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The 7-Stage Model of Alzheimer's Dementia.
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Alzheimer's disease is the leading cause of dementia. However, neither Alzheimer's disease nor Alzheimer's dementia are an inevitable consequence of aging. This review provides an overview of the issues involved in a diagnosis of Alzheimer's disease before an individual meets the criteria for Alzheimer's dementia. It examines how Alzheimer's diseas...
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Context 1
... progression of Alzheimer's disease can be broken down into three general stages: preclinical, mild cognitive impairment, and dementia, but can be more accurately described according to a 7-Stage model (Table 1). 9 The progression of the disease may be different for each individual, but most people live between 4 and 8 years following diagnosis. ...Similar publications
Alzheimer’s disease is a progressive, irreversible neurodegenerative disease impacting cognition, function, and behavior. Alzheimer’s disease progresses along a continuum from preclinical disease, to mild cognitive and/or behavioral impairment and then Alzheimer’s disease dementia. Recently, clinicians have been encouraged to diagnose Alzheimer’s e...
Citations
... 2 In recent years, governments, organizations, and advocacy groups have emphasized the need for improved clinical recognition of dementia, including decreased time from symptom onset to detection. 3,4 However, we still know relatively little about factors related to the accuracy and timing of dementia detection in healthcare settings. 5 Identifying individual-level characteristics that make certain older adults more likely to have a missed or delayed diagnosis of dementia is crucial to addressing the problem of clinical underdiagnosis of dementia. ...
INTRODUCTION
There is limited evidence about factors related to the timeliness of dementia diagnosis in healthcare settings.
METHODS
In five prospective cohorts at Rush Alzheimer's Disease Center, we identified participants with incident dementia based on annual assessments and examined the timing of healthcare diagnoses in Medicare claims. We assessed sociodemographic, health, and psychosocial correlates of timely diagnosis.
RESULTS
Of 710 participants, 385 (or 54%) received a timely claims diagnosis within 3 years prior to or 1 year following dementia onset. In logistic regressions accounting for demographics, we found Black participants (odds ratio [OR] = 2.15, 95% confidence interval [CI]: 1.21 to 3.82) and those with better cognition at dementia onset (OR = 1.48, 95% CI: 1.10 to 1.98) were at higher odds of experiencing a diagnostic delay, whereas participants with higher income (OR = 0.89, 95% CI: 0.81 to 0.97) and more comorbidities (OR = 0.94, 95% CI: 0.89 to 0.98) had lower odds.
DISCUSSION
We identified characteristics of individuals who may miss the optimal window for dementia treatment and support.
Highlights
We compared the timing of healthcare diagnosis relative to the timing of incident dementia based on rigorous annual evaluation.
Older Black adults with lower income, higher cognitive function, and fewer comorbidities were less likely to be diagnosed in a timely manner by the healthcare system.
... Early diagnosis of dementia carries significant implications for persons with dementia, carers, and society as a whole. It not only aids in reducing associated risk factors but also helps delay disease progression [15]. Hence, valid and reliable cognitive screening tools have become vital. ...
Background
Visual impairment has been strongly associated with the incidence of dementia. Appropriate cognitive screening for the elderly with visual impairment is crucial for early identification of dementia and its management. Due to challenges in processing visually presented stimuli among participants, the cut-off score of the Hong Kong version of the Montreal Cognitive Assessment for the Visually Impaired (HKMoCA-VI), also known as MoCA-BLIND or MoCA-22, was unknown. Besides, the cognitive status of elderly with visual impairment residing in care homes is rarely investigated. The current study aimed to 1) establish the cut-off score for HKMoCA-VI and 2) examine the general cognitive functioning of elderly with visual impairment living in residential homes in Hong Kong in terms of MoCA-VI percentile scores.
Method
HKMoCA-VI and the Cantonese version of the Mini-Mental State Examination (CMMSE) were administered to 123 visually impaired elderly residents in care homes in Hong Kong. Percentile scores of HKMoCA-VI by age and education level were determined, and the concurrent validity, sensitivity, and specificity of HKMoCA-VI were assessed.
Results
A cut-off score 12 was suggested for HKMoCA-VI, which yielded a sensitivity and specificity of 89.29% and 83.58%, respectively. Moreover, it strongly correlated with CMMSE, indicating satisfactory concurrent validity.
Conclusions
HKMoCA-VI is suggested to be a viable cognitive screening tool for elderly individuals with visual impairment in residential homes. Further modifications to enhance the sensitivity and specificity of the measure are proposed.
... Considering that the risk of developing a neurocognitive disorder increases with age, doubling every 5 years from the age of 64, it is expected that the number of people with dementia will increase significantly in line with demographic aging (Public Health Agency, 2017). Early diagnosis of neurocognitive disorders can help alleviate the consequences of this class of diseases in several ways (Rasmussen & Langerman, 2019). Numerous diagnostic tools are currently available to assess the cognitive functions affected early in the dementia process (e.g., memory, language, executive functions; Carrier et al., 2022). ...
Objective
The mini Social cognition & Emotional Assessment (mini-SEA) is a social cognition battery which assesses theory of mind and emotion recognition. Currently, no psychometrically validated measure of social cognition with adapted normative data exists for the middle-aged and elderly French-Quebec population. This project aims to determine the known-group discriminant validity of a cultural and linguistic adaptation of the mini-SEA between cognitively healthy people, those with mild cognitive impairment (MCI) or living with Alzheimer’s Disease (AD). This study also aims to examine the stability of mini-SEA’s performance over a 3–4-month time period, as well as to produce normative data for French-Quebec people aged 50 years. Normative data are derived for the full and an abbreviated version of the Faux Pas subtest.
Method
The sample included 211 French-speaking participants from Quebec (Canada) aged 50 to 89 years. Mini-SEA’s performance between a sub-sample of cognitively healthy people (n = 20), those with MCI (n = 20) or with AD (n = 20) was compared. A sub-sample of cognitively healthy people (n = 30) performed the task twice to estimate test–retest reliability. Socio-demographic variables’ effects on scores were examined to produce normative data in the form of regression equations or percentile ranks.
Results
Significant differences emerged between cognitively healthy people and those with MCI or AD. Moreover, scores were relatively stable over a period of 3 to 4 months. Finally, for the normative data, age, gender, and education were associated with performance on the mini-SEA or its subtests.
Conclusions
This study improves and standardizes social cognition’s assessment among French–Quebec individuals, which will help characterize their cognitive profile.
... Важно отметить, что положительные биомаркеры БА обнаруживаются задолго до клинических проявлений заболевания (бессимптомная стадия), сохраняются на стадии УКН, легкой, умеренной и выраженной деменции [16]. Ранняя диагностика БА с использованием биомаркеров имеет большое практическое значение, потому что позволяет использовать все имеющиеся методы симптоматической терапии, уменьшающей выраженность симптомов и замедляющей прогрессирование заболевания [17]. В последние годы показана эффективность патогенетической антиамилоидной терапии БА на стадии УКН и ранней деменции, поэтому основанная на использовании биомаркеров ранняя диагностика БА приобретает еще большую значимость [16,18]. ...
Diagnostic hypothesis of Alzheimer's disease (AD) is based on the typical clinical picture of the disease and the exclusion of other diseases manifesting by cognitive and behavioural disorders by MRI scans of the brain and laboratory tests. For an accurate diagnosis of AD and exclusion of other diseases, detection of biological markers (biomarkers) of AD in the cerebrospinal fluid (CSF) is of great importance: a decrease in the level of beta-amyloid (Ав^ -42) and an increase in the level of phosphorylated tau protein. The analysis of AD biomarkers in the CSF of 63 patients (16 men and 47 women, mean age 72±8.7 years) with a typical picture of AD [30 patients in the moderate cognitive impairment (MCI) stage and 33 in the mild dementia stage] allowed us to confirm the diagnosis in 54 cases (85.3%) and to exclude it in the remaining nine patients (14.7%). We present a case of a 59-year-old patient with MCI in whom biomarkers typical of AD were detected in the CSF, confirming the diagnosis of AD. We also present the observations of two patients with possible AD, in whom the results of the CSF examination made it possible to rule out AD and indicated hippocampal sclerosis and tauopathy. At present, an accurate diagnosis of AD based on the study of biomarkers of the disease is of great practical importance, since at the stage of MCI and mild dementia it is possible to prevent the progression of AD with anti-amyloid therapy. Currently, AD is rarely diagnosed in our country, so it is of great importance to inform physicians about modern methods of diagnosis and treatment of AD.
... Another observation is that BBB degradation occurs early in AD [95], likely increasing peripheral blood IgG penetration into the brain [96]. This is why the treatment of NDs is more effective in the early stages [97], it is suggested. ...
Antibodies that can selectively remove rogue proteins in the brain are an obvious choice to treat neurodegenerative disorders (NDs), but after decades of efforts, only two antibodies to treat Alzheimer’s disease are approved, dozens are in the testing phase, and one was withdrawn, and the other halted, likely due to efficacy issues. However, these outcomes should have been evident since these antibodies cannot enter the brain sufficiently due to the blood–brain barrier (BBB) protectant. However, all products can be rejuvenated by binding them with transferrin, preferably as smaller fragments. This model can be tested quickly and at a low cost and should be applied to bapineuzumab, solanezumab, crenezumab, gantenerumab, aducanumab, lecanemab, donanemab, cinpanemab, and gantenerumab, and their fragments. This paper demonstrates that conjugating with transferrin does not alter the binding to brain proteins such as amyloid-β (Aβ) and α-synuclein. We also present a selection of conjugate designs that will allow cleavage upon entering the brain to prevent their exocytosis while keeping the fragments connected to enable optimal binding to proteins. The identified products can be readily tested and returned to patients with the lowest regulatory cost and delays. These engineered antibodies can be manufactured by recombinant engineering, preferably by mRNA technology, as a more affordable solution to meet the dire need to treat neurodegenerative disorders effectively.
... No cure for AD has been found, and diagnosis of AD occurs in the late stage for most of the patients (van der Flier et al., 2023). It is essential to diagnose AD early as early treatments lead to a better prognosis of the patient's cognitive function (Rasmussen and Langerman, 2019). ...
Alzheimer's Disease (AD) is the most common form of dementia, characterised by cognitive decline and biomarkers such as tau-proteins. Tau-positron emission tomography (tau-PET), which employs a radiotracer to selectively bind, detect, and visualise tau protein aggregates within the brain, is valuable for early AD diagnosis but is less accessible due to high costs, limited availability, and its invasive nature. Image synthesis with neural networks enables the generation of tau-PET images from more accessible T1-weighted magnetic resonance imaging (MRI) images. To ensure high-quality image synthesis, we propose a cyclic 2.5D perceptual loss combined with mean squared error and structural similarity index measure (SSIM) losses. The cyclic 2.5D perceptual loss sequentially calculates the axial 2D average perceptual loss for a specified number of epochs, followed by the coronal and sagittal planes for the same number of epochs. This sequence is cyclically performed, with intervals reducing as the cycles repeat. We conduct supervised synthesis of tau-PET images from T1w MRI images using 516 paired T1w MRI and tau-PET 3D images from the ADNI database. For the collected data, we perform preprocessing, including intensity standardisation for tau-PET images from each manufacturer. The proposed loss, applied to generative 3D U-Net and its variants, outperformed those with 2.5D and 3D perceptual losses in SSIM and peak signal-to-noise ratio (PSNR). In addition, including the cyclic 2.5D perceptual loss to the original losses of GAN-based image synthesis models such as CycleGAN and Pix2Pix improves SSIM and PSNR by at least 2% and 3%. Furthermore, by-manufacturer PET standardisation helps the models in synthesising high-quality images than min-max PET normalisation.
... There is no cure for dementia, only drugs to slow its progression 15 . For this reason, early diagnosis is beneficial for patients and their caregivers and can result in substantial cost savings for healthcare systems 16 . In fact, early diagnosis provides numerous benefits to the patient: (a) greater and more effective adherence to pharmacological and rehabilitative treatments, (b) the possibility of participating in treatments that are still experimental, and (3) the possibility of organising one's life in relation to the progression of the disease 17 . ...
The elderly in Peru face significant barriers in healthcare, notably in detecting cognitive impairment and dementia. These difficulties are exacerbated by the scarcity of validated and standardised cognitive assessment instruments for this age group. The Montreal Cognitive Assessment (MoCA) has proven to be a useful tool for the early detection of dementia, evaluating eight domains of cognitive functions, including: visuo-spatial and executive function, naming, memory, attention, language, abstraction, and orientation. This study aims to standardise the Spanish version of the Montreal Cognitive Assessment (MoCA) for the elderly in Lima, addressing the critical need for culturally and demographically adapted cognitive evaluation tools in Peru. The test was administered to 338 ambulatory and homebound elders from three institutions: San Miguel District Municipality, San Jose Obrero Polyclinic in Barranco, and EDMECON in Surco. The study provides normative data and cut-off scores for the Peruvian elderly population, facilitating the clinical application of the MoCA in Peru and potentially other Spanish-speaking countries. Our results indicate high orientation scores and low delayed recall performance, possibly highlighting cognitive strengths and weaknesses in our sample. Moreover, age and education significantly influenced cognitive performance, with education being the strongest predictor. We discuss our findings in relation to the use of appropriate cut-off points and considerations of cultural sensitivity relevant to the Peruvian context.
... An early diagnosis of dementia would potentially allow the involvement and support of the patient's family, the initiation of treatments, and the delay of the patient's institutionalization, ultimately reducing the healthcare costs associated with home and specialized services [71,72]. However, some perspectives suggest that the early diagnosis of dementia (e.g., at preclinical stages) in the absence of an effective treatment is not sufficiently justified, increasing the suffering of the patient and family due to stigma and the anticipation of progressive disability [73,74]. ...
... The early detection of dementia could lead to savings from delayed institutionalization, making it a potential cost-effective investment [72,225]. For example, it could provide early access to available pharmacological and psychosocial treatments. ...
... Given the current limitations for detecting CI on time, it is worth asking whether this debate makes sense [236][237][238]. To this end, collaborative and transdisciplinary working groups are needed to provide early professional support to patients and caregivers, including diagnostic assistance and holistic interventions [72,79,239]. ...
Dementia remains an underdiagnosed syndrome, and there is a need to improve the early detection of cognitive decline. This narrative review examines the role of neuropsychological assessment in the characterization of cognitive changes associated with dementia syndrome at different states. The first section describes the early indicators of cognitive decline and the major barriers to their identification. Further, the optimal cognitive screening conditions and the most widely accepted tests are described. The second section analyzes the main differences in cognitive performance between Alzheimer’s disease and other subtypes of dementia. Finally, the current challenges of neuropsychological assessment in aging/dementia and future approaches are discussed. Essentially, we find that current research is beginning to uncover early cognitive changes that precede dementia, while continuing to improve and refine the differential diagnosis of neurodegenerative disorders that cause dementia. However, neuropsychology faces several barriers, including the cultural diversity of the populations, a limited implementation in public health systems, and the adaptation to technological advances. Nowadays, neuropsychological assessment plays a fundamental role in characterizing cognitive decline in the different stages of dementia, but more efforts are needed to develop harmonized procedures that facilitate its use in different clinical contexts and research protocols.
... [5] Early diagnosis of Alzheimer's disease is crucial for several reasons, including providing timely support and care, reducing the financial burden on healthcare systems, and possibly decreasing the progression of the disease. [6] The diagnosis rate for Alzheimer's disease remains low, and there is an urgent need to improve diagnosis rates so that those at greatest risk can be identified. [6] The urgency of Alzheimer's disease is also underscored by the growing body of research on risk factors and the need for effective prevention strategies. ...
... [6] The diagnosis rate for Alzheimer's disease remains low, and there is an urgent need to improve diagnosis rates so that those at greatest risk can be identified. [6] The urgency of Alzheimer's disease is also underscored by the growing body of research on risk factors and the need for effective prevention strategies. [7,8] Besides, there are currently only two fully approved non-modifyingdisease therapies for AD, including N-methyl d-aspartate receptor antagonists and acetylcholinesterase inhibitors. ...
Background: Alzheimer's Disease (AD) is a progressive neurodegenerative disorder with a rapidly increasing prevalence. Current therapeutic options primarily manage symptoms, not modifying the disease. Secretome-based therapies have emerged as a promising avenue for AD treatment in targeting multiple pathways and promoting neuroprotection and regeneration. This systematic review evaluated the preclinical and clinical evidences for secretome-based therapies in AD.Methods: A systematic search was conducted across Scopus, PubMed, ScienceDirect, and Cochrane Library. The SYRCLE risk of bias (RoB) tool was used for preclinical studies and Cochrane RoB 2.0 for clinical studies. We performed qualitative analysis of study results.Results: Included 21 in vivo studies and 2 clinical trials revealed promising outcomes of treatments involving secretomes, exosomes, and extracellular vesicles from different cell sources. The therapies could reduce amyloid plaque load, reactive gliosis, and enhance neuronal density. These findings suggested the treatments reveal mechanism of action in neuroprotection, neuroregeneration, and inflammation modulation, which are critical in AD pathology. Ongoing trials also supported the safety and efficacy of the treatment strategies. However, translational medical study faces several challenges regarding large-scale production, optimization of protocols, and understanding biomarkers. The heterogeneity in secretome-based therapies administration have complicated the comparison of study outcomes and the translation of preclinical findings into clinical settings. Deeper understanding of the secretome's mechanisms of action, optimal dosing, and delivery methods are needed to maximize therapeutic outcomes.Conclusion: Despite secretome-based therapies hold significant promise for AD treatment, addressing the identified gaps and limitations is crucial for advancing these therapies from preclinical research to clinical practice.
... Therefore, early detection and intervention are crucial components in assisting families to traverse this challenging path. In addition to physicians, engineers are developing automated technology for enhanced AD monitoring, diagnosis, and treatment [8] . ...
