Cognitive decline in Parkinson’s disease: the impact of the motor phenotype on cognition

ObjectivesParkinson’s disease (PD) is the second most common neurodegenerative disorder and is further associated with progressive cognitive decline. In respect to motor phenotype, there is some evidence that akinetic-rigid PD is associated with a faster rate of cognitive decline in general and a greater risk of developing dementia.The objective of this study was to examine cognitive profiles among patients with PD by motor phenotypes and its relation to cognitive function.MethodsDemographic, clinical and neuropsychological cross-sectional baseline data of the DEMPARK/LANDSCAPE study, a multicentre longitudinal cohort study of 538 patients with PD were analysed, stratified by motor phenotype and cognitive syndrome. Analyses were performed for all patients and for each diagnostic group separately, controlling for age, gender, education and disease duration.ResultsCompared with the tremor-dominant phenotype, akinetic-rigid patients performed worse in executive functions such as working memory (Wechsler Memory Scale-Revised backward; p=0.012), formal-lexical word fluency (p=0.043), card sorting (p=0.006), attention (Trail Making Test version A; p=0.024) and visuospatial abilities (Leistungsprüfungssystem test 9; p=0.006). Akinetic-rigid neuropsychological test scores for the executive and attentive domain correlated negatively with non-tremor motor scores. Covariate-adjusted binary logistic regression analyses showed significant odds for PD-mild cognitive impairment for not-determined as compared with tremor-dominant (OR=3.198) and akinetic-rigid PD (OR=2.059). The odds for PD-dementia were significant for akinetic-rigid as compared with tremor-dominant phenotype (OR=8.314).ConclusionThe three motor phenotypes of PD differ in cognitive performance, showing that cognitive deficits seem to be less severe in tremor-dominant PD. While these data are cross-sectional, longitudinal data are needed to shed more light on these differential findings.

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Influence of Hypertension on Neurocognitive Domains in Nondemented Parkinson’s Disease Patients

Parkinson s Disease ◽

10.1155/2014/507529 ◽

2014 ◽

Vol 2014 ◽

pp. 1-10 ◽

Cited By ~ 3

Author(s):

Jacob D. Jones ◽

Charles Jacobson ◽

Martina Murphy ◽

Catherine Price ◽

Michael S. Okun ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Executive Function ◽

Cognitive Decline ◽

Verbal Memory ◽

Rating Scale ◽

Cognitive Status ◽

Cross Sectional ◽

The Impact ◽

Health Comorbidities

Objective. Health comorbidities, particularly cardiovascular risk factors, are well known to pose risks for cognitive decline in older adults. To date, little attention has focused on the impact of these comorbidities on Parkinson’s disease (PD). This study examined the prevalence and contribution of comorbidities on cognitive status in PD patients, above and beyond the effects of disease severity.Methods. A cross sectional design was used, including neuropsychological data on 341 PD patients without severe cognitive decline. Comorbidity data were collected via medical chart review. Data were analyzed using a series of multiple hierarchical regressions, controlling for PD-related disease variables.Results. Overall sample characteristics are 69% male, disease duration 9.7 years, Unified Parkinson’s Disease Rating Scale 26.4, and age 64.7 years. Hypercholesterolemia (41.6%), hypertension (38.1%), and hypotension (30.2%) were the most reported comorbidities. The presence of hypertension significantly contributed to domains of executive function and verbal memory. The cooccurrence of orthostatic hypotension moderated the relationship between hypertension and executive function.Conclusions. This study on a large cohort of PD patients provides evidence for a detrimental influence of health comorbidities, particularly hypertension, on cognitive domains that have traditionally been conceptualized as being frontally and/or temporally mediated.

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Differential effects of sex on longitudinal patterns of cognitive decline in Parkinson’s disease

Journal of Neurology ◽

10.1007/s00415-020-10367-8 ◽

2021 ◽

Author(s):

Megan C. Bakeberg ◽

Anastazja M. Gorecki ◽

Jade E. Kenna ◽

Alexa Jefferson ◽

Michelle Byrnes ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Cognitive Decline ◽

Cognitive Performance ◽

Repeated Measures ◽

Cross Sectional ◽

Domain Specific ◽

Global Cognition ◽

The Impact

Abstract 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.

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Validation of Cognitive Rehabilitation as a Balance Rehabilitation Strategy in Patients with Parkinson’s Disease: Study Protocol for a Randomized Controlled Trial

Medicina ◽

10.3390/medicina57040314 ◽

2021 ◽

Vol 57 (4) ◽

pp. 314

Author(s):

Aida Arroyo-Ferrer ◽

Francisco José Sánchez-Cuesta ◽

Yeray González-Zamorano ◽

María Dolores del Castillo ◽

Carolina Sastre-Barrios ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Therapy ◽

Cognitive Processing ◽

Processing Speed ◽

Cognitive Rehabilitation ◽

Neurodegenerative Disorder ◽

Control Group ◽

Motor Symptoms ◽

The Impact

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disorder. This disease is characterized by motor symptoms, such as bradykinesia, tremor, and rigidity. Although balance impairment is characteristic of advanced stages, it can be present with less intensity since the beginning of the disease. Approximately 60% of PD patients fall once a year and 40% recurrently. On the other hand, cognitive symptoms affect up to 20% of patients with PD in early stages and can even precede the onset of motor symptoms. There are cognitive requirements for balance and can be challenged when attention is diverted or reduced, linking a worse balance and a higher probability of falls with a slower cognitive processing speed and attentional problems. Cognitive rehabilitation of attention and processing speed can lead to an improvement in postural stability in patients with Parkinson’s. Methods: We present a parallel and controlled randomized clinical trial (RCT) to assess the impact on balance of a protocol based on cognitive rehabilitation focused on sustained attention through the NeuronUP platform (Neuronup SI, La Rioja, Spain) in patients with PD. For 4 weeks, patients in the experimental group will receive cognitive therapy three days a week while the control group will not receive any therapy. The protocol has been registered at trials.gov NCT04730466. Conclusions: Cognitive therapy efficacy on balance improvement may open the possibility of new rehabilitation strategies for prevention of falls in PD, reducing morbidity, and saving costs to the health care system.

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Impact of Aging on the 6-OHDA-Induced Rat Model of Parkinson’s Disease

International Journal of Molecular Sciences ◽

10.3390/ijms21103459 ◽

2020 ◽

Vol 21 (10) ◽

pp. 3459 ◽

Cited By ~ 2

Author(s):

Sandra Barata-Antunes ◽

Fábio G. Teixeira ◽

Bárbara Mendes-Pinheiro ◽

Ana V. Domingues ◽

Helena Vilaça-Faria ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Animal Welfare ◽

Neurodegenerative Disorder ◽

Negative Impact ◽

Substantia Nigra Pars Compacta ◽

Nigrostriatal Pathway ◽

Aged Rats ◽

Age Related ◽

The Impact

Parkinson’s disease (PD) is the second most common age-related neurodegenerative disorder. The neurodegeneration leading to incapacitating motor abnormalities mainly occurs in the nigrostriatal pathway due to the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Several animal models have been developed not only to better understand the mechanisms underlying neurodegeneration but also to test the potential of emerging disease-modifying therapies. However, despite aging being the main risk factor for developing idiopathic PD, most of the studies do not use aged animals. Therefore, this study aimed at assessing the effect of aging in the unilateral 6-hydroxydopamine (6-OHDA)-induced animal model of PD. For this, female young adult and aged rats received a unilateral injection of 6-OHDA into the medial forebrain bundle. Subsequently, the impact of aging on 6-OHDA-induced effects on animal welfare, motor performance, and nigrostriatal integrity were assessed. The results showed that aging had a negative impact on animal welfare after surgery. Furthermore, 6-OHDA-induced impairments on skilled motor function were significantly higher in aged rats when compared with their younger counterparts. Nigrostriatal histological analysis further revealed an increased 6-OHDA-induced dopaminergic cell loss in the SNpc of aged animals when compared to young animals. Overall, our results demonstrate a higher susceptibility of aged animals to 6-OHDA toxic insult.

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Evaluation of quality of life and psychological aspects of Parkinson's disease patients who participate in a support group

Dementia & Neuropsychologia ◽

10.1590/1980-57642015dn93000013 ◽

2015 ◽

Vol 9 (3) ◽

pp. 295-300 ◽

Cited By ~ 4

Author(s):

Nathalie Ribeiro Artigas ◽

Vera Lúcia Widniczck Striebel ◽

Arlete Hilbig ◽

Carlos Roberto de Mello Rieder

Keyword(s):

Quality Of Life ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Social Phobia ◽

Support Group ◽

Neurodegenerative Disorder ◽

Control Group ◽

Asymmetric Distribution ◽

Cross Sectional

Parkinson's disease (PD) is a neurodegenerative disorder that can dramatically impair patient quality of life (QoL). Objective: To analyze the QoL, motor capacity, depression, anxiety and social phobia of individuals who attended a patient support group (PSG) compared to non-participants. Methods: A cross-sectional study was performed. The sample consisted of 20 individuals with PD who attended a PSG and another 20 PD patients who did not attend a support group for PD patients, serving as the control group (nPSG). All patients answered questionnaires on motor capacity (UPDRS), QoL (Parkinson's Disease Questionnaire- PDQ-39), depression (Beck Depression Inventory), anxiety (Beck Anxiety Inventory) and social phobia (Liebowitz Social Anxiety Scale). To determine data distribution, the Shapiro-Wilk test was performed. For comparison of means, Student's t-test was applied. In cases of asymmetry, the Mann-Whitney test was employed. To assess the association between the scales, Pearson's correlation coefficient (symmetric distribution) and Spearman's coefficient (asymmetric distribution) were applied. For the association between qualitative variables, Pearson's Chi-squared test was performed. A significance level of 5% (p≤0.05) was adopted. Results: Individuals in the PSG had a significantly better QoL (p=0.002), and lower depression (p=0.026), anxiety (p<0.001) and social phobia (p=0.01) scores compared to the nPSG. Conclusion: The participation of PD patients in social activities such as support groups is associated with better QoL and fewer symptoms of depression, anxiety and social phobia.

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The Impact of Sex on the Neurocognitive Functions of Patients with Parkinson’s Disease

Brain Sciences ◽

10.3390/brainsci11101331 ◽

2021 ◽

Vol 11 (10) ◽

pp. 1331

Author(s):

Mei-Ling Chen ◽

Chun-Hsiang Tan ◽

Hui-Chen Su ◽

Pi-Shan Sung ◽

Chia-Yi Chien ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Sex Differences ◽

Healthy Aging ◽

Neuroprotective Effect ◽

Wisconsin Card Sorting Test ◽

Neurocognitive Function ◽

Card Sorting ◽

Yahr Stage ◽

The Impact

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.

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The Neuro-Protective Effects of the TSPO Ligands CB86 and CB204 on 6-OHDA-Induced PC12 Cell Death as an In Vitro Model for Parkinson’s Disease

Biology ◽

10.3390/biology10111183 ◽

2021 ◽

Vol 10 (11) ◽

pp. 1183

Author(s):

Sheelu Monga ◽

Nunzio Denora ◽

Valentino Laquintana ◽

Rami Yashaev ◽

Abraham Weizman ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cell Death ◽

Neurodegenerative Disorder ◽

Reactive Oxygen ◽

Ros Generation ◽

Oxygen Species ◽

The Impact

Parkinson’s disease (PD) is a progressive neurodegenerative disorder which is characterized by the degeneration of dopaminergic neurons in substantia nigra (SN). Oxidative stress or reactive oxygen species (ROS) generation was suggested to play a role in this specific type of neurodegeneration. Therapeutic options which can target and counteract ROS generation may be of benefit. TSPO ligands are known to counteract with neuro-inflammation, ROS generation, apoptosis, and necrosis. In the current study, we investigated an in vitro cellular PD model by the assessment of 6-hydroxydopamine (6-OHDA, 80 µM)-induced PC12 neurotoxicity. Simultaneously to the exposure of the cells to 6-OHDA, we added the TSPO ligands CB86 and CB204 (25 µM each) and assessed the impact on several markers of cell death. The two ligands normalized significantly (57% and 52% respectively, from 44%; whereas the control was 68%) cell proliferation at different time points from 0–24 h. Additionally, we evaluated the effect of these two TSPO ligands on necrosis using propidium iodide (PI) staining and found that the ligands inhibited significantly the 6-OHDA-induced necrosis. As compared to control, the red count was increased up to 57-fold whereas CB86 and CB204 inhibited to 2.7-fold and 3.2-fold respectively. Necrosis was also analyzed by LDH assay which showed significant effect. Both assays demonstrated similar potent anti-necrotic effect of the two TSPO ligands. Reactive oxygen species (ROS) generation induced by 6-OHDA was also inhibited by the two TSPO ligand up to 1.3 and 1.5-fold respectively, as compared to 6-OHDA group. CB86 and CB204 inhibited also normalized the cell viability up to 1.8-fold after the exposure to 6-OHDA, as assessed by XTT assay. The two TSPO ligands also inhibited apoptosis significantly (1.3-fold for both) as assessed by apopxin green staining. In summary, it appears that the two TSPO ligands CB86 and CB204 can suppress cell death of PC12 induced by 6-OHDA. The results may be relevant to the use of these two TSPO ligands as therapeutic option neurodegenerative diseases like PD.

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INFLUENCE OF SLEEP DISTURBANCES ON COGNITIVE DECLINE IN PATIENTS WITH PARKINSON’S DISEASE

Ukrainian Scientific Medical Youth Journal ◽

10.32345/usmyj.3(117).2020.58-67 ◽

2020 ◽

Vol 117 (3) ◽

pp. 58-67

Author(s):

Anastasiia Shkodina ◽

Kateryna Tarianyk ◽

Dmytro Boiko

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Cognitive Decline ◽

Sleep Disorders ◽

Sleep Disturbances ◽

Rating Scale ◽

Early Stages ◽

The Impact

The article summarizes the arguments and counter-arguments within the scientific discussion on the impact of sleep disorders on the development of cognitive decline in patients with Parkinson's disease. The main purpose of the study is to study the possibility of predicting the development of cognitive decline by assessing the severity of sleep disorders and their differences in the presence of cognitive impairment. Systematization of literature sources and approaches to solving the problem showed that sleep disorders develop in the early stages of Parkinson's disease and are often accompanied by cognitive impairment. Cognitive decline is manifested throughout Parkinson's disease and ranges from moderate in the early stages to dementia in the late stages. The relevance of the study of the relationship between sleep disorders and cognitive functions lies in the possibility of further improving the prediction of the development of cognitive decline in order to effectively correct it. Treatment of sleep disorders can be accompanied by improved memory and even morphological changes in the brain. Therefore, the question arises about the possibility of correcting cognitive decline by influencing sleep disorders. The methodology of the study included assessment of the overall status of patients on a unified scale of Parkinson's disease, Montreal cognitive rating scale and sleep scale in Parkinson's disease. The duration of the study was 8 months. Patients with Parkinson's disease were selected as the study. The article presents the results of a survey of patients who show that patients with Parkinson's disease and cognitive decline showed a predominance of motor disorders, sleep disorders and the overall score on the sleep scale in Parkinson's disease. In the presence of cognitive decline more pronounced disorders of motor functions in everyday life, which can lead to sleep disorders and its quality. The study empirically confirms and theoretically proves that the assessment of sleep disorders can be used to predict the risk of developing cognitive impairment in patients with Parkinson's disease. The results of this study may be useful for improving the early diagnosis and prevention of cognitive impairment in patients with Parkinson's disease, which, in turn, leads to improved quality of treatment of these patients. Such changes can directly affect the choice of therapeutic tactics and improve the quality of life of patients with Parkinson's disease. The question of the features of various sleep disorders and their prognostic value in relation to cognitive decline in patients with various forms of Parkinson's disease remains open.

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Quality of life in a Brazilian sample of patients with Parkinson's disease and their caregivers

Brazilian Journal of Psychiatry ◽

10.1590/s1516-44462006000300013 ◽

2006 ◽

Vol 28 (3) ◽

pp. 209-211 ◽

Cited By ~ 21

Author(s):

Pedro Schestatsky ◽

Vanessa Cassina Zanatto ◽

Regina Margis ◽

Eduardo Chachamovich ◽

Mateus Reche ◽

...

Keyword(s):

Quality Of Life ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Neurodegenerative Disorder ◽

Short Form ◽

Inverse Correlation ◽

Significant Finding ◽

Cross Sectional ◽

Social Domain

OBJECTIVE: Parkinson's disease is a common neurodegenerative disorder characterized by motor disabilities and increasing dependence on others for daily life activities with consequent impact on patients' and caregivers' quality of life. METHOD: A cross-sectional study was performed in which quality of life was assessed by the WHOQOL-BREF questionnaire in 21 patients with Parkinson's disease and their respective caregivers. RESULTS: Significant differences between patients and caregivers were found in physical (p < 0.001) and psychological (p = 0.002) domains. In the Parkinson's disease group there was a significant inverse correlation between the psychological domain and duration of disease (p = 0.01), as well as between social domain and severity of disease (p = 0.001). There was a positive correlation between physical domain scores and number of people living in the same house (p = 0.02). The only significant finding in the group of caregivers was an inverse correlation between the social domain and the patients´ age (p = 0.04). CONCLUSION: Duration, severity of the disease and the number of people living in the same house were the most important predictors of quality of life of Parkinson's disease patients. The age of the patients was the only significant predictor found in the caregivers' quality of life. In order to complement our findings, further short-form questionnaires should be validated for Brazilian samples of Parkinson's disease.

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Progression of Neuropsychiatric Symptoms over Time in an Incident Parkinson’s Disease Cohort (ICICLE-PD)

Brain Sciences ◽

10.3390/brainsci10020078 ◽

2020 ◽

Vol 10 (2) ◽

pp. 78

Author(s):

J. K. Dlay ◽

G. W. Duncan ◽

T. K. Khoo ◽

C. H. Williams-Gray ◽

D. P. Breen ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Neuropsychiatric Symptoms ◽

Caregiver Distress ◽

Cross Sectional ◽

Efficient Delivery ◽

Distress Scale ◽

The Impact ◽

Over Time

Background: Cross-sectional studies have identified that the prevalence of neuropsychiatric symptoms (NPS) in Parkinson’s disease (PD) ranges from 70–89%. However, there are few longitudinal studies determining the impact of NPS on quality of life (QoL) in PD patients and their caregivers. We seek to determine the progression of NPS in early PD. Methods: Newly diagnosed idiopathic PD cases (n = 212) and age-matched controls (n = 99) were recruited into a longitudinal study. NPS were assessed using the Neuropsychiatric Inventory with Caregiver Distress scale (NPI-D). Further neuropsychological and clinical assessments were completed by participants, with reassessment at 18 and 36 months. Linear mixed-effects modelling determined factors associated with NPI-D and QoL over 36 months. Results: Depression, anxiety, apathy and hallucinations were more frequent in PD than controls at all time points (p < 0.05). Higher motor severity at baseline was associated with worsening NPI-D scores over time (β = 0.1, p < 0.05), but not cognition. A higher NPI total score was associated with poorer QoL at any time point (β = 0.3, p < 0.001), but not changed in QoL scores. Conclusion: NPS are significantly associated with poorer QoL, even in early PD. Screening for NPS from diagnosis may allow efficient delivery of better support and treatment to patients and their families.

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