Depression and risk of developing dementia

Abstract

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.

Hospital-treated mental and behavioral disorders and risk of Alzheimer's disease: A nationwide nested case-control study

“…Further, the association between depression and AD/dementia may be dependent on the age when depression was diagnosed, or severity or episodic nature of the disease (3,6), but this was beyond the scope of our study.…”

“…Most of the previous studies have assessed the association between depression and AD, with inconsistent findings (6). A meta-analysis (7) concluded that depression is a risk factor rather than a prodromal symptom of AD as the width of time window between exposure and outcome was positively related to the risk of developing AD.…”

“…Thus, in these studies the mental and behavioral disorders can actually have been prodromal symptoms or consequences of AD. (6) Due to the long latency period of AD/dementia, having an adequate time window between exposure and outcome (i.e., allowing a large enough time gap between them) is crucial. Otherwise the identified "risk factors", may actually be manifestations of the outcome.…”

The Age-by-Disease Interaction Hypothesis of Late-Life Depression

“…30 These hypotheses are not mutually exclusive and data exists to support aspects of all three. Moreover, all three hypotheses are consistent with a neural network model of depression described above, as well as the idea of multi-process biological vulnerability, which we will elaborate on later in this article.…”

“…The dementia prodrome hypothesis 30 is based on the observation that older adults with depressive symptoms have a much greater risk of developing dementia upon follow-up compared to those without depressive symptoms. 44-45 Multiple, non-mutually exclusive etiological causes have been proposed to explain this association between depression and dementia 46 and, generally, they all propose that the processes that play an etiological role in disrupting the neural circuitry underlying cognitive function and thus lead to dementia, also disrupt the neural network underlying mood.…”