Background Physical frailty is associated with increased risk for dementia and other neurologic sequelae. However, the neurobiological changes underlying frailty and frailty risk remain unknown. We examined the association of cerebral white matter structure with current and future frailty. Methods Atherosclerosis Risk in Communities Study Neurocognitive Study participants who underwent 3T brain MRI were included. Frailty status was classified according to the Fried criteria. Cerebral white matter integrity was defined using white matter hyperintensity (WMH) volume and microstructure, measured using diffusion tensor imaging fractional anisotropy (FA) and mean diffusivity (MD). Multivariable linear regression was used to relate baseline frailty to white matter structure; multivariable logistic regression was used to relate baseline white matter to frailty risk among participants non-frail at baseline. Results In the cross-sectional analysis (N=1,754; mean age: 76) frailty was associated with greater WMH volume, lower FA, and greater MD. These associations remained consistent after excluding participants with history of stroke or dementia. Among participants non-frail at baseline who completed follow-up frailty assessment (N=1,379; 6.6-year follow-up period), each standard deviation increase in WMH volume was associated with 1.46 higher odds of frailty at follow-up. Composite FA and MD measures were not associated with future frailty; however, secondary analyses found several significant white matter tract-specific associations with frailty risk. Conclusions The current study demonstrates a robust association of WMH volume with current and future frailty. Although measures of white matter microstructure were altered in frail individuals, these measures were not generally associated with progression from non-frail to frail status.

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身体虚弱和脑白质异常：ARIC 研究


背景 身体虚弱与痴呆和其他神经系统后遗症的风险增加有关。然而，衰弱和衰弱风险背后的神经生物学变化仍然未知。我们研究了大脑白质结构与当前和未来虚弱的关系。方法 社区研究中的动脉粥样硬化风险神经认知研究的参与者均接受了 3T 脑部 MRI 检查。根据 Fried 标准对虚弱状态进行分类。脑白质完整性通过白质高信号（WMH）体积和微观结构来定义，并使用扩散张量成像分数各向异性（FA）和平均扩散率（MD）进行测量。使用多变量线性回归将基线虚弱与白质结构联系起来；使用多变量逻辑回归将基线白质与基线非衰弱参与者的衰弱风险相关联。结果 在横断面分析中（N=1,754；平均年龄：76），虚弱与 WMH 体积增大、FA 降低和 MD 增大相关。在排除有中风或痴呆病史的参与者后，这些关联仍然保持一致。在完成随访虚弱评估的基线时不虚弱的参与者中（N = 1,379；6.6 年随访期），WMH 量的标准差每增加一次，随访时虚弱的几率就会增加 1.46。 FA 和 MD 综合测量与未来的虚弱程度无关；然而，二次分析发现，白质束特异性与衰弱风险存在一些显着的关联。结论 当前的研究表明 WMH 体积与当前和未来的虚弱程度之间存在密切关联。 尽管体弱个体的白质微结构测量发生了改变，但这些测量通常与从非体弱到体弱状态的进展无关。