Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.
Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA.
J Gerontol A Biol Sci Med Sci. 2023 Mar 1;78(3):504-513. doi: 10.1093/gerona/glac128.
Understanding 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.
We 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.
In 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.
Different 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.
了解导致老年运动能力下降异质性的病理基础可能会导致针对性治疗。我们研究了不同的脑部病变是否与握力和步态功能下降有关。
我们研究了接受年度运动测试的老年人大脑的尸检结果。尸检检查测量了 6 种神经退行性疾病和 5 种脑血管疾病（CVD）病变。使用手持测力计双侧测量握力，步态功能是基于行走 8 英尺和两次完成 360°转弯所需的时间和步数的综合测量。
在包括所有尸检成年人（N = 1217）的单独线性混合效应模型中，包括tau 缠结、TDP-43 和黑质神经元丧失在内的神经退行性病变与握力下降有关，但与 CVD 病变无关。相比之下，尽管 CVD 和神经退行性病变都与步态功能下降有关，但 CVD 病变占大脑病变和神经退行性病变解释步态功能下降率的 75%，而神经退行性病变占 25%。在没有中风史的成年人（n = 970）中，这些发现没有改变。在没有痴呆症的成年人（n = 661）中进行分析限制，CVD 病变仍然占步态下降的大部分变异。然而，在该亚组中，我们未能检测到神经退行性或 CVD 病变解释的握力下降的变异。
在衰老大脑中积累的不同病变可能导致运动能力下降的表型异质性。需要在没有痴呆症的老年人中进行更大的研究，以评估不同脑病变对运动后果的差异。
