体力活动与基因型与早发性帕金森病纵向认知变化的关联。

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

机构信息

From the Department of Neurology (R.K.), Inha University Hospital, Incheon; Department of Neurology (S.P.), School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu; Department of Neurology (D.Y.), Kyung Hee University Hospital; Department of Neurology (J.-S.J.), Kangnam Sacred Heart Hospital, Hallym University College of Medicine; and Department of Neurology (B.J.), College of Medicine, Seoul National University Hospital, Korea.

出版信息

Neurology. 2021 May 11;96(19):e2429-e2437. doi: 10.1212/WNL.0000000000011852. Epub 2021 Mar 31.

DOI:10.1212/WNL.0000000000011852

PMID:33790041

Abstract

OBJECTIVE

To determine whether greater physical activity could modify the negative association of 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 Parkinson's 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 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% ε4 carriers) were included. The ε4 allele showed a steeper rate of cognitive decline than the non- ε4 allele (estimate -1.33, 95% confidence interval [CI] -2.12 to -0.47, = 0.002). However, there was a significant interaction between physical activity and ε4 such that higher physical activity was related to slower ε4-related cognitive decline (estimate 0.007, 95% CI 0.003-0.011, = 0.001). No significant interaction was found between physical activity and the ε4 allele regarding the change in striatal DAT activities.

CONCLUSION

Increased physical activity attenuated 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 ε4-related early cognitive decline in patients with PD.

摘要

目的

确定更多的身体活动是否可以改变 ε4 与早期帕金森病（PD）纵向认知变化之间的负相关关系，并揭示身体活动带来益处的特定疾病机制。

方法

我们使用帕金森病进展标志物倡议队列的数据。由于身体活动是通过老年人体适能量表来衡量的，并且是在入组后 2 年开始测量，因此这项纵向分析基于入组后 2、3 和 4 年进行的评估。认知功能每年使用蒙特利尔认知评估（MoCA）进行测量。多巴胺转运蛋白（DAT）成像在第 2 年和第 4 年进行。我们评估了身体活动和 ε4 等位基因与 MoCA 评分和纹状体 DAT 活性纵向变化之间的交互关联。

结果

共纳入 173 例早期 PD 患者（年龄 63.3±10.0 岁，27%为 ε4 携带者）。ε4 等位基因的认知下降速度比非 ε4 等位基因更快（估计值-1.33，95%置信区间[CI] -2.12 至-0.47， =0.002）。然而，身体活动和 ε4 之间存在显著的交互作用，表明更高的身体活动与更慢的 ε4 相关认知下降有关（估计值 0.007，95%CI 0.003-0.011， =0.001）。在纹状体 DAT 活性的变化方面，未发现身体活动和 ε4 等位基因之间存在显著的相互作用。