Linking late life depression and Alzheimer's disease: mechanisms and resilience

This review summarizes recent literature linking Alzheimer's disease (AD) and late life depression (LLD). It describes shared neurobiological features associated with both conditions, as well as factors that may increase resilience to onset and severity of cognitive decline and AD. Finally, we pose a number of future research directions toward improving detection, management, and treatment of both conditions.

Epidemiological studies have consistently shown a significant relationship between LLD and AD, with support for depression as a prodromal feature of AD, a risk factor for AD, and observation of some shared risk factors underlying both disease processes. Three major neurobiological features shared by LLD and AD include neurodegeneration, disruption to cerebrovascular functioning, and increased levels of neuroinflammation. There are also potentially modifiable factors that can increase resilience to AD and LLD, including social support, physical and cognitive engagement, and cognitive reserve.

We propose that, in the context of depression, neurobiological events, such as neurodegeneration, cerebrovascular disease, and neuroinflammation result in a brain that is more vulnerable to the consequences of the pathophysiological features of AD, lowering the threshold for the onset of the behavioral presentation of AD (i.e., cognitive decline and dementia). We discuss factors that can increase resilience to AD and LLD, including social support, physical and cognitive engagement, and cognitive reserve. We conclude with a discussion of future research directions.