Brain-age in midlife is associated with accelerated biological aging and cognitive decline in a longitudinal birth cohort
Brain-age in midlife is associated with accelerated biological aging and cognitive decline in a longitudinal birth cohort
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DOI：
10.1038/s41380-019-0626-7
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发表时间：
2021-08-01
影响因子：
11
通讯作者：
Hariri, Ahmad R.
中科院分区：
文献类型：
--
作者：
Elliott, Maxwell L.;Belsky, Daniel W.;Hariri, Ahmad R.
一个人的大脑年龄是实际年龄和大脑成像数据的机器学习模型预测的年龄之间的差异。BrainAGE已被提议作为与年龄相关的大脑退化的生物标志物。大脑老化与阿尔茨海默氏症、痴呆症和死亡率有关。然而，这些发现主要是基于横截面的关联，这可能会混淆年龄差异和队列差异。为了阐明brainAGE作为大脑加速老化的生物标志物的有效性，需要对同一年出生但brainAGE不同的大型队列进行研究。在达尼丁研究中，一个具有人口代表性的1972-73年出生队列，我们测量了45岁时的脑年龄，以及从儿童到中年的纵向数据中的生物老化和认知下降的速度（N = 869）。在这个队列中，所有的实际年龄45岁，脑年龄测量可靠（ICC = 0.81），范围从24至72岁。那些中年脑AGEs年龄较大的人在成年和儿童时期的认知功能往往较差，并且在3岁时大脑健康受损。此外，那些大脑AGEs年龄较大的人的生物衰老速度加快，面部外观更老，从童年到中年认知能力下降的早期迹象。这些发现有助于验证brainAGE作为中年干预研究的潜在替代生物标志物，这些研究旨在衡量中年痴呆症的预防工作。然而，研究结果也警告说，brainAGE分数只代表与年龄相关的大脑退化的假设，因为它们也可能指示自童年以来存在的中枢神经系统变异。
An individual's brainAGE is the difference between chronological age and age predicted from machine-learning models of brain-imaging data. BrainAGE has been proposed as a biomarker of age-related deterioration of the brain. Having an older brainAGE has been linked to Alzheimer's, dementia, and mortality. However, these findings are largely based on cross-sectional associations which can confuse age differences with cohort differences. To illuminate the validity of brainAGE as a biomarker of accelerated brain aging, a study is needed of a large cohort all born in the same year who nevertheless vary on brainAGE. In the Dunedin Study, a population-representative 1972-73 birth cohort, we measured brainAGE at age 45 years, as well as the pace of biological aging and cognitive decline in longitudinal data from childhood to midlife (N = 869). In this cohort, all chronological age 45 years, brainAGE was measured reliably (ICC = 0.81) and ranged from 24 to 72 years. Those with older midlife brainAGEs tended to have poorer cognitive function in both adulthood and childhood, as well as impaired brain health at age 3. Furthermore, those with older brainAGEs had an accelerated pace of biological aging, older facial appearance, and early signs of cognitive decline from childhood to midlife. These findings help to validate brainAGE as a potential surrogate biomarker for midlife intervention studies that seek to measure dementia-prevention efforts in midlife. However, the findings also caution against the assumption that brainAGE scores represent only age-related deterioration of the brain as they may also index central nervous system variation present since childhood.