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BACKGROUND: Cognitive impairment is common in Parkinson's disease (PD) and often leads to dementia, with no effective treatment. Aging studies suggest that physical activity (PA) intensity has a positive impact on cognition and enhanced functional connectivity may underlie these benefits. However, less is known in PD. This cross-sectional study examined the relationship between PA intensity, cognitive performance, and resting state functional connectivity in PD and whether PA intensity influences the relationship between functional connectivity and cognitive performance. METHODS: 96 individuals with mild-moderate PD completed a comprehensive neuropsychological battery. Intensity of PA was objectively captured over a seven-day period using a wearable device (ActiGraph). Time spent in light and moderate intensity PA was determined based on standardized actigraphy cut points. Resting-state fMRI was assessed in a subset of 50 individuals to examine brain-wide functional connectivity. RESULTS: Moderate intensityPA (MIPA), but not light PA, was associated with better global cognition, visuospatial function, memory, and executive function. Individuals who met the WHO recommendation of ≥150 min/week of MIPA demonstrated better global cognition, executive function, and visuospatial function. Resting-state functional connectivity associated with MIPA included a combination of brainstem, hippocampus, and regions in the frontal, cingulate, and parietal cortices, which showed higher connectivity across the brain in those achieving the WHO MIPA recommendation. Meeting this recommendation positively moderated the associations between identified functional connectivity and global cognition, visuospatial function, and language. CONCLUSION: Encouraging MIPA, particularly the WHO recommendation of ≥150 min of MIPA/week, may represent an important prescription for PD cognition.

Background and Purpose: Resting-state functional MRI (rs-fMRI) studies in Parkinson’s disease (PD) patients with freezing of gait (FOG) have implicated dysfunctional connectivity over multiple resting-state networks. While these findings provided network-specific insights and information related to the aberrant or altered regional functional connectivity, whether these alterations have any effect on topological reorganization in PD-FOG patients is incompletely understood. Understanding the higher-order functional organization, which could be derived from the ‘hub’ and the ‘rich-club’ organization of the functional networks could be crucial to identifying the distinct and unique pattern of the network connectivity associated with PD-FOG. Methods: In this study, we use rs-fMRI data and graph theoretical approaches to explore the reorganization of resting-state network topology in PD-FOG when compared to those without FOG (PD-nFOG). We also compared the higher-order functional organization derived using the hub and rich-club measures in the functional connectivity networks of these PD-FOG patients to understand whether there is a topological reorganization of these hubs in PD-FOG. Results: We found that the PD-FOG patients showed a noticeable reorganization of hub regions. Regions that are part of the prefrontal cortex, primary somatosensory, motor, and visuomotor coordination areas showed were some of the regions exhibiting altered hub measures in PD-FOG patients. We also found a significantly altered feeder and local connectivity in PD-FOG. Conclusions: Overall our findings demonstrate a widespread topological reorganization and disrupted higher-order functional network topology in PD-FOG which may further assist in improving our understanding of functional network disturbances associated with PD-FOG.

Objectives People who identify as lesbian, gay, bisexual, transgender, queer/questioning, intersex, asexual, other non-cisgender, and non-heterosexual identities (LGBTQIA+) experience discrimination when accessing health care. We investigated specific experiences of LGBTQIA+ people with Parkinson’s disease (PwP) as they are less known. Methods Data were obtained from Fox Insight for PwP identifying as LGBTQIA+ (n = 210), cisgender, heterosexual women (n = 2,373) or cisgender, heterosexual men (n = 2,453). Discrimination in Medical Settings Scale responses and reports of whether gender identity or sexual orientation played a role in the perceived discrimination were compared across the groups. Results Parkinson’s diagnosis age was the youngest for LGBTQIA+ PwP. Despite similar levels of education with cisgender, heterosexual men, LGBTQIA+ people had lower levels of income and were more likely to be unemployed. Cisgender, heterosexual women and LGBTQIA+ PwP reported greater discrimination than cisgender, heterosexual men. Compared to cisgender, heterosexual men; LGBTQIA+ people (25%) and cisgender, heterosexual women (20%) were more likely to report their gender affected how they were treated; LGBTQIA+ PwP (19%) were more likely to report their sexual orientation affected how they were treated. Discussion Women and LGBTQIA+ PwP may be at a higher risk for discrimination in medical settings. Facing disparities while receiving health care based on gender or sexual orientation can affect the health care utilization of PwP. Health care providers should consider their behaviors and interactions with PwP to ensure inclusive and welcoming health care environments.

BackgroundLewy body (LB) dementias have limited clinical diagnostic accuracy because of frequent copathologies contributing to clinical heterogeneity. Although sex differences in clinical prevalence and frequency of pure LB pathology were shown, differences for clinicopathological correlations are less known.ObjectiveThe aim of this study was to determine sex differences for clinical associations of Alzheimer's disease (AD) copathology in those with LB pathology.MethodsData were from National Alzheimer's Coordinating Center for 223 women and 468 men with limbic or neocortical LB, separated into two groups as those with high likelihood and low/intermediate likelihood for LB clinical phenotype based on pathology. Clinical associations of sex and interaction of sex and pathology for the clinical phenotype were analyzed.ResultsMore severe AD copathology was associated with worse cognitive decline and lower likelihood of LB disease clinical phenotype. Women with more severe AD copathology and tau had worse cognitive decline and higher likelihood of AD clinical phenotype than men. Men with more severe AD copathology had lower likelihood of LB clinical phenotype than women. Interaction of sex and pathology was more pronounced in those aged between 70 and 80 years.ConclusionsAD copathology reduces the likelihood of LB clinical phenotype for both women and men; however, men may be at higher risk for LB disease underdiagnosis and women at higher risk for dementia. The use of both LB and AD biomarkers, even when LB or AD pathology is not clinically expected, is necessary for the accurate clinical diagnosis of both LB diseases and AD. © 2022 International Parkinson and Movement Disorder Society.

Background and Purpose: Resting-state functional MRI (rs-fMRI) studies in Parkinson’s disease (PD) patients with freezing of gait (FOG) have implicated dysfunctional connectivity over multiple resting-state networks. While these findings provided network-specific insights and information related to the aberrant or altered regional functional connectivity, whether these alterations have any effect on topological reorganization in PD-FOG patients is incompletely understood. Understanding the higher-order functional organization, which could be derived from the ‘hub’ and the ‘rich-club’ organization of the functional networks could be crucial to identifying the distinct and unique pattern of the network connectivity associated with PD-FOG. Methods: In this study, we use rs-fMRI data and graph theoretical approaches to explore the reorganization of resting-state network topology in PD-FOG when compared to those without FOG (PD-nFOG). We also compared the higher-order functional organization derived using the hub and rich-club measures in the functional connectivity networks of these PD-FOG patients to understand whether there is a topological reorganization of these hubs in PD-FOG. Results: We found that the PD-FOG patients showed a noticeable reorganization of hub regions. Regions that are part of the prefrontal cortex, primary somatosensory, motor, and visuomotor coordination areas showed were some of the regions exhibiting altered hub measures in PD-FOG patients. We also found a significantly altered feeder and local connectivity in PD-FOG. Conclusions: Overall our findings demonstrate a widespread topological reorganization and disrupted higher-order functional network topology in PD-FOG which may further assist in improving our understanding of functional network disturbances associated with PD-FOG.

Repeated data are increasingly collected in studies to investigate the trajectory of change in measurements over time. Determining a link between one repeated measurement with another that is considered as the biomarker for disease progression, may provide a new target for drug development. When a third variable is associated with one of the two measurements, partial correlation after eliminating the effect of that variable is able to provide reliable estimate for association as compared to the existing raw correlation for repeated data. We propose using linear regression models to compute residuals by modeling a relationship between each measurement and a third variable. The computed residuals are then used in a linear mixed model (implemented by SAS Proc Mixed) to compute partial correlation for repeated data. Alternatively, the partial correlation may be computed as the average of partial correlations at each visit. We provide two real examples to illustrate the application of the proposed partial correlation, and conduct extensive numerical studies to compare the proposed partial correlation coefficients.