The ε4 allele of the apolipoprotein-E (APOE) gene is associated with poor outcome following various cerebral insults. The relationship between APOE genotype and cognitive function in patients with type 1 diabetes is unknown. In a cross-sectional study of 96 people with type 1 diabetes, subjects were APOE genotyped, previous exposure to severe hypoglycemia was estimated by questionnaire, and cognition was assessed by neuropsychological testing. Cognitive abilities were compared using multivariate general linear modeling (multiple analysis of covariance, MANCOVA) in those with (n = 21) and without (n = 75) the APOE ε4 allele. APOE ε4 selectively influenced cognitive ability in a sex-specific manner (F = 2.3, P = 0.044, Eta2 = 0.15); women with APOE ε4 performed less well on tests of current, nonverbal intellectual ability (Wechsler Adult Intelligence Scale-Revised performance test score, P = 0.001, Eta2 0.26) and frontal lobe and executive function (Borkowski verbal fluency, P = 0.016, Eta2 = 0.15). Previous exposure to severe hypoglycemia did not interact with APOE ε4 to produce cognitive disadvantage. The APOE ε4 genotype is associated with specific cognitive disadvantage in young women with type 1 diabetes. APOE ε4 is unlikely to mediate susceptibility to hypoglycemia-induced cognitive disadvantage.
Address correspondence and reprint requests to Prof. Ian J. Deary, Department of Psychology, University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, Scotland. E-mail:.
Received for publication 13 May 2002 and accepted in revised form 7 October 2002.
APOE, apolipoprotein-E; MANCOVA, multiple analysis of covariance; NART, National Adult Reading Test; WAIS-R, Wechsler Adult Intelligence Scale-Revised.