No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Relation Between Clinical Characteristics of Parkinson's Disease and Cognitive Decline
Journal of Clinical and Experimental Neuropsychology
Abstract
This study examined how cognitive impairments in Parkinson's disease (PD) are related to clinical characteristics such as age at testing, duration of illness, motor impairment, and especially age at disease onset. To address these issues, we administered 14 tests of memory, language, visuospatial, and frontal lobe capacities to 104 PD patients and 60 healthy volunteers of comparable age and education. The participants completed 1-9 test sessions over 1-10 years. Duration of PD was associated with deteriorating performance on most cognitive tests, independent of age-related decline. Severity of motor impairment, indexed by Hoehn and Yahr stages, was positively related to impairment on almost all cognitive tests, holding age and duration constant. For some tests, especially those that were motorically demanding and those that assessed language skills, cognitive deficits appeared earlier in the disease course for late-onset than for early-onset PD patients. These late onset deficits were synergistic effects beyond the additive contributions of disease duration and normal aging. These findings may assist physicians in advising PD patients and their families about the future course of the illness.
... Some studies have suggested the potential impact of sex on the neurocognitive function of patients with PD. Female patients with PD were found to perform better in terms of verbal fluency [13,16,17,28], verbal memory [12,29], and processing speed than male patients with PD [13,15,16], while male patients with PD performed better on visuospatial ability tests [16,[28][29][30]. However, in our study, male and female patients with PD showed no difference in any of the neurocognitive domains examined in the current study. ...
... Some studies have suggested the potential impact of sex on the neurocognitive function of patients with PD. Female patients with PD were found to perform better in terms of verbal fluency [13,16,17,28], verbal memory [12,29], and processing speed than male patients with PD [13,15,16], while male patients with PD performed better on visuospatial ability tests [16,[28][29][30]. However, in our study, male and female patients with PD showed no difference in any of the neurocognitive domains examined in the current study. ...
... However, in our study, male and female patients with PD showed no difference in any of the neurocognitive domains examined in the current study. These diverging results may be due to the fact that most patients with PD recruited in the previous studies had shorter disease duration [12,13,16,17,28,29] or intact neurocognitive function [13], while we recruited patients in the later stages of the disease as well. Moreover, the lack of sex differences in the neurocognitive function of patients with PD and the presence of sex differences in the healthy aging population indicates the differential effect of sex between healthy aging and the neurodegeneration of PD, which may be because of the protective effect of estrogen, which has been shown to be neuroprotective and reduces the risk of PD in women [31]. ...
This study aimed to understand the impact of sex on the neurocognitive function of patients with Parkinson’s disease (PD). Ninety-four participants with idiopathic PD and 167 age-matched healthy individuals as normal controls (NCs) were recruited and underwent comprehensive neuropsychological assessments. Sex differences were found in NCs, but not in patients with PD. Among male participants, patients with PD showed worse performance on the Digit Symbol Substitution (DSS) (p < 0.001) test and Symbol Search (SS) (p < 0.001) than NCs. Among female participants, patients with PD showed worse performance on the category score of the Modified Wisconsin Card Sorting Test (p < 0.001), SS (p < 0.001), and pentagon copying (p < 0.001) than NCs. After controlling for the effects of age and years of education, Hoehn and Yahr stage was found to predict the performance of the Color Trails Test part A (βA = 0.241, pA = 0.036), Stroop Color and Word Test (β = −0.245, p = 0.036), and DSS (β = −0.258, p = 0.035) in men with PD. These results indicate the differential effect of sex on the neurocognitive function among healthy aging and PD populations. The disappearance of sex differences, which is present in healthy aging, in patients with PD suggests a gradual loss of the neuroprotective effect of estrogen after the initiation of the neurodegenerative process. This study also found mental flexibility and visuospatial function to be the susceptible cognitive domains in women with PD, while the disease severity could predict the working memory and processing speed in men with PD.
... Furthermore, some results revealed no signi cant difference in attention 11,13 . Among all the executive functions that are frequently impaired in PD patients, males perform worse on verbal uency 13, 16,17,21,22 , while another study showed no signi cant difference 12 . In addition, some studies suggested that female PD patients have poor executive 11,23 , and visuospatial-function 11,12,16,21 . ...
... The patients' heterogeneity may explain the discrepancy. Most PD patients recruited in the prior studies had shorter disease duration 12,13,16,17,21,22 or have intact mentality ability 13 , and we recruited patients at all stages. Estrogen may have a protective ability and consequently reduce PD risk for females 32,33 . ...
... Previous studies showed that PD patients' clinical characteristics (e.g., onset age, disease duration, LED, and H&Y stage) are correlated to the neurocognitive function 4,18,22 . In the present study, we found a gender difference in the relationship between clinical characteristics and speci c neurocognitive function. ...
This study aimed to elucidate the role of sex in neurocognitive function in patients with Parkinson’s disease (PD). Ninety-four idiopathic PD and 167 healthy elderly as normal controls (NCs) were recruited and underwent comprehensive neuropsychological assessments. The sex difference were found in NCs but not in PD. In male, PD patients had worse performance on the Digit symbol substitution (DSS) (p < 0.001) and the Symbol Searching (SS) (p < 0.001) than NCs. In female, PD patients had the worse score on the category score of the Modified Wisconsin Card Sorting Test (p < 0.001), the SS (p < 0.001), and the pentagon copying (p < 0.001) than NCs. After controlling age and years of education, Hoehn and Yahr Stage can predict the performance of the Color Trail Test part A (βA = 0.241, pA = 0.036), the Stroop Word-Color Test (β = -0.245, p = 0.036), and the DSS (β = -0.258, p = 0.035) in male PD patients. Sex differences were found in NCs but not in PD. The mental flexibility and visuospatial function are susceptible to female in the PD course. Male PD patients’ working memory and processing speed can be predicted by the disease severity.
... For example, lower global cognition scores in nondemented men with PD have been reported in studies using the Mini Mental State Examination (MMSE; Lyons et al. 1998;Hariz et al. 2003;Uc et al. 2009) and the Montreal Cognitive Assessment (MoCA; Nazem et al. 2009;Hu et al. 2014;Szewczyk-Krolikowski et al. 2014). Regarding specific domains, non-demented females with PD were found to be superior in both semantic and phonemic verbal fluency (Locascio et al. 2003;Szewczyk-Krolikowski et al. 2014). Furthermore, a result found both in studies comparing male and female PD patients ) and comparing PD patients with a healthy control group (Carey et al. 2002;Locascio et al. 2003) demonstrated that women with PD have poorer visuospatial abilities. ...
... Regarding specific domains, non-demented females with PD were found to be superior in both semantic and phonemic verbal fluency (Locascio et al. 2003;Szewczyk-Krolikowski et al. 2014). Furthermore, a result found both in studies comparing male and female PD patients ) and comparing PD patients with a healthy control group (Carey et al. 2002;Locascio et al. 2003) demonstrated that women with PD have poorer visuospatial abilities. In line with these findings, in the largest investigation so far that specifically examined this topic, Pasotti et al. (2012) tested 162 male and 144 female PD patients and reported that women with PD had significantly higher scores on a delayed verbal recall task, whereas men had better visuospatial abilities. ...
... One is to include a healthy control group and compare male and female PD patients to healthy men and women, respectively, and the other is to include only patients but to use gender-corrected normative data. Remarkably, only two of the studies described above (Carey et al. 2002;Locascio et al. 2003) included a control group and, even more striking, no study so far has used gendercorrected data. Indeed, using a control group permits an explicit definition of whether patients have dysfunction compared to sex-matched controls. ...
Background:
Data on gender-specific profiles of cognitive functions in patients with Parkinson's disease (PD) are rare and inconsistent, and possible disease-confounding factors have been insufficiently considered.
Method:
The LANDSCAPE study on cognition in PD enrolled 656 PD patients (267 without cognitive impairment, 66% male; 292 with mild cognitive impairment, 69% male; 97 with PD dementia, 69% male). Raw values and age-, education-, and gender-corrected Z scores of a neuropsychological test battery (CERAD-Plus) were compared between genders. Motor symptoms, disease duration, l-dopa equivalent daily dose, depression - and additionally age and education for the raw value analysis - were taken as covariates.
Results:
Raw-score analysis replicated results of previous studies in that female PD patients were superior in verbal memory (word list learning, p = 0.02; recall, p = 0.03), while men outperformed women in visuoconstruction (p = 0.002) and figural memory (p = 0.005). In contrast, gender-corrected Z scores showed that men were superior in verbal memory (word list learning, p = 0.02; recall, p = 0.02; recognition, p = 0.04), while no difference was found for visuospatial tests. This picture could be observed both in the overall analysis of PD patients as well as in a differentiated group analysis.
Conclusions:
Normative data corrected for gender and other sociodemographic variables are relevant, since they may elucidate a markedly different cognitive profile compared to raw scores. Our study also suggests that verbal memory decline is stronger in women than in men with PD. Future studies are needed to replicate these findings, examine the progression of gender-specific cognitive decline in PD and define different underlying mechanisms of this dysfunction.
... The same EF differences hold true for women and men with PD. The available data suggests that women with PD have better verbal memory C o r r e c t e d P r o o f [86], executive and global cognitive functioning than men [93][94][95][96][97][98]. Conversely, men with PD have better visuospatial memory than women [93,[99][100][101][102][103]. ...
... The available data suggests that women with PD have better verbal memory C o r r e c t e d P r o o f [86], executive and global cognitive functioning than men [93][94][95][96][97][98]. Conversely, men with PD have better visuospatial memory than women [93,[99][100][101][102][103]. Data suggest that women learn verbal lists faster, have more efficient frontostriatal DA regulation, and higher DA receptor expression in the striatum that may be associated with higher estrogen levels [86,104]. ...
Up to 23% of newly diagnosed, non-demented, Parkinson’s disease (PD) patients experience deficits in executive functioning (EF). In fact, EF deficits may occur up to 39-months prior to the onset of motor decline. Optimal EF requires working memory, attention, cognitive flexibility, and response inhibition underlying appropriate decision-making. The capacity for making strategic decisions requires inhibiting imprudent decisions and are associated with noradrenergic and dopaminergic signaling in prefrontal and orbitofrontal cortex. Catecholaminergic dysfunction and the loss of noradrenergic and dopaminergic cell bodies early in PD progression in the aforementioned cortical areas likely contribute to EF deficits resulting in non-strategic decision-making. Thus, detecting these deficits early in the disease process could help identify a significant portion of individuals with PD pathology (14–60%) before frank motor impairment. A task to evaluate EF in the domain of non-strategic decision-making might be useful to indicate the moderate loss of catecholamines that occurs early in PD pathology prior to motor decline and cognitive impairment. In this review, we focus on the potential utility of the Iowa Gambling Task (IGT) for this purpose, given significant overlap between in loss of dopaminergic and noradrenergic cells bodies in early PD and the deficits in catecholamine function associated with decreased EF. As such, given the loss of catecholamines already well-underway after PD diagnosis, we evaluate the potential utility of the IGT to identify the risk of therapeutic non-compliance and a potential companion approach to detect PD in premotor stages.
... Identifying the interplay between sex and the disease has the potential to develop disease-modifying therapy as well as to inform patient management and the planning of more efficient clinical trials. Researchers have investigated the sex-associated differences in phenotypes among patients with PD. 1 Male PD patients were reported to have more akinesia/rigid features, 2 cognitive impairment, 3,4 and rapid eye movement sleep behavioral disorder. 5,6 On the other hand, depression, 7-10 and dyskinesia 7,[11][12][13] were documented to occur more frequently in female patients. ...
... The slower development of cognitive decline in female patients was reported from some longitudinal studies. 3,4,21 The executive and attention features were primarily affected in PD. We observed the discrepancy between MoCA and MMSE in the baseline analyses and this discrepancy may be partly because MoCA is more sensitive in detecting executive dysfunction than MMSE. ...
Objectives: Identifying the contribution of biological sex to the heterogeneity in presentation and progression of Parkinson's disease (PD).
Background: The different prevalence of Parkinson's disease (PD) in men and women suggests that sex-associated mechanisms influence disease mechanisms. Investigating the contribution of sex to disease heterogeneity may uncover disease processes, and lead to new therapeutic targets. Also, understanding these differences in phenotypes will result in better patient management and the planning of more efficient clinical trials.
Methods: We tested 40 clinical phenotypes using longitudinal clinic-based patient cohorts consisting of 5,946 patients with a median follow-up of 3.1 years. For continuous outcomes, we used linear regressions at baseline to test the sex-associated differences in presentation, and linear mixed-effects models to test the sex-associated differences in progression. For binomial outcomes, we used logistic regression models at baseline and Cox models for survival analyses. We adjusted for age, disease duration and dopaminergic medication usage. In the secondary analyses, data from 28,809 PD patients and 10,556 non-PD participants from Fox Insight, an online-only self-assessment cohort for PD research, were analyzed to check whether the sex-associated differences observed in the primary analyses were consistent in the cohort and whether the differences were unique to PD or not.
Results: Female PD patients had a higher risk for developing dyskinesia early during the follow-up period; with a slower progression in their difficulties of activities of daily living as measured by the Unified Parkinson's Disease Rating Scale Part II (classic/MDS-revised version); and a lower risk of developing cognitive impairment than male patients. The findings in the longitudinal clinic-based cohorts were mostly consistent with the results in the online-only cohort.
Conclusions: This large-scale analysis observed the sex contribution to the heterogeneity of Parkinson's disease. The results highlight the necessity of future research of the underlying mechanism and importance of personalized clinical management.
... Manche Untersuchungen fi nden gar keinen Geschlechtseff ekt (Amick, Schendan, Ganis & Cronin-Golomb, 2006;Crizzle, Classen & Uc, 2012;Schendan, Amick & Cronin-Golomb, 2009 Hu et al., 2014;Nazem et al., 2009;Szewczyk-Krolikowski et al., 2014). Weiterhin schneiden Frauen mit IPS typischerweise besser in verbalen Gedächtnistests (Pasotti et al., 2012) und formallexikalischen und semantischen Wortfl üssigkeitsaufgaben (Locascio, Corkin & Growdon, 2003;Szewczyk-Krolikowski et al., 2014) ab. Männer mit IPS hingegen scheinen bessere Leistungen in visuell-räumlichen Tests zu erbringen (Carey, Deskin, Josephson & Wichmann, 2002;Locascio et al., 2003;Pasotti et al., 2012;Riedel et al., 2008). ...
... Weiterhin schneiden Frauen mit IPS typischerweise besser in verbalen Gedächtnistests (Pasotti et al., 2012) und formallexikalischen und semantischen Wortfl üssigkeitsaufgaben (Locascio, Corkin & Growdon, 2003;Szewczyk-Krolikowski et al., 2014) ab. Männer mit IPS hingegen scheinen bessere Leistungen in visuell-räumlichen Tests zu erbringen (Carey, Deskin, Josephson & Wichmann, 2002;Locascio et al., 2003;Pasotti et al., 2012;Riedel et al., 2008). Entsprechend kommen auch die zwei Übersichtsarbeiten, die zu diesem Thema bislang verfasst wurden (Heller, Dogan, Schulz & Reetz, 2014;Miller & Cronin-Golomb, 2010), zu dem Ergebnis, dass vor allem in verbalen Gedächtnisleitungen und visuell-räumlichen Funktionen Unterschiede bestehen. ...
This review aims to summarize (neuro-)psychological gender effects in Parkinson’s Disease (IPS). Women with IPS experience depressive symptoms more frequently than men; however, the gender distribution is more balanced than in the general population. Regarding cognition, recent research indicates that women with IPS show more verbal memory decline than men. HrQoL gender differences become more prevalent, when specific HrQoL domains are assessed separately. Summarizing, gender differences in IPS exist in several (neuro-)psychological areas and seem to be of clinical relevance. However, the current state of knowledge and underlying mechanisms are far from being clear. Thus, more research in this context is needed.
... 19 PD hastens deterioration of these cognitive abilities over time, with the incidence and prevalence of cognitive impairments increasing with duration and severity of illness. 20,21 In this sense, PD can be considered a risk factor for dementia. Formal criteria have been developed for mild cognitive impairment (MCI) in PD ( Table 4-2). ...
... 28 The risk of developing cognitive impairment and dementia in PD has been associated with older age, greater severity of extrapyramidal motor impairment, and longer duration of illness. 20,24,25 Additional risk factors have been identified as well, including male gender, atypical motor syndromes (notably the postural instability gait disorder (PIGD) variant, axial symmetrical parkinsonism, and akinetic dominant parkinsonism), and the early development of hallucinations ( Table 4-3). 24,27 The cognitive profile in PD dementia overlaps significantly with that observed in DLB. 4 Patients typically demonstrate executive dysfunction and visual-spatial impairment. ...
Purpose of review:
This article provides an overview of the clinical features, neuropathologic findings, diagnostic criteria, and management of dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD), together known as the Lewy body dementias.
Recent findings:
DLB and PDD are common, clinically similar syndromes that share characteristic neuropathologic changes, including deposition of α-synuclein in Lewy bodies and neurites and loss of tegmental dopamine cell populations and basal forebrain cholinergic populations, often with a variable degree of coexisting Alzheimer pathology. The clinical constellations of DLB and PDD include progressive cognitive impairment associated with parkinsonism, visual hallucinations, and fluctuations of attention and wakefulness. Current clinical diagnostic criteria emphasize these features and also weigh evidence for dopamine cell loss measured with single-photon emission computed tomography (SPECT) imaging and for rapid eye movement (REM) sleep behavior disorder, a risk factor for the synucleinopathies. The timing of dementia relative to parkinsonism is the major clinical distinction between DLB and PDD, with dementia arising in the setting of well-established idiopathic Parkinson disease (after at least 1 year of motor symptoms) denoting PDD, while earlier cognitive impairment relative to parkinsonism denotes DLB. The distinction between these syndromes continues to be an active research question. Treatment for these illnesses remains symptomatic and relies on both pharmacologic and nonpharmacologic strategies.
Summary:
DLB and PDD are important and common dementia syndromes that overlap in their clinical features, neuropathology, and management. They are believed to exist on a spectrum of Lewy body disease, and some controversy persists in their differentiation. Given the need to optimize cognition, extrapyramidal function, and psychiatric health, management can be complex and should be systematic.
... • Volume 5, Number 1, February 2014 67 specific. Capturing this aspect Locascio, Corkin, & Growdon [69] investigated 104 PD patients (68 men, 36 women) and 60 healthy controls (25 men, 35 women) on a variety of cognitive tests. Women, across PD and control subjects, were found to perform worse in the Money Road Map test, a trial requiring egocentric mental rotation in space in a right-left discrimination task [70]. ...
... Moreover, it has not been well acknowledged, if these results are disease specific or just a matter of a general gender effect. While women with PD might show up with a slower decline of cognitive functioning compared to men with PD [69], there seems to be evidence for an accelerated age-related cognitive decline in healthy men compared to healthy women as well, as elderly men present an increased decline in performance on attention, verbal memory, spatial memory, and spatial abilities compared to elderly women [64]. This again raises the question of estrogen having a potential neuroprotective effect on cognitive performance. ...
Objectives: Impaired facial emotion identification in Parkinson's disease (PD) has been reported for negative basic emotions, but results are quite heterogeneous1. In this context, gender is believed to be a major moderator variable, however, data are very limited2,3. Using a neuropsychological test battery and functional Magnetic Resonance Imaging (fMRI), we aim to investigate gender effects on behavioral data and functional neural correlates of emotion processing in PD. Methods: A detailed clinical and neuropsychological test battery including the Ekman 60 faces task and event-related fMRI as well as anatomical images using a 3T Siemens MR Scanner were acquired in PD patients and age- and gender-matched healthy controls. During scanning subjects were presented video-sequences of trained actors performing one of six facial expressions (sadness, happiness, disgust, fear, anger, neutral; 20 videos each). Results: Preliminary behavioral data showed a significant worse performance of PD patients in the recognition of fear compared to controls. This deficit in the recognition of fear was more pronounced in male than female PD patients. A corresponding gender difference was not found in healthy controls. Conclusion: Our data suggest a relative impairment in PD patients for the recognition of fear. Moreover, our results indicate that gender may play a role in emotion processing in PD. The identification of respective neural correlates will provide further evidence for PD-related gender differences in emotion processing. References: [1] Gray HM, Tickle-Degnen L (2010), 'A meta-analysis of performance on emotion recognition tasks in Parkinson's disease' Neuropsychology, vol. 24, pp. 176 – 91. [2] Clark US, Neargarder S, Cronin-Golomb A (2008), 'Specific impairments in the recognition ofemotional facial expressions in Parkinson's disease' Neuropsychologia, vol. 46, pp. 2300 – 9. [3] Heller J, Dogan I, Schulz JB, Reetz K (2014), 'Evidence for gender differences in cognition, emotion and quality of life in Parkinson's disease?' Aging and Disease, In press.
... Conversely, others have reported that males have greater cognitive impairment and more rapid progression than females. 56,57 Our report was based only on MoCA scores over an epoch (15 years), whereas these latter studies 56,57 utilized a broad battery of neurocognitive tests and shorter follow-up period. Thus, the discordance between our data and previous studies may suggest that males are more affected by changes to specific high-level tasks, but that changes in routine cognitive function is affected similarly in both sexes. ...
Background
Parkinson’s disease (PD) therapeutic strategies have evolved since the introduction of levodopa in the 1960s, but there is limited data on their impact on disease progression markers.
Objective
Delineate the current landscape of PD progression at tertiary subspecialty care and research centers.
Method
Using Accelerating Medicine Partnership-PD (AMP-PD) data harmonized from seven biomarker discovery studies (2010-2020), we extracted: overall [Schwab and England (S&E), PD Questionnaire (PDQ-39)]; motor [Movement Disorders Society Unified PD Rating Scale (MDS-UPDRS)-II and -III and Hoehn & Yahr (HY)]; and non-motor [MDS-UPDRS-I, University of Pennsylvania Smell Identification Test (UPSIT), Montreal Cognitive Assessment (MoCA), and Epworth Sleepiness Scale (ESS)] scores. Age at diagnosis was set as 0 years, and data were tracked for 15 subsequent years.
Results
Subjects’ (3,001 PD cases: 2,838 white, 1,843 males) mean age at diagnosis was 60.2±10.3 years and disease duration was 9.9±6.0 years at the baseline evaluation. Participants largely reported independence (S&E, 5y : 86.6±12.3; 10y : 78.9±19.3; 15y : 78.5±17.0) and good quality of life (PDQ-39, 5y : 15.5±12.3; 10y : 22.1±15.8; 15y : 24.3±14.4). Motor scores displayed a linear progression, whereas non-motor scores plateaued ∼10-15 years. Younger onset age correlated with slower overall (S&E), motor (MDS-UPDRS-III), and non-motor (UPSIT/MoCA) progression, and females had better overall motor (MDS-UPDRS-II-III) and non-motor (UPSIT) scores than males.
Conclusions
Twenty-first century PD patients remain largely independent in the first decade of disease. Female and young age of diagnosis were associated with better clinical outcomes. There are data gaps for non-whites and metrics that gauge non-motor progression for >10 years after diagnosis.
... Regarding cognitive domains, such as memory and visuo-spatial and attention/executive skills, it has been argued that men and women can be affected in different ways, but the results are still controversial [3,18,35,36]. It has been stated that women with PD might show up with a slower decline of cognitive functioning compared to men [37,38]. In our cohort, men and women showed no significant difference (p < 0.01); they present the same cognitive impairment over time. ...
Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment of PD for both women and men. However, discussions have been reported about the impact of STN-DBS surgery in PD. The aim of our study is to identify differences between men and women in terms of pre- and post-DBS symptoms and try to explain the possible causes. In the current study, we evaluated the gender impact on STN-DBS in PD at the Department of Neurosurgery of University of Naples “Federico II” from 2013 to 2021. Motor and non-motor symptoms were evaluated. To compare the data before and after surgery and between the genders, Wilcoxon-Mann–Whitney tests were performed. A total of 43 patients with PD were included; of them, 17 (39%) were female. Baseline evaluation revealed no gender differences in the age of onset ( p = 0.87). Not significant differences were noted in the Unified Parkinson’s Disease Rating Scale (UPDRS) pre-surgery score, but if we consider UPDRS subscores of motor examination, significant clinical improvement was reported in both male and female in terms of UPDRS pre- and post-surgery ( p < 0.001). STN-DBS is a highly effective treatment for motor and non-motor symptoms of PD for both women and men but our study hints towards gender-specific outcomes in motor domains. Improving our knowledge in this field can allow us to implement strategies to identify new directions in the development of an adequate treatment of PD in terms of surgical intervention and in consideration of the gender.
... Several studies have focused on the analysis of gender differences in the manifestation of cognitive damage in patients with PD and the affected sub-processes. Gender differences have been observed on the Road Map Test of Direction Sense, a right-left discrimination task that requires egocentric mental rotation in space, with men being superior [136]. Davidsdottir et al. [132] examined spatial navigation and visuospatial functioning. ...
Non-motor symptoms in Parkinson's disease (PD) include ocular, visuoperceptive, and visuospatial impairments, which can occur as a result of the underlying neurodegenerative process. Ocular impairments can affect various aspects of vision and eye movement. Thus, patients can show dry eyes, blepharospasm, reduced blink rate, saccadic eye movement abnormalities, smooth pursuit deficits, and impaired voluntary and reflexive eye movements. Furthermore, visuopercep-tive impairments affect the ability to perceive and recognize visual stimuli accurately, including impaired contrast sensitivity and reduced visual acuity, color discrimination, and object recognition. Visuospatial impairments are also remarkable, including difficulties perceiving and interpreting spatial relationships between objects and difficulties judging distances or navigating through the environment. Moreover, PD patients can present visuospatial attention problems, with difficulties attending to visual stimuli in a spatially organized manner. Moreover, PD patients also show perceptual disturbances affecting their ability to interpret and determine meaning from visual stimuli. And, for instance, visual hallucinations are common in PD patients. Nevertheless, the neurobiological bases of visual-related disorders in PD are complex and not fully understood. This review intends to provide a comprehensive description of visual disturbances in PD, from sensory to perceptual alterations, addressing their neuroanatomical, functional, and neurochemical correlates. Structural changes, particularly in posterior cortical regions, are described, as well as functional alterations, both in cortical and subcortical regions, which are shown in relation to specific neuropsychological results. Similarly, although the involvement of different neurotransmitter systems is controversial, data about neurochemical alterations related to visual impairments are presented, especially dopaminergic, cholinergic, and serotoninergic systems.
... The risk of developing MCI and dementia in PD is 2.5-6 times higher than in the general population [64]. Risk factors for cognitive impairment in PD include age, motor symptoms severity, disease duration, early development of hallucinations, axial motor symptoms, low education, depression, male gender [65][66][67][68][69][70][71][72]. ...
Introduction
Non-motor symptoms (NMS) affect patients with Parkinson’s disease (PD) from the prodromal to the advanced stages. NMS phenotypes greatly vary and have a huge impact on patients’ and caregivers’ quality of life (QoL). The management of cognitive and neuropsychiatric NMS remains an unmet need.
Areas covered
The authors, herein, review the dopaminergic and non-dopaminergic pathogenesis, clinical features, assessment, and pharmacological and non-pharmacological treatment of cognitive and neuropsychiatric NMS in PD. They discuss the current evidence and report the findings of an overview on ongoing trials on pharmacological and selected non-pharmacological strategies.
Expert opinion
The treatment of cognitive and neuropsychiatric NMS in PD is poorly explored, and therapeutic options are unsatisfactory. Pharmacological treatment of cognitive NMS is based on symptomatic active principles used in Alzheimer’s disease. Dopamine agonists, selective serotonin and serotonin-norepinephrine reuptake inhibitors have some evidence in PD-related depression. Clozapine, quetiapine, and pimavanserin may be considered for psychosis in PD. Evidence on the treatment of other neuropsychiatric NMS is limited or lacking. Addressing pathophysiological and clinical issues, which hamper solid evidence on the treatment of cognitive and neuropsychiatric NMS, may reduce the impact on QoL for PD patients and their caregivers.
... Around 3%e 10% of PD patients develop dementia per year, and 78% of PD patients eventually develop dementia. 275e279 The deterioration of the cognitive ability of PD patients increases with time, and the incidence and prevalence of cognitive impairment increase with the duration and severity of PD. 280,281 The average time to dementia after PD diagnosis is about 10e20 years. 282 It is thought that the joint decreasing of ACh and dopamine levels cause PDD. ...
Acetylcholine (ACh) is one of the most important neurotransmitters in the central cholinergic system; it specifically binds to muscarinic and nicotinic receptors and is degraded by acetylcholinesterase (AChE). ACh plays a crucial role in learning and memory. It is generally believed that, in the central nervous system, ACh promotes the conduction of brain nerves and accelerates information transmission. Besides, increasing central ACh levels can enhance memory ability and comprehensively improve brain function. Thus, AChE inhibitors (AChEI), which inhibit the degradation of ACh by AChE, have been used to treat Alzheimer's disease (AD) and Parkinson's disease dementia (PDD). However, recent studies have shown that excessive ACh in the central nervous system impairs learning and memory. Here we review the roles of ACh in learning and memory; we focus on the adverse effects of excessive ACh, the possible mechanisms, and the bidirectional role of ACh in the pathology and cure of AD and PDD. We conclude that the timing and dose of ACh administration should be carefully prescreened when using it to alleviate learning and memory in dementia patients.
... Poor performance on the BNT can indicate a variety of neurologic conditions, including left hemisphere cerebrovascular accidents (Kohn and Goodglass, 1985), anoxia (Tweedy and Schulman, 1982), multiple sclerosis, Parkinson disease (Beatty and Monson, 1989;Lezak et al, 1990;Locascio et al, 2003), and small white matter infarcts in the brain stem (Strauss et al, 2006;Van Zandvoort et al, 2003). Word-finding problems are common in individuals with aphasia, dementia, and epilepsy (Busch et al, 2009;Calero et al, 2002;Drane et al, 2008;Er et al, 2017;Howard et al, 2020;Katsumata et al, 2015;Loring et al, 2008;Mack et al, 1992). ...
Background: Abbreviated neurocognitive tests offer a practical alternative to full-length versions but often lack clear interpretive guidelines, thereby limiting their clinical utility.
Objective: To replicate validity cutoffs for the Boston Naming Test —Short Form (BNT–15) and to introduce a clinical classification system for the BNT–15 as a measure of object-naming skills.
Method: We collected data from 43 university students and 46 clinical patients. Classification accuracy was computed against psychometrically defined criterion groups. Clinical classification ranges were developed using a z-score transformation.
Results: Previously suggested validity cutoffs (≤11 and ≤12) produced comparable classification accuracy among the university students. However, a more conservative cutoff (≤10) was needed with the clinical patients to contain the false-positive rate
(0.20–0.38 sensitivity at 0.92–0.96 specificity). As a measure of cognitive ability, a perfect BNT–15 score suggests above average performance; ≤11 suggests clinically significant deficits. Demographically adjusted prorated BNT–15 T-scores correlated strongly (0.86) with the newly developed z-scores.
Conclusion: Given its brevity (< 5 minutes), ease of administration and scoring, the BNT–15 can function as a useful and cost-effective screening measure for both object-naming/English proficiency and performance validity. The proposed clinical classification ranges provide useful guidelines for practitioners.
Key Words: Boston Naming Test, performance validity, normative
data
... While the influence of mood is likely a contributing component to their performance, the cluster differences had small effect sizes, suggesting a minimal impact of mood on cluster membership. We did not find broad evidence for demographic differences between the three clusters, a finding that conflicts with prior research that older age, less education, and longer disease duration are associated with worse cognition [68][69][70]. Of note, the cognitive clusters were based on composite scores of "normed" neuropsychological measures, which controls for certain demographic factors. ...
Prevalence rates for mild cognitive impairment in Parkinson’s disease (PD-MCI) remain variable, obscuring the diagnosis’ predictive utility of greater dementia risk. A primary factor of this variability is inconsistent operationalization of normative cutoffs for cognitive impairment. We aimed to determine which cutoff was optimal for classifying individuals as PD-MCI by comparing classifications against data-driven PD cognitive phenotypes. Participants with idiopathic PD (n = 494; mean age 64.7 ± 9) completed comprehensive neuropsychological testing. Cluster analyses (K-means, Hierarchical) identified cognitive phenotypes using domain-specific composites. PD-MCI criteria were assessed using separate cutoffs (−1, −1.5, −2 SD) on ≥2 tests in a domain. Cutoffs were compared using PD-MCI prevalence rates, MCI subtype frequencies (single/multi-domain, executive function (EF)/non-EF impairment), and validity against the cluster-derived cognitive phenotypes (using chi-square tests/binary logistic regressions). Cluster analyses resulted in similar three-cluster solutions: Cognitively Average (n = 154), Low EF (n = 227), and Prominent EF/Memory Impairment (n = 113). The −1.5 SD cutoff produced the best model of cluster membership (PD-MCI classification accuracy = 87.9%) and resulted in the best alignment between PD-MCI classification and the empirical cognitive profile containing impairments associated with greater dementia risk. Similar to previous Alzheimer’s work, these findings highlight the utility of comparing empirical and actuarial approaches to establish concurrent validity of cognitive impairment in PD.
... In addition to statistical approaches, research has suggested that analyzing male and female PD patients separately may yield noteworthy findings. Biological sex appears to play a significant role in Parkinson's disease, as various differences in the presentation of PD and its comorbidities for males vs. females have been reported, including aspects such as rapid eye movement sleep behavior disorder, verbal fluency, depression, dyskinesia and visuospatial function (Fernandez et al., 2000;Scott et al., 2000;Locascio et al., 2003;Baba et al., 2005;Ozekmekci et al., 2005;Accolla et al., 2007;Davidsdottir et al., 2008;Yoritaka et al., 2009). Furthermore, studies have shown the incidence of PD in men are 1.5 times higher than that of women (Wooten et al., 2004). ...
Introduction: Numerous non-motor symptoms are associated with Parkinson’s disease (PD) including fatigue. The challenge in the clinic is to detect relevant non-motor symptoms while keeping patient-burden of questionnaires low and to take potential subgroups such as sex differences into account. The Fatigue Severity Scale (FSS) effectively detects clinically significant fatigue in PD patients. Machine learning techniques can determine which FSS items best predict clinically significant fatigue yet the choice of technique is crucial as it determines the stability of results.
Methods: 182 records of PD patients were analyzed with two machine learning algorithms: random forest (RF) and Boruta. RF and Boruta calculated feature importance scores, which measured how much impact an FSS item had in predicting clinically significant fatigue. Items with the highest feature importance scores were the best predictors. Principal components analysis (PCA) grouped highly related FSS items together.
Results: RF, Boruta and PCA demonstrated that items 8 (“Fatigue is among my three most disabling symptoms”) and 9 (“Fatigue interferes with my work, family or social life”) were the most important predictors. Item 5 (“Fatigue causes frequent problems for me”) was an important predictor for females, and item 6 (“My fatigue prevents sustained physical functioning”) was important for males. Feature importance scores’ standard deviations were large for RF (14–66%) but small for Boruta (0–5%).
Conclusion: The clinically most informative questions may be how disabling fatigue is compared to other symptoms and interference with work, family and friends. There may be some sex-related differences with frequency of fatigue-related complaints in females and endurance-related complaints in males yielding significant information. Boruta but not RF yielded stable results and might be a better tool to determine the most relevant components of abbreviated questionnaires. Further research in this area would be beneficial in order to replicate these findings with other machine learning algorithms, and using a more representative sample of PD patients.
... A study on relationship between motor impairment and cognitive impairments in PD had also revealed that the severity of motor impairment positively correlated to impairment on cognitive domains such as memory, language, visuospatial, and frontal lobe functions. [13] Deficits in motor speed is found to have major impact on the performance on other neuropsychological tests and clinicians often keep this in mind before interpreting the performance of patients on other neuropsychological tests. A study on 170 elderly patients (83 men, 87 women; M age = 82.1 yr., SD = 6.2) underwent cognitive assessment and 15 seconds of finger tapping and results indicated a significant increase in the length and variability of the finger-touch phase among participants with mild cognitive impairment or dementia compared to participants who did not have cognitive impairment, thus suggesting a relationship between finger tapping and attention, short-term memory and cognitive functions. ...
Background: Parkinson’s disease (PD) is characterized by bradykinesia, tremor, rigidity, postural instability
and cognitive deficits in attention, executive functions, learning and memory. Motor speed, measured using
Finger Tapping Test (FTT), is an important indicator and predictor of cognitive and motor functions. Deficits
in motor speed have significant impact on performance on other neuropsychological tests.
Objective: This study aimed to understand and compare the cognitive profile of patients with and without
deficits in motor speed as evaluated on the FTT.
Method and Material: A detailed neuropsychological evaluation using the NIMHANS Neuropsychological
Battery was carried out on 70 PD patients. The PD patients were divided into patients with (n = 46) and
without (n = 24) motor speed deficits. The two groups were comparable with regard to age (P = 0.591),
years of formal education (up to 10th – 24.3, above 10th – 75.7) duration of illness (P = 0.703) and age of
onset (P = 0.721).
Results: Across the various cognitive domains such as executive functions, verbal recognition, visuospatial
functions, visual learning and memory, the group without deficits in motor speed performed significantly better
in comparison to patients with motor symptoms.
Conclusion: A short and simple test such as FTT may be helpful in predicting the range and severity of cognitive
deficits across other cognitive domains in patients with PD. Future studies on larger cohort examining the
intricate role and association of FTT and other motor functions such as dexterity may be helpful in understanding
the nature and severity of other cognitive functions in this clinical population.
... Available evidence suggests the occurrence of cognitive impairment in PD might be greater in males, and males may show an advantage on visuospatial tasks with females showing an advantage on verbal tasks (Heller, Dogan, Schulz, & Reetz, 2014;Miller & Cronin-Golomb, 2010). Women with PD may also show a slower decline of cognitive functioning compared to men with PD (Locascio, Corkin, & Growdon, 2003). It is not clear whether these patterns of findings are disease specific or a reflection of a general gender effect that is also observed in the healthy population. ...
Hormones of the hypothalamic-pituitary-gonadal axis that regulate reproductive function are also potent neurosteriods that have multiple effects on the development, maintenance and function of the brain. There is a growing body of evidence linking sex hormones to cognitive functioning across the lifespan. Both subjective and objective cognitive changes can occur with aging. For women, cognitive complains are commonly associated with the menopause transition—a time of significant hormone flux. Sex differences in neurodegenerative conditions associated with cognitive dysfunction, such as Alzheimer's disease and Parkinson's disease, suggest a potential link between sex hormones and cognitive decline. Evidence for the effects of hormone therapy on cognition is growing, but remains inconclusive. This chapter provides an overview of sex hormones and cognition in association with healthy aging, including a focus on the menopause transition, as well as reviewing findings linking sex hormones to cognitive decline associated with Alzheimer's disease and Parkinson's disease. An overview of hormone therapy and cognition is also provided.
... However, there have been few previous comprehensive investigations of sex-based differences in individual cognitive domains over time [31], as in the present study. Some prior studies have been purely cross sectional in nature [5,9,10,12,[17][18][19], while longitudinal studies have not examined the sex-specific differences in various cognitive domains [20], or have not focussed primarily on elucidating the impact of sex on cognition [32]. Here, our findings suggest that sex is a significant determinant of domain-specific cognitive performance, in agreement with prior literature. ...
Background
Cognitive impairment is an important and diverse symptom of Parkinson’s disease (PD). Sex is a purported risk variable for cognitive decline in PD, but has not been comprehensively investigated.
Objectives
This cross-sectional and longitudinal study examined sex differences in global and domain-specific cognitive performance in a large PD cohort.
Methods
Cognitive function was evaluated using the Addenbrooke’s Cognitive Examination in 392 people with PD (PwP) from the Australian Parkinson’s Disease Registry. The influence of sex on domain-specific cognitive performance was investigated using covariate-corrected generalised linear models. In a repeated measures longitudinal subset of 127 PwP, linear mixed models were used to assess the impact of sex on cognition over time, while accounting for covariates.
Results
Cross-sectional-corrected modelling revealed that sex was significantly predictive of cognitive performance, with males performing worse than females on global cognition, and memory and fluency domains. Longitudinally, sex was significantly predictive of cognitive decline, with males exhibiting a greater reduction in global cognition and language, whereas females showed a greater decline in attention/orientation, memory and visuospatial domains, despite starting with higher baseline scores. At follow-up, a significantly higher proportion of males than females fulfilled criteria for mild cognitive impairment or PD dementia.
Conclusions
Sex was revealed as a significant determinant of overall cognitive performance as well as specific cognitive domains, with a differential pattern of decline in male and female participants. Such sex-specific findings appear to explain some of the heterogeneity observed in PD, warranting further investigation of mechanisms underlying this sexual dimorphism.
... Data from studies by Locascio et al. [84], Clark et al. [85], and Davidsdottir et al. [86] suggested that gender could influence cognitive impairment in subjects with PD. Gender differences emerged in the Road Map Test of Direction Sense, highlighting better skills in men for right-to-left discrimination and the cognition of space, and better scores for verbal fluency tests for women. ...
Parkinson’s disease has been found to significantly affect health-related quality of life. The gender differences of the health-related quality of life of subjects with Parkinson’s disease have been observed in a number of studies. These differences have been reported in terms of the age at onset, clinical manifestations, and response to therapy. In general, women with Parkinson’s disease showed more positive disease outcomes with regard to emotion processing, non-motor symptoms, and cognitive functions, although women report more Parkinson’s disease-related clinical manifestations. Female gender predicted poor physical functioning and socioemotional health-related quality of life, while male gender predicted the cognitive domain of health-related quality of life. Some studies reported gender differences in the association between health-related quality of life and non-motor symptoms. Depression and fatigue were the main causes of poorer health-related quality of life in women, even in the early stages of Parkinson’s disease. The aim of this review was to collect the best available evidence on gender differences in the development of Parkinson’s disease symptoms and health-related quality of life.
... The slower development of cognitive declines in female patients was reported by some longitudinal studies. 5,6,24 The executive and attention features were primarily affected in PD patients. Although Alzheimer's disease, for which women confer more risk, is emphasized as disability in the memory feature, the executive and attention features are primarily affected in PD patients. ...
Background:
Previous studies reported various symptoms of Parkinson's disease (PD) associated with sex. Some were conflicting or confirmed in only one study.
Objectives:
We examined sex associations to PD phenotypes cross-sectionally and longitudinally in large-scale data.
Methods:
We tested 40 clinical phenotypes, using longitudinal, clinic-based patient cohorts, consisting of 5946 patients, with a median follow-up of 3.1 years. For continuous outcomes, we used linear regressions at baseline to test sex-associated differences in presentation, and linear mixed-effects models to test sex-associated differences in progression. For binomial outcomes, we used logistic regression models at baseline and Cox regression models for survival analyses. We adjusted for age, disease duration, and medication use. In the secondary analyses, data from 17 719 PD patients and 7588 non-PD participants from an online-only, self-assessment PD cohort were cross-sectionally evaluated to determine whether the sex-associated differences identified in the primary analyses were consistent and unique to PD.
Results:
Female PD patients had a higher risk of developing dyskinesia early during the follow-up period, with a slower progression in activities of daily living difficulties, and a lower risk of developing cognitive impairments compared with male patients. The findings in the longitudinal, clinic-based cohorts were mostly consistent with the results of the online-only cohort.
Conclusions:
We observed sex-associated contributions to PD heterogeneity. These results highlight the necessity of future research to determine the underlying mechanisms and importance of personalized clinical management. © 2020 International Parkinson and Movement Disorder Society.
... Extant literature shows that Parkinson's disease affects males with a higher incidence rate and has an earlier average age of onset as compared to females (48). Males also show greater severity of initial motor and cognitive symptoms (49,50). This is supported by the sex-specific differences in cellular and biochemical endpoints in PD (47,51). ...
Parkinson's Disease (PD) is a progressive neurodegenerative movement disorder that is characterized by motor symptoms like tremor, bradykinesia, muscle rigidity and postural instability and non-motor symptoms like cognitive dysfunction, anosmia, constipation, sleep disorder, mood disorders and orthostatic hypotension. Parkinson's disease patients display mild cognitive impairment which disrupts their day-today life. Premotor cognitive deficits can precede clinical diagnosis of PD by several years. PD patients display executive planning dysfunction which is similar to patients with frontal lobe damage. Studies have reported that a disruption in neostriatal outflow from caudate to prefrontal cortex disrupts working memory and associated self-governing processes required to perform cognitive tasks. Findings from Kritzer lab indicated that parkinsonian male rats had trouble deploying an organized search strategy in a Barnes Maze test despite showing no spatial reference memory deficits. This called for a closer examination of spatial working memory in healthy and parkinsonian male rats. To achieve this goal, we used a bigger open field arena for better visualization of how they form a home-base locus (a place characterised by high dwelling time) and conduct their voluntary excursions outside the locus. We also wanted to observe if the lesion group had a higher tendency to spend time in the middle of the arena. Present study evaluates the changes in open field behavior after bilateral dopamine lesion surgery in lateral caudate of the rats. We found no appreciable group difference between the sham and lesion rats for the distance covered and level of activity in the center of arena. Both the groups formed a home base in one of the corners in the absence of environmental cues. The tendency to stay in the middle was also about the same in both the groups. It is proposed that environmental cues will guide the rats to form a stable home base and thus their voluntary trips away from and back to the home-base can be evaluated. A better understanding of voluntary exploration behavior and the role of neostriatum outflow to prefrontal cortex will lead to key insights in the etymology of loss of working memory deficits in PD patients.
... However, not many studies considered gender when examining cognition in PD patients. There were some studies investigated the gender differences with a remarkable number of participants, but the lack of control groups did not permit to determine if these differences could be specific to PD patients [26,27]. The present study highlights the role of gender differences associated with cognitive functions. ...
Background
Cognitive impairment is one of the non-motor symptoms in Parkinson’s disease (PD). In the present study, we aim to examine the cognitive function of non-demented Parkinson’s disease patients and compare the results between male and female patients as well as control groups in search of any gender effect. Methods
Sixty PD Patients (30 males and 30 females) from the Movement Disorders Clinic at Huashan Hospital Affiliated to Fudan University were recruited to participate in the study. One hundred age and gender matched control subjects without neurological or psychiatric disorders were voluntarily recruited. The participants were administered measures of cognition in five domains including memory, language, spatial processing abilities, attention and executive function. ResultsPD patients attained significantly lower scores in the visual spatial function, language and attention/executive function compared with the control group. Anti-parkinsonian treated patients performed worse in Rey-copy score, Clock Drawing Test (CDT) and Verbal Fluency-City than untreated ones. In regard to gender differences, though no general cognitive differences were found in Mini-mental State Examination (MMSE), men surpassed women on Boston naming test (BNT) while women were superior on Auditory Verbal Learning Test-long (AVLT) delayed cued recall test. Conclusions
Cognitive impairments were common in PD patients even in the absence of dementia. PD patients with anti-parkinsonian medication had worse cognitive impairment than untreated patients. Genders may have different manifestations of cognitive impairment in PD patients.
... female, but female subjects fared better in non-motor aspects which included SDMT performance and daily functioning (36). Moreover, male subjects have faster decline of cognitive abilities in verbal, letter, and category fluency tests; while females tend to have worse visuospatial abilities (37,38). Our results also demonstrated that females performed better in SDMT, verbal fluency tests, and overall cognition measured by MoCA, but presented worse visuospatial function, consistent with previous research. ...
The clinicopathological correlations between aspects of cognition, disease severity and imaging in Parkinson's Disease (PD) have been unclear. We studied cognitive profiles, demographics, and functional connectivity patterns derived from resting-state fMRI data (rsFC) in 31 PD subjects from the Parkinson's Progression Markers Initiative (PPMI) database. We also examined rsFC from 19 healthy subjects (HS) from the Pacific Parkinson's Research Centre. Graph theoretical measures were used to summarize the rsFC patterns. Canonical correlation analysis (CCA) was used to relate separate cognitive profiles in PD that were associated with disease severity and demographic measures as well as rsFC network measures. The CCA model relating cognition to demographics suggested female gender and education supported cognitive function in PD, age and depression scores were anti-correlated with overall cognition, and UPDRS had little influence on cognition. Alone, rsFC global network measures did not significantly differ between PD and controls, yet some nodal network measures, such as network segregation, were distinguishable between PD and HS in cortical “hub” regions. The CCA model relating cognition to rsFC global network values, which was not related to the other CCA model relating cognition to demographic information, suggested modularity, rich club coefficient, and transitivity was also broadly related to cognition in PD. Our results suggest that education, aging, comorbidity, and gender impact cognition more than overall disease severity in PD. Cortical “hub” regions are vulnerable in PD, and impairments of processing speed, attention, scanning abilities, and executive skills are related to enhanced functional segregation seen in PD.
... In a study of serial assessments of cognition, Biggins et al. (1992) demonstrated that PD patients who developed dementia had longer disease duration and older age of onset. Advanced age of onset has also been shown to predispose patients to dementia or cognitive deficits earlier in the disease process (Locascio, Corkin, & Growdon, 2003;Stern, Marder, Tang, & Mayeux, 1993). ...
The clinical definition of Parkinson's disease (PD) is based on cardinal motor features including bradykinesia as well as an additional symptom of tremor, postural instability, or rigidity. Evidence from neuropathological, imaging, and clinical research suggests a premotor, early phase of PD pathology. Further understanding of the earliest biomarkers of PD is crucial for the development of neuroprotective, disease modifying, cognitive, and psychiatric interventions. Recent research has explored early non-motor markers of PD pathology. This issue is especially timely as the International Parkinson and Movement Disorder Society has recently provided a research definition for prodromal PD which includes combinations of prodromal markers and risk factors aimed at identifying target populations for disease-prevention trials. In this review of early PD, we will outline early non-motor symptoms, early cognitive and neuropsychiatric features, neuropsychological assessment strategies, emerging evidence for early biomarkers, and treatment recommendations.
... The motor speech problems in PD negatively affect conversational discourse by altering listeners' perceptions of speakers with PD wherein listeners rate persons with PD as less interested, less involved, less happy, less friendly, and more anxious (Pitcairn et al. 1990;Jaywant and Pell 2010). While investigators have not explored specifically the phenomenon of motor speech problems in PDD and DLB, there is evidence to suggest that worsening motor impairment, including declining motor speech performance, is associated with risk of developing cognitive decline or dementia in PD (Burn et al. 2003;Elgh et al. 2009;Gago et al. 2009;Green et al. 2002;Verbaan et al. 2007;Locascio, Corkin, and Growdon 2003;Sollinger et al. 2010 ...
... The age at onset of the disease has been associated with an increased risk of cognitive impairment, in other words the older the age at onset, the greater risk of cognitive decline, as measured with the Mini-Mental State Examination [111]. The study of relationship between age at onset of the disease and different cognitive functions revealed that the older the patient was at onset, the more likely the patient was to perform poorly in declarative memory (verbal and visual), executive, visuospatial and language functions (naming) [10,15,112,113]. ...
Parkinson’s disease (PD) is a neurodegenerative disorder of unknown etiology, not only characterized by motor signs but also by non-motor symptoms, including neuropsychiatric and cognitive dysfunction. The results obtained in the last decades show that the cognitive changes in PD are heterogeneous; impairment in different cognitive domains such as attention, executive, language, memory, and visuospatial functions can be present even in the early stages of the disease. Mild cognitive impairment is frequent in non-demented PD patients and is considered as a risk factor for the development of dementia. As a response to the heterogeneity of cognitive impairment associated with PD, the Movement Disorders Society has recently developed formal diagnostic criteria for mild cognitive impairment and dementia associated with PD. In the present chapter, the authors have conducted a revision of cognitive impairment in PD, describing the results obtained in numerous investigations, from the first studies in the1970s to the advances of the last few years.
... Greater than 95% of PD is sporadic, without any genetic linkage or predisposition identified, although α-synuclein mutations have been linked to familial forms of PD. 96,97 Clinical symptoms of PD range from tremors, rigidity, absence of voluntary movements, stooped posture and abnormal facial expressions as a result of muscle spasticity. [98][99][100][101] Prominent neuropathological features of PD include intraneuronal deposition of cytoplasmic inclusions called Lewy bodies and nigrostriatal dopaminergic neuron loss [102][103][104] , which results in dopamine depletion in the brain. [105][106][107] Besides striatal dopaminergic neuron loss, PD is also occasionally associated with the death of noradrenergic and serotonergic neurons in the raphe nucleus, as well as cholinergic neurons in the entorhinal cortex. ...
Selective neuron loss in discrete brain regions is a hallmark of various neurodegenerative disorders, although the mechanisms responsible for this regional vulnerability of neurons remain largely unknown. Earlier studies attributed neuron dysfunction and eventual loss during neurodegenerative diseases as exclusively cell autonomous. Although cell-intrinsic factors are one critical aspect in dictating neuron death, recent evidence also supports the involvement of other central nervous system cell types in propagating non-cell autonomous neuronal injury during neurodegenerative diseases. One such example is astrocytes, which support neuronal and synaptic function, but can also contribute to neuroinflammatory processes. Indeed, aberrations in astrocyte function have been shown to negatively impact neuronal integrity in several neurological diseases. The present review focuses on neuroinflammatory paradigms influenced by neuron–astrocyte cross-talk in the context of select neurodegenerative diseases.
... Future studies should therefore control for the duration of disease and side of disease onset. The extent of cognitive deterioration may depend on side and type of motor symptoms (Tomer, Levin & Weiner, 1993;Katzen, Levin & Weiner, 2006), and also on the duration of disease (Locascio, Corkin & Growdon, 2003). ...
We examined face memory deficits in patients with Idiopathic Parkinson’s disease (IPD) with specific regard to the moderating role of sex and the different memory processes involved. We tested short- and long-term face recognition memory in 18 nonclinical participants and 18 IPD-patients matched for sex, education and age. We varied the duration of item presentation (1, 5, 10s), the time of testing (immediately, 1hr, 24hrs) and the possibility to re-encode items. In accordance with earlier studies, we report face memory deficits in IPD. Moreover, our findings indicate that sex and encoding conditions may be important moderator variables. In contrast to healthy individuals, IPD-patients cannot gain from increasing duration of presentation. Furthermore, our results suggest that IPD leads to face memory deficits in women, only.
... Therefore, for the languageimpaired PD patient, age at onset of PD is an independent risk factor for the deterioration rate in language ability; that is, the later the age at onset of PD, the faster the rate of language dysfunction. This is in accord with a study by Locascio et al. [41], in which language deterioration in PD was related to late onset of the disease only. Yet, our study went a step further and isolated late onset as an independent risk factor. ...
Language impairment is relatively common in Parkinson's disease (PD), but not all PD patients are susceptible to language problems. In this study, we identified among a sample of PD patients those pre-disposed to language impairment, describe their clinical profiles, and consider factors that may precipitate language disability in these patients.
A cross-sectional cohort of 31 PD patients and 20 controls were administered the Chinese version of the Western Aphasia Battery (WAB) to assess language abilities, and the Montreal Cognitive Assessment (MoCA) to determine cognitive status. PD patients were then apportioned to a language-impaired PD (LI-PD) group or a PD group with no language impairment (NLI-PD). Performance on the WAB and MoCA was investigated for correlation with the aphasia quotient deterioration rate (AQDR).
The PD patients scored significantly lower on most of the WAB subtests than did the controls. The aphasia quotient, cortical quotient, and spontaneous speech and naming subtests of the WAB were significantly different between LI-PD and NLI-PD groups. The AQDR scores significantly and positively correlated with age at onset and motor function deterioration.
A subset group was susceptible to language dysfunction, a major deficit in spontaneous speech. Once established, dysphasia progression is closely associated with age at onset and motor disability progression.
... PD patients who show early pathological insults in non-dopaminergic nuclei may be more likely to show deficits in attention and cognitive control in the early stages of the disease. Support for this view comes from studies that have identified groups of patients with distinct patterns of cognitive impairment (Mortimer et al., 1987;Lewis et al., 2003;Locascio et al., 2003). This finding raises the possibility that a subgroup of idiopathic PD patients may be at greater risk for developing memory impairments and dementia, which may correspond to a greater degree of BF degeneration, resulting in a more extensive disruption of cholinergic innervation of the neocortex. ...
This dissertation documents how healthy aging and Parkinson's disease (PD) affect brain anatomy and physiology and how these neural changes relate to measures of cognition and perception. While healthy aging and PD are both accompanied by a wide-range of cognitive impairments, the neural underpinnings of cognitive decline in each is likely mediated by deterioration of different systems. The four chapters of this dissertation address specific aspects of how healthy aging and PD affect the neural circuits that support sensory processes and high-level cognition. The experiments in Chapters 2 and 3 examine the effects of healthy aging on the integrity of neural circuits that modulate cognitive control processes. In Chapter 2, we test the hypothesis that the patterns of age-related change differ between white matter and gray matter regions, and that changes in the integrity of anterior regions correlate most strongly with performance on cognitive control tasks. In Chapter 3, we build upon the structural findings by examining the hypothesis that age-related changes in white matter integrity are associated with disrupted oscillatory dynamics observed during a visual search task. Chapter 4 investigates healthy age-related changes in somatosensory mu rhythms and evoked responses and uses a computational model of primary somatosensory cortex to predict the underlying cellular and neurophysiolgical bases of these alterations. In contrast to the widespread cortical changes seen in healthy OA, the cardinal motor symptoms of PD are largely explained by degeneration of the dopaminergic substantia nigra, pars compacta (SNc). Cognitive sequelae of PD, however, likely result from disruptions in multiple neurotransmitter systems, including nondopaminergic nuclei, but research on these aspects of the disease has been hindered by a lack of sensitive MRI biomarkers for the affected structures. Chapter 5 presents new multispectral MRI tools that visualize the SNc and the cholinergic basal forebrain (BF). We applied these methods to test the hypothesis that degenerative processes in PD affect the SNc before the BF. This experiment lays important groundwork for future studies that will examine the relative contribution of the SNc and BF to cognitive impairments in PD.
... This result was in agreement with previous studies which focused on cognitive decline in non-demented PD as well as PD dementia. 6,7 Age influenced not only the population of PDMCI but also the pattern of PDMCI. Whereas PDMCI was mainly restricted to single domain in the younger group, the involvement of multiple domain of PDMCI was more common in older group, demonstrating that patients beginning PD at later age had more widespread brain damage. ...
Background: To determ ine the frequency of m ild cognitive im pairm ent (M CI) of Parkinson's disease (PD, PDM CI) and its subtypes am ong non-dem ented PD patients, and to identify the influence of the age and presenting sym ptom on the development of PDMCI. Methods: A total 141 non-demented PD patients underwent a comprehensive neuropsychological assessm ent including attention, language, visuospatial, m em ory and frontal functions. PDM CI was defined by neuro-psychological testing and was classified into five subtypes. Patients were divided into two groups (trem or vs. akinetic-rigid type) for presenting sym ptom and three groups according to the age. Neuropsychological perform ance of patients was com pared with norm ative data. Results: Alm ost half (49.6%) of non-dem ented PD patients had im pairm ent in at least one dom ain and can be considered as having PDM CI. Executive type of PDM CI was the m ost frequent and am nestic, visuospatial, linguistic and attention types followed in the order of frequency. The population of PDM CI was increasing as the age of disease onset was higher. W hereas the frequency of executive and am nestic types of PDM CI was com parable in younger group, executive type was the m ost frequent in older group. The patients with trem or dom inant type perform ed worse on tests, particularly on attention test. Conclusions: M CI was com m on even in the early stage of PD and the subtype was diverse. Unlike M CI developing Alzheim er's disease later, executive type of PDM CI was the m ost com m on. Age was an im portant risk factor for developm ent of M CI in PD.
... In the last few decades, it has become increasingly apparent that PD involves a variety of cognitive impairments (Whittington, Podd, & Stewart-Williams, 2006). Numerous studies have reported cognitive dysfunctions in patients with Parkinson's disease relative to healthy volunteers on measures of declarative memory, working memory, visuospatial skills, language, frontal lobe capacities, and attentional processes (Locascio, Corkin, & Growdon, 2003). ...
... The identification of clusters of patients with distinct patterns of cognitive impairment raises the possibility that a subgroup of idiopathic PD patients may be at greater risk for developing memory impairments and dementia, which may stem from exacerbated BF degeneration, and more extensive disruption of cholinergic innervation of the neocortex. [87][88][89] Evidence of such heterogeneity stems from the observation that some advanced nondemented PD patients actually showed higher levels of AchE activity than a sample of drug-naïve patients in the earliest stages of the disease. 69 Pharmaceutical augmentation of cholinergic activity led to a significantly reduced frequency of falling in some PD patients. ...
The pathophysiology of idiopathic Parkinson disease (PD) is traditionally characterized as substantia nigra degeneration, but careful examination of the widespread neuropathological changes suggests individual differences in neuronal vulnerability. A major limitation to studies of disease progression in PD has been that conventional MRI techniques provide relatively poor contrast for the structures that are affected by the disease, and thus are not typically used in experimental or clinical studies. Here, we review the current state of structural MRI as applied to the analysis of the PD brain. We also describe a new multispectral MRI method that provides improved contrast for the substantia nigra and basal forebrain, which we recently used to show that these structures display different trajectories of volume loss early in the disease.
... Moreover, it has not been well acknowledged, if these results are disease specific or just a matter of a general gender effect. While women with PD might show up with a slower decline of cognitive functioning compared to men with PD [69], there seems to be evidence for an accelerated age-related cognitive decline in healthy men compared to healthy women as well, as elderly men present an increased decline in performance on attention, verbal memory, spatial memory, and spatial abilities compared to elderly women [64]. This again raises the question of estrogen having a potential neuroprotective effect on cognitive performance. ...
A number of gender differences have been documented in the incidence and symptomatology of the second most common age-related neurodegenerative disorder, idiopathic Parkinson's disease (PD). Overall, previous reports suggest a less frequent incidence and a more benign phenotype in women mainly in Western populations, which is thought to be mediated by estrogens in particular in early stages of the disease. Not only motor symptoms seem to underlie gender effects, but also non-motor symptoms such as psychiatric and cognitive impairments, which can often precede motor manifestation. However, reliable results for gender differences in PD in particular of cognitive function and emotion processing, having a major impact on quality of life, are lacking. Moreover, studies investigating gender effects in PD in these areas have revealed highly heterogeneous results. The present review summarizes findings of currently available studies on gender effects on neuropsychological tests covering major cognitive domains, emotion processing as well as quality of life in patients with PD. Overall, the occurrence of cognitive impairment in PD seems to be associated with male gender, though inconsistent results were shown in cognitive screening tests. Regarding emotion recognition, men with PD were found to be less accurate than women with PD at identifying fearful expressions, whereas vice versa results appeared in healthy subjects. Lower quality of life and greater disability were reported by women compared to men with PD, which corresponds with the results in healthy subjects. Several disease-specific mediators as well as the question of a general gender and age-related effect as observed in healthy individuals are discussed. Increased knowledge on possible gender effects in PD would provide an enhanced insight in underlying pathological mechanisms, and has potential implications for the diagnosis and treatment of PD.
Objectives:
This study aims to address a gap in the data on cognitive sex differences in persons living with Parkinson disease (PD). There is some evidence that cognitive dysfunction is more severe in male PD, however data on episodic memory and processing speed is incomplete.
Methods:
One hundred and sixty-seven individuals with a diagnosis of PD were included in this study. Fifty-six of those individuals identified as female. The California Verbal Learning Test 1st edition and the Wechsler Memory Scale 3rd edition were used to evaluate verbal and visuospatial episodic memory and the Wechsler Adult Intelligence Scale 3rd edition was used to evaluate processing speed. Multivariate analysis of covariance was used to identify sex-specific differences across groups.
Results:
Our results show that males with PD performed significantly worse than females in verbal and visuospatial recall as well as a trend for the processing speed task of coding.
Conclusions:
Our finding of superior performance among females with PD in verbal episodic memory is consistent with reports in both healthy and PD individuals; however, females outperforming males in measures of visuospatial episodic memory is unique to PD. Cognitive deficits preferentially affecting males appear to be associated with frontal lobe-related function. Therefore, males may represent a disease subgroup more susceptible to disease mechanisms affecting frontal lobe deterioration and cognitive disturbances in PD.
Parkinson's disease (PD) is characterized by heterogeneity in clinical syndromes, prognosis, and pathophysiology mechanisms. Gender differences in neural anatomy and function are emerging as fundamental determinants of phenotypic variability. Different clinical subtypes, defined as mild motor predominant, intermediate, and diffuse-malignant, have been recently proposed in PD.
This study investigated gender influence on clinical features, dopaminergic dysfunction, and connectivity in patients with de novo idiopathic PD stratified according to the clinical criteria for subtypes (i.e., mild motor, intermediate, and diffuse-malignant). We included 286 drug-naïve patients (Males/Females: 189/97, age [mean ± standard deviation]: 61.99 ± 9.67; disease duration: 2.08 ± 2.21) with available [123I]FP-CIT-SPECT and high-resolution T1-weighted MRI from the Parkinson's Progression Markers Initiative. We assessed gender differences for clinical and cognitive features, and dopaminergic presynaptic dysfunction in striatal or extra-striatal regions using molecular analysis of [123I]FP-CIT-bindings. We applied an advanced multivariate analytical approach – partial correlations molecular connectivity analyses – to assess potential gender differences in the vulnerability of the nigrostriatal and mesolimbic dopaminergic pathways.
In the mild motor and intermediate subtypes, male patients with idiopathic PD showed poorer cognitive performances than females, who – in contrast – presented more severe anxiety symptoms. The male vulnerability emerged also in the motor system in the same subtypes with motor impairment associated with a lower dopamine binding in the putamen and more severe widespread connectivity alterations in the nigrostriatal dopaminergic pathway in males than in females. In the diffuse-malignant subtype, males showed more severe motor impairments, consistent with a lower dopamine uptake in the putamen than females. On the other hand, a severe dopaminergic depletion in several dopaminergic targets of the mesolimbic pathway, together with extensive altered connectivity in the same system, characterized females with idiopathic PD in all the subtypes. The anxiety level was associated with a lower dopaminergic binding in the amygdala only in females.
This study provides evidence on gender differences in idiopathic PD across clinical subtypes, and remarkably, since the early phase. The clinical correlations with the nigrostriatal or mesolimbic systems in males and females support different vulnerabilities and related disease expressions. Gender differences must be considered in a precision medicine approach to preventing, diagnosing, and treating idiopathic PD.
Introduction
Global cognition screening tests can be used to diagnose mild cognitive impairment (MCI) in Parkinson’s disease (PD). However, they provide incomplete information on the cognitive profile, which limits the knowledge of the specific characteristics of MCI in PD. This study characterized the cognitive profile of people with and without PD diagnosed with MCI based on their score on a global cognition screening test.
Methods
Sixty-six control participants (71.19 [7.08] years old; 15.8 [2.8] years of education; 31 males) and sixty-six participants with PD (71.3 [6.44] years old; 15.27 [2.86] years of education; 49 males) were recruited. Participants completed the Montreal Cognitive Assessment (MOCA) and a neuropsychological battery. They were divided into four groups based on their disease and cognitive status determined using the MOCA (cut-off for MCI: < 26): controls with normal cognition (NC), PD with normal cognition (PD-NC), PD-MCI and MCI. Groups were compared on cognitive composite scores computed using a traditional division of tests into cognitive domains, and a division using factor analysis. Profiles were also characterized using Movement Disorder Society (MDS) level II criteria for MCI, and MCI subtyping at different impairment cut-offs.
Results
At the least stringent cut-off, 48.84% of PD-NC participants with normal cognition on the MOCA fit level II MCI criteria. This proportion was significantly lower in the NC group. MCI subtyping and comparison of composite scores with both approaches showed the similarity of PD-MCI and MCI profiles. Composite scores derived from factor analysis had better (although not always adequate) internal consistency.
Conclusion
Screening tests differentiate groups with normal cognition from groups with MCI but may overlook very mild cognitive decline in PD. The composition of neuropsychological batteries and definition of impairment cut-offs should be refined.
Parkinson’s disease, a degenerative neurologic condition, manifests itself differently in women than in men. Women are less likely to develop the disease and, when they do develop it, have a later onset than men. This chapter looks at a number of factors that may impact how the disease affects women differently than men including how genetic and hormonal differences may play a role. The expression of the disease, both motor and nonmotor symptoms, tends to be different in men and women also and treatment may be impacted by these differences. Finally, the data regarding pregnancy in Parkinson’s disease patients is reviewed.
Introduction:
Better awareness of the cognitive domains affected in non-demented Parkinson's Disease (PD) should improve understanding of cognitive disease mechanisms. A complete understanding of the cognitive areas impaired in non-demented PD is hindered because most studies use small clinical samples without comparison to healthy controls. This meta-analysis examined cumulative evidence across studies to determine if there were impairments in non-demented PD in the three cognitive domains thought to be most widely affected in PD: frontal executive, visuospatial, and verbal memory. Because there are well-documented sex differences in PD, a second objective was to explore sex differences in these findings.
Methods:
MEDLINE, EMBASE and PsycINFO databases were searched (1988-March 2017). Random effects models were used to compute and compare effect sizes of differences between PD patients and controls within cognitive domains. Sex differences in effect sizes were also examined in these comparisons. Moderating factors including age, disease duration, motor symptom severity, levodopa dosage, and depression were examined through meta-regression.
Results:
PD patients showed deficits of moderate effect sizes in all three cognitive domains relative to controls. Significant sex differences were observed only for frontal executive abilities, with male PD patients showing greater deficits than female PD patients relative to controls. No moderators of effect sizes were identified in the domain specific overall or sex-segregated meta-analyses.
Conclusions:
Results indicate that non-demented PD patients have deficits of moderate magnitude in frontal executive, verbal memory, and visuospatial abilities. Our findings of greater frontal executive deficits in males warrant further confirmation.
Introduction:
The relationship between motor impairment and cognitive deterioration has long been described in Parkinson's disease (PD). The aim of the study was to compare cognitive performance of de novo PD patients in relation to the motor impairment severity according to Hoehn and Yahr (HY) stages.
Methods:
Forty de novo PD patients at HY stage I and 40 patients at HY stage II completed a standardized neuropsychological battery. A multivariate analysis of covariance was used to compare cognitive performance between HY groups. Odds ratios (ORs) were employed to explore the risk of cognitive impairment between HY stages. Finally, the prevalence of mild cognitive impairment (MCI) was estimated for patients in HY stage I and II.
Results:
Patients at HY stage I obtained better scores on neuropsychological tests than patients at HY stage II (p = 0.001). Univariate analysis of covariance revealed significant differences between HY stages on Rey's auditory verbal learning test -immediate recall (p < 0.0001), 10 points Clock Drawing Test (p = 0.002), and Rey-Osterrieth Complex Figure Test -copy (p < 0.0001). ORs of having cognitive impairment were greater for HY stage II than stage I group. MCI occurred in 7.5% of patients in HY stage I, and in 42.5% of patients in HY stage II.
Conclusion:
In de novo PD patients, the severity of motor impairment at the diagnosis is associated to cognitive deficits and higher risk of MCI.
Over the course of the past half century, Suzanne Hammond Corkin (1937-2016) has made a remarkable number of contributions to our understanding of the neural bases of human cognition. She is, of course, best known for her career-long association with the amnesic patient H.M., eloquently summarized in her book Permanent Present Tense: The Unforgettable Life of the Amnesic Patient, H.M. (Corkin, 2013). From this association have come foundational insights into the functions of the hippocampus and surrounding tissue of the medial temporal lobe (MTL), and into the organization of memory. In addition to these contributions, her wide-ranging research has also explored the neural bases of perception and working memory, the interaction of emotion and memory, and the effects of aging and of age-related neurodegenerative disease on cognition. Throughout her celebrated career, she set a pioneering example for how to be successful as a woman in science. This article is protected by copyright. All rights reserved.
Parkinson’s disease (PD) is well known for motor deficits such as bradykinesia. However, patients often experience additional deficits in working memory, behavioral selection, decision-making and other executive functions. Like other features of PD, the incidence and severity of these cognitive symptoms differ in males and females. However, preclinical models have not been used to systematically investigate the roles that sex or sex hormones may play in these complex signs. To address this, we used a Barnes maze spatial memory paradigm to compare the effects of a bilateral nigrostriatal dopamine lesion model of early PD on cognitive behaviors in adult male and female rats and in adult male rats that were gonadectomized or gonadectomized and supplemented with testosterone or estradiol. We found that dopamine lesions produced deficits in working memory and other executive operations, albeit only in male rats where circulating androgen levels were physiological. In males where androgen levels were depleted, lesions produced no additional Barnes maze deficits and attenuated those previously linked to androgen deprivation. We also found that while most measures of Barnes maze performance were unaffected by dopamine lesions in the females, lesions did induce dramatic shifts from their preferred use of thigmotactic navigation to the use of spatially guided place strategies similar to those normally preferred by males. These and other sex- and sex hormone-specific differences in the effects of nigrostriatal dopamine lesions on executive function highlight the potential of gonadal steroids as protective and/or therapeutic for the cognitive symptoms of PD. However, their complexity also indicates the need for a more thorough understanding of androgen and estrogen effects in guiding the development of hormone therapies that might effectively address these non-motor signs.
Parkinson's disease is a progressive disorder of the nervous system that affects movement. It develops gradually, often starting with a barely noticeable tremor in just one hand. But, while tremors may be the most well-known sign of Parkinson's disease, the disorder also commonly causes a slowing or freezing of movement. The authors aim to reflect on different features of a poliedric structure, like Parkinson's disease, and try to help clinicians and students to reflect on these aspects that mainly interfere with the daily life experience of patients and caregivers.
This chapter focuses on errors that are not predicted by formalist models of language production and that support the assumption that language production is an embodied cognitive process. The analyses of speech and coverbal gestures presented in this chapter draw on videotaped stories told by healthy individuals and by individuals with Parkinson's disease. Unrehearsed storytelling performances of both speaker groups are examined and compared for evidence that coverbal gestures may function as embodied representations of meaning that help build and maintain cohesive storylines. This chapter suggests that this line of research could contribute to the reconsideration of the modularist, amodal, and symbol manipulation models of human language use that have dominated psycholinguistic research for decades.
To investigate sex differences in cognitive function in Parkinson’s disease patients, a cohort of 172 male patients and 139 female patients were recruited for this study. Their demographic and clinical features, including age, disease duration, education level, Unified Parkinson’s Disease Rating Scale-III, Hoehn–Yahr Scale, activities of daily living, Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale score were recorded. The Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Wechsler Adult Intelligence Scale-Chinese Revision (WAIS-RC) and Wechsler Memory Scale-Chinese Revision (WMS-RC) scores were compared to distinguish the cognitive properties between the two groups. The MMSE values did not show a significant difference between the groups. However, the MoCA scores of male patients were significantly higher than those of female patients (adjusted p < 0.05). The male group demonstrated better performances with respect to visuospatial function, naming and abstraction (adjusted p < 0.05). The WAIS-RC data showed that female patients had lower scores in information, vocabulary, picture completion, block design and picture arrangement (adjusted p < 0.05), and the WMS-RC data showed that 100-1 and cumulative addition abilities were significantly weaker in females than males (adjusted p < 0.05). Cognitive disturbances were more prevalent and severe in women among Chinese Parkinson’s disease patients.
Cognitive impairment and dementia are significant sequelae of Parkinson disease (PD) and comprise a key feature of dementia with Lewy bodies (DLB), a disease with similar clinical and neuropathological features. Multiple independent causes have been implicated in PD dementia (PDD) and DLB, among them the accumulation of β-amyloid, a neuropathological hallmark of Alzheimer disease. Over the last decade, PET imaging has emerged as a viable method to measure amyloid burden in the human brain and relate it to neurodegenerative diseases. This article reviews what amyloid imaging has taught us about PDD and DLB. Current data suggest that brain amyloid deposition tends to be more marked in DLB, yet contributes to cognitive impairment in both DLB and PD. These results are broadly consistent with neuropathology and CSF studies. β-Amyloid may interact synergistically with other pathological processes in PD and DLB to contribute to cognitive impairment.
Parkinson disease (PD) is an age-related degenerative disease of the brain, characterized by motor, cognitive, and psychiatric symptoms. Neurologists and neuroscientists now understand that several symptoms of the disease, including hallucinations and impulse control behaviors, stem from the dopaminergic medications used to control the motor aspects of PD. Converging evidence from animals and humans suggests that individual differences in the genes that affect the dopamine system influence the response of PD patients to dopaminergic medication. In this study, we tested the hypothesis that patients taking dopamine replacement therapy who carry candidate alleles that increase dopamine signaling, exhibit greater amounts of motor impulsivity. We examined the relation between inhibitory ability (measured by the Stop Signal Task) and polymorphisms of COMT Val158Met and DRD2 C957T in patients with idiopathic PD. On the Stop Signal Task, carriers of COMT Val/Met and Met/Met genotypes were more impulsive than Val/Val carriers, but we did not find a link between DRD2 polymorphisms and inhibitory ability. These results support the hypothesis that the Met allele of COMT confers an increased risk for behavioral impulsivity in PD patients, whereas DRD2 polymorphisms appear to be less important in determining whether PD patients exhibit a dopamine overdose in the form of motor impulsivity.
(
This reprinted article originally appeared in the Journal of Experimental Psychology,
1935, Vol 18, 643–662. The following abstract of the original article appeared in PA, Vol 10:1863.) In this study pairs of conflicting stimuli, both being inherent aspects of the same symbols, were presented simultaneously (a name of one color printed in the ink of another color—a word stimulus and a color stimulus). The difference in time for reading the words printed in colors and the same words printed in black is the measure of the interference of color stimuli on reading words. The difference in the time for naming the colors in which the words are printed and the same colors printed in squares is the measure of the interference of conflicting word stimuli on naming colors. The interference of conflicting color stimuli on the time for reading 100 words (each word naming a color unlike the ink-color of its print) caused an increase of 2.3 sec or 5.6% over the normal time for reading the same words printed in black. This increase is not reliable, but the interference of conflicting word stimuli on the time for naming 100 colors (each color being the print of a word which names another color) caused an increase of 47.0 sec or 74.3% of the normal time for naming colors printed in squares.… (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Groups of patients with idiopathic Parkinson's disease, either medicated or unmedicated, were compared with matched groups of normal controls on a computerized battery previously shown to be sensitive to frontal lobe dysfunction, including tests of planning, spatial working memory and attentional set-shifting. In a series of problems based on the ‘Tower of London’ test, medicated patients with Parkinson's disease were shown to be impaired in the amount of time spent thinking about (planning) the solution to each problem. Additionally, an impairment in terms of the accuracy of the solution produced on this test was only evident in those patients with more severe clinical symptoms and was accompanied by deficits in an associated test of spatial short-term memory. Medicated patients with both mild and severe clinical symptoms were also impaired on a related test of spatial working memory. In contrast, a group of patients who were unmedicated and ‘early in the course’ of the disease were unimpaired in all three of these tests. However, all three Parkinson's disease groups were impaired in the test of attentional set-shifting ability, although unimpaired in a test of pattern recognition which is insensitive to frontal lobe damage.
These data are compared with those previously published from a group of young neurosurgical patients with localized excisions of the frontal lobes and are discussed in terms of the specific nature of the cognitive deficit at different stages of Parkinson's diseas.
One hundred de novo patients with Parkinson's disease (PD) were classified into two groups according to age of onset of symptoms. Seventy two patients were under 70 years and 28 were 70 years and over. All patients were given neurological and neuropsychological assessments, and the severity of the signs was rated on a modified Columbia scale. The neuropsychological assessment was also administered to 50 age-and-education-matched controls. The neuropsychological test battery included tests of verbal learning, visual memory, verbal fluency, visuospatial skill, simple and choice reaction time, language and maze learning. The late-onset patients had significant impairment in nonverbal reasoning, auditory verbal learning, visual memory and choice reaction time in contrast to early-onset patients and controls. A relationship was found between bradykinesia and widespread cognitive impairment. Severity of tremor was found to be significantly correlated with impairment in auditory verbal learning, visual memory and increased choice reaction time, while rigidity was found to be associated with cognitive impairment in verbal fluency and visuospatial skill. Using DSM II criteria, 39% of the late-onset and 8% of the early-onset group were classified as demented. Dementia was more common in patients with bilateral symmetrical disease and in those patients with marked tremor and bradykinesia. The pattern of cognitive impairment in PD was consistent with that associated with a subcortical dementia. This study confirms that the expression of PD is markedly influenced by the age of onset.
The authors hypothesized that the pathophysiology of early Parkinson's disease (PD) may selectively target structures that support visual working memory for spatial relations but leave structures that support working memory for featural characteristics of objects relatively intact. Fifteen PD and 15 normal control participants took a visual delayed-response test with a spatial condition and a (nonspatial) object condition, equating the perceptual difficulty of the tests for each participant. The stimuli were irregular polygons presented at different locations on a computer screen. Results revealed a selective impairment of spatial delayed response in PD, indicating a disruption of spatial working memory unconfounded by sensory processing difficulties. The selectivity of this deficit may reflect the circumscribed nature of pathophysiological change affecting the caudate nucleus in early PD.
Parkinson's disease (PD) is characterized by spatial memory dysfunction, but the selectivity of the deficit remains unclear. We addressed this issue by comparing performance on spatial and object variants of a conditional associative learning task, and by analysing the data with time series analytical techniques. The 11 PD subjects and 15 normal control subjects learned stimulus-stimulus pairings through trial-and-error learning. PD subjects were selectively impaired on the spatial condition: they required more trials to achieve criterion, learned at a slower rate and displayed a working memory deficit. The groups did not differ in the object condition. These results suggest a distinction between material-specific spatial and object visual memory systems. Further, they indicate that spatial learning and memory are selectively impaired in early PD, suggesting that interactions between the basal ganglia and prefrontal cortex are important for the mediation of high-level cognition.
Although the title of this book is not inaccurate, it may be somewhat misleading. Rather than being a comprehensive text on Parkinson's disease, it is a collection of almost 90 papers from the Ninth International Symposium on Parkinson's Disease held in Jerusalem, Israel, in June 1988. As such, it probably has little appeal for medical students, nonneurologists, or, possibly, even general neurologists. On the other hand, for those of us with an interest in Parkinson's disease, this book provides a wonderfully diverse smorgasbord of recent clinical and neurobiological research topics related to Parkinson's disease and the basal ganglia. The papers in this collection are parceled into the following seven sections: "Normal and Pathological Anatomy," "Neurochemistry and Pharmacology," "Neurophysiology," "Toxicology and Environment," "Clinical Aspects," "Current Therapy and Side Effects," and "Therapeutic Research and Developments." The length of the contributions ranges from four to 16 pages and, as might be expected in
Instructions for giving the tests, principles of construction, standardization, and qualitative and quantitative evaluation of test responses are included. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Presents the prototype of a new clinical test of memory function with an analysis of initial data. This measurement instrument, which has 5 alternative forms, is specifically designed for longitudinal studies in those with mild to moderate deficits in storage and retrieval from secondary (long-term) episodic memory. Preliminary results with 119 adults 20–79 yrs old suggest that this test is an improvement over existing memory scales as they are used in this segment of the population. (43 ref) (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Milner's (1963) report of impaired performance on the Wisconsin Card Sorting Test (WCST) in a group of patients with frontal lobe lesions suggested that this test might be a useful one in the investigation of individual patients with suspected brain lesions. However, for many of our older hospital population the WCST was found to be too difficult and distressing, and also the inherent ambiguities associated with certain responses limited the test's usefulness for research purposes. Therefore, a simpler and less ambiguous modification was devised (MCS) and a new method of measuring perseverative errors proposed. In a group of 53 patients with unilateral cerebral lesions, those with frontal lobe lesions performed less well with the MCST and made a higher proportion of perseverative errors than those with lesions elsewhere: there were no laterality effects in either frontal or non-frontal groups. The usefulness of the MCST for detecting frontal lobe lesions in individual patients was established, and the use of cut-off scores briefly discussed.
One hundred and seven newly diagnosed, untreated patients with Parkinson's disease (PD) were divided into two groups according to their age at reported onset of symptoms. Of these, 79 patients were under age 70 (early-onset) and 28 patients were age 70 and over (late-onset). The group of 50 control subjects comprised spouses, friends of the PD patients, and community volunteers. The patients were participants in a multicenter drug study of Parkinson's disease. Each had received a detailed neurological and neuropsychological assessment in the baseline placebo phases of the study. Thirty-4 patients with early-onset and 12 patients with late-onset were reassessed 3 years after treatment with low-dose levodopa, with bromocriptine, or with a combination of the two drugs. The results of the baseline phase of the study revealed that 8% of the early-onset group and 32% of the late-onset group were classified as demented. The 3-year follow-up revealed that the prevalence of dementia had increased to 17% in the early-onset group and to 83% in the late-onset group. This study confirms that at least two distinct subtypes of Parkinson's disease exist. The subtypes differ both clinically and neuropsychologically. The age at onset of symptoms is a critical determinant of the rate and type of cognitive decline in Parkinson's disease.
In 38 old aged parkinsonian patients, two major subgroups could be established: one with predominant akinesia, rigidity, postural instability and accompanying cognitive impairment with intellectual deterioration correlated with duration of disease but not with age of onset and another with predominant tremor and relatively intact intellectual functions. The mean somatostatin-like immunoreactivity (SLI) level in the cerebrospinal fluid (CSF) was significantly lower in parkinsonian patients (21.4 +/- 8.1 fmol ml-1) compared to senile control patients (29.5 +/- 9.4 fmol ml-1). In contrast to senile dementia of Alzheimer's type SLI was not correlated with dementia scores but with motor disease progression. Homovanillic acid (HVA) significantly decreased only in patients without L-DOPA treatment. Correlations between SLI, HVA and 5-hydroxyindole acetic acid (5-HIAA) indicate a degeneration of multiple neuronal networks which includes somatostatinergic neurons.
Patients with predominantly unilateral parkinsonian signs may provide a unique opportunity to evaluate the cerebral representation of cognitive functions characteristically affected in idiopathic Parkinson's disease. Twenty hemiparkinsonian patients (ten left and ten right) and 10 healthy controls, matched for age and education, were studied with neuropsychological tests and positron emission tomography. Both right and left hemiparkinsonians evidenced impairments in visuospatial and verbal episodic memory function, but had no deficits in executive abilities, compared to controls. None of the neuropsychological test scores distinguished right from left hemiparkinsonians. Glucose metabolic profiles were identical for the three groups in all cortical areas assessed; in the subcortex however, lenticular hypermetabolism contralateral to the predominant side of motor involvement was evident in the left hemiparkinsonian group. Correlational analysis revealed that higher glucose metabolic rates in the basal ganglia of these hemiparkinsonians were associated with lower visuospatial test scores. In frontal and parietal cortex, decreasing glucose metabolism was positively associated with neurobehavioral function; in temporal cortex, measures of attention and memory decreased with increasing glucose metabolic rates.
From the large body of empirical evidence on cognitive function in Parkinson's disease, a number of attempts have been made to describe the characteristics of the deficits and the conditions under which they are observed. This review considers descriptions limited to specific domains of cognition such as visuospatial function, memory and 'frontal' function, and more general descriptions relating to 'set-shifting', sequencing, temporal ordering and recency discrimination, the locus of cognitive control and bradyphrenia. Later in the paper an attempt is made to provide some theoretical framework for the various descriptions. Two theories are discussed representing contrasting, but complementary approaches. The first is a 'psychological' theory in which the concept of depleted processing resources is suggested as a possible mechanism to explain the observable deficits. The second is a neurobiological model that attempts to integrate information from diverse sources to provide a model for the neuroanatomical and neurochemical substrate that may underlie some of the behavioural deficits.
Young-onset Parkinson's disease (YOPD) is arbitrarily defined as that which produces initial symptoms between the ages of 21 and 39, inclusive. The special problems and concerns of the patient with YOPD present as much of a challenge and opportunity for the clinician as the disease itself does for the researcher. In contrast to juvenile parkinsonism, which is a heterogeneous group of clinicopathologic entities presenting (also arbitrarily) before age 21, YOPD appears to be the same nosologic entity as older-onset PD. It comprises approximately 5% of referral populations in Western countries and about 10% in Japan. Its annual incidence relative to the population at risk is about 1/10 that of PD at age sixty. YOPD tends to have more gradual progression of parkinsonian signs and symptoms, earlier appearance of levodopa-related dyskinesias and levodopa-dose-related motor fluctuations, and frequent presence of dystonia as an early or presenting sign. Studies conflict with regard to the suspected greater familial frequency and lesser frequency of dementia than in older-onset PD.
We investigated the influence of age on the occurrence of cognitive disturbances in Parkinson's disease (PD), by evaluating neuropsychological performances in early- and late-onset groups of patients (less than 45 and greater than 65 years, respectively), individually paired for all the variables of parkinsonism and compared with age-matched controls. Cognitive disorders were limited in the early-onset PD group compared with their age-matched controls. Conversely, we found global cognitive changes, including marked frontal lobe dysfunction, in the late-onset group. This specific cognitive impairment in older patients related to a significant interaction between the aging and disease processes. Late onset seemed to compound the subtle cognitive changes associated with the disease for which the early-onset group compensated. This compounding effect of aging may explain, at least partially, the high frequency of dementia in older PD patients.
Parkinson's disease patients are frequently impaired in a variety of neuropsychological tasks involving memory, perceptual motor performance and cognitive flexibility. Although various theories have been forwarded to explain specific impairments, few attempts have been made to account for all the deficits within a single theoretical framework. Furthermore, the frequent occurrence of dementia, the adverse side effects of medication and the motor symptoms of the disease tend to interfere with neuropsychological performance. This has hindered the clear delineation of the neuropsychological profile of Parkinsonian patients. The present paper examines the evidence for intellectual deficits in non-demented Parkinson's disease patients. A number of problems inherent in cognitive research on Parkinson's disease are discussed. The contribution of dementia, motor symptom severity and medication in the expression of these intellectual impairments is examined. It is suggested that many of the neuropsychological deficits described in Parkinson's disease may result from a common underlying deficit in some aspect of information processing. Although it is not possible to pinpoint the precise mechanism(s) involved on the basis of the available evidence, several possibilities are suggested by cognitive and electrophysiological data.
We examined longitudinal disability scores in 54 patients with Parkinson's disease followed for 6 years at UCLA. We sorted data into 3 groups based on age at onset of symptoms: group A, onset under 50 years; group B, 50 to 59 years; group C, 60 years or older. There were no significant differences between groups initially. All 3 groups improved dramatically when levodopa was given, but group A showed significantly less disability in years 4, 5, and 6 than did group C. The groups did not differ with respect to side effects. To determine if age at onset affected mortality, we sorted records from 4 geographically diverse centers into the same 3 groups. Results on 359 patients followed for 3,314 person-years, covering a period of 17 years after onset of symptoms, showed that group A had the most favorable observed-to-expected mortality ratio, 1.82, compared with 2.17 and 2.20 for groups B and C respectively, but the difference was not statistically significant. Results from the disability analyses indicate that patients with onset of Parkinson's disease under 50 years of age may have a more favorable prognosis than those whose symptoms begin in later years.
Using case-control methodology, we assessed prevalence and duration of exposure to putative risk factors for rapid progression of Parkinson's disease (PD) in patients not taking levodopa or direct dopamine agonists. We identified 31 patients termed "rapidly progressive" who were stage I or II (Hoehn and Yahr) on their first visit to our center and who progressed to stage III during the study period; we pair-matched this group with 31 "slowly progressive" patients who had the same symptom duration and the same Hoehn and Yahr stage at study entry, but whose parkinsonism did not progress to stage III during the study. Only age of PD onset was associated with different rates of PD progression; older patients at PD onset progressed more rapidly than younger patients.
Analysis of the results of 143 adult patients with circumscribed cerebral lesions on the Picture Arrangement subtest of the Wechsler scales shows significantly lower means for those with right-hemisphere than with left-hemisphere lesions. Counting the number of pairs of pictures on this test which were left incorrectly in the presented order shows that this error was infrequent with left-hemisphere lesions, but with right-hemisphere lesions occurred significantly more often with frontal than with non-frontal lesions.
It is suggested that this tendency to leave pictures in the presented order reflects a specific inability to correct a response in spite of evidence that it is wrong, which is maximal with right frontal lesions; and that this may account for aspects of the `frontal lobe syndrome' in cognitive terms.
We studied 60 patients with idiopathic Parkinson disease with motor and neuropsychologic tests to ascertain whether the severity of motor symptoms was associated with the degree of neuropsychologic deficity. Significant correlations were found between the severity of brady kinesia and impaired performance on tests assessing visual-spatial reasoning and psychomotor speed. More severe tremor was associated with better performance on a spatial orientation memory test. There relationships remained when age, age at onset, and self-rated depression were controlled. The findings suggested that cognitive impairment may result from the same subcortical lesions that cause motor symptoms.
A detailed analysis of the mnestic deficits associated with Parkinson's disease (PD) contributes to explaining the cognitive disorders and their well documented consequences. This study was designed to show that, in PD declarative as well as procedural memory is severely impaired. Three tests designed to explore this aspect of mnestic functioning were proposed to a group of 16 parkinsonian patients whose motoricity was controlled: inverted reading, braille reading, sound form association. The results obtained, compared with those of young and aged controls, show that PD is associated with marked deficits in both declarative and procedural memory. Declarative memory impairment was similar to that observed in the control population (healthy elderly subjects, age-matched with the PD patients) but more marked in PD subjects. The procedural memory deficit was linked with age and pathology. Procedural memory involves a variety of processing modules dedicated to the type of information (visual, auditive, tactile codes). The deficits observed were more like a loss of automatism than procedural impairment stricto sensu ('knowing how'). It would be worth pursuing research by studying akinesia and motor disorders from the angle of automatic memory impairment.
The study assessed cognitive decline in non-demented, non-depressed patients with well defined Parkinson's disease and determined the predictive value for cognitive decline of different motor symptoms. Motor disability was measured with the Unified Parkinson's disease rating scale, impairment in activities of daily living, levodopa test, and long term clinical follow up. Neuropsychological evaluations included modified mini mental state, fluency, Wechsler logical memory, Wisconsin card sorting test, and the Montgomery and Asberg depression rating scale. Fifty three patients fulfilling clinical criteria for idiopathic Parkinson's disease were studied. Cognitive performance on initial testing was significantly correlated with education and disease duration but not with age at disease onset. Cognitive performance on retesting after three years of follow up was significantly reduced. This reduction was significantly greater in the late onset group, in patients with isolated dystonic dyskinesiae, and in patients with a lower percentage of motor improvement on levodopa. Cognitive decline in idiopathic Parkinson's disease may depend on both the prevalence of non-dopaminergic lesions and the topography of dopaminergic denervation. Predictive factors for cognitive decline, especially in executive tasks, relate more to non-dopaminergic than to dopaminergic lesions.
The contribution of cognitive slowing to the slowed performance of patients with Parkinson's disease (PD) is a matter of long-standing debate. In this study, we contrasted the performance of PD patients on two reaction-time tasks with the performance of Alzheimer's disease (AD) patients, young normal subjects, and elderly normal subjects. Both nondemented and demented PD patients showed cognitive as well as motor slowing, and the extent of cognitive slowing varied with overall cognitive status. Moreover, by comparison with the cognitive slowing in AD patients, cognitive slowing in PD patients was disproportionate to their general level of cognitive performance. We suggest that this disproportionality be used to differentiate the concepts of bradyphrenia and nonspecific cognitive slowing.
Cognitive functions of 24 patients with early onset parkinsonism (age of onset before 40 years) and 24 controls were investigated by a battery of neuropsychological tests. Patients were shown to be impaired in performance IQ (PIQ), conceptual ability and regulation behavior, memory, visuospatial perception, and manual dexterity. Patients were also shown to have a higher Zung Depression score. However, analysis of the testing scores appeared to indicate that only a small portion of poor performance on neuropsychological tests are depression related. The results demonstrated that patients with early onset parkinsonism, in whom the factor of aging is not as important, still show cognitive dysfunction and suggested that Parkinson's disease itself can cause cognitive impairment.
Language ability in patients with idiopathic Parkinson's disease (PD) and normal control subjects (NC) matched on age, sex, education and socioeconomic status (SES) was investigated. The two groups of subjects were tested on eight sentence types in Greek in the form of main and complement clause with eight matrix verbs. These matrix verbs were ask (ask information), promise (commissive meaning), tell1 (order, command) and tell2 (give information) in sentences with no semantic constraints, and confess, sell, trust and scold in sentences with semantic constraints (implicit causality). The results show that language ability, despite relative preservation is significantly impaired in PD patients as compared to that of NC. More specifically, syntax with semantic constraints was the most effective independent variable to classify PD patients and NC subjects into two distinct groups according to a Logistic Regression Analysis. To restrict the algorithmic process in sentence comprehension, PD patients seem to make use of the minimal distance principle (MDP) and the "experiencer constraint" heuristic strategies. Possible similarities in language behavior between PD patients and aphasics, in general, are suggested.
We performed a longitudinal study (mean follow-up 86.7 months) to evaluate motor and mental deterioration in patients with Parkinson's disease. Of the original 91 patients, only 61 could be re-examined 7 years later and 11 of these had become demented (PD-Dems). PD-Dems were older with worse motor and, obviously, cognitive performance than non-demented parkinsonian patients (PDs). A global cognitive decay index (DI) was calculated for each patient. Based on this, non-demented PDs were further split into 38 stable parkinsonian patients (S-PDs) with DI-30% to +30%, and 10 deteriorated but non-demented parkinsonian patients (D-PDs) with a DI worse than -30% (as had PD-Dems). D-PDs were older and had greater motor impairment than S-PDs but did not differ from PD-Dems on these measures. D-PDs and PD-Dems deteriorated especially in attention, visuospatial and executive ability tests. Ageing seems to be the main predictive factor for mental deterioration.
Controversy surrounds the presence of deficits of visual cognition in Parkinson's Disease. This literature has been seriously undermined by a number of methodological and theoretical faults that make interpretation of this hypothesis difficult. This review proposes a structure of visual cognition composed of 13 aspects. A meta-analysis of these components on 70 studies that used standardised neuropsychological tests and an appropriate normal control group indicates that the PD subjects are significantly compromised on tests of attention and concentration, complex visuospatial functions, and multifactorial spatial functions. More detailed analysis of the basic components of visual cognition was not undertaken due to low statistical power; hence, it remains unclear whether these subjects have primary visual processing deficits in association with their higher order deficits. The observed deficits may be interpreted as being a consequence of either undetermined lower level visual cognitive deficits or a compromise in executive functioning.
This study investigated the possibility that a specific age at onset factor in Parkinson's disease results in qualitative differences in cognitive functioning between early- and late-onset patients without dementia. Both early- and late-onset patients performed more poorly than matched controls on face-matching, recognition memory for unfamiliar faces and famous face identification. When the performance of the early- and late-onset patients was contrasted, alongside that of controls, both Parkinson's disease and age were found to be factors that influenced cognitive ability. No interaction between these factors emerged. These results suggest that performance of early- and late-onset Parkinson's disease patients without dementia may be quantitatively different and lend no further support to the proposal that two separate disorders exist.
The purpose of the study was to evaluate the neuropsychological performance of younger Parkinson's disease (PD) patients compared to healthy controls. A group of young optimally treated PD patients younger than 56 years was pair-matched with a group of healthy controls for age, social class and the two WAIS subtests "vocabulary" and "similarities". As a group, the PD patients were satisfactory in verbal logical intelligence, but evaluation of neuropsychological tests showed difficulties in short memory span, constructional function and logical visual sequential cognition. Young PD patients have some cognitive impairment for which they are able to compensate for a time because of preserved intelligence. More attention should be paid to possible problems in their jobs and social life.
Are the striato-frontal neuronal circuits implicated in learning of item-specific spatial coordinates? To answer this question, we compared the performance of 20 patients with Parkinson's disease to that of 14 controls matched for age, global cognitive efficiency and mood, on a visuo-spatial learning task with little involvement of motor and constructive functions, allowing control of encoding and comparison of free recall, cued recall and recognition. Compared to controls, patients showed a severe memory impairment for visuo-spatial location of pictures, contrasting with relative preservation of verbal memory, and mild difficulties in perceptive visuo-spatial and executive functions. These results implicate striato-frontal neuronal circuits in memory for spatial location.
We studied event-related potentials and the cognitive state for 2 years in 29 patients with Parkinson's disease (PD). Of those patients, 11 were at stage II and 18 were at stage III at initial assessment, as measured on the Hoehn and Yahr scale. The peak latency of P300 in patients at stage III was significantly prolonged, as compared with that in age-matched normal controls or PD patients at stage II. There was no significant change in P300 latency among patients whose motor ability remained unchanged at stage II or stage III during follow-up period. The mean P300 latency prolonged significantly in patients whose motor ability worsened from stage III to stage IV. The cognitive state in the patients with PD was characterized by impairment in the categories of orientation, recall and constructional ability. The degree of impairment of these items increased as the motor disability increased. These results suggest that cognitive dysfunctions and abnormality of P300 latency increased as the motor disabilities progressed.
To study the effects of Parkinson disease (PD) on cognitive function by determining the frequency and amount of change in Mini-Mental State Examination (MMSE) performance.
During a 4-year period, 77 patients with idiopathic PD and 43 normal elders were administered a neuropsychological test battery twice at 2 years apart.
A 4-point score difference on the MMSE was the amount that was statistically calculated to be a significant difference at the .05 probability level. Using this metric, 17 (22%) patients with PD had a change in their MMSE performance during a 2-year period. Fifteen individuals performed poorer, and 2 individuals improved. Using the same metric, no normal subjects changed in their MMSE performance. The groups of patients with PD who had a change and did not have a change in their MMSE performance were not characterized by significant differences in their years of education, duration of illness, age at onset, age at test time 1, estimated premorbid intelligence, Hamilton Psychiatric Rating Scale for Depression score at test time I, or Unified Parkinson's Disease Rating Scale score. The singular difference was the higher frequency of change that was found in subjects who were taking dopamine agonists at the second test time.
A change in cognitive function in patients with PD, as measured by a change of 4 points or more in their MMSE performance, was observed in only 22% of a sample of 77 patients with idiopathic PD during a 2-year period.
To analyze chronometrically the evidence for possible cognitive slowing in Parkinson's disease, we measured visual event-related potentials (ERPs) and reaction times (RTs) in 29 patients with nondemented Parkinson's disease and 19 age-equivalent normal controls during the performance of semantic discrimination tasks. The components of the N1, P2, NA, N2 and P3 and simple and GO/NOGO RTs were observed. The N2 was measured from difference waveforms, subtracting the ERPs to frequent stimuli from those to infrequent stimuli in the discrimination task. Difference waveforms were also derived to delineate NA by subtracting the ERPs in the simple RT task from those of the frequent stimuli of the discrimination task. The N2 and P3 latencies and GO/NOGO RT in patients with Parkinson's disease were significantly longer than those in the controls, although there were no differences in N1, P2 and NA latencies or simple RT between the two groups. The results are interpreted as electrophysiological signs of cognitive slowing, particularly with respect to stimulus classification and attention processes in Parkinson's disease, independent of sensory problems. As for the automatic/controlled processes, the present results suggest that the automatic processing stage associated with NA may be less impaired than the attention-controlled processing reflected by N2 in patients with Parkinson's disease.
The nature of cognitive performance in subjects with Parkinson disease (PD) without dementia is controversial, perhaps because of failure to exclude subjects with unrecognized very mild dementia.
To compare cognitive and motor functioning in well-characterized subjects with PD without overt dementia with healthy elderly control subjects.
Subjects' conditions were evaluated clinically and psychometrically at entry into a longitudinal study of cognitive and motor performance in elderly subjects. Measures included a global dementia staging scale, the Washington University Clinical Dementia Rating; psychometric tests, including Logical Memory, Digit Span, Associate Learning, Information, Block Design, Digit Symbol, Trail-making A, Crossing-off, Boston Naming Test, and Word Fluency; and motor measures, including finger tapping, gait velocity, reaction time, and movement time.
A university-based research facility.
There were 3 groups of subjects: healthy elderly control subjects (n=43), subjects with PD without dementia (n=58), and subjects with PD with questionable dementia (n=22), each evaluated at time of entry.
As expected, both PD groups were impaired on motor measures (gait velocity, finger tapping, and movement time) compared with the healthy elderly control group. Neither PD group showed slowing in reaction time. The subjects with PD with questionable dementia were more impaired on Logical Memory, Block Design, Digit Symbol, and Trailmaking A compared with the subjects with PD without dementia. Although free of clinically evident cognitive dysfunction (Clinical Dementia Rating score, 0), the PD group without dementia was impaired with respect to the healthy elderly control group on all measures from the psychometric assessment except Digit Span, Associate Learning, and Word Fluency.
The PD group without dementia showed global cognitive impairments in comparison with the healthy elderly control group, possibly because the healthy elderly control subjects represented idealized aging. Although the deficits were of small magnitude, this finding suggests that PD may predispose to subclinical cognitive impairment. Longitudinal follow-up is required to determine whether subjects with PD destined to develop overt dementia can be distinguished from those who do not.
It is controversial whether age of disease onset is related to cognitive decline in Parkinson's disease (PD). We administered 7 cognitive measures assessing visuospatial skills, memory, and executive functions to 222 patients with idiopathic PD and 108 normal control participants. Regression analyses demonstrated that older age of disease onset consistently predicted cognitive decline above and beyond normative aging and duration of illness. These findings suggest that older age of disease onset is a critical determinant of cognitive deterioration in PD.
Idiopathic Parkinson's disease (IPD) has been subclassified on the basis of predominant motor symptomatology, age at disease onset, depressive affect, and cognitive performance. However, subgroups are usually arbitrarily defined and not reliably based on qualitatively distinct neuropathology. We explored heterogeneity in IPD in a data-driven manner using comprehensive demographic, motor, mood, and cognitive information collected from 176 patients with IPD. Cluster analysis revealed three subgroups of patients at a disease duration of 5.6 years and two subgroups at 13.4 years. The subgroups may represent the clinical progression of three distinct subtypes of IPD. The "motor only" subtype was characterized by motor symptom progression in the absence of intellectual impairment. Equivalent motor symptom progression was shown by the "motor and cognitive" subtype which was accompanied by executive function deficits progressing to global cognitive impairment. The "rapid progression" subtype was characterized by an older age at disease onset and rapidly progressive motor and cognitive disability. There was no relationship between the motor and cognitive symptoms in any subtype of IPD. We conclude that the clinical heterogeneity of IPD is governed by distinct neuropathologic processes with independent etiologic influences.
Frequency estimation of dementia in Parkinson's disease (PD) has often been the source of controversy owing to variations in the case selection methods and diagnosis criteria used. We examined the frequency of dementia and differences found in some clinical features between PD patients with or without cognitive impairment, to determine the risk factors for incident dementia in PD patients.
A diagnosis of PD was taken according to the United Kingdom Parkinson's Disease Society Brain Bank criteria. Subjects were considered as affected from cognitive impairment if Minimental State Examination score was below to 21.
Cognitive impairment was present in 36% of PD patients. The mean age was higher in PD patients with cognitive impairment (76 vs 69 years old, respectively; p < 0.001). The age onset of PD was higher in patients with cognitive impairment (68 vs 63 years old, respectively; p < 0.01). The rate of PD patients with low educational level were higher in patients with cognitive impairment (59 vs 30%, respectively; p < 0.01). Patients with cognitive impairment had higher rating scale score (p < 0.001).
Cognitive impairment was present in 36% of examined PD patients, based in our operative diagnostic criteria. The cognitive status decrease continuously with age. It's also evidence an inverse relation between educational level and rating scale score with cognitive impairment.
By revealing how brain activity during cognitive performance changes as a function of aging, studies using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) are contributing to the development of a new discipline of Cognitive Neuroscience of Aging. This article reviews functional neuroimaging studies of cognitive aging in the domains of visual perception, episodic memory encoding and semantic memory retrieval, episodic memory retrieval, implicit memory, and working memory. The most consistent finding of these studies was that brain activity tends to be less lateralized in older adults than in younger adults. This finding is conceptualized in terms of a model called Hemispheric Asymmetry Reduction in Old Adults (HAROLD). According to a compensation hypothesis, bihemispheric involvement could help counteract age-related neurocognitive decline, whereas, according to a dedifferentiation hypothesis, it reflects a difficulty in recruiting specialized neural mechanisms.
A Standard Road Map Test of Direction Sense
- J Money
Money, J. (1976). A Standard Road Map Test of Direction Sense. San Rafael, CA: Academic Ther-apy Publications.
Research diagnostic criteria for Parkinson's disease Advances in neurology Parkin-son's disease: Anatomy, pathology, and therapy
- C Ward
- W Gibb
Ward, C., & Gibb, W. (1990). Research diagnostic criteria for Parkinson's disease. In M.B. Streifler, A.D. Korczyn, E. Melamed, & M.B.H. Youdim, (Eds.), Advances in neurology: Volume 53: Parkin-son's disease: Anatomy, pathology, and therapy (pp. 245–249). New York: Raven Press.