Long-term cumulative depressive symptom burden and risk of cognitive decline and dementia among very old women

Abstract

Depressive symptoms and cognitive impairment are separate clinical entities that are strongly interrelated (1), associated with poor quality of life (1,2), and both very common in old age. For example, as many as 25% of community-living older adults experience depressive symptoms (3) that continue to occur at high rates during late life (4). Additionally, the risk of cognitive impairment and dementia increases sharply after age 65 years, to more than 50% in the oldest old (aged 80 years and older) (5,6). There are several potential mechanisms by which depressive symptoms processes could influence cognitive impairment and dementia-specific neuropathology. Some of the most prominent mechanisms include vascular disease and amyloid-β plaque formation (7). In line with the “vascular depression” hypothesis, there is strong evidence that vascular disease is a major mechanism underlying depression and cognitive outcomes (8–10). Behavioral risk factors such as smoking and physical inactivity are suggested to play a role in the mechanisms linking vascular disease, depression, and cognitive outcomes (7). In addition, cross-sectional and longitudinal results have suggested amyloid-β plaques formation and neurofibrillary tangles, which are major hallmarks of Alzheimer’s disease, as possible mechanisms linking depression to dementia and cognitive decline (11–13). Importantly, rates of depression and depressive symptoms tend to fluctuate over time during late life (4,14), and the elderly adult may exhibit different trajectories of depressive symptoms compared with younger adults (15–18). Recent findings in a cohort of elderly women have shown approximately 20% had persistently high or increasing depressive symptoms over nearly 20 years (14). Given the fluctuating nature of depressive symptoms over time and their complex interrelationship and co-occurrence with cognitive outcomes and dementia; therefore characterizing the long-term course and chronicity of depressive symptoms may be more informative to our understanding of these relationships. Yet, and in addition to inconsistent findings in the literature, the vast majority of longitudinal studies of depressive symptoms and cognitive outcomes in older adults have examined single-time (usual baseline) measure of depressive symptoms (7,19–27). In this study, we sought to capture the cumulative burden and chronicity of depressive symptom trajectories over nearly 20 years of follow-up. And then to investigate its association with cognitive decline and the risk for development of cognitive impairment and dementia in elderly women who were followed into their 9th and 10th decades of life. A better understanding of the relationship of depressive symptoms and cognitive function and dementia over the long term is vital, as it may provide important clinical implications for early intervention and prevention strategies.