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APOE genotype and cognitive decline in a middle-aged cohort.

TitleAPOE genotype and cognitive decline in a middle-aged cohort.
Publication TypeJournal Article
Year of Publication2005
AuthorsBlair CK, Folsom AR, Knopman DS, Bray MS, Mosley TH, Boerwinkle E
Corporate AuthorsAtherosclerosis Risk in Communities(ARIC) Study Investigators
Date Published2005 Jan 25
KeywordsAged, Alleles, Apolipoprotein E2, Apolipoprotein E4, Apolipoproteins E, Black or African American, Carotid Artery Diseases, Cognition Disorders, Cohort Studies, Diabetes Mellitus, Disease Progression, Female, Genetic Predisposition to Disease, Genotype, Humans, Hypercholesterolemia, Male, Middle Aged, Neuropsychological Tests, Prospective Studies, Ultrasonography, White People

BACKGROUND: Most longitudinal studies of nondemented persons have reported greater cognitive decline among APOE epsilon4 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 (epsilon2/2 + epsilon2/3, epsilon3/3 (referent), epsilon4/2 + epsilon4/3, epsilon4/4). 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 epsilon2 group to the epsilon4/4 group in Caucasians for two of the three tests. The combination of APOE epsilon4 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 epsilon4 is associated with greater cognitive decline in middle-aged Caucasian individuals, with a reduced decline among epsilon2 carriers. This suggests that the processes by which APOE genotype mediates dementia risk are operative well in advance of overt dementia.

Alternate JournalNeurology
PubMed ID15668424
Grant ListHL073366 / HL / NHLBI NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States
UR6/CCU617218 / CC / ODCDC CDC HHS / United States