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

载脂蛋白E 蒙特利尔认知评估 认知 多巴胺转运体 内科学 置信区间 医学 心理学 体力活动 老年学 疾病 纵向研究 认知障碍 物理疗法 多巴胺 精神科 病理 多巴胺能
作者
Ryul Kim,Sang Min Park,Dallah Yoo,Jin‐Sun Jun,Beomseok Jeon
出处
期刊:Neurology [Lippincott Williams & Wilkins]
卷期号:96 (19) 被引量:17
标识
DOI:10.1212/wnl.0000000000011852
摘要

Objective

To determine whether greater physical activity could modify the negative association of APOE ε4 with longitudinal cognitive changes in early Parkinson disease (PD) and to uncover the disease-specific mechanism for explaining such benefits of physical activity.

Methods

We used data from the Parkinson9s Progression Markers Initiative cohort. Because self-reported physical activity, measured by the Physical Activity Scale of the Elderly, was initiated at 2 years after enrollment, this longitudinal analysis was based on assessments performed at years 2, 3, and 4. Cognitive function was measured annually with the Montreal Cognitive Assessment (MoCA). Dopamine transporter (DAT) imaging was performed at years 2 and 4. We assessed the interactive associations between physical activity and the APOE ε4 allele on the longitudinal changes in MoCA scores and striatal DAT activities.

Results

A total of 173 patients with early PD (age 63.3 ± 10.0 years, 27% APOE ε4 carriers) were included. The APOE ε4 allele showed a steeper rate of cognitive decline than the non–APOE ε4 allele (estimate −1.33, 95% confidence interval [CI] −2.12 to −0.47, p = 0.002). However, there was a significant interaction between physical activity and APOE ε4 such that higher physical activity was related to slower APOE ε4-related cognitive decline (estimate 0.007, 95% CI 0.003–0.011, p = 0.001). No significant interaction was found between physical activity and the APOE ε4 allele regarding the change in striatal DAT activities.

Conclusion

Increased physical activity attenuated APOE ε4-related vulnerability to early cognitive decline in patients with PD. This protective effect did not appear to be mediated by striatal dopaminergic function.

Trial Registration Information

ClinicalTrials.gov Identifier: NCT01141023.

Classification of Evidence

This study provides Class II evidence that increased physical activity was associated with decreased APOE ε4-related early cognitive decline in patients with PD.
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