AbstractBackgroundUnderstanding the pathological bases underlying the heterogeneity of motor decline in old age may lead to targeted treatments. We examined whether different brain pathologies are related to declining grip strength and gait function.MethodsWe examined postmortem brains of older adults who underwent annual motor testing. Postmortem exam measured 6 neurodegenerative and 5 cerebrovascular disease (CVD) pathologies. Grip strength was measured twice bilaterally using a hand-held dynamometer, and gait function was a composite measure based on time and steps taken to walk 8 ft and perform a 360° turn twice.ResultsIn separate linear mixed-effects models including all autopsied adults (N = 1 217), neurodegenerative pathologies including tau tangles, TDP-43, and nigral neuronal loss were associated with declining grip strength, but not CVD pathologies. In contrast, although both CVD and neurodegenerative pathologies were associated with declining gait function, CVD pathologies accounted for 75% of the variance of declining rate of gait function explained by brain pathologies and neurodegenerative pathologies accounted for 25%. These findings were unchanged in adults (n = 970) without a history of stroke. Restricting analyses to only adults without dementia (n = 661), CVD pathologies continued to account for the majority of the variance of declining gait. However, we failed to detect in this subgroup the variance of declining grip strength explained by neurodegenerative or CVD pathologies.ConclusionDifferent pathologies accumulating in aging brains may contribute to the phenotypic heterogeneity of motor decline. Larger studies are needed in older adults without dementia to assess differences in the motor consequences of varied brain pathologies.

中文翻译：

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神经退行性和脑血管病变与老年人握力和步态下降存在不同的相关性

摘要背景了解老年运动衰退异质性的病理基础可能会导致有针对性的治疗。我们研究了不同的大脑病理是否与握力和步态功能下降有关。方法我们检查了每年接受运动测试的老年人的死后大脑。尸检测量了 6 种神经退行性疾病和 5 种脑血管疾病 (CVD) 病理。使用手持式测力计对双侧握力进行两次测量，步态功能是基于步行 8 英尺和两次 360° 转身的时间和步数的综合测量。结果在包括所有尸检成人的单独线性混合效应模型中（N = 1 217），神经退行性病理学（包括 tau 缠结、TDP-43 和黑质神经元损失）与握力下降相关，但与 CVD 病理学无关。相比之下，尽管CVD和神经退行性病理学都与步态功能下降相关，但CVD病理学占脑病理学解释的步态功能下降率方差的75%，而神经退行性病理学占25%。这些发现在没有中风病史的成年人（n = 970）中没有变化。将分析仅限于没有痴呆症的成年人 (n = 661)，CVD 病理学仍然是步态下降变异的大部分原因。然而，我们未能在该亚组中检测到由神经退行性或CVD病理解释的握力下降的方差。结论衰老大脑中积累的不同病理可能导致运动衰退的表型异质性。需要对没有痴呆症的老年人进行更大规模的研究，以评估不同大脑病变对运动后果的差异。