Supplementary Material for: The temporal relation of physical function with cognition and the influence of brain health in the oldest-old

Introduction Physical function and cognition seem to be interrelated, especially in the oldest-old. However, the temporal order in which they are related and the role of brain health remain uncertain. Methods We included 338 participants (mean age 93.1 years) from two longitudinal cohorts: The UCI 90+ Study and EMIF-AD 90+ Study. We tested the association between physical function (Short Physical Performance Battery, gait speed and handgrip strength) at baseline with cognitive decline (MMSE, memory tests, Animal fluency, Trail Making Test (TMT) A and Digit Span Backward), and the association between cognition at baseline with physical decline (mean follow-up 3.3 years). We also tested whether measures for brain health (hippocampal, white matter lesion and gray matter volume) were related to physical function and cognition, and whether brain health was a common driver of the association between physical function and cognition by adding it as confounder (if applicable). Results Better performance on all physical tests at baseline was associated with less decline on MMSE, memory and TMT A. Conversely, fewer associations were significant but better scores on memory, TMT A and Digit Span Backward were associated with less physical decline. When adding measures for brain health as confounder, all associations stayed significant except for memory with gait speed decline. Discussion In the oldest-old, physical function and cognition are strongly related, independently of brain health. Also, the association between physical function and cognitive decline is more pronounced than the other way around, suggesting a potential for slowing cognitive decline by optimizing physical function.

引言
躯体功能与认知似乎存在密切关联，这一现象在极高龄人群中尤为显著。然而，二者相关联的时间顺序以及脑健康所发挥的作用仍未明确。
方法
本研究纳入来自两项纵向队列的338名参与者，其平均年龄为93.1岁，分别来自UCI 90+研究与EMIF-AD 90+研究。我们检验了基线躯体功能（简易体能状况量表（Short Physical Performance Battery）、步速与握力）与认知衰退（简易精神状态检查表（MMSE）、记忆测验、动物流畅性测验、连线测验A（Trail Making Test A, TMT A）以及数字倒背测验）之间的关联，同时还检验了基线认知水平与躯体衰退之间的关联，本研究的平均随访时长为3.3年。此外，我们还评估了脑健康指标（海马体积、白质病变与灰质体积）与躯体功能及认知的相关性，并通过将脑健康作为混杂因素（若适用），探究脑健康是否为躯体功能与认知之间关联的共同驱动因子。
结果
基线时各项躯体功能测验表现更佳，与MMSE、记忆测验及连线测验A的衰退程度更低显著相关。反之，虽具有统计学显著性的关联数量较少，但基线时记忆、连线测验A及数字倒背测验得分更高，与躯体衰退程度更低相关。当将脑健康指标作为混杂因素纳入分析后，除记忆与步速衰退之间的关联外，其余所有关联均保持统计学显著性。
讨论
在极高龄人群中，躯体功能与认知存在强关联，且该关联独立于脑健康水平。此外，躯体功能与认知衰退之间的关联要强于反向的关联，这提示通过优化躯体功能，或可实现认知衰退的延缓。