Apolipoprotein E ε4 genotype and the temporal relationship between depression and dementia
Open accessAbstract
To investigate how apolipoprotein E (APOE) affects the temporal relationship between depression and dementia, we conducted a nested case-control study with longitudinal depression and dementia evaluations from several population studies by using 804 dementia cases and 1600 matched controls, totaling 1519 unique individuals. Depression within 10 years of onset of dementia was strongly associated with dementia diagnosis regardless of APOE status (incidence rate ratio [IRR] 5.25, 95% confidence interval [95% CI] 3.32-8.31 for ε4 carriers, IRR 4.40, 95%CI 3.23-5.99 for noncarriers). However, we found a significant interaction between depression more than 10 years before the onset of dementia and APOE (p = 0.01), with depression more distal to dementia being a risk factor only in ε4 carriers (IRR 3.39, 95% CI 1.69-6.78 for carriers, IRR 1.01, 95% CI 0.60-1.70 for noncarriers). Thus, depression with onset close in time to dementia onset is associated with disease irrespective of APOE genotype, whereas depression more distal to dementia onset is a risk factor only in ε4-carriers. This is the first study to show the interaction between APOE and depression to be dependent on timing of depression onset.
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Depression is associated with an increased risk of dementia (RR 2.25, 1.69-2.98, I2=82.8%).
“we performed a random effects meta-analysis using the seven studies with a 10 to 14-year follow-up (104-111) and found an increased risk of dementia (RR 2.25, 1.69 -2.98 I 2 = 82.8% )”
From Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission (2024) · cites this paper as [105]
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- Authors
- Karlsson, I. K., Bennet, A. M., Ploner, A., Andersson, T. M.-L., Reynolds, C. A., Gatz, M., & Pedersen, N. L.
- Affiliations
- Karolinska Institutet (SE)
- University of California, Riverside (US)
- University of Southern California (US)
- Corresponding author
- Pedersen, Nancy L.
- ORCID
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2015-04
- Volume
- 36
- Issue
- 4
- Pages
- 1751-1756
- ISSN
- 0197-4580 (ISSN-L)
- PMC
- PMC4380668
- OpenAlex
- W2038505122
- Cited by
- 38
- References
- 36
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 7 · 2023: 5 · 2022: 2 · 2021: 4 · 2020: 1 · 2019: 3 · 2018: 3 · 2016: 4 · 2015: 4
- FWCI
- 2.97
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. National Institutes of Health (AG028555, AG08724, AG08861, AG10175, AG04563)
- MacArthur Foundation Research Network
- Axel and Margaret Ax:son Johnsons Foundation
- Swedish Council
- Swedish Foundation
- Eva and Oscar Ahrén Research Foundation
- 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 › Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- APOE ε4, APOE genotype, depression, dementia, temporal relations, genetic interactions, dementia risk factors, Alzheimer's disease
- MeSH terms
- Aged, Aged, 80 and over, Dementia, Depression, Female, Genotype, Heterozygote, Humans, Longitudinal Studies, Male, Risk Factors, Time Factors, Case-Control Studies, Apolipoprotein E4, Genetic Association Studies
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