- •What is the primary question addressed by this study?We investigated whether recent and/or remote depression was associated with increased risk of Alzheimer's Dementia (AD) and whether this risk differed between men and women.
- •What is the main finding of this study?Recent depression was independently associated with increased risk of incident AD while remote depression was not. Recent depression was predictive of AD development in females, but not in males, while sex did not moderate recent depression-associated risk of developing AD.
- •What is the meaning of the finding?Depression may be part of the behavioral prodrome of AD rather than a true risk factor, but further research should determine if findings extend to other populations and whether variable distribution of risk factors accounts for the difference observed between men and women.
Our understanding of why older adults with depression are at increased risk of Alzheimer's disease (AD) remains incomplete. Most adults living with AD are women, and women have a near twofold lifetime risk of depression. We examined the risk of depression upon incident AD, and how sex influences this risk.
Using the National Alzheimer's Coordinating Center database, older adults (age 50+) with normal cognition, who visited memory clinics across the United States between September 2005 and December 2019, were followed until first diagnosis of AD or loss to follow up. Multivariable survival analyses were performed to determine if recent and/or remote depression were independent risk factors for AD, if this depression-related risk exists for each sex or was moderated by sex.
Six hundred and fifty-two of 10,739 enrolled participants developed AD over a median follow-up of 55.3 months. Recent depression (active within the last 2 years) was independently associated with increased risk of AD (hazard ratio [HR] = 2.0; 95%CI, 1.5–2.6) while a remote history of depression was not (HR = 1.0; 95%CI, 0.7–1.5). After stratification by sex, recent depression was an independent predictor in females (HR = 2.3; 95%CI, 1.7–3.1) but not in males (HR = 1.4; 95%CI, 0.8–2.6). No interaction between recent depression and sex was observed.
Only a recent history of depression was associated with higher risk of AD. This association was significant among women only, but was not moderated by sex. Future analyses should determine if these findings extend to other populations and may be explained by variable distribution of neurobiological or other modifiable risk factors between the sexes.
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Published online: January 06, 2021
Accepted: December 24, 2020
Received in revised form: December 11, 2020
Received: July 16, 2020
© 2021 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.