Amy L. Byers, PhD, MPH and Kristine Yaffe, MDAuthor informationCopyright and License informationDisclaimerThe publisher’s final edited version of this article is available at Nat Rev NeurolSee other articles in PMC that cite the published article.Go to:
Depression is highly common throughout the life course and dementia is common in late life. The literature suggests an association between depression and dementia, and growing evidence implies that timing of depression may be important to defining the nature of the association. In particular, earlier-life depression or depressive symptoms consistently have been shown to be associated with a 2-fold or greater increase in risk of dementia. In contrast, studies of late-life depression have been more conflicting but the majority support an association; yet, the nature of this association is unclear (e.g., if depression is a prodrome or consequence or risk factor for dementia). The likely biological mechanisms linking depression to dementia include vascular disease, alterations in glucocorticoid steroids and hippocampal atrophy, increased deposition of β-amyloid plaques, inflammatory changes, and deficits of nerve growth factors. Treatment strategies for depression might intervene on these pathways and in turn may alter risk for dementia. Given the projected increase of dementia in the coming decades, it is critically important that we understand whether treatment for depression alone or combined with other regimens improves cognition. In this review, we summarize and analyze current evidence for late-life and earlier-life depression and their relationship to dementia, discuss the primary underlying mechanisms and implications for treatment.Go to:
Depression is common across the lifespan with 1 in 5 individuals experiencing a depressive episode during their lifetime.1 Dementia is also very common in late life with the risk doubling every five years after age 65,2 increasing up to 50% among those ≥ 90 years.3,4 There are several ways in which depression and dementia may be related. First, depressive symptoms often occur among patients with dementia. Second, depression may be a reaction to early cognitive deficits. Third, depression can impair cognitive function leading to a “pseudodementia” presentation. Finally, depression may be a risk factor or early symptom of dementia.
Given the current and projected growth of the older segment of the population,5 a better understanding of the link between depression and risk of dementia is important, especially for possible treatment and prevention. However, several challenges to this understanding exist. Major depressive disorder is common among patients with dementia, occurring in up to 20% of patients with Alzheimer’s disease (AD) and up to 50% of patients with vascular dementia (VaD)6–8 and, thus, disentangling which came first can be difficult. In addition, although depression and dementia are considered distinct clinical entities, they share some common features, including impairment in attention and working memory, changes in sleep patterns and reduction of social and occupational function.9 In fact, the concept of “pseudodementia” highlights how the distinction between depression and dementia may be blurry.10,11 Thus, the inter-relationship of depression and dementia is complex and when co-occurring the two entities may be indistinguishable, complicating the ability to determine the exact relationship of depression to dementia.
In this article, we review current knowledge on late-life and earlier-life depression and their associated risk of developing dementia, and focus on mechanisms that may underlie the link between depression and dementia. We primarily focus on the evidence suggesting that depression is a prodromal symptom or risk factor for dementia and discuss potential implications for screening and treatment.