Can we predict development of impulsive–compulsive behaviours in Parkinson’s disease?

ObjectiveTo determine clinical and structural imaging predictors of impulsive–compulsive behaviour (ICB) in de novo Parkinson’s disease (PD).MethodsFrom a cohort of 1116 subjects from the Parkinson’s Progression Marker Initiative database, we created a subcohort of 42 de novo PD without ICB at baseline with available 3T MRI and who developed ICB during follow-up. PD-ICB were matched for age, gender and disease duration to 42 patients with PD without ICB over follow-up (PD-no-ICB) and 42 healthy controls (HCs). Baseline demographic and clinical predictors of ICB were analysed. For the longitudinal neuroimaging analysis, we selected 27 patients with PD-ICB with available neuroimaging after ICB onset, who were matched with 32 PD-no-ICB and 35 HCs. Baseline and longitudinal structural differences were compared using voxel-based morphometry and voxel-based quantification.ResultsPeople who went on to develop ICB had more severe anxiety, worse autonomic and global cognitive functions and were more likely to have rapid eye movement sleep behaviour disorder. Logistic regression confirmed that worse autonomic and cognitive functions were predictors of ICB. We could not find any morphological feature on baseline MRI that predicted later onset of ICB. When comparing PD groups at follow-up, a small region of increased atrophy in the anterior limb of the left internal capsule adjacent to the head of the left caudate nucleus was found in PD-ICB, but not surviving correction for multiple comparisons.ConclusionsWorse autonomic and cognitive functions predict development of ICB at the time of PD diagnosis. Structural imaging fails to identify morphological features associated with the development of ICB.

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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.

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Disentangling the PIGD classification for the prediction of cognitive impairment in de novo Parkinson’s disease

Journal of Neurology ◽

10.1007/s00415-021-10730-3 ◽

2021 ◽

Author(s):

Daniele Urso ◽

Valentina Leta ◽

Lucia Batzu ◽

Tayyabah Yousaf ◽

Chloe Farrell ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Cognitive Decline ◽

De Novo ◽

Postural Instability ◽

Time To Event ◽

Clinical Predictors ◽

Kaplan Meier

Abstract Background Postural Instability and Gait difficulties (PIGD) subtype has been associated with worse cognitive performance in Parkinson’s disease (PD). Objective To investigate whether PIGD subtype classification or PIGD-related clinical features predict the development of cognitive decline in de novo PD patients. Methods Data from 422 PD patients with de novo PD were obtained from the PPMI database. At follow-up (up to 6 years), patients were categorized as having cognitive impairment or not. Multivariate Cox survival analysis was carried out including motor subtype and individual MDS-UPDRS items defining PIGD phenotype as predictors. Previously validated clinical predictors of cognitive impairment were included in the model as covariates. Occurrence of cognitive impairment at follow-up was used as the time-to-event and Kaplan–Meier curve was generated. Results At baseline, 76 patients were classified as PIGD, 299 tremor-dominant and 47 as indeterminate. Development of cognitive impairment was not associated with PIGD subtype (p = 0.252). When individual MDS-UPDRS items were interrogated in the model, postural instability proved to be an independent predictor of cognitive impairment (HR = 2.045; 95%CI: 1.068–3.918; p = 0.031), while gait difficulties were not associated with cognitive decline (p = 0.870). Conclusions Our findings suggest that postural instability, as assessed by MDS-UPDRS III, may serve as a possible indicator of the risk of developing cognitive impairment in de novo PD patients rather than the PIGD phenotype.

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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.

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

Journal of the International Neuropsychological Society ◽

10.1017/s1355617719001085 ◽

2019 ◽

Vol 26 (2) ◽

pp. 241-249 ◽

Cited By ~ 1

Author(s):

Ece Bayram ◽

Sarah J. Banks ◽

Guogen Shan ◽

Nikki Kaplan ◽

Jessica Z.K. Caldwell

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Sex Differences ◽

Verbal Memory ◽

Healthy Aging ◽

De Novo ◽

Cognitive Changes ◽

Progression Markers ◽

Cognitively Intact

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.

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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.

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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.

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