Apolipoprotein E e4 and Cognitive Function: A Modifiable Association Results from Two Independent Cohort Studies.
BACKGROUND
The apolipoprotein E (APOE) e4 genetic polymorphism is a major risk factor for Alzheimer' s disease, hence the possible prevention of its detrimental effects on cognition is of high relevance.


METHODS
We used linear regression models to assess associations of APOE e4 with cognitive performance in a population-based cohort study (n = 1,434) and in a cohort of patients with coronary heart disease (n = 366), and restricted cubic splines to explore dose-response relationships between serum cholesterol levels and cognition depending on APOE polymorphism.


RESULTS
The association of APOE e4 with cognitive function was strongly amplified in the presence of hypercholesterolemia and cardiovascular disease in both independent cohorts; hypercholesterolemia was associated with cognitive function only among APOE e4 carriers in the presence of cardiovascular disease. The interaction effect between APOE genotype and hypercholesterolemia was statistically significant in both cohorts.


CONCLUSIONS
The detrimental effects of APOE e4 polymorphism on cognition may strongly depend on modifiable risk factors.
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Laura
L
Perna
Ute
U
Mons
Dan
D
Rujescu
Matthias
M
Kliegel
Hermann
H
Brenner
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000209:etiology / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000097:blood / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000150:complications*; D002784:Cholesterol / Q000097:blood / Q000235:genetics; D003071:Cognition / Q000502:physiology*; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic; D012307:Risk Factors
D053327:Apolipoprotein E4; D002784:Cholesterol