The development of preventive strategies in early-stage Alzheimer's disease (AD) requires measures that can predict future brain atrophy. Gray matter network measures are related to amyloid burden in cognitively normal older individuals and predict clinical progression in preclinical AD. Here, we show that within individuals with preclinical AD, gray matter network measures predict hippocampal atrophy rates, whereas other AD biomarkers (total gray matter volume, cerebrospinal fluid total tau, and Mini-Mental State Examination) do not. Furthermore, in brain areas where amyloid is known to start aggregating (i.e. anterior cingulate and precuneus), disrupted network measures predict faster atrophy in other distant areas, mostly involving temporal regions, which are associated with AD. When repeating analyses in age-matched, cognitively unimpaired individuals without amyloid or tau pathology, we did not find any associations between network measures and hippocampal atrophy, suggesting that the associations are specific for preclinical AD. Our findings suggest that disrupted gray matter networks may indicate a treatment opportunity in preclinical AD individuals but before the onset of irreversible atrophy and cognitive impairment.

中文翻译：

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单受试者灰质网络预测临床前阿尔茨海默病的未来皮质萎缩

早期阿尔茨海默病 (AD) 预防策略的制定需要能够预测未来脑萎缩的措施。灰质网络测量与认知正常老年人的淀粉样蛋白负担有关，并预测临床前 AD 的临床进展。在这里，我们表明，在患有临床前 AD 的个体中，灰质网络测量可以预测海马萎缩率，而其他 AD 生物标志物（总灰质体积、脑脊液总 tau 蛋白和简易精神状态检查）则不能。此外，在已知淀粉样蛋白开始聚集的大脑区域（即前扣带回和楔前叶），被破坏的网络测量预测其他远处区域的萎缩速度更快，主要涉及与 AD 相关的颞区。在年龄匹配中重复分析时，在没有淀粉样蛋白或 tau 蛋白病理的认知未受损个体中，我们没有发现网络测量和海马萎缩之间有任何关联，这表明这些关联是临床前 AD 特有的。我们的研究结果表明，灰质网络中断可能表明临床前 AD 个体有治疗机会，但在不可逆萎缩和认知障碍开始之前。