Depression is associated with markers of accelerated aging, but it is unclear how this relationship changes across the lifespan. We examined whether a brain-based measure of accelerated aging differed between depressed and never-depressed subjects across the adult lifespan and whether it was related to cognitive performance and disability. We applied a machine-learning approach that estimated brain age from structural MRI data in two depressed cohorts, respectively 170 midlife adults and 154 older adults enrolled in studies with common entry criteria. Both cohorts completed broad cognitive batteries and the older subgroup completed a disability assessment. The machine-learning model estimated brain age from MRI data, which was compared to chronological age to determine the brain–age gap (BAG; estimated age-chronological age). BAG did not differ between midlife depressed and nondepressed adults. Older depressed adults exhibited significantly higher BAG than nondepressed elders (Wald χ² = 8.84, p = 0.0029), indicating a higher estimated brain age than chronological age. BAG was not associated with midlife cognitive performance. In the older cohort, higher BAG was associated with poorer episodic memory performance (Wald χ² = 4.10, p = 0.0430) and, in the older depressed group alone, slower processing speed (Wald χ² = 4.43, p = 0.0354). We also observed a statistical interaction where greater depressive symptom severity in context of higher BAG was associated with poorer executive function (Wald χ² = 5.89, p = 0.0152) and working memory performance (Wald χ² = 4.47, p = 0.0346). Increased BAG was associated with greater disability (Wald χ² = 6.00, p = 0.0143). Unlike midlife depression, geriatric depression exhibits accelerated brain aging, which in turn is associated with cognitive and functional deficits.

抑郁症与加速衰老的标志有关，但尚不清楚这种关系在整个生命周期中如何变化。我们检查了基于大脑的加速衰老测量在成年期间抑郁和从未抑郁的受试者之间是否存在差异，以及它是否与认知表现和残疾有关。我们应用了一种机器学习方法，根据两个抑郁队列的结构 MRI 数据估计大脑年龄，分别有 170 名中年成年人和 154 名老年人参加了具有共同进入标准的研究。两个队列都完成了广泛的认知电池，年龄较大的亚组完成了残疾评估。机器学习模型根据 MRI 数据估计大脑年龄，将其与实足年龄进行比较以确定大脑-年龄差距（BAG；估计的年龄-实足年龄）。BAG 在中年抑郁和非抑郁成人之间没有差异。老年抑郁成人的 BAG 显着高于未抑郁的老年人（Waldχ ²  = 8.84, p  = 0.0029)，表明估计的脑年龄高于实足年龄。BAG 与中年认知能力无关。在年龄较大的队列中，较高的 BAG 与较差的情景记忆表现（Wald χ ²  = 4.10，p  = 0.0430）有关，并且仅在老年抑郁组中，处理速度较慢（Wald χ ²  = 4.43，p  = 0.0354）。我们还观察到一种统计相互作用，其中在较高 BAG 的背景下，较大的抑郁症状严重程度与较差的执行功能（Wald χ ²  = 5.89，p  = 0.0152）和工作记忆表现（Wald χ²  = 4.47，p  = 0.0346）。增加的 BAG 与更大的残疾相关（Wald χ ²  = 6.00，p  = 0.0143）。与中年抑郁症不同，老年抑郁症表现出加速的大脑衰老，这反过来又与认知和功能缺陷有关。