This article is more than 5 years old. Information may no longer be current.

Depression may be early sign of dementia

Depressive symptoms in midlife, even if chronic or recurring, did not increase risk for dementia; however, symptoms later in life did increase risk.

“The histopathological hallmarks of [Alzheimer’s disease] begin decades prior to its clinical expression; a recent study estimated that amyloid- deposits form over a period of more than 2 decades,” Archana Singh-Manoux, PhD, of Centre for Research in Epidemiology and Population Health, Paris, and colleagues wrote. “The long preclinical phase of dementia has implications for the timing of interventions. There is growing consensus that interventions should target the earliest possible phase, perhaps the asymptomatic stage, to be effective. The other major implication, which has received less attention to date, is the analytic framework used to identify putative risk factors for dementia.”

To determine the trajectory of depression symptoms more than 28 years prior to dementia diagnosis and any associated risks, researchers followed 10,189 participants in the Whitehall II cohort study from 1985 to 2015. Depression symptoms were assessed nine times during the study period, using the General Health Questionnaire.

Cox regression analyses adjusted for sociodemographic covariates, health behaviors and chronic conditions indicated that participants with depressive symptoms in 1985 did not have a significantly increased risk for dementia (HR = 1.21; 95% CI, 0.95-1.54).

However, participants with depressive symptoms in 2003 had increased risk for dementia (HR = 1.72; 95% CI, 1.21-2.44).

Participants with chronic or recurring depressive symptoms early in the study period — with a mean follow-up of 22 years — did not have increased risk for depressive symptoms, while those with chronic or recurring depressive symptoms late in the study — with a mean follow-up of 11 years — did have increased risk for dementia (HR = 1.67; 95% CI, 1.11-2.49).

Analysis of retrospective depressive trajectories over 28 years indicated differences in depressive symptoms among participants with or without dementia became apparent 11 years before dementia diagnosis (P = .02). Further, differences in depressive symptoms became more than nine times larger at the year of diagnosis (P < .001).

“In sum, the approach by Singh-Manoux et al linking depression to a preclinical phase of [Alzheimer’s disease] opens up new opportunities for the field to conceptualize the relationship of depression and later dementia. It forces us to think more mechanistically, as we explore the underlying pathophysiological processes occurring in the decade prior to expression of cognitive symptoms, looking for common underpinnings of depression and dementia,” David Carl Steffens, MD, MHS, of University of Connecticut School of Medicine, wrote in an accompanying editorial. “Yet, while expanding our thinking about a neural basis of prodrome that might have a decade-long time horizon, we cannot abandon clinical notions of prodrome that may stretch over just a few years.” – by Amanda Oldt

Disclosure: The researchers report no relevant financial disclosures.