Pathways linking late-life depression to persistent cognitive impairment and dementia

Meryl A Butters, Jeffrey B Young, Oscar Lopez, Howard J Aizenstein, Benoit H Mulsant, Charles F Reynolds 3rd, Steven T DeKosky, James T Becker, Meryl A Butters, Jeffrey B Young, Oscar Lopez, Howard J Aizenstein, Benoit H Mulsant, Charles F Reynolds 3rd, Steven T DeKosky, James T Becker

Abstract

There is a strong association between late-life depression, cognitive impairment, cerebrovascular disease, and poor cognitive outcomes, including progressive dementia, especially Alzheimer's disease. While neuroimaging evidence suggests that cerebrovascular disease plays a prominent role, it seems that depression alone may also confer substantial risk for developing Alzheimer's disease. The relationships between the prominent cerebrovascular changes, other structural abnormalities, specific forms of cognitive dysfunction, and increased risk for developing Alzheimer's disease among those with late-life depression have been difficult to reconcile. The varied findings suggest that there are likely multiple pathways to poor cognitive outcomes. We present a framework outlining multiple, non-mutually exclusive etiologic links between depression, cognitive impairment, and progressive decline, including dementia. Importantly, the model is both testable and falsifiable. Going forward, using models such as this to inform research should accelerate knowledge acquisition on the depression/dementia relationship that may be useful for dementia prevention, monitoring the impact of depression treatment on clinical status and course of illness.

Figures

Figure 1.. Proposed predominant mechanisms by which…
Figure 1.. Proposed predominant mechanisms by which depression increases risk for Alzheimer's dementia (AD). *The very recently postulated direct pathway leading from hypercortisolemia or elevated glucocorticoids to AD neuropathology is represented with a dashed line because, while evidence is growing, it has at present relatively less support than the other proposed pathways.
Figure 2.. Pathways linking depression to predominant…
Figure 2.. Pathways linking depression to predominant cognitive outcomes. MCI, mild cognitive impairment; AD, Alzheimer's disease; CVD, cerebrovascular disease.

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