Profiling Parkinson's disease cognitive phenotypes via resting-state magnetoencephalography

2021 ◽  
Author(s):  
Olivier B Simon ◽  
Donald Rojas ◽  
Debashis Ghosh ◽  
Xinyi Yang ◽  
Sarah E Rogers ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Resting State ◽  
Source Analysis ◽  
Beta Band ◽  
Cognitive Changes ◽  
Cross Sectional ◽  
Normal Cognition

Aberrant brain oscillations are a hallmark of Parkinson's disease (PD) pathophysiology and may be related to motor and non-motor symptoms. Mild cognitive impairment (MCI) affects many people with PD even at the time of diagnosis and conversion risks to PD dementia (PDD) are very high. Unfortunately, pharmacotherapies are not addressing cognitive symptoms in PD. Profiling PD cognitive phenotypes (eg. MCI, PDD...) may therefore help inform future treatments. Neurophysiological methods, such as magnetoencephalography (MEG), offer the advantage of observing oscillatory patterns, whose regional and temporal profiles may elucidate how cognitive changes relate to neural mechanisms. We conducted a resting state MEG cross-sectional study of 89 persons with PD stratified into three phenotypic groups: normal cognition, MCI and PDD, in order to identify brain regions and frequencies most associated with each cognitive profile. In addition, a neuropsychological battery was administered to assess each domain of cognition. Our data showed higher power in lower frequency bands (delta and theta) observed along with more severe cognitive impairment, and associated with memory, language, attention and global cognition. Of the total 119 brain parcels assessed during source analysis, widespread group differences were found in the beta band, with significant changes mostly occurring between the normal cognition and MCI groups. Moreover, bilateral frontal and left-hemispheric regions were particularly affected in the other frequencies as cognitive decline becomes more pronounced. Our results suggest MCI and PDD may be qualitatively distinct cognitive phenotypes, and most dramatic changes seem to have happened when the PD brain shows mild cognitive decline.

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

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.

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

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.

scholarly journals Altered Cerebellar Resting-State Functional Connectivity in Early-Stage Parkinson's Disease Patients With Cognitive Impairment

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaojuan Dan ◽  
Yang Hu ◽  
Junyan Sun ◽  
Linlin Gao ◽  
Yongtao Zhou ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Functional Connectivity ◽  
Cognitive Deficits ◽  
Resting State ◽  
Early Stage ◽  
Cognitive Status ◽  
Elderly Subjects ◽  
Normal Cognition

Background: Cognitive impairment is one of the most prominent non-motor symptoms in Parkinson's disease (PD), due in part to known cerebellar dysfunctions. Furthermore, previous studies have reported altered cerebellar functional connectivity (FC) in PD patients. Yet whether these changes are also due to the cognitive deficits in PD remain unclear.Methods: A total of 122 non-dementia participants, including 64 patients with early PD and 58 age- and gender-matched elderly controls were stratified into four groups based on their cognitive status (normal cognition vs. cognitive impairment). Cerebellar volumetry and FC were investigated by analyzing, respectively, structural and resting-state functional MRI data among groups using quality control and quantitative measures. Correlation analysis between MRI metrics and clinical features (motor and cognitive scores) were performed.Results: Compared to healthy control subjects with no cognitive deficits, altered cerebellar FC were observed in early PD participants with both motor and cognitive deficits, but not in PD patients with normal cognition, nor elderly subjects showing signs of a cognitive impairment. Moreover, connectivity between the “motor” cerebellum and SMA was positively correlated with motor scores, while intracerebellar connectivity was positively correlated with cognitive scores in PD patients with cognitive impairment. No cerebellar volumetric difference was observed between groups.Conclusions: These findings show that altered cerebellar FC during resting state in early PD patients may be driven not solely by the motor deficits, but by cognitive deficits as well, hence highlighting the interplay between motor and cognitive functioning, and possibly reflecting compensatory mechanisms, in the early PD.

scholarly journals Which Neuropsychological Tests? Predicting Cognitive Decline and Dementia in Parkinson’s Disease in the ICICLE-PD Cohort

2021 ◽  
pp. 1-12
Author(s):  
Rachael A. Lawson ◽  
Caroline H. Williams-Gray ◽  
Marta Camacho ◽  
Gordon W. Duncan ◽  
Tien K. Khoo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Verbal Fluency ◽  
Neuropsychological Tests ◽  
Visual Memory ◽  
Attention And Memory ◽  
Memory And Attention ◽  
Global Cognition

Background: Cognitive impairment is common in Parkinson’s disease (PD), with 80% cumulatively developing dementia (PDD). Objective: We sought to identify tests that are sensitive to change over time above normal ageing so as to refine the neuropsychological tests predictive of PDD. Methods: Participants with newly diagnosed PD (n = 211) and age-matched controls (n = 99) completed a range of clinical and neuropsychological tests as part of the ICICLE-PD study at 18-month intervals over 72 months. Impairments on tests were determined using control means (<1-2SD) and median scores. Mild cognitive impairment (PD-MCI) was classified using 1-2SD below normative values. Linear mixed effects modelling assessed cognitive decline, while Cox regression identified baseline predictors of PDD. Results: At 72 months, 46 (cumulative probability 33.9%) participants had developed PDD; these participants declined at a faster rate in tests of global cognition, verbal fluency, memory and attention (p <  0.05) compared to those who remained dementia-free. Impaired baseline global cognition, visual memory and attention using median cut-offs were the best predictors of early PDD (area under the curve [AUC] = 0.88, p <  0.001) compared to control-generated cut-offs (AUC = 0.76–0.84, p <  0.001) and PD-MCI (AUC] = 0.64–0.81, p <  0.001). Impaired global cognition and semantic fluency were the most useful brief tests employable in a clinical setting (AUC = 0.79, p <  0.001). Conclusion: Verbal fluency, attention and memory were sensitive to change in early PDD and may be suitable tests to measure therapeutic response in future interventions. Impaired global cognition, attention and visual memory were the most accurate predictors for developing a PDD. Future studies could consider adopting these tests for patient clinical trial stratification.

Analyses of Visuospatial and Visuoperceptual Errors as Predictors of Dementia in Parkinson’s Disease Patients with Subjective Cognitive Decline and Mild Cognitive Impairment

2020 ◽  
pp. 1-11
Author(s):  
Iván Galtier ◽  
Antonieta Nieto ◽  
María Mata ◽  
Jesús N. Lorenzo ◽  
José Barroso
Keyword(s):  
Risk Factors ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Poor Performance ◽  
Subjective Cognitive Decline ◽  
Independent Risk Factors

ABSTRACT Objective: Subjective cognitive decline (SCD) and mild cognitive impairment (MCI) in Parkinson’s disease (PD) are considered as the risk factors for dementia (PDD). Posterior cortically based functions, such as visuospatial and visuoperceptual (VS-VP) processing, have been described as predictors of PDD. However, no investigations have focused on the qualitative analysis of the Judgment of Line Orientation Test (JLOT) and the Facial Recognition Test (FRT) in PD-SCD and PD-MCI. The aim of this work was to study the VS-VP errors in JLOT and FRT. Moreover, these variables are considered as predictors of PDD. Method: Forty-two PD patients and 19 controls were evaluated with a neuropsychological protocol. Patients were classified as PD-SCD and PD-MCI. Analyses of errors were conducted following the procedure described by Ska, Poissant, and Joanette (1990). Follow-up assessment was conducted to a mean of 7.5 years after the baseline. Results: PD-MCI patients showed a poor performance in JLOT and FRT total score and made a greater proportion of severe intraquadrant (QO2) and interquadrant errors (IQO). PD-SCD showed a poor performance in FRT and made mild errors in JLOT. PD-MCI and QO2/IQO errors were independent risk factors for PDD during the follow-up. Moreover, the combination of both PD-MCI diagnosis and QO2/IQO errors was associated with a greater risk. Conclusions: PD-MCI patients presented a greater alteration in VS-VP processing observable by the presence of severe misjudgments. PD-SCD patients also showed mild difficulties in VS-SP functions. Finally, QO2/IQO errors in PD-MCI are a useful predictor of PDD, more than PD-MCI diagnosis alone.

scholarly journals Cognitive impairment and resting-state network connectivity in Parkinson's disease

2014 ◽  
Vol 36 (1) ◽  
pp. 199-212 ◽  
Author(s):  
Hugo-Cesar Baggio ◽  
Bàrbara Segura ◽  
Roser Sala-Llonch ◽  
Maria-José Marti ◽  
Francesc Valldeoriola ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Resting State ◽  
Network Connectivity ◽  
Resting State Network

scholarly journals “Resting-state fMRI in Parkinson's disease patients with cognitive impairment: A meta-analysis”: Answer to Wang and colleagues

2019 ◽  
Vol 66 ◽  
pp. 253-254
Author(s):  
Amée F. Wolters ◽  
Sjors C.F. van de Weijer ◽  
Albert F.G. Leentjens ◽  
Annelien A. Duits ◽  
Heidi I.L. Jacobs ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Resting State ◽  
Meta Analysis ◽  
Resting State Fmri

scholarly journals Region-Specific Neurovascular Decoupling Associated With Cognitive Decline in Parkinson’s Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Song’an Shang ◽  
Hongying Zhang ◽  
Yuan Feng ◽  
Jingtao Wu ◽  
Weiqiang Dou ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Cognitive Deficits ◽  
Inferior Frontal Gyrus ◽  
Neurovascular Coupling ◽  
Angular Gyrus ◽  
Visual Spatial ◽  
The Right

Background: Cognitive deficits are prominent non-motor symptoms in Parkinson’s disease (PD) and have been shown to involve the neurovascular unit (NVU). However, there is a lack of sufficient neuroimaging research on the associated modulating mechanisms. The objective of this study was to identify the contribution of neurovascular decoupling to the pathogenesis of cognitive decline in PD.Methods: Regional homogeneity (ReHo), a measure of neuronal activity, and cerebral blood flow (CBF), a measure of vascular responses, were obtained from patients with PD with mild cognitive impairment (MCI) and normal cognition (NC) as well as matched healthy controls (HCs). Imaging metrics of neurovascular coupling (global and regional CBF-ReHo correlation coefficients and CBF-ReHo ratios) were compared among the groups.Results: Neurovascular coupling was impaired in patients with PD-MCI with a decreased global CBF-ReHo correlation coefficient relative to HC subjects (P &lt; 0.05). Regional dysregulation was specific to the PD-MCI group and localized to the right middle frontal gyrus, right middle cingulate cortex, right middle occipital gyrus, right inferior parietal gyrus, right supramarginal gyrus, and right angular gyrus (P &lt; 0.05). Compared with HC subjects, patients with PD-MCI showed higher CBF-ReHo ratios in the bilateral lingual gyri (LG), bilateral putamen, and left postcentral gyrus and lower CBF-ReHo ratios in the right superior temporal gyrus, bilateral middle temporal gyri, bilateral parahippocampal gyri, and right inferior frontal gyrus. Relative to the HC and PD-NC groups, the PD-MCI group showed an increased CBF-ReHo ratio in the left LG, which was correlated with poor visual–spatial performance (r = −0.36 and P = 0.014).Conclusion: The involvement of neurovascular decoupling in cognitive impairment in PD is regionally specific and most prominent in the visual–spatial cortices, which could potentially provide a complementary understanding of the pathophysiological mechanisms underlying cognitive deficits in PD.

scholarly journals Parkinson’s Disease-Cognitive Rating Scale for Evaluating Cognitive Impairment in Parkinson’s Disease: A Systematic Review

2020 ◽  
Vol 10 (9) ◽  
pp. 588
Author(s):  
Elena Cecilia Rosca ◽  
Mihaela Simu
Keyword(s):  
Systematic Review ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Psychometric Properties ◽  
Rating Scale ◽  
Cross Sectional Study ◽  
Index Test ◽  
Cross Sectional ◽  
Level Ii

The aim of the present systematic review was to examine the evidence on the accuracy and psychometric properties of the Parkinson’s Disease-Cognitive Rating Scale (PD-CRS) for evaluating the presence of cognitive impairment in patients with Parkinson’s disease (PD) as well as to highlight the quality and quantity of research available on the use of the PD-CRS in this population. We searched four databases from inception until July 2020. Eight studies, published between 2008 and 2020, met the inclusion criteria: One cross-sectional study in which participants were assessed with the index test (PD-CRS) and a reference standard diagnostic assessment, in accordance with the Level II criteria of the International Parkinson and Movement Disorder Society (MDS); one case-control study comparing the PD-CRS to an extensive battery of tests (i.e., MDS Level II diagnosis); and six studies comparing the PD-CRS to other short cognitive batteries. In patients with Parkinson’s disease, the PD-CRS test provides information about cortical and sub-cortical cognitive functions. Even if it demonstrated good psychometric properties, the results regarding the optimal threshold for detecting mild cognitive impairment and dementia in PD are somewhat inconsistent. Further cross-sectional studies are necessary to examine the optimum cut-off score for detecting cognitive dysfunction in PD patients.

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