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Depression, Apolipoprotein E Genotype, and the Incidence of Mild Cognitive Impairment: A Prospective Cohort Study

Geda, Yonas E., Knopman, David S., Mrazek, David A., Jicha, Gregory A., Smith, Glenn E., Negash, Selamawit, Boeve, Bradley F., Ivnik, Robert J. +3 more·2006·Archives of Neurology
DOI 10.1001/archneur.63.3.435
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Abstract

BACKGROUND: It remains unknown whether depression and apolipoprotein E genotype are risk factors for incident mild cognitive impairment (MCI). OBJECTIVE: To determine whether elderly individuals with depression (measured by the short Geriatric Depression Scale) are at increased risk of developing incident MCI. DESIGN: Prospective cohort study. SETTING: Primary care clinic. PARTICIPANTS: A cohort of 840 cognitively normal elderly subjects without depression at recruitment who were followed up prospectively for a median of 3.5 years (range, 0.4-12.8 years). Subjects who developed depression (score of >/=6 on the short Geriatric Depression Scale; depression cohort) were compared with all remaining subjects (referent cohort). MAIN OUTCOME MEASURES: Incidence of MCI (primary outcome) and incidence of MCI or dementia (composite secondary outcome). RESULTS: Individuals in the depression cohort were at significantly increased risk of subsequent incident MCI (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.2-4.1) after adjusting for age (time scale), sex, and education, and considering dementia as a competing outcome. The association was stronger in men but did not vary by severity of depression. We observed a synergistic interaction between apolipoprotein E genotype (epsilon3/epsilon4 or epsilon4/epsilon4) and depression (joint effect HR, 5.1; 95% CI, 1.9-13.6; test for additive interaction, P = .03). We found a similar association between depression and the subsequent composite outcome of incident MCI or dementia (HR, 2.6; 95% CI, 1.6-4.3). CONCLUSIONS: Cognitively normal elderly individuals who develop depression are at increased risk of subsequent MCI. We found a synergistic interaction between depression and apolipoprotein E genotype.

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  • Depression is characterized not only by feelings of sadness and worthlessness, but also by inertia, lethargy, and impaired cognition that is more prevalent in the elderly.

    “Depression is characterized not only by feelings of sadness and worthlessness, but also by inertia, lethargy, and impaired cognition that is more prevalent in the elderly (Geda et al., 2006) (Jorm, 2000; Kumar et al., 2006).”

    From Biological rhythms, higher brain function, and behavior: Gaps, opportunities, and challenges (2009) · cites this paper as Geda et al., 2006

  • In humans, the incidence of depression and impairments in cognitive function, most notably spatial memory, are higher among the elderly.

    “In humans, the incidence of depression and impairments in cognitive function, most notably spatial memory, are higher among the elderly (Geda et al, 2006; Jorm, 2000; Kumar et al., 2006).”

    From Biological rhythms, higher brain function, and behavior: Gaps, opportunities, and challenges (2009) · cites this paper as Geda et al, 2006

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Authors
Geda, Y. E., Knopman, D. S., Mrazek, D. A., Jicha, G. A., Smith, G. E., Negash, S., Boeve, B. F., Ivnik, R. J., Petersen, R. C., Pankratz, V. S., & Rocca, W. A.
Affiliations
Mayo Clinic (US)
ORCID
Venue
Archives of Neurology
Publisher
American Medical Association (AMA)
Published
2006-03-01
Volume
63
Issue
3
Pages
435
ISSN
0003-9942 (ISSN-L)
DOI
10.1001/archneur.63.3.435
OpenAlex
W2167153475
Cited by
230
References
36
Citations by year
2026: 2 · 2025: 7 · 2024: 6 · 2023: 8 · 2022: 8 · 2021: 7 · 2020: 8 · 2019: 8 · 2018: 14 · 2017: 6 · 2016: 12 · 2015: 12 · 2014: 12 · 2013: 10 · 2012: 21
FWCI
10.41
Type
journal article
Language
en
Open access
closed
Locations
  • Archives of Neurology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Mayo Clinic
  • National Institute on Aging (P50‐AG16574, U01AG06786, U01AG006786, P50AG016574)
  • National Institute of Mental Health (K01-MH68351, K01MH068351)
  • National Institute of Neurological Disorders and Stroke (R01-NS33978, R01NS033978)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
depression, APOE genotype, mild cognitive impairment, dementia, older adults, Geriatric Depression Scale, genetic risk factors, synergistic interaction, cognitive decline
MeSH terms
Aged, Aged, 80 and over, Apolipoproteins E, Cognition Disorders, Demography, Depression, Female, Follow-Up Studies, Humans, Male, Middle Aged, Prospective Studies, Risk, Geriatric Assessment, Incidence, Proportional Hazards Models, Survival Analysis

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