Sex Differences in Cognitive Changes in De Novo Parkinson’s Disease

AbstractObjective:To evaluate the sex differences in cognitive course over 4 years in Parkinson’s disease (PD) patients with and without mild cognitive impairment (MCI) compared to controls.Methods:Four-year longitudinal cognitive scores of 257 cognitively intact PD, 167 PD-MCI, and 140 controls from the Parkinson’s Progression Markers Initiative were included. Longitudinal scores of men and women, and PD with and without MCI were compared.Results:Women had better verbal memory, men had better visuospatial function. There was no interaction between sex, diagnostic group, and/or time (4-year follow-up period).Conclusions:Sex differences in cognitive course in de novo PD are similar to healthy aging. Cognitive decline rates in PD with and without MCI are similar for the first 4 years of PD.

Download Full-text

Network structure of brain atrophy in de novo Parkinson's disease

eLife ◽

10.7554/elife.08440 ◽

2015 ◽

Vol 4 ◽

Cited By ~ 97

Author(s):

Yashar Zeighami ◽

Miguel Ulla ◽

Yasser Iturria-Medina ◽

Mahsa Dadar ◽

Yu Zhang ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Medial Temporal Lobe ◽

Healthy Aging ◽

De Novo ◽

Progression Markers ◽

Magnetic Resonance Imaging Mri ◽

Cortical Regions ◽

Clinical Measures ◽

Deformation Based Morphometry

We mapped the distribution of atrophy in Parkinson's disease (PD) using magnetic resonance imaging (MRI) and clinical data from 232 PD patients and 117 controls from the Parkinson's Progression Markers Initiative. Deformation-based morphometry and independent component analysis identified PD-specific atrophy in the midbrain, basal ganglia, basal forebrain, medial temporal lobe, and discrete cortical regions. The degree of atrophy reflected clinical measures of disease severity. The spatial pattern of atrophy demonstrated overlap with intrinsic networks present in healthy brain, as derived from functional MRI. Moreover, the degree of atrophy in each brain region reflected its functional and anatomical proximity to a presumed disease epicenter in the substantia nigra, compatible with a trans-neuronal spread of the disease. These results support a network-spread mechanism in PD. Finally, the atrophy pattern in PD was also seen in healthy aging, where it also correlated with the loss of striatal dopaminergic innervation.

Download Full-text

Longitudinal Change and Progression Indicators Using the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale in Two Independent Cohorts with Early Parkinson’s Disease

Journal of Parkinson s Disease ◽

10.3233/jpd-212860 ◽

2021 ◽

pp. 1-16

Author(s):

Michael Bartl ◽

Mohammed Dakna ◽

Sebastian Schade ◽

Tamara Wicke ◽

Elisabeth Lang ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Clinical Trials ◽

Rating Scale ◽

De Novo ◽

Longitudinal Change ◽

Single Center ◽

Square Roots ◽

Disease Rating

Background: The MDS-Unified Parkinson’s disease (PD) Rating Scale (MDS-UPDRS) is the most used scale in clinical trials. Little is known about the predictive potential of its single items. Objective: To systematically dissect MDS-UPDRS to predict PD progression. Methods: 574 de novo PD patients and 305 healthy controls were investigated at baseline (BL) in the single-center DeNoPa (6-year follow-up) and multi-center PPMI (8-year follow-up) cohorts. We calculated cumulative link mixed models of single MDS-UPDRS items for odds ratios (OR) for class change within the scale. Models were adjusted for age, sex, time, and levodopa equivalent daily dose. Annual change and progression of the square roots of the MDS-UDPRS subscores and Total Score were estimated by linear mixed modeling. Results: Baseline demographics revealed more common tremor dominant subtype in DeNoPa and postural instability and gait disorders-subtype and multiethnicity in PPMI. Subscore progression estimates were higher in PPMI but showed similar slopes and progression in both cohorts. Increased ORs for faster progression were found from BL subscores I and II (activities of daily living; ADL) most marked for subscore III (rigidity of neck/lower extremities, agility of the legs, gait, hands, and global spontaneity of movements). Tremor items showed low ORs/negative values. Conclusion: Higher scores at baseline for ADL, freezing, and rigidity were predictors of faster deterioration in both cohorts. Precision and predictability of the MDS-UPDRS were higher in the single-center setting, indicating the need for rigorous training and/or video documentation to improve its use in multi-center cohorts, for example, clinical trials.

Download Full-text

Evolution of impulsive–compulsive behaviors and cognition in Parkinson’s disease

Journal of Neurology ◽

10.1007/s00415-019-09584-7 ◽

2019 ◽

Vol 267 (1) ◽

pp. 259-266

Author(s):

Aleksander H. Erga ◽

Guido Alves ◽

Ole Bjørn Tysnes ◽

Kenn Freddy Pedersen

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Short Form ◽

Population Based ◽

Self Report ◽

Cognitive Changes ◽

Compulsive Behaviors ◽

Changes Over Time ◽

Over Time

Abstract The longitudinal course of ICBs in patients with Parkinson’s disease (PwP) relative to controls has not been explored as of yet. The aim of this study is to determine the frequency, evolution and associated cognitive and clinical features of impulsive and compulsive behaviors (ICBs) over 4 years of prospective follow-up in a population-based cohort with early Parkinson’s disease (PD). We recruited 124 cognitively intact participants with early PD and 156 matched controls from the Norwegian ParkWest study. ICBs were assessed using the self-report short form version of the Questionnaire for Impulsive–Compulsive Disorders in PD. Cognitive changes were examined in PwP with and without ICBs who completed the 4-year follow-up. Generalized linear mixed modelling and mixed linear regression were used to analyze clinical factors and cognitive changes associated with ICBs in PwP over time. ICBs were more common in PwP than controls at all visits, with an age-adjusted odds ratio (OR) varying between 2.5 (95% CI 1.1–5.6; p = 0.022) and 5.1 (95% CI 2.4–11.0; p < 0.001). The 4-year cumulative frequency of ICBs in PwP was 46.8% and 23.3% developed incident ICBs during the study period, but the presence of ICBs was non-persistent in nearly 30%. ICBs were independently associated with younger age (OR 0.95, 95% CI 0.91–0.99: p = 0.008) and use of dopamine agonist (OR 4.1, 95% CI 1.56–10.69). Cognitive changes over time did not differ between patients with and without ICBs. In conclusion, ICBs are common in PwP, but are often non-persistent and not associated with greater cognitive impairment over time.

Download Full-text

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.

Download Full-text

White Matter Hyperintensities and Cognitive Decline in de Novo Parkinson’s Disease Patients

10.1101/230896 ◽

2017 ◽

Author(s):

Mahsa Dadar ◽

Yashar Zeighami ◽

Yvonne Yau ◽

Seyed-Mohammad Fereshtehnejad ◽

Josefina Maranzano ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

White Matter ◽

Cognitive Decline ◽

White Matter Hyperintensities ◽

De Novo ◽

Cognitive Test ◽

Cortical Thinning

AbstractObjectiveWhite Matter Hyperintensities (WMHs) are associated with cognitive decline in normative aging and Alzheimer’s disease. However, the pathogenesis of cognitive decline in Parkinson’s disease (PD) is not directly related to vascular causes, and therefore the role of WMHs in PD remains unclear. If WMH has a higher impact on cognitive decline in PD, vascular pathology should be assessed and treated with a higher priority in this population. Here we investigate whether WMH leads to increased cognitive decline in PD, and if these effects relate to cortical thinningMethodsTo investigate the role of WMHs in PD, it is essential to study recently-diagnosed/non-treated patients.De novoPD patients and age-matched controls (NPD=365,NControl=174) with FLAIR/T2-weighted scans at baseline were selected from Parkinson’s Progression Markers Initiative (PPMI). WMHs and cortical thickness were measured to analyse the relationship between baseline WMHs and future cognitive decline (follow-up:4.09±1.14 years) and cortical thinning (follow-up:1.05±0.10 years).ResultsHigh WMH load (WMHL) at baseline in PD was associated with increased cognitive decline, significantly more than i) PDs with low WMHL and ii) controls with high WMHL. Furthermore, PD patients with higher baseline WMHL showed more cortical thinning in right frontal lobe than subjects with low WMHL. Cortical thinning of this region also predicted decline in performance on a cognitive test.InterpretationPresence of WMHs inde novoPD patients predicts greater future cognitive decline and cortical thinning than in normal aging. Recognizing WMHs as a potential predictor of cognitive deficit in PD provides an opportunity for timely interventions.

Download Full-text

Predicting the onset of freezing of gait in de novo Parkinson’s disease

10.1101/2021.03.11.21253192 ◽

2021 ◽

Author(s):

Fengting Wang ◽

Yixin Pan ◽

Miao Zhang ◽

Kejia Hu

Keyword(s):

Risk Factors ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

De Novo ◽

Freezing Of Gait ◽

Poor Quality ◽

Csf Biomarkers ◽

Genetic Characteristics ◽

Progression Markers ◽

Independent Risk Factors

AbstractFreezing of gait (FoG) is a debilitating symptom of Parkinson’s disease (PD) related to higher risks of falls and poor quality of life. In this study, we predicted the onset of FoG in PD patients using a battery of risk factors from patients enrolled in the Parkinson’s Progression Markers Initiative (PPMI) cohort. The endpoint was the presence of FoG, which was assessed every year during the five-year follow-up visit. Overall, 212 PD patients were included in analysis. Seventy patients (33.0%) developed FoG during the visit (pre-FoG group). Age, bradykinesia, TD/PIGD classification, fatigue, cognitive impairment, impaired autonomic functions and sleep disorder were found to be significantly different in patients from pre-FoG and non-FoG groups at baseline. The logistic regression model showed that motor factors such as TD/PIGD classification (OR = 2.67, 95% CI = 1.41-5.09), MDS-UPDRS part III score (OR = 1.05, 95% CI = 1.01-1.09) were associated with FoG occurrence. Several indicators representing non-motor symptoms such as SDMT total score (OR = 0.95, 95% CI = 0.91-0.98), HVLT immediate/Total recall (OR = 0.91, 95% CI = 0.86-0.97), MOCA (OR = 0.87, 95% CI = 0.76-0.99), Epworth Sleepiness Scale (OR = 1.13, 95% CI = 1.03-1.24), fatigue(OR = 1.98, 95% CI = 1.32-3.06), SCOPA-AUT gastrointestinal score (OR = 1.27, 95% CI = 1.09-1.49) and SCOPA-AUT urinary score (OR = 1.18, 95% CI = 1.06-1.32) were found to have the predictive value. PD patients that developed FoG showed a significant reduction of DAT uptake in the striatum. However, no difference at baseline was observed in genetic characteristics and CSF biomarkers between the two patient sets. Our model indicated that TD/PIGD classification, MDS-UPDRS total score, and Symbol Digit Modalities score were independent risk factors for the onset of FoG in PD patients. In conclusion, the combination of motor and non-motor features including the akinetic subtype and poor cognitive functions should be considered in identifying PD patients with high risks of FoG onset.

Download Full-text

Trait Anxiety as a Risk Factor for Impulse Control Disorders in de novo Parkinson’s Disease

Journal of Parkinson s Disease ◽

10.3233/jpd-212959 ◽

2021 ◽

pp. 1-9

Author(s):

Pauline Waskowiak ◽

Vincent Koppelmans ◽

Marit F.L. Ruitenberg

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Risk Factor ◽

Trait Anxiety ◽

Impulse Control ◽

De Novo ◽

Impulse Control Disorders ◽

Motor Symptoms ◽

Depression And Anxiety

Background: In addition to the well-known motor symptoms, patients with Parkinson’s disease (PD) also frequently experience disabling non-motor symptoms including impulse control disorders (ICDs). ICDs are characterized by a loss of voluntary control over impulses, drives, or temptations regarding excessive hedonic behavior. Objective: The present study examined whether depression and anxiety in de novo PD patients predict the prospective development of ICDs. Methods: We selected 330 de novo PD patients from the Parkinson’s Progression Markers Initiative database who were free of ICDs at the start of the study. ICD presence at baseline and follow-up assessments was evaluated via the shortened version of the Questionnaire for Impulsive-Compulsive Disorders (QUIP-S). Baseline depression and anxiety were measured via the Geriatric Depression Scale (GDS-15) and State-Trait-Anxiety Inventory (STAI-Y), respectively. Results: A total of 149 participants (45.2%) developed an ICD at follow-up and average time of ICD onset was 35 months after baseline. Results of a Cox regression analysis showed that STAI-Y scores but not GDS-15 scores significantly predicted ICD presence. Specifically, scores reflecting higher trait anxiety were associated with an increased risk of developing an ICD. This effect was not confounded by age, gender or UPDRS motor score. We also replicated the well-established result that dopamine agonist use is predictive of ICDs. Conclusion: Our findings indicate that higher anxiety levels in de novo PD patients represent a risk factor for ICD development during the course of the disorder. This highlights the need for early and routine based anxiety screening in these patients.

Download Full-text

Constipation and sleep behaviour disorder associate with processing speed and attention in males with Parkinson’s disease over five years follow-up

Scientific Reports ◽

10.1038/s41598-020-75800-4 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Wee Lee Kong ◽

Yue Huang ◽

Elizabeth Qian ◽

Margaret J. Morris

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Verbal Learning ◽

Cognitive Outcomes ◽

Behaviour Disorder ◽

Early Assessment ◽

Cognitive Changes ◽

Early Stages ◽

Sleep Behaviour

Abstract Constipation and REM sleep behaviour disorder (RBD) are the earliest non-motor manifestations of Parkinson’s disease (PD). Among non-motor symptoms of PD, it is unclear whether constipation and RBD at early stages of PD are related to cognitive outcomes at later stages. Herein, this study aims to investigate whether the presence of constipation and RBD have an impact on future cognitive outcomes in PD. Access to Parkinson’s Progression Markers Initiative (PPMI) database of 360 PD patients with longitudinal observation was requested. Constipation, probable RBD (pRBD) and neuropsychological task scores of PD patients were assessed at baseline and after 5 years. Linear mixed-effects modelling, controlling for gender, age, years of education and LEDD was used to evaluate the association between baseline constipation, pRBD and cognitive performance on follow-up. Gender differences in neuropsychological test performances were found, with men having worse global cognition, speed-attention processing, verbal learning and memory than women at early stages of the disease. We found constipation and pRBD are strongly associated with future decline in some cognitive measures among PD patients, more prominently in men. Our data suggest that early assessment of pRBD and constipation may allow better understanding of the progression of cognitive changes in later phases of PD.

Download Full-text

Does Gut Microbiota Influence the Course of Parkinson’s Disease? A 3-Year Prospective Exploratory Study in de novo Patients

Journal of Parkinson s Disease ◽

10.3233/jpd-202297 ◽

2020 ◽

pp. 1-12

Author(s):

Roberto Cilia ◽

Marco Piatti ◽

Emanuele Cereda ◽

Carlotta Bolliri ◽

Serena Caronni ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Gut Microbiota ◽

Cognitive Functions ◽

Exploratory Study ◽

Dietary Habits ◽

De Novo ◽

Repeated Measurements ◽

Lower Abundance

Background: Although abnormalities in gut microbiota are hypothesized to influence the pathogenesis and clinical phenotype of Parkinson’s disease (PD), prospective studies on de novo patients are lacking. Objective: To preliminarily investigate whether gut microbiota in early untreated PD may predict motor and non-motor features progression over a 3-year period. Methods: 16S ribosomal RNA gene amplicons were sequenced on fecal samples of 39 de novo PD patients. Multiple confounders were taken into account, including dietary habits. Motor and non-motor symptoms were assessed using validated scales at baseline and followed-up yearly for 3 years. At last follow-up, a detailed neuropsychological assessment was additionally performed. A general linear model for repeated measurements— adjusted by dopaminergic therapy at follow-up— was used to investigate the relationship between bacterial taxa abundance at baseline (stratified by the median of distribution at baseline) and outcome variables. Results: Twenty-five patients were included (11 refused, 2 lost at follow-up, 1 died). Lower abundance of Roseburia (Firmicutes phylum) at baseline was associated with worse evolution of motor, non-motor and cognitive functions at 3-year follow-up. Similarly, lower abundance of Ruminococcaceae and Actinobacteria at baseline was associated with faster worsening of global cognitive functions. At follow-up, frontal lobe functions were the features most robustly associated with baseline microbial abnormalities. Conclusion: In the present exploratory study on de novo PD, we found an association between abnormal distribution of specific bacterial taxa and the progression of motor and non-motor features over a 3-year period. This proof-of-principle study supports the design of a larger observational study aiming to determine whether these differences survive multiple-comparison correction and define microbiota-specific subgroups suitable for therapeutic targeting.

Download Full-text

Constipation Predicts Cognitive Decline in Parkinson’s Disease: Results from the COPPADIS Cohort at 2-Year Follow-up and Comparison with a Control Group

Journal of Parkinson s Disease ◽

10.3233/jpd-212868 ◽

2021 ◽

pp. 1-17

Author(s):

Diego Santos García ◽

Lucía García Roca ◽

Teresa de Deus Fonticoba ◽

Carlos Cores Bartolomé ◽

Lucía Naya Ríos ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Cognitive Decline ◽

Rating Scale ◽

Cognitive Status ◽

Control Group ◽

Cognitive Changes ◽

Non Motor Symptoms

Background: Constipation has been linked to cognitive impairment development in Parkinson’s disease (PD). Objective: Our aim was to analyze cognitive changes observed in PD patients and controls from a Spanish cohort with regards to the presence or not of constipation. Methods: PD patients and controls recruited from 35 centers of Spain from the COPPADIS cohort from January 2016 to November 2017 were followed-up during 2 years. The change in cognitive status from baseline (V0) to 2-year follow-up was assessed with the PD-CRS (Parkinson’s Disease Cognitive Rating Scale). Subjects with a score ≥1 on item 21 of the NMSS (Non-Motor Symptoms Scale) at baseline (V0) were considered as “with constipation”. Regression analyses were applied for determining the contribution of constipation in cognitive changes. Results: At V0, 39.7% (198/499) of PD patients presented constipation compared to 11.4% of controls (14/123) (p < 0.0001). No change was observed in cognitive status (PD-CRS total score) neither in controls without constipation (from 100.24±13.72 to 100.27±13.68; p = 0.971) and with constipation (from 94.71±10.96 to 93.93±13.03; p = 0.615). The PD-CRS total score decreased significantly in PD patients with constipation (from 89.14±15.36 to 85.97±18.09; p < 0.0001; Coehn’s effect = –0.35) compared to patients without constipation (from 93.92±15.58 to 93.14±17.52; p = 0.250) (p = 0.018). In PD patients, to suffer from constipation at V0 was associated with a decrease in the PD-CRS total score from V0 to V2 (β= –0.1; 95% CI, –4.36 – –0.27; p = 0.026) and having cognitive impairment at V2 (OR = 1.79; 95% CI, 1.01 – 3.17; p = 0.045). Conclusion: Constipation is associated with cognitive decline in PD patients but not in controls.

Download Full-text