Highlights
- •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.
ABSTRACT
Objective
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.
Methods
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.
Results
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.
Conclusion
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.
Key Words
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Article info
Publication history
Published online: January 06, 2021
Accepted:
December 24,
2020
Received in revised form:
December 11,
2020
Received:
July 16,
2020
Identification
Copyright
© 2021 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.
