Hypothesis Busted: Depression Not a Risk Factor for Dementia

Megan Brooks

May 17, 2017

There's no support for the hypothesis that depressive symptoms increase dementia risk, new research suggests.

In a 28-year follow-up study, depressive symptoms in later life were significantly associated with development of dementia. However, depressive symptoms in midlife, even when chronic or recurring, were not significantly associated with development of dementia.

"If you measure depressive symptoms close to dementia diagnosis, then there is an association, but if you're looking at the entire trajectory of depressive symptoms, there isn't really an association," first author Archana Singh-Manoux, PhD, from Hôpital Paul Brousse, Villejuif Cedex, France, said a JAMA author interview.

"If depressive symptoms were really a risk factor for dementia, if they caused dementia, then we'd see associations throughout the follow-up. It wouldn't just be confined to the end of the follow-up," said Dr Singh-Manoux. Therefore, "what we can say with confidence is that it doesn't look as if depressive symptoms are a cause of dementia."

The study was published online May 17 in JAMA Psychiatry.

Up for Debate

Depressive symptoms are common in patients with dementia, but whether in adulthood they raise the risk for dementia remains the subject of hot debate, the authors note.

To investigate, they used the Whitehall II cohort study to characterize trajectories of depressive symptoms over a 28-year period before dementia diagnosis to see whether depressive symptoms carry risk for dementia. Their analysis included 10,189 individuals (67% male) who were 35 to 55 years old when they entered the study in 1985.

Depressive symptoms were assessed on nine occasions between 1985 and 2012 using the General Health Questionnaire. Incident cases of dementia accrued mainly between 1995 and 2015, with roughly 73% of cases recorded during the last 5 years of follow-up.

In Cox regression analysis adjusted for relevant cofactors, individuals with depressive symptoms in 1985 did not have a significantly increased risk for dementia (hazard ratio [HR], 1.21; 95% confidence interval [CI], 0.95 - 1.54). However, those with depressive symptoms later in life (in 2003) did have an increased risk for dementia (HR, 1.72; 95% CI, 1.21 - 2.44).

In addition, individuals with chronic/recurring depressive symptoms in the early study period (around midlife) did not have excess risk for dementia (HR, 1.02; 95% CI, 0.72 - 1.44), whereas those with chronic/recurring symptoms in later life did have higher risk for dementia (HR, 1.67; 95% CI, 1.11 - 2.49).

These findings "do not support the hypothesis that depressive symptoms increase the risk for dementia," the authors conclude.

"There are two ways of looking at our results," said Dr Singh-Manoux. Namely, that depressive symptoms represent a prodrome of dementia, or that the two conditions share common causes.

Even if depressive symptoms only emerge in the preclinical phase of dementia, the "really interesting question is whether treating depressive symptoms would delay the clinical manifestation of dementia," she added.

Important Line of Research

In a linked editorial, David Carl Steffens, MD, of the Department of Psychiatry, University of Connecticut School of Medicine in Farmington, said it's "well established and hardly surprising" that there is a high incidence of depression among patients with dementia.

"What is less intuitive is an established literature linking depression with subsequent cognitive decline and development of dementia. The conclusions drawn by Singh-Manoux and colleagues contribute to an important line of research for the field of geriatric mood and cognitive disorders," said Dr Steffens.

This study linking depression to a preclinical phase of dementia "opens up new opportunities for the field to conceptualize the relationship of depression and later dementia," he added.

"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," Dr Steffens writes.

"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," he cautioned.

"Going forward, studies might incorporate both constructs, thus demanding more precision in our terminology. We should embrace research that examines both a 'neurally based prodrome' and a 'clinically based prodrome.' "

The study had no commercial funding. The authors and Dr Steffens have disclosed no relevant financial relationships.

JAMA Psychiatry. Published online May 17, 2017. Full text, Editorial

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