50 years. This cross-sectional study investigated dietary patterns associated with cognitive function among older adults hospitalized in Gwangju province. Global cognitive function was assessed using the Mini-Mental State Examination. Diet information was obtained using a food frequency questionnaire with 112 food items and 24-h dietary recall. Using a principal component analysis, we identified three dietary patterns, "legumes and vegetables", "beverage and nuts", and "white rice". The "beverage and nuts" pattern was inversely associated with the prevalence of high MCI after adjusting for covariates (third vs. first tertile, adjusted odds ratio: 0.333; 95% confidence interval: 0.133∼0.831; P<0.05). The white rice pattern was associated with the prevalence of MCI in the crude analysis. However, after adjusting for all confounding factors, no association was found. The "beverage and nuts" pattern was inversely associated with the prevalence of MCI. In the future, longitudinal population-based studies and randomized clinical trials are required to confirm the effect of potential dietary patterns on cognitive impairment and reveal the underlying mechanism of their association.
... Further caffeine intake comes from tea, energy or sports drinks, and various chocolate products (Fitt et al., 2013). While many advocates for the neuroprotective and cognitive-enhancing effects of caffeine (McLellan et al., 2016;Panza et al., 2015), others proposed that the magnitude of these benefits are negligible, furthermore, a higher dose can have detrimental effects on physical and mental health (Nehlig, 2010(Nehlig, , 1999. As past literature tended to treat memory as a subset of cognitive functions, the specific effect of caffeine on memory has not been thoroughly discussed. ...
... Similar interactions between caffeine and sex, where a larger protective effect for females than males has been reported in a systematic review (Panza et al., 2015). However, Panza et al. (2015) focused on the role of habitual caffeine consumption in preventing cognitive decline and dementia, without detailing mechanisms underlying this sex effect. ...
... Similar interactions between caffeine and sex, where a larger protective effect for females than males has been reported in a systematic review (Panza et al., 2015). However, Panza et al. (2015) focused on the role of habitual caffeine consumption in preventing cognitive decline and dementia, without detailing mechanisms underlying this sex effect. Given the various metabolic pathways of caffeine, habitual consumption may participate in physiological processes that affect global cognition (de Mejia and Ramirez-Mares, 2014), but this does not translate to the effect of caffeine on memory tasks in the healthy population. ...
Caffeine is a widely used nootropic drug, but its effects on memory in healthy participants have not been sufficiently evaluated. Here we review evidence of the effects of caffeine on different types of memory, and the associated drug, experimental, and demographical factors. There is limited evidence that caffeine affects performance in memory tasks beyond improved reaction times. For drug factors, a dose-response relationship may exist but findings are inconsistent. Moreover, there is evidence that the source of caffeine can modulate its effects on memory. For experimental factors, past studies often lacked a baseline control for diet and sleep and none discussed the possible reversal of withdrawal effect due to pre-experimental fasting. For demographic factors, caffeine may interact with sex and age, and the direction of the effect may depend on the dose, individual tolerance, and metabolism at baseline. Future studies should incorporate these considerations, as well as providing continued evidence on the effect of caffeine in visuospatial, prospective, and implicit memory measures.
... Some dietary components of the Mediterranean diet have been traditionally considered as preventing factors of cardiovascular diseases (including stroke), and some age-related cognitive disorders (such as AD and VaD) [32][33][34][35][36]. Recently, there has been increasing interest in the exploration of the role of coffee intake in some neurological and neuropsychiatric disorders, although large epidemiological investigations are still inconclusive in terms of a protective role of caffeine in the risk of cognitive disorders. Indeed, while many studies have found a protective role of coffee in cognitive impairment [37], an extensive neuropsychological evaluation was not always performed, and the association was not found, or at least not for all, cognitive domains [37]. Similarly, there is still no consensus regarding a dose-response effect on cognition or mood [37][38][39][40][41]. ...
... Some dietary components of the Mediterranean diet have been traditionally considered as preventing factors of cardiovascular diseases (including stroke), and some age-related cognitive disorders (such as AD and VaD) [32][33][34][35][36]. Recently, there has been increasing interest in the exploration of the role of coffee intake in some neurological and neuropsychiatric disorders, although large epidemiological investigations are still inconclusive in terms of a protective role of caffeine in the risk of cognitive disorders. Indeed, while many studies have found a protective role of coffee in cognitive impairment [37], an extensive neuropsychological evaluation was not always performed, and the association was not found, or at least not for all, cognitive domains [37]. Similarly, there is still no consensus regarding a dose-response effect on cognition or mood [37][38][39][40][41]. ...
... Indeed, while many studies have found a protective role of coffee in cognitive impairment [37], an extensive neuropsychological evaluation was not always performed, and the association was not found, or at least not for all, cognitive domains [37]. Similarly, there is still no consensus regarding a dose-response effect on cognition or mood [37][38][39][40][41]. ...
To date, interest in the role of coffee intake in the occurrence and course of age-related neurological and neuropsychiatric disorders has provided an inconclusive effect. Moreover, no study has evaluated mocha coffee consumption in subjects with mild vascular cognitive impairment and late-onset depression. We assessed the association between different quantities of mocha coffee intake over the last year and cognitive and mood performance in a homogeneous sample of 300 non-demented elderly Italian subjects with subcortical ischemic vascular disease. Mini Mental State Examination (MMSE), Stroop Colour-Word Interference Test (Stroop T), 17-items Hamilton Depression Rating Scalfe (HDRS), Activities of Daily Living (ADL), and Instrumental ADL were the outcome measures. MMSE, HDRS, and Stroop T were independently and significantly associated with coffee consumption, i.e., better scores with increasing intake. At the post-hoc analyses, it was found that the group with a moderate intake (two cups/day) had similar values compared to the heavy drinkers (≥three cups/day), with the exception of MMSE. Daily mocha coffee intake was associated with higher cognitive and mood status, with a significant dose-response association even with moderate consumption. This might have translational implications for the identification of modifiable factors for vascular dementia and geriatric depression.
... Furthermore, caffeine and caffeine-containing beverages, such as coffee and tea, appear to act as protective factors when consumed regularly [67,68]. Coffee consumption appears to reduce the risk of depression, with the most significant protective impact observed at 400 mL/day [67]. ...
... Additionally, cross-sectional and longitudinal population-based investigations also imply that coffee, tea, and caffeine alone may protect against cognitive impairment/decline in later life. However, this link was not consistently observed across all cognitive domains that were tested [68]. ...
(1) Background: Attention-deficit/hyperactivity disorder (ADHD) is typically treated with stimulant medications, which may lead to several adverse effects. Recent animal studies have shown that caffeine can improve the symptoms of ADHD. This systematic review and meta-analysis sought to evaluate the effect of caffeine on ADHD symptoms in children. (2) Methods: PubMed, Embase, and Cochrane databases were searched for randomized controlled trials comparing caffeine with placebo in children, comparing overall symptoms of ADHD, inattention, hyperactivity, and impulsivity. (3) Results: We included seven RCTs in the systematic review for qualitative assessment, with 104 patients aged 5 to 15 years. Four of these studies (n = 76) were included in the meta-analysis. After qualitative analysis, four studies indicated no improvement in any of the ADHD symptoms compared with placebo. One study showed improvement in ADHD symptoms based on 1 of 5 scales applied. One study indicated significant improvement in general symptoms, inattention, and hyperactivity. One study indicated improvement in sustained attention but a worsening of impulsivity. In contrast, when using a quantitative analysis of the general symptoms of ADHD, the data showed no significant difference when comparing placebo with caffeine (standardized mean difference −0.12; 95% CI −0.44 to 0.20; p = 0.45; I2 = 0%). (4) Conclusion: overall, the totality of the evidence suggests no significant benefit of caffeine over placebo in the treatment of children with ADHD.
... Tea is a beloved beverage enjoyed in many cultures worldwide, which consumes in staggering quantities of more than two billion cups daily (Kochman et al., 2020). Experimental evidences indicate that caffeine and tea polyphenols contained in tea have neuroprotective effects, such as anti-inflammatory, or anti-oxidant effects Panza et al., 2015;Feng et al., 2018). In addition, research reveals that tea may protect against AD, through reducing amyloid-β (Aβ) in the brain (Arendash & Cao, 2010;Polito et al., 2018). ...
... It is consistent with previous studies. A systematic review which enrolled several cross-sectional and longitudinal population-based studies demonstrated a protective effect of coffee, tea, and caffeine against cognitive impairment regression in later life, further supporting our findings (Panza et al., 2015). ...
Purpose
Dementia affects as many as 130 million people, which presents a significant and growing medical burden globally. This meta-analysis aims to assess whether tea intake, tea consumption can reduce the risk of dementia, Alzheimer’s disease (AD) and Vascular dementia (VD).
Patients and methods
Cochrane Library, PubMed and Embase were searched for cohort studies from inception to November 1, 2022. The Newcastle Ottawa Quality Assessment Scale (NOS) was applied to evaluate the risk of bias of the included studies. We extracted the data as the relative risks (RRs) for the outcome of the interest, and conducted the meta-analysis utilizing the random effect model due to the certain heterogeneity. Sensitivity analysis were performed by moving one study at a time, Subgroup-analysis was carried out according to different ages and dementia types. And the funnel plots based on Egger’s and Begger’s regression tests were used to evaluate publication bias. All statistical analyses were performed using Stata statistical software version 14.0 and R studio version 4.2.0.
Results
Seven prospective cohort studies covering 410,951 individuals, which were published from 2009 and 2022 were included in this meta-analysis. The methodological quality of these studies was relatively with five out of seven being of high quality and the remaining being of moderate. The pooling analysis shows that the relationship between tea intake or consumption is associated with a reduced risk of all-cause dementia (RR = 0.71, 95% CI [0.57–0.88], I ² = 79.0%, p < 0.01). Further, the subgroup-analysis revealed that tea intake or consumption is associated with a reduced risk of AD (RR = 0.88, 95% CI [0.79–0.99], I ² = 52.6%, p = 0.024) and VD (RR = 0.75, 95% CI [0.66–0.85], I = 0.00%, p < 0.001). Lastly, tea intake or consumption could reduce the risk of all-cause dementia to a greater degree among populations with less physical activity, older age, APOE carriers, and smokers.
Conclusion
Our meta-analysis demonstrated that tea (green tea or black tea) intake or consumption is associated with a significant reduction in the risk of dementia, AD or VD. These findings provide evidence that tea intake or consumption should be recognized as an independent protective factor against the onset of dementia, AD or VD.
... A meta-analysis by Wu et al. has shown that a diminished risk of development of dementias in humans (including AD) was observed with daily consumption of one-two cups of coffee [146]. Interestingly, research part of the Italian Longitudinal Study on Aging (ILSA) suggested that older people with normal cognitive function who increased their coffee consumption had a higher rate of developing MCI, while constant-over-time, moderate coffee consumption was linked to a lower rate of MCI incidence [147,148]. However, research does not support the theory that caffeine could prevent AD [149], although as reported in epidemiological research, drinking coffee and caffeine can possibly help treat AD [147]. ...
... Interestingly, research part of the Italian Longitudinal Study on Aging (ILSA) suggested that older people with normal cognitive function who increased their coffee consumption had a higher rate of developing MCI, while constant-over-time, moderate coffee consumption was linked to a lower rate of MCI incidence [147,148]. However, research does not support the theory that caffeine could prevent AD [149], although as reported in epidemiological research, drinking coffee and caffeine can possibly help treat AD [147]. ...
Alzheimer's disease is the most common cause of dementia in the world. Lack of an established pathology makes it difficult to develop suitable approaches and treatment for the disease. Besides known hallmarks, including amyloid β peptides cumulating in plaques and hyperphosphorylated tau forming NFTs, inflammation also plays an important role, with known connections to the diet. In AD, adhering to reasonable nutrition according to age-related principles is recommended. The diet should be high in neuroprotective foods, such as polyunsaturated fatty acids, antioxidants, and B vitamins. In addition, foods capable of rising BDNF should be considered because of the known profitable results of this molecule in AD. Adhering to beneficial diets might result in improvements in memory, cognition, and biomarkers and might even reduce the risk of developing AD. In this review, we discuss the effects of various diets, foods, and nutrients on brain health and possible connections to Alzheimer's disease.
... When compared to genetic risk factors, modifiable factors have the advantage that they can be targeted for intervention. Extensive research has suggested that modifiable risk factors, such as diet, physical activity, smoking, and caffeine intake, influence the risk for development of dementia and AD, and behavioral modification could reduce disease risk [1][2][3][4]. Thus, modifiable risk factors provide a potential window for dementia and AD prevention and intervention. ...
... Engagement in moderate physical activity has been associated with higher cerebrospinal fluid (CSF) amyloid β (Aβ) 42 and lower total tau (T-tau)/ Aβ42 and phosphorylated tau (P-tau)/Aβ42 ratios, which further confirms the protective role of physical activity in AD development [7]. A systematic review [4] of caffeine found evidence supporting favorable effects of coffee consumption on AD risk and cognitive decline. For example, the Cardiovascular Risk Factors, Aging and Dementia study followed 1409 participants for 21 years and found that daily coffee consumption of 3-5 cups was associated with a 65% decrease in dementia and a 64% decrease in AD [8]. ...
Modifiable factors can influence the risk for Alzheimer's disease (AD) and serve as targets for intervention; however, the biological mechanisms linking these factors to AD are unknown. This study aims to identify plasma metabolites associated with modifiable factors for AD, including MIND diet, physical activity, smoking, and caffeine intake, and test their association with AD endophenotypes to identify their potential roles in pathophysiological mechanisms. The association between each of the 757 plasma metabolites and four modifiable factors was tested in the wisconsin registry for Alzheimer's prevention cohort of initially cognitively unimpaired, asymptomatic middle-aged adults. After Bonferroni correction, the significant plasma metabolites were tested for association with each of the AD endophenotypes, including twelve cerebrospinal fluid (CSF) biomarkers, reflecting key pathophysiologies for AD, and four cognitive composite scores. Finally, causal mediation analyses were conducted to evaluate possible mediation effects. Analyses were performed using linear mixed-effects regression. A total of 27, 3, 23, and 24 metabolites were associated with MIND diet, physical activity, smoking, and caffeine intake, respectively. Potential mediation effects include beta-cryptoxanthin in the association between MIND diet and preclinical Alzheimer cognitive composite score, hippurate between MIND diet and immediate learning, glutamate between physical activity and CSF neurofilament light, and beta-cryptoxanthin between smoking and immediate learning. Our study identified several plasma metabolites that are associated with modifiable factors. These metabolites can be employed as biomarkers for tracking these factors, and they provide a potential biological pathway of how modifiable factors influence the human body and AD risk.
... Coffee, the most heavily consumed caffeinated beverage, has been a popular research topic in AD, with several epidemiological studies positing its neuroprotective effect [9]. Coffee comprises a few independently neuroprotective components: caffeine, chlorogenic acid, caffeic acid, and trigonelline [10]. ...
... Trigonelline from coffee beans has been shown to alleviate neuronal loss by reducing oxidative stress, astrocyte activity, and neuroinflammation while preserving mitochondrial integrity [13]. The neuroprotective properties of coffee have been heavily linked to its high caffeine content, but this has been difficult to demonstrate independently through epidemiological studies due to the confounding effect of other components in caffeinated beverages [9]. ...
Alzheimer's disease (AD) is the leading cause of dementia, predicted to be the most significant health burden of the 21st century, with an estimated 131.5 million dementia patients by the year 2050. This review aims to provide an overview of the effect of caffeine on AD and cognition by summarizing relevant research conducted on this topic. We searched the Web of Science core collection and PubMed for studies related to the effect of caffeine on AD and cognition using title search terms: caffeine; coffee; Alzheimer's; cognition. There is suggestive evidence from clinical studies that caffeine is neuroprotective against dementia and possibly AD (20 out of 30 studies support this), but further studies, such as the "ideal" study proposed in this review, are required to prove this link. Clinical studies also indicate that caffeine is a cognitive normalizer and not a cognitive enhancer. Furthermore, clinical studies suggest the neuroprotective effect of caffeine might be confounded by gender. There is robust evidence based on in vivo and in vitro studies that caffeine has neuroprotective properties in AD animal models (21 out of 22 studies support this), but further studies are needed to identify the mechanistic pathways mediating these effects.
... In non-clinical populations, poor cognitive functioning has been associated with increased smoking (Campos, Serebrisky, & Castaldelli-Maia, 2016), alcohol drinking (Topiwala & Ebmeier, 2018), and cannabis use (Curran et al., 2016), although for impaired response inhibition specifically there are contradicting findings (Liu et al., 2019b). Although caffeine is often thought to have acute beneficial effects on cognition (Irwin, Khalesi, Desbrow, & McCartney, 2020), there is evidence that contests this (Galindo, Navarro, & Cavas, 2020;Weibel et al., 2020) and its long(er) term effects remain unclear (Cornelis, Weintraub, & Morris, 2020;Panza et al., 2015). ...
... For caffeine, research has focussed predominately on cognitive functioning or sleep. The largest available systematic review, including 28 studies, concluded that there is some evidence that caffeine is protective against cognitive decline (Panza et al., 2015). Despite the fact that caffeine has stimulating properties which are thought to interfere with sleep acutely, a cohort study in 26 305 adolescents with a follow-up of 4 years found no association between average daily caffeine consumption and sleep duration (Patte, Qian, & Leatherdale, 2018). ...
Background
Poor mental health has consistently been associated with substance use (smoking, alcohol drinking, cannabis use, and consumption of caffeinated drinks). To properly inform public health policy it is crucial to understand the mechanisms underlying these associations, and most importantly, whether or not they are causal.
Methods
In this pre-registered systematic review, we assessed the evidence for causal relationships between mental health and substance use from Mendelian randomization (MR) studies, following PRISMA. We rated the quality of included studies using a scoring system that incorporates important indices of quality, such as the quality of phenotype measurement, instrument strength, and use of sensitivity methods.
Results
Sixty-three studies were included for qualitative synthesis. The final quality rating was ‘−’ for 16 studies, ‘– +’ for 37 studies, and ‘+’for 10 studies. There was robust evidence that higher educational attainment decreases smoking and that there is a bi-directional, increasing relationship between smoking and (symptoms of) mental disorders. Another robust finding was that higher educational attainment increases alcohol use frequency, but decreases binge-drinking and alcohol use problems, and that mental disorders causally lead to more alcohol drinking without evidence for the reverse.
Conclusions
The current MR literature increases our understanding of the relationship between mental health and substance use. Bi-directional causal relationships are indicated, especially for smoking, providing further incentive to strengthen public health efforts to decrease substance use. Future MR studies should make use of large(r) samples in combination with detailed phenotypes, a wide range of sensitivity methods, and triangulate with other research methods.
... In addition to its pathological causes, for example, inflammation [7], oxidative stress [8], and endothelial damage [9], physical activity [10], such as tai chi [11], activity participation [12], and sleep duration [13], were also found to be associated with cognitive decline. As there is no effective treatment to slow down the progression of dementia, early prevention is gaining attention [14], among them, nutrition intake is considered as a possible strategy to prevent cognitive decline in the older adult [15]. ...
Background
Numerous studies have demonstrated a positive correlation between diet quality and cognitive performance, indicating that improving diet quality may be beneficial in preventing cognitive decline in older adults. However, few study has investigated the causal relationship between diet quality and cognitive performance. The purpose of this study is to evaluate the causal effects of diet quality on cognitive performance in Chinese adults aged 55 years and older. Particularly, we utilize the Chinese Diet Quality Index (CHEI), a dietary assessment tool tailored for Chinese populations, as a proxy for older adults’ diet quality.
Methods
Data were obtained from the China Health and Nutrition Survey (CHNS) (N=2337\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$N = 2337$$\end{document}, ≥\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\ge$$\end{document}55 years old) conducted in 2004 and 2006. Cognitive function was tested by a subset of items from the Telephone Interview for Cognitive Status-Modified (TICS-m). Data on dietary intake was retrieved from three consecutive 24 hour recalls by participants and its quality was assessed by the 17-items Chinese Healthy Eating Index (CHEI). An Instrumental Variable technique was used to deal with the potential endogeneity of dietary quality. The instrumental variable used in our study is the community mean of CHEI.
Results
After adjusting for socio-demographic factors (age, gender, education, per capita household income), lifestyle habits (smoking, alcohol consumption, physical activity, BMI), and chronic diseases (hypertension, diabetes), our findings revealed that improving diet quality had a significant positive effect on cognitive performance (P=0.020\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$P = 0.020$$\end{document}), particularly in females aged 55-65 years (P=0.003\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$P = 0.003$$\end{document}) and females with primary education and below (P<0.001\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$P < 0.001$$\end{document}).
Conclusion
Our study suggests that improving diet quality and adhering to the Dietary Guidelines for Chinese may enhance cognitive performance in Chinese adults aged 55 years and older.
... We also find that drinking tea and taking exercise can help prevent vascular dementia, while physical discomfort will increase the risk of vMCI and VaD. A systematic review suggests that tea consumption may be protective against late-life cognitive impairment/decline and dementia 34 . A meta-Analysis of prospective studies reveals a protective effect for high physical activity on all-cause dementia 35 , and another study also further reveals the link between physical discomfort and dementia 36 . ...
Hypertension is considered as an independent risk factor for vascular mild cognitive impairment (vMCI) and vascular dementia (VaD). This study was performed to investigate the prevalence, influencing factors and cognitive characteristics of vMCI and VaD in elderly patients with hypertension in China. In the cross-sectional study, we performed cluster random sampling of 3246 people age 60 years and older across the country. All participants were interviewed and screened for hypertension. Among the 1495 hypertensive patients, 57 were diagnosed with vMCI and 48 with VaD according to the criteria of Petersen and DSM-IV, respectively. Logistic regression analyses were performed to evaluate risk and protective factor for vMCI and VaD with Hypertension. And we also assessed their cognitive function by a series of neuropsychological tests. We finally found that: 1) the prevalence of vMCI and VaD in hypertension was 3.8% and 3.2%, respectively, which was much higher than that of normal controls (p<0.05). 2)Multivariate logistic regression analyses showed that advanced age (p<0.001, OR=1.066, 95%CI: 1.030~1.104), sleep too little (p=0.011, OR=2.279, 95%CI: 1.210~4.291) and physical discomfort (p<0.001, OR=6.380, 95%CI: 2.956~13.774) were the risk factors for the development of vMCI in patients with hypertension; advanced age (p=0.002, OR=1.061, 95%CI: 1.021~1.011), physical discomfort (p=0.005, OR=3.922, 95%CI: 1.506~10.214) and depressive symptoms (p<0.001, OR=8.363, 95%CI: 3.023~23.138) were also the risk factor for VaD, while education (p=0.040, OR=0.941, 95%CI: 0.888~0.997), tea drinker (p=0.017, OR=0.483, 95%CI: 0.266~0.878) as well as take exercise (p=0.003, OR=0.416, 95%CI: 0.234~0.737) were protective factors of VaD;3) both overall and specific areas of cognitive function decrease in hypertension patients with vMCI and VaD, and show a gradual trend of aggravation.
... The results of the review suggest that moderate coffee and tea consumption may have a protective effect against cognitive decline and dementia, but the evidence for caffeine consumption is inconclusive. The need for further research to clarify the relationship between coffee, tea, and caffeine consumption and cognitive decline and dementia, as well as to investigate the potential underlying mechanisms of any protective effects observed [13] . Cognitive impairment is a common health issue among older adults. ...
This review aims to examine the effects of tea, coffee, and green tea consumption on human cognitive performance and mental health. Tea, coffee, and green tea are widely consumed beverages worldwide and contain various bioactive compounds that may influence cognitive function and mental health. Research has suggested that caffeine, the primary psychoactive compound in coffee and tea, can improve cognitive function, including attention, alertness, and working memory. The effect of caffeine on cognitive performance may be moderated by individual differences in caffeine metabolism and genetic factors. Green tea contains high levels of catechins, which have been linked to improved cognitive function, such as attention and working memory, as well as reduced risk of cognitive decline and dementia. Theanine, an amino acid found in green tea, has also been associated with relaxation and reduced anxiety. In addition to cognitive performance, tea, coffee, and green tea consumption have been linked to improved mental health outcomes. Research has suggested that coffee consumption may be associated with a lower risk of depression, while green tea consumption has been linked to reduced symptoms of anxiety and stress. However, the evidence regarding the effects of tea, coffee, and green tea on cognitive function and mental health is mixed, and further research is needed to fully understand the potential benefits and risks of these beverages. Additionally, individual differences in caffeine metabolism, genetic factors, and other lifestyle factors may influence the effects of tea, coffee, and green tea on cognitive function and mental health.
... Fruits and beverages such as tea and coffee are the main sources of dietary polyphenols, which have a positive effect on cognition and memory [19,48,49]. However, one study found that habitual coffee and tea drinking had mixed effects on cognitive improvement [50]. Scientific evidence confirmed that adequate vegetable and fruit consumption has a beneficial influence on health and can prevent cognitive impairment due to the presence of antioxidants and anti-inflammatory factors [51,52]. ...
The aim of this study was to quantify the dietary patterns (DPs) of Polish esports players aged 18–26 years. Data were obtained via questionnaires that assessed dietary habits and frequency of food consumption. Dietary patterns were derived using Principal Component Analysis (PCA) and Factor Analysis (FA). In total, nine distinct DPs were identified. Eight DPs were considered unhealthy; fast food', 'High-processed food, meat and confectionery', 'Sweet', 'Fat-diary products', 'Vegetable-fruit', 'Spices and additives', 'Fats' and 'Cereal'; and only one was deemed healthy. E-athletes presented mostly poor dietary habits, which included: irregular eating of meals, frequent snacking, at least three meals a day and composition of snacks, frying of meat dishes and sweetening of hot drinks. Healthy dietary habits included proper hydration during the day and consumption of mainly non-sparkling water. The unbalanced and largely unhealthy dietary habits of esports players raise health concerns for these e-athletes, particularly when combined with a sedentary lifestyle. Future research could assess the nutritional knowledge of this group as it relates to national guidelines, investigate interventions designed to introduce healthier eating options into their lifestyle and examine the relationship between DPs and health or cognitive performance.
... Bioactive compounds abundant in matcha such as caffeine, theanine and catechins have been linked to multiple benefits to the cognitive function. Caffeine is a psychoactive stimulant that results in increased alertness and enhanced cognitive performance as reported by multiple studies and systematic reviews (Smit and Rogers, 2000;Snel and Lorist, 2011;McLellan et al., 2016;Panza et al., 2015). In addition, previous literature showed that theanine influences neurogenesis and cognitive function positively in a manner independent of other compounds found in matcha (Yoneda et al., 2019;Camfield et al., 2014). ...
Matcha is a powdered form of Japanese green tea that has been gaining global popularity recently. Matcha tea has various health benefits, including an enhancing effect on cognitive function, cardio-metabolic health, and anti-tumorogenesis. To date, randomized clinical trials (RCT) showed that matcha decreases stress, slightly enhances attention and memory, and has no effect on mood. Results regarding the effect of matcha on cognitive function are contradictory and more RCTs are warranted. The cardio-metabolic effects of matcha have only been studied in animals, but findings were more homogenous. Consuming matcha with a high-fat diet resulted in decreased weight gain velocity, food intake, improved serum glucose and lipid profile, reduced inflammatory cytokines and ameliorated oxidative stress. Evidence regarding the anti-tumor function of matcha is very limited. Findings showed that matcha can affect proliferation, viability, antioxidant response, and cell cycle regulation of breast cancer cells. Nonetheless, more studies are needed to examine this effect on different types of cancer cells, and there is also a need to verify it using animal models. Overall, the evidence regarding the effect of matcha tea on cognitive function, cardio-metabolic function, and anti-tumor role is still limited, and conclusions cannot be drawn.
... Although from the current clinical research, it seems uncertain to draw the conclusion that the consumption of tea, especially green tea, is significantly related to the improvement of cognitive impairment in AD patients. However, scientists do not deny that tea and its effective ingredients have certain neuroprotective effects [105][106][107]. Especially in animal experiments and in vitro experiments, tea has shown a better effect on improving cognitive function [108,109]. ...
Alzheimer’s disease (AD) is an incurable degenerative disease of the central nervous system and the most common type of dementia in the elderly. Despite years of extensive research efforts, our understanding of the etiology and pathogenesis of AD is still highly limited. Nevertheless, several hypotheses related to risk factors for AD have been proposed. Moreover, plant-derived dietary polyphenols were also shown to exert protective effects against neurodegenerative diseases such as AD. In this review, we summarize the regulatory effects of the most well-known plant-derived dietary polyphenols on several AD-related molecular mechanisms, such as amelioration of oxidative stress injury, inhibition of aberrant glial cell activation to alleviate neuroinflammation, inhibition of the generation and promotion of the clearance of toxic amyloid-β (Aβ) plaques, inhibition of cholinesterase enzyme activity, and increase in acetylcholine levels in the brain. We also discuss the issue of bioavailability and the potential for improvement in this regard. This review is expected to encourage further research on the role of natural dietary plant polyphenols in the treatment of AD.
... Arguably the most popular supplement used to enhance performance is caffeine, which can be consumed through various drinks (e.g., coffee and energy drinks) or as pills. Caffeine increases the excitability of the sympathetic nervous system [11,46] and consequently is used to enhance alertness-although there are large individual differences with regards to the response to caffeine and its effect on cognition or physical performance [21,23,81]. However, there are many more foods and food supplements that potentially enhance performance-and the market for such products exceeds 100 billion USD, with an annual growth rate of 3-4% [87]. ...
This work explores perceptions of performance enhancer usage in esports. Specifically, we explored the perception of: food and food supplements; non-medical use of prescription drugs; drugs with some social acceptance (e.g. alcohol, nicotine, cannabis); drugs with lower social acceptance (e.g., psychedelics, opioids); and non-invasive brain stimulation (e.g. transcranial direct current stimulation). A mixed-methods approach was used to triangulate findings around three data sets, including both prompted and unprompted online forum comments, as well as survey data. The studies evidence that players are willing to use or are already using enhancers to increase their in-game performance, and that players are generally concerned about the use of enhancers in professional esports contexts. Furthermore, the community perceives that a substantial number of e-athletes use enhancers. The core contribution of this work is a comprehensive investigation into perspectives of esports performance enhancement, which highlights the urgent need for further research, as well as regulation by esports leagues.
... This suggests that cognition enhancements seen with caffeine intake could be partly due to its ability to promote cholinergic neurotransmission in the CNS. Numerous studies indicate that caffeine could help treat AD due to its beneficial effects on cognition, learning, memory, and neuroprotective effects (Arendash & Cao, 2010;Ikram et al., 2020;Mohamed et al., 2013;Panza et al., 2015;Ribeiro et al., 2002;Zhou & Zhang, 2021). Caffeine also reduces β-site amyloid precursor protein cleaving enzyme-1 (BACE-1) expression and activity (Tabaton, 2009). ...
Natural products have significantly contributed to drug discovery for neurodegenerative diseases. Caffeine is one of the well‐known central nervous system(CNS)‐active natural products. Besides its CNS stimulant properties, it is a mild inhibitor of acetylcholinesterase (AChE) and possesses memory‐enhancing properties. The present work aimed to improve the AChE inhibition activity of the caffeine. The rationally designed caffeine‐based triazoles were synthesized and evaluated in vitro for cholinesterase and β‐site amyloid precursor protein cleaving enzyme‐1 (BACE‐1) inhibitory activities. The attachment of triazole to the caffeine enhances its AChE inhibition activity from half‐maximal inhibitory concentration (IC50) of 129 µM to 0.49 µM (derivative, 6l). The caffeine core interacts with the peripheral anionic site, whereas the benzyl triazole occupies the catalytic anionic site located at the bottom of the active site gorge. The structure–activity relationship revealed that the four‐atom ester linker is superior to shorter linkers for connecting the caffeine core to the triazole. The 2,6‐difluorobenzyl triazole‐linked caffeine derivative, 6d, exhibits dual inhibition of AChE and BACE‐1 with IC50 values of 1.43 and 10.9 µM, respectively. The derivative 6d inhibits AChE via a mixed‐type mode with an inhibition rate constant (Ki) value of 2.35 μM, which was corroborated by docking studies. The triazole 6d has an acceptable stability profile in human liver microsomes (t1/2 = 54 min) and was found to possess CNS permeability when evaluated using the parallel artificial membrane permeability blood–brain barrier assay. The results presented herein warrant investigating caffeine‐based triazoles in preclinical models of Alzheimer's disease.
... The health benefit of tea includes prevention of cancer, diabetes, cardiovascular and neurodegenerative diseases, reduction of body weight, and alleviation of metabolic syndrome (Zhao et al. 2015a;Yang et al. 2018). The p olyphenols in tea p oss ess antiproliferative, anti-inflammatory, antioxidant, antiviral, and antibacterial properties (Zhang et al. 2013a;Abd El-Aty et al. 2014;Panza et al. 2015;Chung et al. 2020). Besides, theanine, a unique amino acid derived during tea fermentation, has been shown to have neuroprotective effects and antiviral activities against the influenza and SARS (Severe Acute Respiratory Syndrome) viruses including the new SARSCoV-2 (Mitsui et al. 2020;Sharma et al. 2020). ...
Tea (Camellia sinensis L.) is a high valued beverage worldwide since ancient times; more than three billion cups of tea are consumed each day. Leaf extracts of the plant are used for food preservation, cosmetics, and medicinal purposes. Nevertheless, tea contaminated with mycotoxins poses a serious health threat to humans. Mycotoxin production by tea fungi is induced by a variety of factors,
including poor processing methods and environmental factors such as high temperature and humidity. This review summarizes the studies published to date on mycotoxin prevalence, toxicity, the effects of climate change on mycotoxin production, and the methods used to detect and decontaminate tea mycotoxins. While many investigations in this domain have been carried out on the prevalence of aflatoxins and ochratoxins in black, green, pu-erh, and herbal teas, much less information is available on zearalenone, fumonisins, and Alternaria toxins. Mycotoxins in teas were detected using several methods; the most commonly used being the High-Performance Liquid Chromatography (HPLC) with fluorescence detection, followed by HPLC with tandem mass spectrometry, gas chromatography and enzyme-linked immunosorbent assay. Further, mycotoxins
decontamination methods for teas included physical, chemical, and biological methods, with physical methods being most prevalent. Finally, research gaps and future directions have also been discussed.
... Therefore, it is crucial that a long term, low-toxicity, and cost-effective method to treat or even prevent AD is discovered. Research has demonstrated that coffee may pose as a potential substance for AD treatment or prevention (49)(50)(51)(52)(53)(54)(55)(56). ...
Background
Alzheimer's disease (AD) is a multifactorial neurological disease with neurofibrillary tangles and neuritic plaques as histopathological markers. Due to this, although AD is the leading cause of dementia worldwide, clinical AD dementia cannot be certainly diagnosed until neuropathological post-mortem evaluation. Coffee has been reported to have neurologically protective factors, particularly against AD, but coffee brand and type have not been taken into consideration in previous studies. We examined the discrepancies among popular commercial and instant coffees in limiting the development and progression through Aβ1-40 and Aβ1-42 production, and hypothesized that coffee consumption, regardless of brand or type, is beneficial for stalling the progression and development of Aβ-related AD.
Methods
Coffee samples from four commercial coffee brands and four instant coffees were purchased or prepared following given instructions and filtered for the study. 5, 2.5, and 1.25% concentrations of each coffee were used to treat N2a/APPswe cell lines. MTT assay was used to assess cell viability for coffee concentrations, as well as pure caffeine concentrations. Sandwich ELISA assay was used to determine Aβ concentration for Aβ1-40 and Aβ1-42 peptides of coffee-treated cells.
Results
Caffeine concentrations were significantly varied among all coffees (DC vs. MDC, PC, SB, NIN, MIN p < 0.05). There was no correlation between caffeine concentration and cell toxicity among brands and types of coffee, with no toxicity at 0.5 mg/ml caffeine and lower. Most coffees were toxic to N2a/APPswe cells at 5% (p < 0.05), but not at 2.5%. Most coffees at a 2.5% concentration reduced Aβ1-40 and Aβ1-42 production, with comparable results between commercial and instant coffees.
Conclusion
All coffees tested have beneficial health effects for AD through lowering Aβ1-40 and Aβ1-42 production, with Dunkin' Donuts® medium roast coffee demonstrating the most consistent and optimal cell survival rates and Aβ concentration. On the other hand, Starbucks® coffee exhibited the highest cell toxicity rates among the tested coffees.
... 2 Whether long-term, habitual, caffeine intake reduces or delays age-related cognitive impairment is unclear. 3 Most studies of cognitive decline or dementia present results separately for each dietary source of caffeine, thus separating beverage-specific associations from caffeine-specific associations is difficult. Meta-analyses of prospective studies of coffee consumption report no association with incident dementia or a nonlinear shaped association whereby light to moderate coffee drinking is protective, whereas none or very high intakes are relatively deleterious. ...
Objective:
To examine the association between caffeine intake and cognitive impairment. Caffeine-neuropathology correlations and interactions with lifestyle and genetic factors impacting caffeine metabolism and response were also tested.
Methods:
We included 888 participants aged 59+ from the Rush Memory and Aging Project(MAP) and 303,887 participants aged 55+ from UK Biobank(UKB). MAP participants took part in annual cognitive testing. Diagnosis of dementia was based on clinical neurological examination and standardized criteria. A subset provided postmortem tissue for neuropathologic evaluation for common age-related diseases (e.g. AD, Lewy bodies, vascular). For UKB, dementia was determined by linked hospital and death records. Self-reported caffeine intake was estimated using food-frequency questionnaires in both cohorts. Cox proportional hazard ratio(HR), regression and mixed models were used to examine associations of caffeine intake with incident dementia, cognitive decline, and neuropathology.
Results:
In MAP, compared to ≤100mg/d, caffeine intake >100mg/d was associated with a significantly higher HR(95%CI) of all-cause[1.35(1.03,1.76)] and Alzheimer's[1.41(1.07,1.85)] dementia. Caffeine intake was not associated with cognitive decline. In UKB, compared to ≤100mg/d, the HRs(95%CI) of all-cause dementia for consuming 100≤200, 200≤300, 300≤400 and >400mg/d were 0.83(0.72,0.94), 0.74(0.64,0.85), 0.74(0.64,0.85) and 0.92(0.79,1.08), respectively. Similar results were observed for Alzheimer's dementia. In MAP, caffeine intake was inversely associated with postmortem Lewy bodies but no other age-related pathologies. Caffeine intake >100mg/d was associated with lower neocortical type Lewy bodies[Odds ratio(95%CI): 0.40(0.21,0.75)].
Interpretation:
Caffeine intake was inconsistently associated with clinical dementia; potentially explained by cohort differences in underlying dementia etiology. Lewy bodies may link caffeine to lower risk in some persons. This article is protected by copyright. All rights reserved.
... In animal experiments, caffeine has been shown to promote improved memory and reverse the pathophysiology of Alzheimer's disease. Drinking caffeine-containing substances can thus help maintain cognitive function [53]. ...
Background:
This study examines correlates of disabilities related to ADL, IADL, mobility, and frailty in men and women with a nationally representative sample of older adults living in the community.
Methods:
A total of 10,898 noninstitutionalized Taiwanese nationals aged 65 years and older enrolled in the 2001 (N = 2,064), 2005 (N = 2,727), 2009 (N = 2,904), and 2013 (N = 3,203) National Health Interview Survey (NHIS) were analyzed.
Results:
The prevalence of mobility disabilities and frailty in older adults in Taiwan decreased during the past decade ([Formula: see text], [Formula: see text]). Exercise, social engagement, and tea and coffee intake were found to be associated with lower levels of all types of disabilities in both men and women. In addition, a diet based on carbohydrates, falls, depressive symptomatology, lung and metabolic diseases were risks for most of the disabilities under consideration. Gender-specific independent correlates included: being married (OR = 0.63, 95%CI: 0.40-0.98), eggs/beans/fish/meat consumption (OR = 0.35, 95% CI = 0.16-0.80); depressive symptoms, obesity and cataracts, which were associated with higher IADL (OR = 3.61, 1.63, and 1.18, respectively) and frailty limitations (OR = 10.89, 1.27, and 1.20, respectively) in women. Cognitive impairment was found to be an important correlate for ADL limitations in men (OR = 3.64, 95%CI: 2.38-5.57).
Conclusions:
Exercise, social participation and diet (more tea and coffee intake and lower carbohydrates) were correlates for lower levels of disability. Some gender-specific correlates were also identified, including associations of disability with depressive symptoms, obesity, and cataracts that were more distinct in women, and lower levels of disability which were especially significant in men who were married, eat more eggs, beans, fish, and meat, and those free from cognitive impairment.
... Caffeine has also been shown to exhibit anti-neuroinflammatory properties as well as decreasing tau protein phosphorylation in the hippocampus [190]. In low to moderate doses, caffeine inhibits AChE, thereby improving cognitive actions and reducing the progression of AD [191]. Eugenol, found in cloves, has been reported to reduce amyloid plagues and increase memory in rat models induced with Aβ peptides [192]. ...
Alzheimer’s disease (AD) rate is accelerating with the increasing aging of the world’s population. The World Health Organization (WHO) stated AD as a global health priority. According to the WHO report, around 82 million people in 2030 and 152 million in 2050 will develop dementia (AD contributes 60% to 70% of cases), considering the current scenario. AD is the most common neurodegenerative disease, intensifying impairments in cognition, behavior, and memory. Histopathological AD variations include extracellular senile plaques’ formation, tangling of intracellular neurofibrils, and synaptic and neuronal loss in the brain. Multiple evidence directly indicates that oxidative stress participates in an early phase of AD before cytopathology. Moreover, oxidative stress is induced by almost all misfolded protein lumps like α-synuclein, amyloid-β, and others. Oxidative stress plays a crucial role in activating and causing various cell signaling pathways that result in lesion formations of toxic substances, which foster the development of the disease. Antioxidants are widely preferred to combat oxidative stress, and those derived from natural sources, which are often incorporated into dietary habits, can play an important role in delaying the onset as well as reducing the progression of AD. However, this approach has not been extensively explored yet. Moreover, there has been growing evidence that a combination of antioxidants in conjugation with a nutrient-rich diet might be more effective in tackling AD pathogenesis. Thus, considering the above-stated fact, this comprehensive review aims to elaborate on the basics of AD and antioxidants, including the vitality of antioxidants in AD. Moreover, this review may help researchers to develop effectively and potentially improved antioxidant therapeutic strategies for this disease as it also deals with the clinical trials in the stated field.
... which was similar to our results. The caffeine in tea may improve human cognition and catechins contained in tea were strong antioxidants against oxidative stress [46]. ...
Background
Subjective cognitive decline (SCD) may be the first symptomatic manifestation of Alzheimer’s disease, but information on its health correlates is still sparse in Chinese older adults. This study aimed to estimate SCD symptoms and its association with socio-demographic characteristics, common chronic diseases among southern Chinese older adults.
Methods
Participants aged 60 years and older from 7 communities and 2 nursing homes in Guangzhou were recruited and interviewed with standardized assessment tools. Pittsburgh Sleep Quality Index (PSQI), Patient Health Questionnaire–9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) were used to measure poor sleep quality, depression symptoms and anxiety symptoms. The SCD symptoms were measured by SCD questionnaire 9 (SCD-Q9) which ranged from 0 to 9 points, with a higher score indicating increased severity of the SCD. Participants were divided into low score group (SCD-Q9 score ≤ 3) and higher score group (SCD-Q9 score > 3). Chi-square tests and multivariate logistic regression analysis were used for exploring the influences of different characteristics of socio-demographic and lifestyle factors on SCD symptoms. Univariate and multivariate logistic regression analysis were applied to explore the association between SCD symptoms with common chronic diseases.
Results
A total of 688 participants were included in our analysis with a mean age of 73.79 ( SD = 8.28, range: 60–101), while 62.4% of the participants were females. The mean score of the SCD-Q9 was 3.81 ± 2.42 in the whole sample. A total of 286 participants (41.6%) were defined as the low score group (≤3 points), while 402 participants (58.4%) were the high score group (> 3 points). Multivariate logistic regression analysis revealed that female ( OR = 1.99, 95%CI: 1.35–2.93), primary or lower education level ( OR = 2.58, 95%CI : 1.38–4.83), nursing home ( OR = 1.90, 95%CI : 1.18–3.05), napping habits ( OR = 1.59, 95%CI : 1.06–2.40), urolithiasis ( OR = 2.72, 95%CI : 1.15–6.40), gout ( OR = 2.12, 95%CI : 1.14–3.93), poor sleep quality ( OR = 1.93, 95%CI : 1.38–2.71), depression symptoms ( OR = 3.01, 95%CI : 1.70–5.34) and anxiety symptoms ( OR = 3.11, 95%CI : 1.29–7.46) were independent positive related to high SCD-Q9 score. On the other hand, tea-drinking habits ( OR = 0.64, 95%CI : 0.45–0.92), current smoking ( OR = 0.46, 95%CI : 0.24–0.90) were independent negative related to high SCD-Q9 score.
Conclusions
Worse SCD symptoms were closely related to common chronic diseases and socio-demographic characteristics. Disease managers should pay more attention to those factors to early intervention and management for SCD symptoms among southern Chinese older adults.
... In conclusion, contrary to other neurodegenerative diseases [38,39], the potential effect of coffee and tea on MS severity remains to be uncovered. However, this study suggests a possible harmful effect of high doses of coffee and an intriguing possible interaction with HLA genes. ...
Background and aims
The association between lifestyle factors and Multiple Sclerosis (MS) disease severity and progression has been investigated to a lesser extent compared with susceptibility to the disease. We aimed to assess the impact of lifetime coffee and tea consumption on MS severity.
Methods
Design: a cross-sectional study. Two hundred and eight patients (139 women and 69 men) consecutively admitted to the Department of Neurology in Novara, Italy were asked about their lifetime consumption of coffee and tea. The lifetime intensity of consumption (cups/day) was estimated as the weighted sum of the mean number of standard cups drunk per day at different ages. A measure of cumulative lifetime load of the exposure was expressed in terms of cup-years. Disease severity was estimated by the Multiple Sclerosis Severity Score (MSSS). HLA-DRB1*15 and HLA-A*02 genotyping was performed in 167 patients.
Results
The MSSS was not associated with the status of coffee or tea consumer, or the amount of cups/day or cup-years. The Odds Ratios (OR) for falling in the upper tertile of the MSSS distribution was 1.30 (95% Confidence Interval (CI): 0.47-3.58) for coffee consumers of 1-3 cups/day and 1.14 (95%CI: 0.33-3.95) for 4-8 cups/day vs. non-consumers. The OR was 0.69 (95%CI: 0.35-1.34) for tea consumers vs. non-consumers. The results did not change substantially after controlling for age at onset, education, smoking status, and alcoholic drinking. However, heavy consumers of coffee (4-8 cups/day) more frequently had a progressive form than small consumers (1-3 cups/day) and non-consumers (19% vs. 14% vs. 0%), and the age at MS onset was significantly higher (36.6±10.3; 31.5±9.5; 28.6±8.1 years, p=0.001).
Conclusions
Coffee or tea intake is not associated with different severity of MS. However, we cannot exclude a possible effect of higher doses of coffee for a subgroup of patients.
... Interestingly, acute and appropriate caffeine administration could reverse sleep losseinduced cognitive degradation [24]. Besides its acute effect, the review summarized that long-term caffeine consumption protected against late-life cognitive impairment and dementia [25,26]. However, the effect on cognitive function was controversial as Mendelian randomization meta-analysis did not find any evidence to support beneficial or adverse long-term effects of coffee intake on global cognition [27]. ...
Schizophrenia is a common psychiatric disorder which affects approximately 1% of the population worldwide. However, the complexity of etiology, treatment resistance and side effects induced by current antipsychotics, relapse prevention, and psychosocial rehabilitation are still to be uncovered. Caffeine, as the world's most widely consumed psychoactive drug, plays a crucial role in daily life. Plenty of preclinical and clinical evidence has illustrated that caffeine consumption could have a beneficial effect on schizophrenia. In this review, we firstly summarize the factors associated with the caffeine-induced beneficial effect. Then, a variety of mechanism of actions independent of adenosine receptor signaling will be discussed with an emphasis on the potential contribution of the microbiome–gut–brain axis to provide more possibilities for future therapeutic, prognosis, and social rehabilitation strategy.
... It has been shown that coffee and caffeine can have both -positive and negative effects on human health. On the one hand, caffeine is used to treat premature bronchopulmonary dysplasia, it may have a protective effect in some diseases such as Parkinson's disease [5], Alzheimer's disease (but not yet fully proven) [6], and for some types of tumors (hepatocyte, endometrial, prostate) [7]. Caffeine can prevent the death of pancreatic cells in alcohol poisoning [8]. ...
The effects of long-lasting high concentration coffee and caffeine diets on calcium mobilization in rat hippocampal neurons were studied. Changes in the basal calcium level in the hippocampal neurons of control and experimental rats kept on a coffee or caffeine diet were measured. We also recorded the changes in the Ca2+ transients’ amplitude evoked by membrane depolarization or emptying the Ca2+ depot of the endoplasmic reticulum (ER) induced by caffeine activator of the ryanodine receptors. In rats on a coffee or caffeine diet, the basal Ca2+ level was increased by 7.4% and 11%, respectively, compared to control animals. In these groups, the amplitude of Ca2+ transients increased by 70% and 90%, respectively, of the basal level in response to the membrane depolarization. In the same groups, the amount of Ca2+ released from the ER was increased by two and three times, respectively, compared to the control after activation of ryanodine receptors. We concluded that long-term coffee and caffeine diets in rats cause a significant disruption of the hippocampal neurons’ endoplasmic reticulum function. The diets evoke an increase in Ca2+ concentration in the neurons and an excessive release of Ca2+ in response to excitation. The latter can lead to increased excitability of neurons and their further death from excessive Ca2+ levels.
... 3 Salah satu upaya yang dapat dilakukan untuk mencegah dan memperlambat penurunan fungsi kognitif ialah dengan pemberian asupan makanan, berupa makanan atau minuman yang mengandung kafein. 4 Kafein merupakan zat psikoaktif yang paling sering dikonsumsi oleh 80% populasi dunia dan 90% populasi di Amerika Utara. 5 Kafein tersedia secara luas, banyak dipasarkan, dan dapat diterima secara sosial, bahkan beberapa kalangan meyakini bahwa minuman berkafein dapat meningkatkan performa dan keadaan mental dengan mengurangi atau menghilangkan rasa kantuk. ...
Elderly population which continues to increase in number every year causes various social, economic, and health problems inter alia cognitive dysfunction. One of the efforts that can prevent and slow down the decline in cognitive function is consuming caffeinated beverages. This study was aimed to evaluate the relationship between the pattern of caffeinated beverage consumption and cognitive function among the elderly at GKJ Gondokusuman in Yogyakarta. This was an analytical observational study with a cross-sectional design. We used the modified Food Frequency Questionnaire (FFQ) to measure the consumption patterns of caffeinated beverage meanwhile the cognitive function was measured by using the Mini Mental State Examination (MMSE) and the Clock Drawing Test (CDT). Sample size was determined by using the total sampling method. There were 54 samples of elderly population. Data were analyzed by using the Spearman correlation test which obtained (p=0.023; r=-0.309) for the relationship between caffeinated beverage consumption pattern and cognitive function measured with the MMSE, and (p=0.075; r=0.244) for the relationship between caffeinated beverage consumption pattern and cognitive function measured with the the CDT. In conclusion, there was a significant relationship between caffeinated beverage consumption pattern and cognitive function measured with the MMSE, however, there was no significant relationship between caffeinated beverage consumption pattern and cognitive function measured with the the CDT.Keywords: caffeinated beverage consumption patterns, cognitive function, elderlyAbstrak: Populasi lanjut usia (lansia) yang terus mengalami peningkatan setiap tahunnya menimbulkan berbagai masalah sosial, ekonomi, dan kesehatan, antara lain gangguan fungsi kognitif. Salah satu upaya untuk mencegah dan memperlambat penurunan fungsi kognitif ialah dengan minuman yang mengandung kafein. Penelitian ini bertujuan untuk mengetahui adanya hubungan pola konsumsi minuman berkafein dengan fungsi kognitif lansia di GKJ Gondo-kusuman. Jenis penellitian ialah observasional analitik dan desain potong lintang. Pola konsumsi minuman berkafein diukur dengan Food Frequency Questionnaire (FFQ) yang telah dimodifikasi, sedangkan fungsi kognitif diukur dengan Mini Mental (MMSE) dan Clock Drawing Test (CDT). Penghitungan besar sampel dengan metode total sampling mendapatkan 54 sampel dari populasi, yaitu lansia di GKJ Gondokusuman. Hasil analisis data menggunakan uji Spearman terhadap hubungan antara pola konsumsi minuman berkafein dengan fungsi kognitif yang diukur dengan MMSE mendapatkan (p=0,023; r=-0,309) sedangkan dengan fungsi kognitif yang diukur dengan kuisioner CDT mendapatkan (p=0,075; r 0,244). Simpulan penelitian ini ialah terdapat hubungan bermakna antara pola konsumsi minuman berkafein dengan fungsi kognitif lansia yang dinilai menggunakan MMSE, namun tidak terdapat hubungan bermakna dengan fungsi kognitif lansia yang dinilai menggunakan CDT.Kata kunci: pola konsumsi minuman berkafein, fungsi kognitif, lansia
... Overall, there is a compelling amount of epidemiological, clinical and preclinical evidence that selected polyphenols could improve cognitive performance and be considered in a preventive setting against age-related cognitive loss and neurodegenerative diseases [9,79,[81][82][83]. The most compelling evidence documented so far are for coffee, cocoa and tea, the most common sources of polyphenols, mainly flavonoids [14,16,81,[84][85][86][87]. In addition, berries, such as blueberry and grape, have shown potential to prevent neurodegeneration and cognitive decline [82,83,[88][89][90][91][92]. ...
The scope of evidence on the neuroprotective impact of natural products has been greatly extended in recent years. However, a key question that remains to be answered is whether natural products act directly on targets located in the central nervous system (CNS), or whether they act indirectly through other mechanisms in the periphery. While molecules utilized for brain diseases are typically bestowed with a capacity to cross the blood–brain barrier, it has been recently uncovered that peripheral metabolism impacts brain functions, including cognition. The gut–microbiota–brain axis is receiving increasing attention as another indirect pathway for orally administered compounds to act on the CNS. In this review, we will briefly explore these possibilities focusing on two classes of natural products: omega-3 polyunsaturated fatty acids (n-3 PUFAs) from marine sources and polyphenols from plants. The former will be used as an example of a natural product with relatively high brain bioavailability but with tightly regulated transport and metabolism, and the latter as an example of natural compounds with low brain bioavailability, yet with a growing amount of preclinical and clinical evidence of efficacy. In conclusion, it is proposed that bioavailability data should be sought early in the development of natural products to help identifying relevant mechanisms and potential impact on prevalent CNS disorders, such as Alzheimer’s disease.
Background:
The consumption of coffee has been associated with beneficial effects when it comes to Alzheimer's disease (AD). However, to the best of our knowledge, there are no studies on Conilon coffee consumption in elderly people with AD.
Objective:
Evaluate the effects of Conilon coffee consumption in elderly with AD.
Methods:
The study was carried out with 9 participants who consumed a minimum of 2 cups (200 mL cup) of Conilon coffee per day for 90 days. Cognitive assessment was done before (T0) and after 90 days (T90). Blood analysis was conducted at T0 and T90, as well as the assessment of advanced oxidation protein products (AOPP) and thiobarbituric acid reactive species (TBARS). The levels of chlorogenic acids and caffeine in the coffee beverage were quantified by liquid chromatography.
Results:
During the treatment, the participants consumed at least 550 mg and 540 mg of CGAs and caffeine, respectively. A significant improvement in cognition between T0 and T90 was observed as per MMSE, CTP, and clock drawing tests. Furthermore, there was a significant reduction in AOPP (37%) and TBARS (60%), indicating a reduction in oxidative stress. The consumption of the coffee did not significantly alter any blood parameter, which confirms the safety of the coffee treatment during the 90 days.
Conclusions:
Our study demonstrated for the first time that regular consumption of coffee with high amounts of CGAs and caffeine improves cognitive functions and reduces oxidative stress, without altering blood parameters that indicate possible signs of toxicity in classical target organs.
Oxidative phosphorylation causes free radicals to accumulate in the mitochondria. A rise in oxidative stress is triggered by their high reactivity and unoccupied electrons. The brain is particularly affected by this ailment since it often requires a lot of oxygen and has a high potential for collecting “Reacting Species.” Antioxidant molecules have a critical role in preventing free radical disruption, especially in the brain. In particular, oxidative stress appears to accelerate the progression of neurodegenerative disorders. The goal of this chapter is to identify natural antioxidant molecules that have the highest ability to defend against the formation of free radicals while also gaining a knowledge of how these molecules interact with the central nervous system. This chapter also aims to give an outline of the scientific research and professional opinion on the factors associated with the lifestyle that promotes brain health as people age. The topics to be covered include mental health, brain-stimulating activities, sleep, social interaction, diet and nutrition for brain health, physical activity, and brain-protective antioxidant dietary supplements.
Our present knowledge about the efficacy of tea consumption in improving age-related cognitive disorders is incomplete since previous epidemiological studies provide inconsistent evidence. This unified systematic review and meta-analysis based on updated epidemiological cohort studies and randomized controlled trials (RCTs) evidence aimed to overcome the limitations of previous reviews by examining the efficacy of distinct types of tea consumption. PubMed, Embase, and MEDLINE were searched up to May 20, 2022, and 23 cohorts and 12 cross-sectional studies were included. Random-effects meta-analyses were conducted to obtain pooled RRs or mean differences with 95% CIs. The pooled RRs of the highest versus lowest tea consumption categories were 0.81 (95% CIs: 0.75-0.88) and 0.69 (95% CIs: 0.61-0.77), respectively. The pooled mean difference of four included RCTs revealed a beneficial effect of tea on cognitive dysfunction (MMSE ES: 1.03; 95% CI, 0.14-1.92). Subgroup analyses further demonstrated that green and black tea intake was associated with a lower risk of cognitive disorders in eastern countries, especially in women. The evidence quality was generally low to moderate. The present review provides insight into whether habitual tea consumption can be an effective approach against age-related neurodegenerative cognitive disorders and summarizes potential mechanisms based on currently published literature.
The aim of this study was to explore urine caffeine metabolites in relation to cognitive performance among 2011-2014 National Health and Nutrition Examination Survey participants aged ≥60 years. We hypothesized that urine caffeine metabolites were positively associated with cognition in older adults. Caffeine and 14 of its metabolites were quantified in urine by use of high-performance liquid chromatography-electrospray ionization-tandem quadruple mass spectrometry with stable isotope labeled internal standards. Cognitive assessment was based on scores from the word learning and recall modules. Participants were categorized based on the quartiles of caffeine and its metabolites level. The association between caffeine metabolites and each cognitive dimension was analyzed using multiple logistic regression analysis in adjusted models. Stratification analyses by gender were also performed. For CERAD test, there was a significant association between 1-methyluric acid (OR=0.62, 95% CI: 0.42 to 0.92), 7-methylxanthine(OR=0.49, 95% CI: 0.27 to 0.89), theophylline (OR=0.52, 95% CI: 0.29 to 0.92), as well as paraxanthine (OR=0.49, 95% CI: 0.27 to 0.88) and cognitive function. For animal fluency test, there was a positive association between theophylline (TP) (OR=0.44, 95% CI: 0.22 to 0.89) and cognitive function. The trend that the risk of low cognitive function decreased with increasing concentration of 1-methylxanthine (P trend=0.0229) was also observed. Furthermore, the same trend existed for 3-methylxanthine (p trend = 0.0375) in men. In conclusion, there was a significant positive association between urine caffeine metabolites and cognitive performance in older adults, particularly for theophylline, paraxanthine and caffeine; and the association might be dependent on gender.
Approximately two-thirds of individuals diagnosed with Alzheimer’s disease are women. Although women tend to have longer life expectancy than men, this does not entirely explain the differences in the prevalence of dementia and Alzheimer’s disease. Some evidence suggests that men and women have different patterns of risk and protective factors across the lifespan. The goal of this chapter is to summarize the current evidence on sex differences in genetic and modifiable lifestyle factors that are associated with dementia risk. These include demographic factors such education, vascular, metabolic, lifestyle, and psychosocial factors, and sex-specific factors such as menopause and andropause. Potential mechanisms such as neural reserve and resilience are also summarized. The chapter also summarizes the evidence from recent multidomain lifestyle intervention trials, and the intervention response observed in men and women. While there have been insightful advancements in the field, many important questions still remain. Considerations for future research and risk reduction initiatives are also highlighted.
Coffee is a popular beverage, and it contains caffeine, a psychoactive substance. Consuming coffee may reduce the risk of developing Alzheimer’s disease (AD). However, the association between the reduced risk of developing AD and the consumption of coffee is controversial. Therefore, we conducted a systematic literature review and quantitative synthesis meta-analysis that included dose-response analysis on the relationship between the consumption of coffee and the risk of developing AD. Based on PRISMA guidelines, we analysed standard databases of journals published between January 1999 and May 2020. We included the two population-based cohort studies and one case-control study. All studies included looked at the association between consuming many cups of coffee, the amount of coffee consumed in milligrams per day and the risk of developing AD. The systematic literature review and meta-analysis had 1670 participants with follow-up years that ranged from 5 to 21. The consumption of moderate or 3-5 cups per day reduces the risk of developing AD. The pooled relative risk and 95% confidence interval of the 3 included studies were 0.63 (0.3, 1.54). Dose-response curve analysis appears to be U-shaped. The results of the forest plot showed that there is low heterogeneity between the studies. Plotting the funnel plot and the Galbraith plot demonstrated publication bias of the three included studies. More prospective and long-term studies have to be conducted in other countries to determine the exact risk of developing AD.
Alzheimer’s disease is a progressive neurodegenerative disease, usually associated with old age. With the increasing geriatric population throughout the world, it will pose a great socio-economic burden on the healthcare system and the caregivers. The clinically approved drugs for management of this disease include cholinesterase inhibitors and memantine. But these drugs modulate only the symptoms of this disease rather than addressing the underlying pathology. Therefore, there is an urgent need to discover new therapeutic agents which, coupled with effective diagnostics, can prove effective in therapeutic management of this disease. Phosphodiesterase inhibitors represent an emerging class of drugs with several isoforms reported to play a crucial role in the pathology of this disease. This review discusses various phosphodiesterase inhibitors which are in preclinical and clinical studies along with physicochemical properties that impact CNS penetration and subsequent efficacy.
Background
Modifiable factors can influence the risk for Alzheimer’s disease (AD) and serve as targets for intervention; however, the biological mechanisms linking these factors to AD are unknown. This study aims to identify plasma metabolites associated with modifiable factors for AD, including MIND diet, physical activity, smoking, and caffeine intake, and test their association with AD endophenotypes to identify their potential roles in pathophysiological mechanisms.
Methods
The association between each of the 757 plasma metabolites and four modifiable factors was tested in the Wisconsin Registry for Alzheimer’s Prevention cohort of initially cognitively unimpaired, asymptomatic middle-aged adults. After Bonferroni correction, the significant plasma metabolites were tested for association with each of the AD endophenotypes, including twelve cerebrospinal fluid (CSF) biomarkers, reflecting key AD pathophysiologies, and four cognitive composite scores. Finally, causal mediation analyses were conducted to evaluate possible mediation effects. Analyses were performed using linear mixed-effects regression.
Results
A total of 27, 3, 23, and 24 metabolites were associated with MIND diet, physical activity, smoking, and caffeine intake, respectively. Potential mediation effects include beta-cryptoxanthin in the association between MIND diet and Preclinical Alzheimer Cognitive Composite score, hippurate between MIND diet and Immediate Learning, glutamate between physical activity and CSF neurofilament light, and beta-cryptoxanthin between smoking and Immediate Learning.
Conclusion
Our study identified several plasma metabolites that are associated with modifiable factors. These metabolites can be employed as biomarkers for tracking these factors, and they provide a potential biological pathway of how modifiable factors influence the human body and AD risk.
Studying the correlation between cerebrospinal fluid (CSF) metabolites and the Alzheimer's Disease (AD) biomarkers may offer a window to the alterations of the brain metabolome and unveil potential biological mechanisms underlying AD. In this analysis, 308 CSF metabolites from 338 individuals of Wisconsin Registry for Alzheimer's Prevention and Wisconsin Alzheimer's Disease Research Center were included in a principal component analysis (PCA). The resulted principal components (PCs) were tested for association with CSF total tau (t-tau), phosphorylated tau (p-tau), amyloid β 42 (Aβ42), and Aβ42/40 ratio using linear regression models. Significant PCs were further tested with other CSF NeuroToolKit (NTK) and imaging biomarkers. Using a Bonferroni corrected p <0.05, five PCs were significantly associated with CSF p-tau and t-tau and three PCs were significantly associated with CSF Aβ42. Pathway analysis suggested that these PCS were enriched in six pathways, including metabolism of caffeine and nicotinate and nicotinamide. This study provides evidence that CSF metabolites are associated with AD pathology through core AD biomarkers and other NTK markers and suggests potential pathways to follow up in future studies.
Free- radicals (Oxygen and Nitrogen species) are formed in mitochondria during the oxidative phosphorylation. Their high reactivity, due to not-engaged electrons, leads to an increase of the oxidative stress. This condition affects above all the brain, that usually needs a large oxygen amount and in which there is the major possibility to accumulate “Reacting Species.” Antioxidant molecules are fundamental in limiting free-radical damage, in particular in the central nervous system: the oxidative stress, in fact, seems to worsen the course of neurodegenerative diseases. The aim of this review is to sum up natural antioxidant molecules with the greatest neuroprotective properties against free radical genesis, understanding their relationship with the Central Nervous System.
Nutraceuticals have been the focus of numerous research in recent years and accumulating data support their use for promoting some health benefits. Several nutraceuticals have been widely studied as supplements due to their functional properties ameliorating symptoms associated with neurological disorders, such as oxidative stress and chronic inflammatory states. This seems to be the case of some fruits and seeds from the Amazon Biome consumed since the Pre-Columbian period that could have potential beneficial impact on the human nervous system. The beneficial activities of these food sources are possibly related to a large number of bioactive molecules including polyphenols, carotenoids, unsaturated fatty acids, vitamins, and trace elements. In this context, this review compiled the research on six Amazonian fruits and seeds species and some of the major nutraceuticals found in their composition presenting brief mechanisms related to their protagonist action in improving inflammatory responses and neuroinflammation.
Dementia is a chronic condition characterized by the decreased cognitive capacity, which is more severe than in case of normal aging. Cognitive impairment is a major social and economic problem of modern society, which affects about 47 million people worldwide. The first stage of dementia (mild cognitive impairment) is characterized by the decline of memory, executive function, attention, visuospatial skills and speech. Pathogenic links of cognitive impairment are represented by neuroinflammation, excessive amyloid-β protein deposition, oxidative stress, hyperphosphorylation etc. In the recent years, the interest in natural plant-derived compounds for the treatment of cognitive decline has increased. In this chapter, we summarize the available evidence supporting the benevolent action of some botanicals and phytochemicals on cognitive function. The most widely studied plants include Ginkgo biloba, Panax ginseng and Camellia sinensis (green tea), but there also some other promising ones like guarana, grape, soy etc. These nutraceuticals mostly influence memory, learning and attention. At the moment it is quite difficult to make a definite conclusion on the effects of nutraceuticals on cognitive decline, because human trials show significant discrepancies. This underpins the need of future trials and scientific analysis.
There is a large literature on the effects of caffeine on performance. Most of the studies have been conducted in the laboratory and further information is required on the effects of caffeine consumption on performance and safety at work.
The present studies aimed to determine whether the level of caffeine consumption influenced changes in alertness and performance over the working day. Secondary analyses of a large epidemiological database were also conducted to examine associations between caffeine consumption and cognitive failures and accidents at work.
In the first study 110 volunteers, all of whom were regular caffeine consumers, rated their alertness and carried out a simple reaction time task before and after work on a Monday and Friday. Caffeine consumption during the day was recorded and volunteers were sub-divided into low and high consumers on the basis of a median split (220 mg/day). The second study involved secondary analyses of a database formed by combining the Bristol Stress and Health at Work and Cardiff Health and Safety at Work studies. In the first analyses associations between caffeine consumption and frequency of cognitive failures were examined in a sample of 1253 white-collar workers. The second set of analyses examined associations between caffeine consumption and accidents at work in a sample of 1555 workers who were especially at risk of having an accident.
The results from the first study showed that those who consumed higher levels of caffeine reported significantly greater increases in alertness over the working day and a significantly smaller slowing of reaction time. The results from the second study demonstrated significant associations between caffeine consumption and fewer cognitive failures and accidents at work. After controlling for possible confounding factors it was found that higher caffeine consumption was associated with about half the risk of frequent/very frequent cognitive failures and a similar reduction in risk for accidents at work.
Overall, the results from the three analyses show that caffeine consumption may have benefits for performance and safety at work.
Background/objective:
To conduct a systematic review of all studies to determine whether there is an association between the Mediterranean diet (MeDi) and cognitive impairment.
Methods:
We conducted a comprehensive search of the major databases and hand-searched proceedings of major neurology, psychiatry, and dementia conferences through November 2012. Prospective cohort studies examining the MeDi with longitudinal follow-up of at least 1 year and reporting cognitive outcomes (mild cognitive impairment [MCI] or Alzheimer's disease [AD]) were included. The effect size was estimated as hazard-ratio (HR) with 95% confidence intervals (CIs) using the random-effects model. Heterogeneity was assessed using Cochran's Q-test and I2-statistic.
Results:
Out of the 664 studies screened, five studies met eligibility criteria. Higher adherence to the MeDi was associated with reduced risk of MCI and AD. The subjects in the highest MeDi tertile had 33% less risk (adjusted HR = 0.67; 95% CI, 0.55-0.81; p < 0.0001) of cognitive impairment (MCI or AD) as compared to the lowest MeDi score tertile. Among cognitively normal individuals, higher adherence to the MeDi was associated with a reduced risk of MCI (HR = 0.73; 95% CI, 0.56-0.96; p = 0.02) and AD (HR = 0.64; 95% CI, 0.46-0.89; p = 0.007). There was no significant heterogeneity in the analyses.
Conclusions:
While the overall number of studies is small, pooled results suggest that a higher adherence to the MeDi is associated with a reduced risk of developing MCI and AD, and a reduced risk of progressing from MCI to AD. Further prospective-cohort studies with longer follow-up and randomized controlled trials are warranted to consolidate the evidence. Systematic review registration number: PROSPERO 2013: CRD42013003868.
Background
Tea consumption has been reported to be associated with lowered risk of cardiovascular disease, stroke and osteoporosis that cause functional disability, but its association with physical function has not been investigated directly.
Objective
We examined the association between tea consumption and performance in gait and balance, instrumental and basic activities of daily living (IADL and BADL) in a cross-sectional study of community-living older persons.
Method
Baseline data of 2398 adults aged ≥ 55 years in the Singapore Longitudinal Ageing Studies who completed self-reported current tea consumption, Performance Oriented Mobility Assessment (POMA) of gait and balance, and self reports of BADL and IADL were analyzed.
Results
In multivariate analyses controlling for age, gender, education, housing type, co-morbidities, hospitalization, arthritis and hip fracture, GDS depression score, MMSE cognitive score, body mass index, creatinine, serum albumin, haemoglobin, physical activities score and coffee consumption, tea consumption was positively associated with better balance (β=0.06, p<0.01), gait (β=0.01, p=0.02), IADL (β=0.03, p=0.01) and BADL (β=0.01, p=0.05). Strongly positive associations were observed for black/oolong tea in multivariate analyses, and for green tea consumption only in univariate analysis, whereas coffee consumption was not associated at all.
Conclusions
Tea consumption was associated with better physical functional performances in community-living older adults.
Background:
Persons with vascular disorders are at higher risk of cognitive decline.
Objective:
To determine whether caffeine may be associated with cognitive decline reduction in elderly at high vascular risk.
Methods:
We included 2,475 women aged 65+ years in the Women's Antioxidant Cardiovascular Study, a randomized trial of antioxidants and B vitamins for cardiovascular disease secondary prevention. We ascertained regular caffeine intake at baseline (1995-1996) using a validated 116 item-food frequency questionnaire. From 1998-2000 to 2005-2006, we administered four telephone cognitive assessments at two-year intervals evaluating global cognition, verbal memory, and category fluency. The primary outcome was the change in global cognitive score, which was the average of the z-scores of all tests. We used generalized linear models for repeated measures that were adjusted for various sociodemographic, health, and lifestyle factors to evaluate the difference in cognitive decline rates across quintiles of caffeine intake.
Results:
We observed significantly slower rates of cognitive decline with increasing caffeine intake (p-trend = 0.02). The rate difference between the highest and lowest quintiles of usual caffeine intake (>371 versus <30 mg/day) was equivalent to that observed between those who were 7 years apart in age (p = 0.006). Consumption of caffeinated coffee was significantly related to slower cognitive decline (p-trend = 0.05), but not other caffeinated products (e.g., decaf, tea, cola, chocolate). We conducted interaction analyses and observed stronger associations in women assigned to vitamin B supplementation (p-interaction = 0.02).
Conclusions:
Caffeine intake was related to moderately better cognitive maintenance over 5 years in older women with vascular disorders.
A systematic literature review of human studies relating caffeine or caffeine-rich beverages to cognitive decline reveals only 6 studies that have collected and analyzed cognition data in a prospective fashion that enables study of decline across the spectrum of cognition. These 6 studies, in general, evaluate cognitive function using the Mini Mental State Exam and base their beverage data on FFQs. Studies included in our review differed in their source populations, duration of study, and most dramatically in how their analyses were done, disallowing direct quantitative comparisons of their effect estimates. Only one of the studies reported on all 3 exposures, coffee, tea, and caffeine, making comparisons of findings across studies more difficult. However, in general, it can be stated that for all studies of tea and most studies of coffee and caffeine, the estimates of cognitive decline were lower among consumers, although there is a lack of a distinct dose response. Only a few measures showed a quantitative significance and, interestingly, studies indicate a stronger effect among women than men.
Objective:
We examined the longitudinal association between tea drinking frequency and cognitive function in a large sample of oldest-old Chinese.
Design:
population-based longitudinal cohort study.
Setting:
The Chinese Longitudinal Healthy Longevity Survey (CLHLS).
Participants:
7139 participants aged 80 to 115 (mean age 91.4 years) who provided complete data at baseline (year 1998).
Measurements:
Current frequency of tea drinking and past frequency at age 60 were ascertained at baseline, and baseline and follow-up cognitive assessments were performed in the years 1998 (n=7139), 2000 (n=4081), 2002 (n=2288) and 2005 (n=913) respectively. Verbal fluency test was used as measure of cognitive function.
Results:
Tea drinking was associated at baseline with higher mean (SD) verbal fluency scores: daily=10.7 (6.6), occasional=9.2 (5.8), non-drinker=9.0 (5.5). In linear mixed effects model that adjusted for age, gender, years of schooling, physical exercise and activities score, the regression coefficient for daily drinking (at age 60) and occasional drinking was 0.72 (P<0.0001) and 0.41(P=0.01) respectively. Tea drinkers had higher verbal fluency scores throughout the follow-up period but concurrently had a steeper slope of cognitive decline as compared with non-drinkers (coefficient for the interaction term Time*Daily drinking= -0.12, P=0.02; "Time" was defined as the time interval from baseline to follow-up assessments in years). Similar results were found for current tea drinking status at study baseline year (1998) as predictor variable.
Conclusion:
Regular tea drinking is associated with better cognitive function in oldest-old Chinese.
To address the pending public health crisis due to Alzheimer's disease (AD) and related neurodegenerative disorders, the Marian S. Ware Alzheimer Program at the University of Pennsylvania held a meeting entitled "State of the Science Conference on the Advancement of Alzheimer's Diagnosis, Treatment and Care," on June 21-22, 2012. The meeting comprised four workgroups focusing on Biomarkers; Clinical Care and Health Services Research; Drug Development; and Health Economics, Policy, and Ethics. The workgroups shared, discussed, and compiled an integrated set of priorities, recommendations, and action plans, which are presented in this article.
Epidemiological studies have consistently shown that vascular risk factors including hypertension, diabetes, obesity, hypercholesterolemia, smoking, and lack of physical exercise are associated with an increased risk of cognitive decline and dementia. Neuroradiological and neuropathological studies have confirmed the importance of cerebrovascular lesions in the etiology of late onset dementia. We have reviewed the literature and conclude that up until now randomized controlled clinical trials targeting individual risk factors and assessing cognitive decline or dementia as an outcome have not convincingly shown that treatment of vascular risk factors can actually prevent or postpone cognitive decline and dementia. New studies targeting several vascular risk factors at the same time and using cognitive decline or dementia as primary outcome might answer the question whether cognitive decline can really be postponed or even prevented. The design of such studies is not straightforward and long follow-up is required. In this review we discuss several pertinent methodological issues that need to be addressed to achieve an optimal design of new randomized controlled trials.
Regular consumption of fruit and vegetables has been considered to be associated with a reduced risk of dementia and age-associated cognitive decline, although the association is currently unsupported by a systematic review of the literature.
We searched Medline, Embase, Biosis, ALOIS, the Cochrane library, different publisher databases as well as bibliographies of retrieved articles. All cohort studies with a follow-up of 6 months or longer were included if they reported an association of Alzheimer's disease or cognitive decline in regard to the frequency of fruit and vegetables consumption.
Nine studies with a total of 44,004 participants met the inclusion criteria. Six studies analyzed fruit and vegetables separately and five of them found that higher consumption of vegetables, but not fruit is associated with a decreased risk of dementia or cognitive decline. The same association was found by three further studies for fruit and vegetable consumption analytically combined.
Increased intake of vegetables is associated with a lower risk of dementia and slower rates of cognitive decline in older age. Yet, evidence that this association is also valid for high fruit consumption is lacking.
Diabetic conditions are associated with modified brain function, namely with cognitive deficits, through largely undetermined processes. More than understanding the underlying mechanism, it is important to devise novel strategies to alleviate diabetes-induced cognitive deficits. Caffeine (a mixed antagonist of adenosine A(1) and A(2A) receptors) emerges as a promising candidate since caffeine consumption reduces the risk of diabetes and effectively prevents memory deficits caused by different noxious stimuli. Thus, we took advantage of a novel animal model of type 2 diabetes to investigate the behavioural, neurochemical and morphological modifications present in the hippocampus and tested if caffeine consumption might prevent these changes. We used a model closely mimicking the human type 2 diabetes condition, NONcNZO10/LtJ mice, which become diabetic at 7-11 months when kept under an 11% fat diet. Caffeine (1 g/l) was applied in the drinking water from 7 months onwards. Diabetic mice displayed a decreased spontaneous alternation in the Y-maze accompanied by a decreased density of nerve terminal markers (synaptophysin, SNAP25), mainly glutamatergic (vesicular glutamate transporters), and increased astrogliosis (GFAP immunoreactivity) compared to their wild type littermates kept under the same diet. Furthermore, diabetic mice displayed up-regulated A(2A) receptors and down-regulated A(1) receptors in the hippocampus. Caffeine consumption restored memory performance and abrogated the diabetes-induced loss of nerve terminals and astrogliosis. These results provide the first evidence that type 2 diabetic mice display a loss of nerve terminal markers and astrogliosis, which is associated with memory impairment; furthermore, caffeine consumption prevents synaptic dysfunction and astrogliosis as well as memory impairment in type 2 diabetes.
Brain oxidative processes play a major role in age-related cognitive decline, thus consumption of antioxidant-rich foods might help preserve cognition. Our aim was to assess whether consumption of antioxidant-rich foods in the Mediterranean diet relates to cognitive function in the elderly. In asymptomatic subjects at high cardiovascular risk (n = 447; 52% women; age 55-80 y) enrolled in the PREDIMED study, a primary prevention dietary-intervention trial, we assessed food intake and cardiovascular risk profile, determined apolipoprotein E genotype, and used neuropsychological tests to evaluate cognitive function. We also measured urinary polyphenols as an objective biomarker of intake. Associations between energy-adjusted food consumption, urinary polyphenols, and cognitive scores were assessed by multiple linear regression models adjusted for potential confounders. Consumption of some foods was independently related to better cognitive function. The specific associations [regression coefficients (95% confidence intervals)] were: total olive oil with immediate verbal memory [0.755 (0.151-1.358)]; virgin olive oil and coffee with delayed verbal memory [0.163 (0.010-0.316) and 0.294 (0.055-0.534), respectively]; walnuts with working memory [1.191 (0.061-2.322)]; and wine with Mini-Mental State Examination scores [0.252 (0.006-0.496)]. Urinary polyphenols were associated with better scores in immediate verbal memory [1.208 (0.236-2.180)]. Increased consumption of antioxidant-rich foods in general and of polyphenols in particular is associated with better cognitive performance in elderly subjects at high cardiovascular risk. The results reinforce the notion that Mediterranean diet components might counteract age-related cognitive decline.
This review summarizes the literature on the association between tea consumption and cognitive health in late life. Population-based studies reviewed in this article suggest that tea drinking has beneficial effects on cognitive function of elderly persons. However, a cause-effect relationship between tea consumption and cognitive decline and dementia could not be drawn given inconsistent findings from only two longitudinal cohort studies. The neuroprotective effects of tea consumption could be due to catechins, L-theanine and other compounds in tea leaves. More longitudinal observational study is needed. Information on life-time tea consumption and blood concentrations of catechins and L-theanine could be collected in future studies.
Although both human epidemiologic and animal model studies have suggested that caffeine/coffee protects against Alzheimer's disease, direct human evidence for this premise has been lacking. In the present case-control study, two separate cohorts consisting of 124 total individuals (65-88 years old) were cognitively assessed and a blood sample taken for caffeine/biomarker analysis. Subjects were then monitored for cognitive status over the ensuing 2-4 year period to determine the extent to which initial plasma caffeine/biomarkers levels would be predictive of changes in cognitive status. Plasma caffeine levels at study onset were substantially lower (-51%) in mild cognitive impairment (MCI) subjects who later progressed to dementia (MCI→DEM) compared to levels in stable MCI subjects (MCI→MCI). Moreover, none of the MCI→DEM subjects had initial blood caffeine levels that were above a critical level of 1200 ng/ml, while half of stable MCI→MCI subjects had blood caffeine levels higher than that critical level. Thus, plasma caffeine levels greater than 1200 ng/ml (≈6 μM) in MCI subjects were associated with no conversion to dementia during the ensuing 2-4 year follow-up period. Among the 11 cytokines measured in plasma, three of them (GCSF, IL-10, and IL-6) were decreased in MCI→DEM subjects, but not in stable MCI→MCI subjects with high plasma caffeine levels. Coffee would appear to be the major or perhaps only source of caffeine for such stable MCI patients. This case-control study provides the first direct evidence that caffeine/coffee intake is associated with a reduced risk of dementia or delayed onset, particularly for those who already have MCI.
Objective: In several longitudinal studies, light-to-moderate drinking of alcoholic beverages has been proposed as being protective against the development of age-related changes in cognitive function, predementia syndromes, and cognitive decline of degenerative (Alzheimer's disease, AD) or vascular origin (vascular dementia). However, contrasting findings also exist.
Method: The English literature published in this area before September 2011 was evaluated, and information relating to the various factors that may impact upon the relationship between alcohol consumption and dementia or predementia syndromes is presented in the succeeding texts.
Results: Light-to-moderate alcohol consumption may be associated with a reduced risk of incident overall dementia and AD; however, protective benefits afforded to vascular dementia, cognitive decline, and predementia syndromes are less clear. The equivocal findings may relate to many of the studies being limited to cross-sectional designs, restrictions by age or gender, or incomplete ascertainment. Different outcomes, beverages, drinking patterns, and study follow-up periods or possible interactions with other lifestyle-related (e.g., smoking) or genetic factors (e.g., apolipoprotein E gene variation) may all contribute to the variability of findings.
Conclusion: Protective effects of moderate alcohol consumption against cognitive decline are suggested to be more likely in the absence of the AD-associated apolipoprotein E ε4 allele and where wine is the beverage. At present, there is no indication that light-to-moderate alcohol drinking would be harmful to cognition and dementia, and attempts to define what might be deemed beneficial levels of alcohol intake in terms of cognitive performance would be highly problematic and contentious. Copyright
The relation between coffee intake and risk of amyotrophic lateral sclerosis (ALS) was investigated in 377 newly diagnosed ALS patients from 4 Italian population-based registries in the European ALS Consortium (EURALS Group) (2007-2010). For each patient, 2 age- and sex-matched hospital controls were selected, one from a neurology department and one from a nonneurologic department. Two additional healthy control groups were identified from local general practitioners' (GPs') lists (n = 99) and residents of the same area as a cancer cohort (n = 7,057). Coffee intake was defined in terms of status (ever consuming coffee daily for ≥6 months vs. never), duration, and history (never, former, or current). Ever coffee drinkers comprised 74.7% of ALS patients, 80.4% of neurologic controls, 85.6% of nonneurologic controls (P = 0.0004), 88.9% of GP controls (P = 0.0038), and 86.0% of cancer cohort controls (P < 0.0001). Current coffee drinkers comprised 60.2% of ALS patients, 70.2% of neurologic controls (P = 0.0294), 76.4% of nonneurologic controls (P < 0.0001), and 82.3% of GP controls (P = 0.0002); duration of intake was ≥30 years for 62.3%, 67.7%, 74.7%, and 72.6%. ALS patients had lower lifetime coffee exposure: Odds ratios were 0.7 (95% confidence interval (CI): 0.5, 1.1), 0.6 (95% CI: 0.4, 0.8), and 0.4 (95% CI: 0.2, 0.9) in comparison with neurologic, nonneurologic, and GP controls, respectively. In current (vs. never) coffee drinkers, odds ratios were 0.7 (95% CI: 0.5, 1.0), 0.5 (95% CI: 0.3, 0.7), and 0.4 (95% CI: 0.2, 0.8), respectively. These findings provide epidemiologic evidence of an inverse correlation between coffee intake and ALS risk.
Caffeine is the world's most widely used central nervous system stimulant, with approximately 80% consumed in the form of coffee. However, studies that analyze prospectively the relationship between coffee or caffeine consumption and depression risk are scarce.
A total of 50,739 US women (mean age, 63 years) free of depressive symptoms at baseline (in 1996) were prospectively followed up through June 1, 2006. Consumption of caffeine was measured from validated questionnaires completed from May 1, 1980, through April 1, 2004, and computed as cumulative mean consumption with a 2-year latency period applied. Clinical depression was defined as self-reported physician-diagnosed depression and antidepressant use. Relative risks of clinical depression were estimated using Cox proportional hazards regression models.
During 10 years of follow-up (1996-2006), 2607 incident cases of depression were identified. Compared with women consuming 1 or less cup of caffeinated coffee per week, the multivariate relative risk of depression was 0.85 (95% confidence interval, 0.75-0.95) for those consuming 2 to 3 cups per day and 0.80 (0.64-0.99; P for trend<.001) for those consuming 4 cups per day or more. Multivariate relative risk of depression was 0.80 (95% confidence interval, 0.68-0.95; P for trend=.02) for women in the highest (≥550 mg/d) vs lowest (<100 mg/d) of the 5 caffeine consumption categories. Decaffeinated coffee was not associated with depression risk.
In this large longitudinal study, we found that depression risk decreases with increasing caffeinated coffee consumption. Further investigations are needed to confirm this finding and to determine whether usual caffeinated coffee consumption can contribute to depression prevention.
Caffeine intake has been associated with a lower incidence of Alzheimer's disease (AD) in humans. In AD mouse models, caffeine significantly decreases senile plaques and amyloid beta (Aβ) levels while also protecting against or reversing cognitive impairment. To understand the mechanism(s) underlying the protective effects of caffeine against AD pathology, we investigated the effects of a two-week treatment with caffeine (3mg/day) in transgenic (APPswe) mice and non-transgenic (NT) mice on signaling factors involved in neuronal plasticity and survival. We evaluated cAMP-dependent protein kinase A (PKA), phospho-cyclic AMP response-element binding protein (phospho-CREB), and the pro-apoptotic protein kinases extracellular signal-regulated kinase 1/2 (phospho-ERK) and phospho-c-Jun N-terminal kinase 1 (phospho-JNK) in the striatum and frontal cortex of caffeine-treated mice. In the striatum, APPswe control mice exhibited a significant decrease in phospho-CREB, as well as significant increases in phospho-JNK and phospho-ERK in comparison to NT mice. Caffeine treatment stimulated PKA activity, increased phospho-CREB levels, and decreased phospho-JNK and phospho-ERK expression in the striatum of APPswe mice, all of which are thought to be beneficial changes for brain function. Even caffeine-treated NT mice exhibited some of these changes in striatum. In the frontal cortex, caffeine did not significantly increase phospho-CREB and PKA activity, but significantly reduced phospho-JNK and phospho-ERK expression in both APPswe and NT mice. These results suggest that caffeine shifts the balance between neurodegeneration and neuronal survival toward the stimulation of pro-survival cascades and inhibition of pro-apoptotic pathways in the striatum and/or cortex, which may contribute to its beneficial effects against AD.
Although considerable experimental and animal evidence shows that green tea may possess potent activities of neuroprotection, neurorescue, and amyloid precursor protein processing that may lead to cognitive enhancement, no human data are available.
The objective was to examine the association between green tea consumption and cognitive function in humans.
We analyzed cross-sectional data from a community-based Comprehensive Geriatric Assessment (CGA) conducted in 2002. The subjects were 1003 Japanese subjects aged > or =70 y. They completed a self-administered questionnaire that included questions about the frequency of green tea consumption. We evaluated cognitive function by using the Mini-Mental State Examination with cutoffs of <28, <26, and <24 and calculated multivariate-adjusted odds ratios (ORs) of cognitive impairment.
Higher consumption of green tea was associated with a lower prevalence of cognitive impairment. At the <26 cutoff, after adjustment for potential confounders, the ORs for the cognitive impairment associated with different frequencies of green tea consumption were 1.00 (reference) for < or =3 cups/wk, 0.62 (95% CI: 0.33, 1.19) for 4-6 cups/wk or 1 cup/d, and 0.46 (95% CI: 0.30, 0.72) for > or =2 cups/d (P for trend = 0.0006). Corresponding ORs were 1.00 (reference), 0.60 (95% CI: 0.35, 1.02), and 0.87 (95% CI: 0.55, 1.38) (P for trend = 0.33) for black or oolong tea and 1.00 (reference), 1.16 (95% CI: 0.78, 1.73), and 1.03 (95% CI: 0.59, 1.80) (P for trend = 0.70) for coffee. The results were essentially the same at cutoffs of <28 and <24.
A higher consumption of green tea is associated with a lower prevalence of cognitive impairment in humans.
Preventing or postponing the onset of Alzheimer's disease (AD) and delaying or slowing its progression would lead to a consequent improvement of health status and quality of life in older age. Elevated saturated fatty acids could have negative effects on age-related cognitive decline and mild cognitive impairment (MCI). Furthermore, at present, epidemiological evidence suggests a possible association between fish consumption, monounsaturated fatty acids and polyunsaturated fatty acids (PUFA; in particular, n-3 PUFA) and a reduced risk of cognitive decline and dementia. Poorer cognitive function and an increased risk of vascular dementia (VaD) were found to be associated with a lower consumption of milk or dairy products. However, the consumption of whole-fat dairy products may be associated with cognitive decline in the elderly. Light-to-moderate alcohol use may be associated with a reduced risk of incident dementia and AD, while for VaD, cognitive decline and predementia syndromes, the current evidence is only suggestive of a protective effect. The limited epidemiological evidence available on fruit and vegetable consumption and cognition generally supports a protective role of these macronutrients against cognitive decline, dementia and AD. Only recently, higher adherence to a Mediterranean-type diet was associated with decreased cognitive decline, although the Mediterranean diet (MeDi) combines several foods, micro- and macro-nutrients already separately proposed as potential protective factors against dementia and predementia syndromes. In fact, recent prospective studies provided evidence that higher adherence to a Mediterranean-type diet could be associated with slower cognitive decline, reduced risk of progression from MCI to AD, reduced risk of AD and a decreased all-cause mortality in AD patients. These findings suggested that adherence to the MeDi may affect not only the risk of AD, but also of predementia syndromes and their progression to overt dementia. Based on the current evidence concerning these factors, no definitive dietary recommendations are possible. However, following dietary advice for lowering the risk of cardiovascular and metabolic disorders, high levels of consumption of fats from fish, vegetable oils, nonstarchy vegetables, low glycemic index fruits and a diet low in foods with added sugars and with moderate wine intake should be encouraged. Hopefully this will open new opportunities for the prevention and management of dementia and AD.
Cognitive impairment is an age-related condition as the rate of cognitive decline rapidly increases with aging. It is especially important to better understand factors involving in cognitive decline for the countries where the older population is growing rapidly. The aim of this study was to examine the association between socio-demographic and health-related factors and cognitive impairment in the elderly in Taiwan.
We analysed data from 2119 persons aged 65 years and over who participated in the 2005 National Health Interview Survey. Cognitive impairment was defined as having the score of the Mini Mental State Examination lower than 24. The χ2 test and multiple logistic regression models were used to evaluate the association between cognitive impairment and variables of socio-demography, chronic diseases, geriatric conditions, lifestyle, and dietary factors.
The prevalence of cognitive impairment was 22.2%. Results of multivariate analysis indicated that low education, being single, low social support, lower lipid level, history of stroke, physical inactivity, non-coffee drinking and poor physical function were associated with a higher risk of cognitive impairment.
Most of the characteristics in relation to cognitive impairment identified in our analysis are potentially modifiable. These results suggest that improving lifestyle behaviours such as regular exercise and increased social participation could help prevent or decrease the risk of cognitive impairment. Further investigations using longitudinal data are needed to clarify our findings.
While animal data suggest a protective effect of caffeine on cognition, studies in humans remain inconsistent. We examined associations of coffee and caffeine intake in midlife with risk of dementia, its neuropathologic correlates, and cognitive impairment among 3494 men in the Honolulu-Asia Aging Study (mean age 52 at cohort entry, 1965-1968) examined for dementia in 1991-1993, including 418 decedents (1992-2004) who underwent brain autopsy. Caffeine intake was determined according to self-reported coffee, tea, and cola consumption at baseline. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for overall dementia, Alzheimer's disease (AD), vascular dementia (VaD), cognitive impairment (Cognitive Abilities Screening Instrument score <74), and neuropathologic lesions at death (Alzheimer lesions, microvascular ischemic lesions, cortical Lewy bodies, hippocampal sclerosis, generalized atrophy), according to coffee and caffeine intake. Dementia was diagnosed in 226 men (including 118 AD, 80 VaD), and cognitive impairment in 347. There were no significant associations between coffee or caffeine intake and risk of cognitive impairment, overall dementia, AD, VaD, or moderate/high levels of the individual neuropathologic lesion types. However, men in the highest quartile of caffeine intake (>277.5 mg/d) were less likely than men in the lowest quartile (≤115.5 mg) to have any of the lesion types (adjusted-OR, 0.45; 95% CI, 0.23-0.89; p, trend = 0.04). Coffee and caffeine intake in midlife were not associated with cognitive impairment, dementia, or individual neuropathologic lesions, although higher caffeine intake was associated with a lower odds of having any of the lesion types at autopsy.
The non-proteinic amino acid L-theanine and caffeine, a methylxanthine derivative, are naturally occurring ingredients in tea. The present study investigated the effect of a combination of 97 mg L-theanine and 40 mg caffeine as compared to placebo treatment on cognitive performance, alertness, blood pressure, and heart rate in a sample of young adults (n = 44). Cognitive performance, self-reported mood, blood pressure, and heart rate were measured before L-theanine and caffeine administration (i.e. at baseline) and 20 min and 70 min thereafter. The combination of moderate levels of L-theanine and caffeine significantly improved accuracy during task switching and self-reported alertness (both P < 0.01) and reduced self-reported tiredness (P < 0.05). There were no significant effects on other cognitive tasks, such as visual search, choice reaction times, or mental rotation. The present results suggest that 97 mg of L-theanine in combination with 40 mg of caffeine helps to focus attention during a demanding cognitive task.
Alzheimer's disease (AD) is a progressive and fatal neurodegenerative disease characterized by cognitive and memory deterioration, with an increasing prevalence in the industrialized countries and an extraordinary cost of caring for patients. Due to the limited information available on the exact pathophysiology of the disease, over the last years there have been extensive efforts on the identification of possible risk factors, but no conclusive data have been obtained. Some risk factors have been identified but no clear evidence on what is clearly associated with the occurrence and progression of AD are available, and in particular no effective preventive strategies have been found. One of the most intriguing and appealing lines of investigation is the association between lifestyle habits such as diet and dietary compounds and the occurrence of AD. In this review, we focus on studies that investigated the association between nutrition and AD, paying particular attention to the role of a dietary pattern such as a Mediterranean-like diet on the occurrence of such disease. Studies in support of Mediterranean diet as an optimal diet for prevention of cardiovascular and major chronic diseases has rapidly evolved. A recent meta-analysis from our group, comprising prospective studies that investigated the association between adherence to Mediterranean diet and health status, showed a significant association between a greater adherence to Mediterranean diet and a reduced risk of major chronic degenerative diseases, including AD. Moreover, the Mediterranean diet has been extensively reported to be associated with a favorable health outcome and a better quality of life.
Caffeine, the most widely consumed psychoactive drug, enhances attention/vigilance, stabilizes mood, and might also independently enhance cognitive performance. Notably, caffeine displays clearer and more robust beneficial effects on memory performance when memory is perturbed by stressful or noxious stimuli either in human or animal studies. Thus, caffeine restores memory performance in sleep-deprived or aged human individuals, a finding replicated in rodent animal models. Likewise, in animal models of Alzheimer's disease (AD), caffeine alleviates memory dysfunction, which is in accordance with the tentative inverse correlation between caffeine intake and the incidence of AD in different (but not all) cohorts. Caffeine also affords beneficial effects in animal models of conditions expected to impair memory performance such as Parkinson's disease, chronic stress, type 2 diabetes, attention deficit and hyperactivity disorder, early life convulsions, or alcohol-induced amnesia. Thus, caffeine should not be viewed as a cognitive enhancer but instead as a cognitive normalizer. Interestingly, these beneficial effects of caffeine on stress-induced memory disturbance are mimicked by antagonists of adenosine A2A receptors. This prominent role of A2A receptors in preventing memory deterioration is probably related to the synaptic localization of this receptor in limbic areas and its ability to control glutamatergic transmission, especially NMDA receptor-dependent plasticity, and to control apoptosis, brain metabolism, and the burden of neuroinflammation. This opens the real and exciting possibility that caffeine consumption might be a prophylactic strategy and A2A receptor antagonists may be a novel therapeutic option to manage memory dysfunction both in AD and in other chronic neurodegenerative disorders where memory deficits occur.
People with diabetes mellitus are at increased risk of cognitive dysfunction. This review explores the relation between caffeine intake, diabetes, cognition and dementia, focusing on type 2 diabetes (T2DM). Epidemiological studies on caffeine/coffee intake and T2DM risk are reviewed. Next, the impact of T2DM on cognition is addressed. Finally, the potential for caffeine to modulate the risk of cognitive decline in the context of diabetes is explored. The conclusion is that, although epidemiological studies indicate that coffee/caffeine consumption is associated with a decreased risk of T2DM and possibly also with a decreased dementia risk, we can at present not be certain that these associations are causal. For now, recommendations for coffee consumption in individuals with T2DM or pre-diabetic stages are therefore difficult to establish, but it should be acknowledged that caffeine does appear to have several properties that warrant further investigations in this field.
Alzheimer's disease has emerged in recent decades as a major health problem and the role of lifestyles in the modulation of risk has been increasingly recognized. Recent epidemiological studies suggest a protective effect for caffeine intake in dementia. We aimed to quantify the association between caffeine dietary intake and cognitive decline, in a cohort of adults living in Porto. A cohort of 648 subjects aged > or =65 years was recruited between 1999-2003. Follow-up evaluation (2005-2008) was carried out on 58.2% of the eligible participants and 10.9% were deceased. Caffeine exposure in the year preceding baseline evaluation was assessed with a validated food frequency questionnaire. Cognitive evaluation consisted of baseline and follow-up Mini-Mental State Examination (MMSE). Cognitive decline was defined by a decrease > or =2 points in the MMSE score between evaluations. Relative risk (RR) and 95% confidence interval (95%CI) estimates adjusted for age, education, smoking, alcohol drinking, body mass index, hypertension, and diabetes were computed using Poisson regression. Caffeine intake (> 62 mg/day [3rd third] vs. < 22 mg/day [1st third]) was associated with a lower risk of cognitive decline in women (RR=0.49, 95%CI 0.24-0.97), but not significantly in men (RR=0.65, 95%CI 0.27-1.54). Our study confirms the negative association between caffeine and cognitive decline in women.
Few studies to date have looked at the effects of caffeine on synaptic plasticity, and those that did used very high concentrations of caffeine, whereas the brain concentrations attained by regular coffee consumption in humans should be in the low micromolar range, where caffeine exerts pharmacological actions mainly by antagonizing adenosine receptors. Accordingly, rats drinking caffeine (1 g/L) for 3 weeks, displayed a concentration of caffeine of circa 22 microM in the hippocampus. It is known that selective adenosine A1 receptor antagonists facilitate, whereas selective adenosine A2A receptor antagonists attenuate, long term potentiation (LTP) in the hippocampus. Although caffeine is a non-selective antagonist of adenosine receptors, it attenuates frequency-induced LTP in hippocampal slices in a manner similar to selective adenosine A2A receptor antagonists. These effects of low micromolar concentration of caffeine (30 microM) are maintained in aged animals, which is important when a possible beneficial effect for caffeine in age-related cognitive decline is proposed. Future studies will still be required to confirm and detail the involvement of A1 and A2A receptors in the effects of caffeine on hippocampal synaptic plasticity, using both pharmacological and genetic approaches.
In the last decade, advances in understanding the neurobiology of Alzheimer's disease (AD) have translated into an increase in clinical trials assessing various potential AD treatments. At present, drugs used for the treatment of AD only slightly delay the inevitable symptomatic progression of the disease and do not affect the main neuropathological hallmarks of the disease, i.e. senile plaques and neurofibrillary tangles. Brain accumulation of oligomeric species of beta-amyloid (A beta) peptides, the principal components of senile plaques, is believed to play a crucial role in the development of AD. Based on this hypothesis, huge efforts are being made to identify drugs able to interfere with proteases regulating A beta formation from amyloid precursor protein (APP). Compounds that stimulate alpha-secretase, the enzyme responsible for non-amyloidogenic metabolism of APP, are being developed and one of these, EHT-0202, has recently commenced evaluation in a phase II study. The discovery of inhibitors of beta-secretase (memapsin-2, beta-amyloid cleaving enzyme-1 [BACE-1]), the enzyme that regulates the first step of amyloidogenic APP metabolism, has proved to be particularly difficult because of inherent medicinal chemistry issues and only one compound (CTS-21166) has proceeded to clinical testing. Conversely, several compounds that inhibit gamma-secretase, the pivotal enzyme that generates A beta, have been identified, the most advanced being LY-450139 (semagacestat), presently in phase III clinical development. There has been considerable disappointment over the failure of a phase III study of tarenflurbil, a compound believed to modulate the activity of gamma-secretase, after encouraging phase II findings. Nevertheless, other promising gamma-secretase modulators are being developed and are approaching clinical testing. All these therapeutic approaches increase the hope of slowing the rate of decline in patients with AD and modifying the natural history of this devastating disease within the next 5 years.
There is converging evidence that composite dietary patterns such as the Mediterranean diet (MeDi) is related to lower risk for a series of nonneurological medical conditions and diseases. We investigated the association between MeDi and risk for Alzheimer's Disease (AD) in a community-based study of 2,258 nondemented individuals, who were prospectively evaluated every 1.5 years for 4 (± 3.0, 0.2- 13.9) years. Adherence to the MeDi (0-9 point scale with higher scores indicating higher adherence) was the main predictor in Cox models. Adjusting for multiple potential confounders, higher adherence to the MeDi was associated with lower risk of AD (Hazard Ratio [HR], 0.91, 95% CI, 0.83-0.98; p = 0.015). Compared to subjects in the lowest MeDi tertile, subjects in the middle MeDi tertile had a HR of 0.85 (0.63-1.16) and those at the highest tertile a HR of 0.60 (0.42-0.87) for AD (p for trend 0.007). We conclude that higher adherence to the MeDi is associated with a reduction in risk for AD in a dose-responsive manner.
Coffee drinking has been associated with increased serum cholesterol levels in some, but not all, studies. A Medline search of the English-language literature published prior to December 1998, a bibliography review, and consultations with experts were performed to identify 14 published trials of coffee consumption. Information was ed independently by two reviewers using a standardized protocol. With a random-effects model, treatment effects were estimated by pooling results from individual trials after weighting the results by the inverse of total variance. A dose-response relation between coffee consumption and both total cholesterol and LDL cholesterol was identified (p < 0.01). Increases in serum lipids were greater in studies of patients with hyperlipidemia and in trials of caffeinated or boiled coffee. Trials using filtered coffee demonstrated very little increase in serum cholesterol. Consumption of unfiltered, but not filtered, coffee increases serum levels of total and LDL cholesterol.
Cited By (since 1996):12, Export Date: 18 October 2014
Cognitive decline in the elderly, particularly Alzheimer's disease (AD), is a major socio-economic and healthcare concern. We review here the literature on one specific aspect of diet affecting AD, that of the omega3 fatty acids, particularly the brain's principle omega3 fatty acid - docosahexaenoic acid (DHA). DHA has deservedly received wide attention as a nutrient supporting both optimal brain development and for cardiovascular health. Our aim here is to critically assess the quality of the present literature as well as the potential of omega3 fatty acids to treat or delay the onset of AD. We start with a brief description of cognitive decline in the elderly, followed by an overview of well recognized biological functions of DHA. We then turn to epidemiological studies, which are largely supportive of protective effects of fish and DHA against risk of AD. However, biological studies, including blood and brain DHA analyses need careful interpretation and further investigation, without which the success of clinical trials with DHA may continue to struggle. We draw attention to some of the methodological issues that need resolution as well as an emerging mechanism that may explain how DHA could be linked to protecting brain function in the elderly.
We reviewed clinical trials on active and passive anti-β-amyloid (Aβ) immunotherapy for the treatment of Alzheimer's disease with a particular focus on monoclonal antibodies against Aβ.
Studies on anti-Alzheimer's disease immunotherapy published in the period from January 2012 to October 2013 were reviewed.
Both active and passive anti-Aβ immunotherapies were shown to clear brain Aβ deposits. However, an active anti-Aβ vaccine (AN1792) has been discontinued because it caused meningoencephalitis in 6% of Alzheimer's disease patients treated. Among passive immunotherapeutics, two Phase III clinical trials in mild-to-moderate Alzheimer's disease patients with bapineuzumab, a humanized monoclonal antibody directed at the N-terminal sequence of Aβ, were disappointing. Another antibody, solanezumab, directed at the mid-region of Aβ, failed in two Phase III clinical trials in mild-to-moderate Alzheimer's disease patients. A third Phase III study with solanezumab is ongoing in mildly affected Alzheimer's disease patients based on encouraging results in this subgroup of patients. Second-generation active Aβ vaccines (ACC-001, CAD106, and Affitope AD02) and new passive anti-Aβ immunotherapies (gantenerumab and crenezumab) are being tested in prodromal Alzheimer's disease patients, in presymptomatic individuals with Alzheimer's disease-related mutations, or in asymptomatic individuals at risk of developing Alzheimer's disease to definitely test the Aβ cascade hypothesis of Alzheimer's disease.
Higher adherence to a Mediterranean-type diet was associated with decreased cognitive decline, although the Mediterranean diet (MeDi) combines several foods, micronutrients, and macronutrients already separately proposed as potential protective factors against dementia and predementia syndromes. The findings from prospective studies and very recent systematic reviews and meta-analyses suggested that adherence to the MeDi fulfilling the whole-diet approach may affect not only the risk of Alzheimer's disease, but also of predementia syndromes and their progression to overt dementia. However, some concerns exist regarding how these instruments have been developed for measuring adherence to the MeDi, suggesting a better qualitative and quantitative selection of the individual dietary components and/or food groups to improve their reliability.
Therapeutic properties of tea Camellia sinensis are of particular interest since it has been consumed for ages and was always regarded as safe beverage. Tea is most popular beverage in the world because of its attractive aroma, exceptional taste, health promoting and pharmaceutical potential. Current results showed that antioxidative, antibacterial and other health effects are attributed to its caffeine content and caffeine — polyphenols interactions. An overview is given on caffeine content in different tea leaves beverage. Special attention is drawn to caffeine physiological effect on human organism. Controversies concerning the possible caffeine influence on human physical and psychological health are briefly summarized and presented.
A tendency for magnesium deficiency in patients with diabetes mellitus is well-established. Glucosuria-related hypermagnesiuria, nutritional factors and hyperinsulinaemia-related hypermagnesiuria all can contribute. The plasma magnesium level has been shown to be inversely related to insulin sensitivity. Magnesium supplementation improves insulin sensitivity as well as insulin secretion in patients with type 2 diabetes. Nevertheless, no beneficial effects of oral magnesium supplementation has been demonstrated on glycaemic control either in patients with diabetes type 1 or 2. Oral magnesium supplementation reduced the development of type 2 diabetes in predisposed rats. There are some indications that magnesium decreases blood pressure, but negative results have been observed in trials that were, however, not designed to test effect on blood pressure as primary parameter. Patients with (severe) retinopathy have a lower plasma magnesium level compared to patients without retinopathy and a prospective study has shown the plasma magnesium level to be inversely related to occurrence or progression of retinopathy. Further study on magnesium (supplementation) is warranted in the prevention of type 2 and of (progression of) retinopathy as well as a means to reduce high blood pressure.
Objective:
This meta-analysis aims to quantitatively synthesize all studies that examine the association between adherence to a Mediterranean diet and risk of stroke, depression, cognitive impairment, and Parkinson disease.
Methods:
Potentially eligible publications were those providing effect estimates of relative risk (RR) for the association between Mediterranean diet and the aforementioned outcomes. Studies were sought in PubMed up to October 31, 2012. Maximally adjusted effect estimates were extracted; separate analyses were performed for high and moderate adherence.
Results:
Twenty-two eligible studies were included (11 covered stroke, 9 covered depression, and 8 covered cognitive impairment; only 1 pertained to Parkinson's disease). High adherence to Mediterranean diet was consistently associated with reduced risk for stroke (RR = 0.71, 95% confidence interval [CI] = 0.57-0.89), depression (RR = 0.68, 95% CI = 0.54-0.86), and cognitive impairment (RR = 0.60, 95% CI = 0.43-0.83). Moderate adherence was similarly associated with reduced risk for depression and cognitive impairment, whereas the protective trend concerning stroke was only marginal. Subgroup analyses highlighted the protective actions of high adherence in terms of reduced risk for ischemic stroke, mild cognitive impairment, dementia, and particularly Alzheimer disease. Meta-regression analysis indicated that the protective effects of Mediterranean diet in stroke prevention seemed more sizeable among males. Concerning depression, the protective effects of high adherence seemed independent of age, whereas the favorable actions of moderate adherence seemed to fade away with more advanced age.
Interpretation:
Adherence to a Mediterranean diet may contribute to the prevention of a series of brain diseases; this may be of special value given the aging of Western societies.
Background:
Adherence to a Mediterranean diet has been associated with lower risk of various age-related diseases including dementia. Although narrative reviews have been published, no systematic review has synthesized studies on the association between Mediterranean diet adherence and cognitive function or dementia.
Methods:
We conducted a systematic review of 11 electronic databases (including Medline) of published articles up to January 2012. Reference lists, selected journal contents, and relevant websites were also searched. Study selection, data extraction, and quality assessment were performed independently by two reviewers using predefined criteria. Studies were included if they examined the association between a Mediterranean diet adherence score and cognitive function or dementia.
Results:
Twelve eligible papers (11 observational studies and one randomized controlled trial) were identified, describing seven unique cohorts. Despite methodological heterogeneity and limited statistical power in some studies, there was a reasonably consistent pattern of associations. Higher adherence to Mediterranean diet was associated with better cognitive function, lower rates of cognitive decline, and reduced risk of Alzheimer disease in nine out of 12 studies, whereas results for mild cognitive impairment were inconsistent.
Conclusions:
Published studies suggest that greater adherence to Mediterranean diet is associated with slower cognitive decline and lower risk of developing Alzheimer disease. Further studies would be useful to clarify the association with mild cognitive impairment and vascular dementia. Long-term randomized controlled trials promoting a Mediterranean diet may help establish whether improved adherence helps to prevent or delay the onset of Alzheimer disease and dementia.
To estimate the pooled risk of coffee consumption for Alzheimer's disease (AD).
We have reviewed all observational studies that evaluated the association between AD risk and coffee consumption. Four studies were identified: two case-control studies and two cohorts. These studies were carried out between 1990 and 2002.
There was an obvious protective effect of coffee consumption in the pooled estimate [risk estimate: 0.73 (95% confidence interval: 0.58-0.92)]. However, the homogeneity test was highly significant (p<0.01), indicating heterogeneity across the pooled studies. Pooled analysis applying the random effect model was 0.79 with 95% confidence interval overlapping unity (95% confidence interval: 0.46-1.36). Three studies assessed coffee consumption by interview questionnaire. The risk of AD in coffee consumers versus non-consumers in studies that used interview questionnaire had a pooled risk estimate of 0.70 with 95% confidence interval 0.55-0.90.
Although our pooled estimates show that coffee consumption is inversely associated with the risk of AD, the four studies had heterogeneous methodologies and results. Further prospective studies evaluating the association between coffee consumption and AD are strongly needed.
In the last decade, cumulative epidemiological evidence suggested that vascular- and metabolic-based risk factors may be important in the development of mild cognitive impairment and dementia. Epidemiological and basic research have also proposed a model of cognitive impairment linked to metabolic syndrome (MetS) and metabolic disorders, suggesting for research purposes a "metabolic-cognitive syndrome" (MCS) in patients with MetS plus cognitive impairment of degenerative or vascular origin. In particular, MetS has been associated with the risk of age-related cognitive decline and vascular dementia, but contrasting findings also existed on the possible role of MetS in overall dementia and Alzheimer's disease. Among metabolic determinants of cognitive impairment, a better approach to the understanding of mechanisms could be to hypothesize a continuum leading to various degrees of late-life cognitive disorders in older subjects with metabolic-based risk factors. The MCS model could help us to explain the complex relationship between metabolic disorders and cognitive disturbances and the boundaries between normal and pathological conditions, with a better understanding of clinical and neuropathological features of these metabolic-based cognitive disorders. Strategies toward early and effective risk factor management could be of value in reducing the risk of MCS, so delaying the onset or preventing the progression of predementia syndromes. In the near future, clinical trials could be undertaken to determine if addressing MetS and metabolic-based risk factors, including inflammation, through lifestyle modification holds out the possibility of slowing down or ameliorating the cognitive aging process itself.
Progress has been made in characterizing the secretases involved in endoproteolytic processing of the β-amyloid precursor protein — the precursor of the amyloid β-peptide (Aβ), which is the main constituent of amyloid plaques that form in the brains of patients with Alzheimer's disease. It is now thought that Aβ is pivotal in the pathogenesis of Alzheimer's disease, and that reducing brain Aβ levels may help to treat or prevent the disease. Two essential factors for the proteolytic generation of Aβ have been identified, β-secretase and the presenilins, which might aid the design of drugs against this disease.
Chronic caffeine consumption has been inversely associated with the risk of developing dementia and Alzheimer's disease. Here we assessed whether chronic caffeine treatment prevents the behavioral and cognitive decline that male Wistar rats experience from young (≈3 months) to middle age (≈10 months). When animals were young they were evaluated at weekly intervals in three tests: motor activity habituation in the open field (30-min sessions at the same time on consecutive days), continuous spontaneous alternation in the Y-maze (8 min), and elevated plus-maze (5 min). Afterward, rats from the same litter were randomly assigned either to a caffeine-treated group (n=13) or a control group (n=11), which received only tap water. Caffeine treatment (5 mg/kg/day) began when animals were ≈4 months old, and lasted for 6 months. Behavioral tests were repeated from day 14 to day 28 after caffeine withdrawal, a time period that is far in excess for the full excretion of a caffeine dose in this species. Thirty days after caffeine discontinuation brains were processed for Golgi-Cox staining. Compared with controls, we found that middle-aged rats that had chronically consumed low doses of caffeine (1) maintained their locomotor habituation during the second consecutive day exposure to the open field (an index of non-associative learning), (2) maintained their exploratory drive to complete the conventional minimum of nine arm visits required to calculate the alternation performance in the Y-maze in a greater proportion, (3) maintained their alternation percentage above chance level (an index of working memory), and (4) did not increase the anxiety indexes assessed by measuring the time spent in the open arms of the elevated plus maze. In addition, morphometric analysis of hippocampal neurons revealed that dendritic branching (90-140 μm from the soma), length of 4th and 5th order branches, total dendritic length, and spine density in distal dendritic branches were greater in the basal but not the apical dendrites of CA1 pyramidal neurons from rats chronically treated with caffeine, in comparison with their age- and littermate-matched controls. Altogether, the present findings strengthen the epidemiological observations suggesting that prolonged caffeine intake prevents the cognitive decline associated with aging, and open the possibility that this process could be mediated by promoting the growth of dendrites and spines in neurons of the adult mammalian brain.
Although caffeine can enhance cognitive function acutely, long-term effects of consumption of caffeine-containing beverages such as tea and coffee are uncertain. Data on 4,809 participants aged 65 and older from the Cardiovascular Health Study (CHS) were used to examine the relationship of consumption of tea and coffee, assessed by food frequency questionnaire, on change in cognitive function by gender. Cognitive performance was assessed using serial Modified Mini-Mental State (3MS) examinations, which were administered annually up to 9 times. Linear mixed models were used to estimate rates of change in standard 3MS scores and scores modeled using item response theory (IRT). Models were adjusted for age, education, smoking status, clinic site, diabetes, hypertension, stroke, coronary heart disease, depression score, and APOE genotype. Over the median 7.9 years of follow-up, participants who did not consume tea or coffee declined annually an average of 1.30 points (women) and 1.11 points (men) on standard 3MS scores. In fully adjusted models using either standard or IRT 3MS scores, we found modestly reduced rates of cognitive decline for some, but not all, levels of coffee and tea consumption for women, with no consistent effect for men. Caffeine consumption was also associated with attenuation in cognitive decline in women. Dose-response relationships were not linear. These longitudinal analyses suggest a somewhat attenuated rate of cognitive decline among tea and coffee consumers compared to non-consumers in women but not in men. Whether this association is causal or due to unmeasured confounding requires further study.
Alzheimer's disease (AD) is the sixth leading cause of all deaths in the United States and is the fifth leading cause of death in Americans aged ≥65 years. Although other major causes of death have been on the decrease, deaths because of AD have been rising dramatically. Between 2000 and 2008 (preliminary data), heart disease deaths decreased by 13%, stroke deaths by 20%, and prostate cancer‐related deaths by 8%, whereas deaths because of AD increased by 66%.
An estimated 5.4 million Americans have AD; approximately 200,000 people aged <65 years with AD comprise the younger‐onset AD population. Every 69 seconds, someone in America develops AD; by 2050, the time is expected to accelerate to every 33 seconds. Over the coming decades, the baby boom population is projected to add 10 million people to these numbers. In 2050, the incidence of AD is expected to approach nearly a million people per year, with a total estimated prevalence of 11 to 16 million people. Dramatic increases in the numbers of “oldest‐old” (those aged ≥85 years) across all racial and ethnic groups will also significantly affect the numbers of people living with AD.
In 2010, nearly 15 million family and other unpaid caregivers provided an estimated 17 billion hours of care to people with AD and other dementias, a contribution valued at more than $202 billion. Medicare payments for services to beneficiaries aged ≥65 years with AD and other dementias are almost 3 times higher than for beneficiaries without these conditions. Total payments in 2011 for health care, long‐term care, and hospice services for people aged ≥65years with AD and other dementias are expected to be $183 billion (not including the contributions of unpaid caregivers).
This report provides information to increase understanding of the public health effect of AD, including incidence and prevalence, mortality, health expenditures and costs of care, and effect on caregivers and society in general. The report also examines the current state of AD detection and diagnosis, focusing on the benefits of early detection and the factors that present challenges to accurate diagnosis.
Retrospective and prospective epidemiologic studies suggest that enhanced coffee/caffeine intake during aging reduces risk of Alzheimer's disease (AD). Underscoring this premise, our studies in AD transgenic mice show that long-term caffeine administration protects against cognitive impairment and reduces brain amyloid-β levels/deposition through suppression of both β- and γ-secretase. Because coffee contains many constituents in addition to caffeine that may provide cognitive benefits against AD, we examined effects of caffeinated and decaffeinated coffee on plasma cytokines, comparing their effects to caffeine alone. In both AβPPsw+PS1 transgenic mice and non-transgenic littermates, acute i.p. treatment with caffeinated coffee greatly and specifically increased plasma levels of granulocyte-colony stimulating factor (GCSF), IL-10, and IL-6. Neither caffeine solution alone (which provided high plasma caffeine levels) or decaffeinated coffee provided this effect, indicating that caffeine synergized with some as yet unidentified component of coffee to selectively elevate these three plasma cytokines. The increase in GCSF is particularly important because long-term treatment with coffee (but not decaffeinated coffee) enhanced working memory in a fashion that was associated only with increased plasma GCSF levels among all cytokines. Since we have previously reported that long-term GCSF treatment enhances cognitive performance in AD mice through three possible mechanisms (e.g., recruitment of microglia from bone marrow, synaptogenesis, and neurogenesis), the same mechanisms could be complimentary to caffeine's established ability to suppress Aβ production. We conclude that coffee may be the best source of caffeine to protect against AD because of a component in coffee that synergizes with caffeine to enhance plasma GCSF levels, resulting in multiple therapeutic actions against AD.
A combination of green tea extract and l-theanine (LGNC-07) has been reported to have beneficial effects on cognition in animal studies. In this randomized, double-blind, placebo-controlled study, the effect of LGNC-07 on memory and attention in subjects with mild cognitive impairment (MCI) was investigated. Ninety-one MCI subjects whose Mini Mental State Examination-K (MMSE-K) scores were between 21 and 26 and who were in either stage 2 or 3 on the Global Deterioration Scale were enrolled in this study. The treatment group (13 men, 32 women; 57.58 ± 9.45 years) took 1,680 mg of LGNC-07, and the placebo group (12 men, 34 women; 56.28 ± 9.92 years) received an equivalent amount of maltodextrin and lactose for 16 weeks. Neuropsychological tests (Rey-Kim memory test and Stroop color-word test) and electroencephalography were conducted to evaluate the effect of LGNC-07 on memory and attention. Further analyses were stratified by baseline severity to evaluate treatment response on the degree of impairment (MMSE-K 21-23 and 24-26). LGNC-07 led to improvements in memory by marginally increasing delayed recognition in the Rey-Kim memory test (P = .0572). Stratified analyses showed that LGNC-07 improved memory and selective attention by significantly increasing the Rey-Kim memory quotient and word reading in the subjects with MMSE-K scores of 21-23 (LGNC-07, n = 11; placebo, n = 9). Electroencephalograms were recorded in 24 randomly selected subjects hourly for 3 hours in eye-open, eye-closed, and reading states after a single dose of LGNC-07 (LGNC-07, n = 12; placebo, n = 12). Brain theta waves, an indicator of cognitive alertness, were increased significantly in the temporal, frontal, parietal, and occipital areas after 3 hours in the eye-open and reading states. Therefore, this study suggests that LGNC-07 has potential as an intervention for cognitive improvement.
Cholesterol has been linked to the pathogenesis of sporadic Alzheimer's disease (AD) as a risk factor increasing beta-amyloid (Abeta) and oxidative stress levels. Caffeine has antioxidant properties and has been demonstrated to reduce Abeta levels in transgenic mouse models of familial AD. However, the effects of caffeine on cholesterol-induced sporadic AD pathology have not been determined. In this study, we determined the effects of caffeine on Abeta levels, tau phosphorylation, oxidative stress generation, and caffeine-target receptors in rabbits fed a 2% cholesterol-enriched diet, a model system for sporadic AD. Our results showed that the cholesterol-enriched diet increased levels of Abeta, tau phosphorylation, and oxidative stress measured as increased levels of reactive oxygen species and isoprostanes, glutathione depletion, and increased levels of endoplasmic reticulum stress marker proteins. Additionally, the cholesterol-enriched diet reduced the levels of adenosine A(1) receptors (A(1)R) but not ryanodine or adenosine A(2A) receptors. Caffeine, administered at 0.5 and 30mg/day in the drinking water, reduced the cholesterol-induced increase in Abeta, phosphorylated tau, and oxidative stress levels and reversed the cholesterol-induced decrease in A(1)R levels. Our results suggest that even very low doses of caffeine might protect against sporadic AD-like pathology.