The "structural disconnection" hypothesis of cognitive aging suggests that deterioration of white matter (WM), especially myelin, results in cognitive decline, yet in vivo evidence is inconclusive. We examined age differences in WM microstructure using Myelin Water Imaging and Diffusion Tensor Imaging in 141 healthy participants (age 20–79). We used the Virginia Cognitive Aging Project and the NIH Toolbox® to generate composites for memory, processing speed, and executive function. Voxel-wise analyses showed that lower myelin water fraction (MWF), predominantly in prefrontal WM, genu of the corpus callosum, and posterior limb of the internal capsule was associated with reduced memory performance after controlling for age, sex, and education. In structural equation modeling, MWF in the prefrontal white matter and genu of the corpus callosum significantly mediated the effect of age on memory, whereas fractional anisotropy (FA) did not. Our findings support the disconnection hypothesis, showing that myelin decline contributes to age-related memory loss and opens avenues for interventions targeting myelin health.

中文翻译：

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测试结构断开假说：髓磷脂含量与健康衰老中的记忆相关


认知衰老的“结构性脱节”假说表明，白质（WM）尤其是髓磷脂的退化会导致认知能力下降，但体内证据尚无定论。我们使用髓磷脂水成像和扩散张量成像检查了 141 名健康参与者（20-79 岁）的 WM 微观结构的年龄差异。我们使用弗吉尼亚认知老化项目和 NIH Toolbox® 来生成记忆、处理速度和执行功能的复合材料。体素分析表明，在控制年龄、性别和教育程度后，较低的髓磷脂水分数（MWF）（主要存在于前额叶 WM、胼胝体膝部和内囊后肢）与记忆能力下降相关。在结构方程模型中，前额叶白质和胼胝体膝部的 MWF 显着介导了年龄对记忆的影响，而分数各向异性 (FA) 则没有。我们的研究结果支持断开假说，表明髓磷脂下降会导致与年龄相关的记忆丧失，并为针对髓磷脂健康的干预措施开辟了途径。