Department of Psychology, St. John's University, Jamaica, New York, USA.
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
J Gerontol A Biol Sci Med Sci. 2023 Feb 24;78(2):357-364. doi: 10.1093/gerona/glac111.
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.
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 nonfrail at baseline.
In the cross-sectional analysis (N = 1 754; mean age: 76 years), frailty was associated with greater WMH volume, lower FA, and greater MD. These associations remained consistent after excluding participants with a history of stroke or dementia. Among participants nonfrail 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.
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 nonfrail to frail status.
身体虚弱与痴呆和其他神经后遗症的风险增加有关。然而，虚弱和虚弱风险的神经生物学变化尚不清楚。我们研究了大脑白质结构与当前和未来虚弱的关系。
纳入了接受 3T 脑部 MRI 检查的动脉粥样硬化风险社区研究神经认知研究参与者。根据 Fried 标准对虚弱状况进行分类。使用白质高信号（WMH）体积和微观结构来定义脑白质完整性，使用扩散张量成像分数各向异性（FA）和平均弥散度（MD）来测量。多变量线性回归用于将基线虚弱与白质结构相关联；多变量逻辑回归用于将基线白质与基线非虚弱参与者的虚弱风险相关联。
在横断面分析中（N=1754；平均年龄：76 岁），虚弱与更大的 WMH 体积、更低的 FA 和更大的 MD 相关。这些关联在排除有中风或痴呆病史的参与者后仍然一致。在基线非虚弱且完成随访虚弱评估的参与者中（N=1379；6.6 年随访期），WMH 体积每增加一个标准差，与随访时虚弱的几率增加 1.46 倍相关。复合 FA 和 MD 测量与未来虚弱无关；然而，二次分析发现几个与虚弱风险相关的特定白质束特异性关联。
目前的研究表明 WMH 体积与当前和未来虚弱之间存在很强的关联。虽然虚弱个体的白质微观结构测量值发生了改变，但这些测量值通常与从不虚弱到虚弱状态的进展无关。
