Resilience to mid-to-late-life depression as a risk factor for Alzheimer's disease: Physiological factors and the role of neuroimaging.

Depression and Alzheimer's Disease (AD) are both diagnosed in women twice as often as in men. Moreover, a history of untreated depression confers a 2-to-5-fold increase in the risk of developing dementia. Finally, biological factors such as sex differences in immune response increase rates of depressive pathology among women. Importantly, the prevalence of mid-to-late-life depression (MLD) worldwide and its misdiagnosis due to clinical overlap with AD hinder accurate assessment and timely treatment of depression among older adults. Correct diagnosis of depression and AD using neuroimaging will enable early adoption of appropriate management, which will improve cognitive resilience. In the context of neural resilience in late-life depression, this review discusses the involvement of sex-related risk factors such as differences in immune response, and the importance of understanding the mid-life neurological signature of depression. We focus on the role of diffusion-weighted magnetic resonance imaging (MRI), which is also specifically linked to the presence of neuroinflammation in depression and the ability to distinguish it from AD despite cognitive overlaps in clinical manifestation. This review highlights the importance of sex differences in promoting resilience against MLD and AD-related declines, and supports neuroimaging as a feasible approach to advance our understanding of the role of neuroinflammation in both depression and Alzheimer's disease as a sex-dependent phenomenon.