Depression, apolipoprotein E genotype, and the incidence of mild cognitive impairment

A prospective cohort study

Yonas Endale Geda, David S Knopman, David A. Mrazek, Gregory A. Jicha, Glenn E. Smith, Selamawit Negash, Bradley F Boeve, Robert J. Ivnik, Ronald Carl Petersen, V. Shane Pankratz, Walter A Rocca

Research output: Contribution to journalArticle

171 Citations (Scopus)

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 (ε3/ε4 or ε4/ε4) 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.

Original languageEnglish (US)
Pages (from-to)435-440
Number of pages6
JournalArchives of Neurology
Volume63
Issue number3
DOIs
StatePublished - Mar 2006

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Apolipoproteins E
Cohort Studies
Genotype
Prospective Studies
Depression
Incidence
Dementia
Confidence Intervals
Geriatrics
Cognitive Dysfunction
Cohort
Mild Cognitive Impairment
Apolipoprotein E3
Sex Education
Primary Health Care
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Depression, apolipoprotein E genotype, and the incidence of mild cognitive impairment : A prospective cohort study. / Geda, Yonas Endale; Knopman, David S; Mrazek, David A.; Jicha, Gregory A.; Smith, Glenn E.; Negash, Selamawit; Boeve, Bradley F; Ivnik, Robert J.; Petersen, Ronald Carl; Pankratz, V. Shane; Rocca, Walter A.

In: Archives of Neurology, Vol. 63, No. 3, 03.2006, p. 435-440.

Research output: Contribution to journalArticle

Geda, Yonas Endale ; Knopman, David S ; Mrazek, David A. ; Jicha, Gregory A. ; Smith, Glenn E. ; Negash, Selamawit ; Boeve, Bradley F ; Ivnik, Robert J. ; Petersen, Ronald Carl ; Pankratz, V. Shane ; Rocca, Walter A. / Depression, apolipoprotein E genotype, and the incidence of mild cognitive impairment : A prospective cohort study. In: Archives of Neurology. 2006 ; Vol. 63, No. 3. pp. 435-440.
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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 (ε3/ε4 or ε4/ε4) 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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T1 - Depression, apolipoprotein E genotype, and the incidence of mild cognitive impairment

T2 - A prospective cohort study

AU - Geda, Yonas Endale

AU - Knopman, David S

AU - Mrazek, David A.

AU - Jicha, Gregory A.

AU - Smith, Glenn E.

AU - Negash, Selamawit

AU - Boeve, Bradley F

AU - Ivnik, Robert J.

AU - Petersen, Ronald Carl

AU - Pankratz, V. Shane

AU - Rocca, Walter A

PY - 2006/3

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N2 - 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 (ε3/ε4 or ε4/ε4) 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.

AB - 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 (ε3/ε4 or ε4/ε4) 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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