APOE genotype and cognitive decline in a middle-aged cohort

C. K. Blair, A. R. Folsom, David S Knopman, M. S. Bray, T. H. Mosley, E. Boerwinkle

Research output: Contribution to journalArticle

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Abstract

Background: Most longitudinal studies of nondemented persons have reported greater cognitive decline among APOE ε4 carriers vs noncarriers. However, most studies involved elderly samples (aged 65+) and were not large enough to examine the three APOE alleles separately. Methods: Change in cognitive function was examined over a 6-year period using three neuropsychological tests among four APOE genotype groups (ε2/2 + ε2/3, ε3/3 (referent), ε4/2 + ε4/3, ε4/4). The population-based sample included 1,693 African Americans and 6,202 Caucasians initially ages 47 to 68. Results: There was increasingly greater cognitive decline from the ε2 group to the ε4/4 group in Caucasians for two of the three tests. The combination of APOE ε4 with hypercholesterolemia or diabetes showed the greatest cognitive decline. Among African Americans, only the test measuring psychomotor speed showed associations with APOE genotype. Conclusions: APOE ε4 is associated with greater cognitive decline in middle-aged Caucasian individuals, with a reduced decline among ε2 carriers. This suggests that the processes by which APOE genotype mediates dementia risk are operative well in advance of overt dementia.

Original languageEnglish (US)
Pages (from-to)268-276
Number of pages9
JournalNeurology
Volume64
Issue number2
StatePublished - Jan 25 2005

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Genotype
African Americans
Dementia
Neuropsychological Tests
Hypercholesterolemia
Cognition
Longitudinal Studies
Alleles
Cognitive Dysfunction
Population

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Blair, C. K., Folsom, A. R., Knopman, D. S., Bray, M. S., Mosley, T. H., & Boerwinkle, E. (2005). APOE genotype and cognitive decline in a middle-aged cohort. Neurology, 64(2), 268-276.

APOE genotype and cognitive decline in a middle-aged cohort. / Blair, C. K.; Folsom, A. R.; Knopman, David S; Bray, M. S.; Mosley, T. H.; Boerwinkle, E.

In: Neurology, Vol. 64, No. 2, 25.01.2005, p. 268-276.

Research output: Contribution to journalArticle

Blair, CK, Folsom, AR, Knopman, DS, Bray, MS, Mosley, TH & Boerwinkle, E 2005, 'APOE genotype and cognitive decline in a middle-aged cohort', Neurology, vol. 64, no. 2, pp. 268-276.
Blair CK, Folsom AR, Knopman DS, Bray MS, Mosley TH, Boerwinkle E. APOE genotype and cognitive decline in a middle-aged cohort. Neurology. 2005 Jan 25;64(2):268-276.
Blair, C. K. ; Folsom, A. R. ; Knopman, David S ; Bray, M. S. ; Mosley, T. H. ; Boerwinkle, E. / APOE genotype and cognitive decline in a middle-aged cohort. In: Neurology. 2005 ; Vol. 64, No. 2. pp. 268-276.
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