A 9-Year Prospective Population-Based Study on the Association Between the APOE*E4 Allele and Late-Life Depression in Sweden

doi:10.1016/j.biopsych.2015.01.006

Biological Psychiatry

Volume 78, Issue 10, 15 November 2015, Pages 730-736

https://doi.org/10.1016/j.biopsych.2015.01.006 Get rights and content

Abstract

Background

It is well established that there is an association between the apolipoprotein E (APOE) ε4 allele (APOE*E4) and Alzheimerʼs disease. It is less clear whether there is also an association with geriatric depression. We examined the relationship between APOE*E4 and 5-year incidence of depression in a Swedish population-based sample of older adults without dementia and excluding older adults who developed dementia within 4 years after the diagnosis of depression.

Methods

In 2000–2001, 839 women and men (age range, 70–92 years; mean age, 73.8 years) free from dementia and depression underwent neuropsychiatric and neuropsychological examinations and genotyping of the APOE*E4 allele. Follow-up evaluations were conducted in 2005 and 2009.The association between APOE*E4 allele and 5-year incidence of depression was examined, while avoiding possible confounding effects of clinical or preclinical dementia by excluding participants who had dementia at study entry, subsequently developed dementia during the 9-year follow-up period, or had a decline in Mini-Mental State Examination score of ≥5 points.

Results

Among subjects without depression at study entry and without dementia or significant cognitive decline during the subsequent 9 years, APOE*E4 was prospectively associated with more severe depressive symptoms (b = 1.56, p = .007), incident minor depression (odds ratio = 1.99 [confidence interval = 1.11–3.55], p = .020), and any depression (odds ratio = 1.75 [confidence interval = 1.01–3.03], p = .048).

Conclusions

The presence of the APOE*E4 allele predicted future depression in this Swedish population study, even after excluding depressed individuals who later developed dementia, suggesting that the APOE*E4 allele could potentially identify people at high risk for clinically significant depression.

Section snippets

Participants

This analysis originates from two epidemiologic studies in Gothenburg, Sweden, the Prospective Population Study of Women and the Gerontological and Geriatric Population Studies, both of which have been described previously (32, 33, 34, 35). The study was approved by the Ethics Committee for Medical Research at the University of Gothenburg, and informed consent was obtained from all participants and/ or their relatives in cases of dementia.

The participants were sampled from the Swedish

Results

Baseline characteristics are shown in Table 1. In 2000, major depression was diagnosed in 32 participants, and minor depression was diagnosed in 94 participants. No associations could be observed at baseline between the APOE*E4 allele and minor depression (odds ratio [OR] = 1.24 [confidence interval (CI) = .78–1.99], p = .36), major depression (OR = .901 [CI = .39–2.04], p = .802), any depression (OR = 1.16 [CI = .76–1.76], p = .499), or MADRS score (b = −.46, p = .345) in cross-sectional

Discussion

To the best of our knowledge, this is the first longitudinal population-based study of older persons to report a relationship between APOE*E4 and development of depression. We found an association between the presence of the APOE*E4 allele with both incident minor depression and depression symptom severity during 5-year follow-up. People who developed dementia within 9 years of study entry were excluded, and the results remained when controlling for MMSE score at baseline and MMSE decline of ≥5

Acknowledgments And Disclosures

This work was supported by the Swedish Research Council Grant Nos. 11267, 2005-8460, 825-2007-7462, 825-2012-5041, and 2013-8717; Swedish Research Council for Health, Working Life and Wellfare Grant Nos. 2001-2646, 2001-2835, 2003-0234, 2004-0150, 2006-0020, 2008-1229, 2004-0145, 2006-0596, 2008-1111, 2010-0870, AGECAP 2013-2300, 2013-2496, and Epilife 2006-1506; Swedish Brain Power; The Alzheimerʼs Association Zenith Award Grant No. ZEN-01-3151; The Alzheimerʼs Association Stephanie B.

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Citation Excerpt :
This finding indicates that APOE4 carriers have a risk of developing depression that is not related to the behavioral and psychological symptoms of dementia. In addition, in a population-based study in Sweden by Skoog et al. (2015), it was suggested that an APOE4 allele could potentially identify people at high risk for clinically significant depression. In this large, prospective, nine-year study, Skoog et al. examined the effects of APOE4 on the incidence of depression in 839 women and men who were free from dementia and depression (age range, 70–92 years and mean age, 73.8 years).
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Archival ReportA 9-Year Prospective Population-Based Study on the Association Between the APOE*E4 Allele and Late-Life Depression in Sweden

Abstract

Background

Methods

Results

Conclusions

Section snippets

Participants

Results

Discussion

Acknowledgments And Disclosures

Neuron

Lancet Neurol

Biol Psychiatry

Lancet

Atherosclerosis

Biol Psychiatry

Biol Psychiatry

Neurosci Lett

Am J Geriatr Psychiatry

Am J Geriatr Psychiatry

Am J Geriatr Psychiatry

J Affect Disord

Am J Geriatr Psychiatry

J Psychiatr Res

Am J Geriatr Psychiatry

Neurobiol Aging

J Psychiatr Res

Am J Geriatr Psychiatry

World Psychiatry

J Affect Disord

J Affect Disord

J Affect Disord

Am J Geriatr Psychiatry

Neuroimage

J Affect Disord

J Neurol Sci

Cerebrovascular effects of apolipoprotein E: Implications for Alzheimer disease

JAMA Neurol

Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimerʼs disease

Neurology

Meta-analysis: Apolipoprotein E genotypes and risk for coronary heart disease

Ann Intern Med

APOE genotype as a risk factor for ischemic cerebrovascular disease: A meta-analysis

Neurology

A preliminary study of apolipoprotein E genotype and psychiatric manifestations of Alzheimerʼs disease

Neurology

Association of the apolipoprotein E epsilon4 allele with late-onset depression

Neuroepidemiology

APOE is associated with age-of-onset, but not cognitive functioning, in late-life depression

Int J Geriatr Psychiatry

Association of APOE genetic polymorphism with cognitive function and suicide history in geriatric depression

Dement Geriatr Cogn Disord

Perspectives on depression, mild cognitive impairment, and cognitive decline

Arch Gen Psychiatry

ApoE4 is not associated with depression when mild cognitive impairment is considered

Int J Geriatr Psychiatry

Factors associated with depressive symptoms in non-demented community-dwelling elderly

Int J Geriatr Psychiatry

Depression, APOE genotype and subjective memory impairment: A cross-sectional study in an African-Caribbean population

Psychol Med

Apolipoprotein E genotype and major depression in a community of older adults. The Cache County Study

Psychol Med

Apolipoprotein epsilon4 allele status, depressive symptoms, and cognitive decline in middle-aged and elderly persons without dementia

Am J Geriatr Psychiatry

APOE-epsilon4, depressive symptoms, and cognitive decline in Chinese older adults: Singapore Longitudinal Aging Studies

J Gerontol A Biol Sci Med Sci

Depressive symptoms in healthy apolipoprotein E epsilon4 carriers and noncarriers: A longitudinal study

J Clin Psychiatry

Archival Report
A 9-Year Prospective Population-Based Study on the Association Between the APOEE4* Allele and Late-Life Depression in Sweden