Depression and Risk for Alzheimer Disease: Systematic Review, Meta-analysis, and Metaregression Analysis
Open accessAbstract
Context A history of depression may increase risk for developing Alzheimer disease (AD) later in life. Clarifying this relation might improve understanding of risk factors for and disease mechanisms in AD. Objective To systematically review and complete a meta-analysis on the relation of depression and AD. Data sources We conducted electronic bibliographic searches of MEDLINE, PsychLit, EMBASE, and BIOSIS using search terms sensitive to studies of etiology combined with searches on terms related to depression and AD and reviewed reference lists of articles. Study selection Studies with data contrasting depressed vs nondepressed patients who did and did not later develop AD were included. Studies that related continuous measures of depression and cognitive status were excluded. Data extraction Numerical data were independently extracted by 3 reviewers. They also rated studies on a scale that assessed quality indicators for observational studies. Data on the interval between observation of depression and the diagnosis of AD were collected when available. Data synthesis Meta-analytic evaluation with random-effects models resulted in pooled odds ratios of 2.03 (95% confidence interval, 1.73-2.38) for case-control and of 1.90 (95% confidence interval, 1.55-2.33) for cohort studies. Findings of increased risk were robust to sensitivity analyses. Interval between diagnoses of depression and AD was positively related to increased risk of developing AD, suggesting that rather than a p…
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Depression itself increases risk of AD.
“The most consistent observation is that depression itself increases risk of AD (39–41).”
From Serotonin signaling is associated with lower amyloid-β levels and plaques in transgenic mice and humans (2011) · cites this paper as [40]
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Gildengers, A. G., Butters, M. A., Albert, S. M., Anderson, S. J., Dew, M. A., Erickson, K., Garand, L., Karp, J. F., Lockovich, M. H., Morse, J., et al. (2016) · The American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2015.10.010 · Cited by 15 · see citing works
Auvelity as a Potential Treatment for Alzheimer’s Disease
Lepkowsky, C. M. (2022) · Medical Research Archives · doi:10.18103/mra.v10i10.3206 · Cited by 2 · see citing works
Primary Cilia and Cardiovascular Risk Factors in Alzheimer's Disease
Sunderman, C. L., Forero, K. V., Alorjani, Q., Buqaileh, R., Gallagher, G. M., Ventresca, S. M., Messer, W. S., & AbouAlaiwi, W. A. (2025) · Brain Sciences · doi:10.3390/brainsci15091004 · Cited by 1 · see citing works
“Associations have been documented between AD and different disease states, such as gastrointestinal disorders, diabetes, depression, and cardiovascular diseases [16–19].”
- Authors
- Ownby, R. L., Crocco, E., Acevedo, A., John, V., & Loewenstein, D.
- Affiliations
- University of Miami (US)
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2006-05-01
- Volume
- 63
- Issue
- 5
- Pages
- 530
- ISSN
- 0003-990X (ISSN-L)
- PMC
- PMC3530614
- OpenAlex
- W2137944397
- Cited by
- 1,493
- References
- 12
- Citations by year
- 2026: 68 · 2025: 71 · 2024: 86 · 2023: 85 · 2022: 80 · 2021: 111 · 2020: 92 · 2019: 88 · 2018: 93 · 2017: 71 · 2016: 91 · 2015: 91 · 2014: 83 · 2013: 69 · 2012: 78
- FWCI
- 25.06
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- NSUWorks (Nova Southeastern University) (submittedVersion)
- Funders
- National Institute on Aging (K23 AG 19745, K23AG019745)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- depression, Alzheimer's disease, risk factors, dementia
- MeSH terms
- Alzheimer Disease, Cross-Cultural Comparison, Depressive Disorder, Humans, Regression Analysis, Risk Factors, Cohort Studies, Comorbidity, Prevalence, Case-Control Studies, Publication Bias
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