Association of Physical Activity and
            <i>APOE</i>
            Genotype With Longitudinal Cognitive Change in Early Parkinson Disease

Kim, Ryul; Park, Sang Min; Yoo, Dallah; Jun, Jin-Sun; Jeon, Beomseok

doi:10.1212/wnl.0000000000011852

Cited by 18 publications

(18 citation statements)

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“… 4 Inspired by these observations, we aimed at assessing whether low lymphocyte count is associated with the subsequent development of the key milestones in PD's disease course, specifically cognitive impairment, with a particular attention to the apolipoprotein E (ApoE) ε4 allele, a crucial modifying factor in cognitive impairment. 5 , 6 …”

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confidence: 99%

Lower Circulating Lymphocyte Count Predicts ApoEε4‐Related Cognitive Decline in Parkinson's Disease

2021

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In conclusion, this study yields first evidence from longitudinal data of individual patients for the potential of iron and ferritin as progression marker in PD. A validation of our findings in a larger cohort, more advanced PD patients and a longer follow-up period is warranted. Acknowledgments:We gratefully appreciate the participation of our patients in this study. We thank our Parkinson's and study nurses Gudrun Leyerer and Jennifer Heinemann for their excellent assistance. We also thank Peter Lange for providing helpful advice on assay-related issues. Open Access funding enabled and organized by Projekt DEAL.

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confidence: 99%

Lower Circulating Lymphocyte Count Predicts ApoEε4‐Related Cognitive Decline in Parkinson's Disease

2021

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“…Previous observational studies have preferentially focused on the effect of baseline physical activity levels and have shown that high baseline exercise habits and regular overall physical activity levels are associated with better clinical course of PD over a few years. 13 - 17 Therefore, we were initially surprised by our observation that not their baseline level but the maintenance of their level is the key factor associated with better clinical course of PD over a longer period of time. However, given the gradual decline in physical activity levels in patients with PD ( Figure 1A ) and the reported gradual decline in the effectiveness of interventional exercise, 43 , 44 it seems quite plausible that the focus should be on a sustained increase in exercise and regular physical activity levels to improve long-term clinical outcomes.…”

Section: Discussionmentioning

confidence: 98%

“…It remains possible that we have overlooked some of effects of regular physical activity if it has different effects on different genotypes, as suggested by a recent important observational study showing the interaction effects among regular physical activity, APOE genotype, and global cognitive function. 17 …”

Section: Discussionmentioning

confidence: 99%

“…Previous observational studies have shown that not only exercise habits but also overall regular physical levels at baseline are associated with slower motor and cognitive decline over a few years. [14][15][16][17] However, again, the short follow-up period and the lack of sufficient adjustment of confounding factors remain important issues. Therefore, no reliable conclusions have yet been drawn regarding the longterm disease-modifying effects of exercise and high daily physical activity levels in patients with PD.…”

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confidence: 99%

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Long-term Effect of Regular Physical Activity and Exercise Habits in Patients With Early Parkinson Disease

2022

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Objective:Owing to the lack of long-term observations and/or comprehensive adjustment for confounding factors, reliable conclusions regarding long-term effects of exercise and regular physical activity in Parkinson’s disease (PD) have yet to be drawn. Here, using data from the Parkinson’s Progression Markers Initiative study that includes longitudinal and comprehensive evaluations of many clinical parameters, we examined the long-term effects of regular physical activity and exercise habits on the course of PD.Methods:In this observational cohort study, we primarily used the multivariate linear mixed-effects models to analyze the interaction effects of their regular physical activity and moderate-to-vigorous exercise levels, measured through the Physical Activity Scale for the Elderly questionnaire, on the progression of clinical parameters, after adjusting for age, sex, levodopa-equivalent dose, and disease duration. We also calculated bootstrapping 95% confidence intervals (CIs), and conducted sensitivity analyses using the multiple imputation method and subgroup analyses using the propensity score matching to match for all baseline background factors.Results:237 early PD patients [median (interquartile range); age, 63.0 (56.0–70.0) years; Male, 69.2%; follow-up duration, 5.0 (4.0–6.0) years] were included. Regular physical activity and moderate-to-vigorous exercise levels at the baseline did not significantly affect the subsequent clinical progression of PD. However, average regular overall physical activity levels over time were significantly associated with slower deterioration of postural and gait stability [standardized fixed-effects coefficients of the interaction term (βinteraction) = -0.10 (95% CI, -0.14 to -0.06)], activities of daily living [βinteraction = 0.08 (95% CI, 0.04 to 0.12)], and processing speed [βinteraction = 0.05 (95% CI, 0.03 to 0.08)] in PD patients. Moderate-to-vigorous exercise levels were preferentially associated with slower decline of postural and gait stability [βinteraction = -0.09 (95% CI, -0.13 to -0.05)] and work-related activity levels were primarily associated with slower deterioration of processing speed [βinteraction = 0.07 (95% CI, 0.04 to 0.09)]. Multiple imputation and propensity score matching confirmed the robustness of our results.Conclusions:In the long-term, the maintenance of high regular physical activity levels and exercise habits was robustly associated with better clinical course of PD, with each type of physical activity having different effects.Trial Registration Information:Clinicaltrials.gov (NCT01176565). A link to trial registry page is https://clinicaltrials.gov/ct2/show/NCT01141023.Classification of Evidence:This study provides Class II evidence that sustained increase in overall regular physical activity levels in patients with early Parkinson disease was associated with slower decline of several clinical parameters.

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“…11,12,13,14,15 Extracellular-vesicle-associated tau and amyloid β42 have also been reported to correlate with cognition in PD. 16 Additionally, genetic variants have been linked to cognitive trajectory in PD, 17,18,19 with the most well-replicated effects on cognition seen for the APOE E4 allele 20,21,22,23 and PD-associated GBA variants. 17,24,25,26 Studies to date, however, have limitations that hamper translation of biomarkers of PD cognitive decline into clinical contexts.…”

Section: Introductionmentioning

confidence: 99%

Plasma MIA, CRP, and albumin predict cognitive decline in Parkinson’s Disease

Shen

Amari

Zack

et al. 2022

Preprint

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Objective: Using a multi-cohort, Discovery-Replication-Validation design, we sought new plasma biomarkers that predict which PD individuals will experience cognitive decline. Methods: In 108 Discovery Cohort PD individuals and 83 Replication Cohort PD individuals, we measured 940 plasma proteins on an aptamer-based platform. Using proteins associating with subsequent cognitive decline in both cohorts, we trained a logistic regression model to predict which PD patients showed fast (>=1 point drop/year on Montreal Cognitive Assessment (MoCA)) vs. slow (<1 point drop/year on MoCA) cognitive decline in the Discovery Cohort,testing it in the Replication Cohort. We developed alternate assays for the top three proteins and confirmed their ability to predict cognitive decline - defined by change in MoCA or development of incident Mild Cognitive Impairment (MCI) or dementia - in a Validation Cohort of 118 PD individuals. We investigated the top plasma biomarker for causal influence by Mendelian randomization. Results: A model with only three proteins (Melanoma Inhibitory Activity Protein (MIA), C-Reactive Protein (CRP), albumin) separated Fast vs. Slow cognitive decline subgroups with an AUC of 0.80 in the Validation Cohort. Validation Cohort PD individuals in the top quartile of risk for cognitive decline based on this model were 4.4 times more likely to develop incident MCI or dementia than those in the lowest quartile. Genotypes at MIA SNP rs2233154 associated with MIA levels and cognitive decline, providing evidence for MIA's causal influence. Conclusions: An easily-obtained plasma-based predictor identifies PD individuals at risk for cognitive decline. MIA may participate causally in development of cognitive decline.

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Association of Physical Activity and APOE Genotype With Longitudinal Cognitive Change in Early Parkinson Disease

Cited by 18 publications

References 50 publications

Lower Circulating Lymphocyte Count Predicts ApoEε4‐Related Cognitive Decline in Parkinson's Disease

Lower Circulating Lymphocyte Count Predicts ApoEε4‐Related Cognitive Decline in Parkinson's Disease

Long-term Effect of Regular Physical Activity and Exercise Habits in Patients With Early Parkinson Disease

Plasma MIA, CRP, and albumin predict cognitive decline in Parkinson’s Disease

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