APOE and aging-related cognitive change in a longitudinal cohort of men.
We examined associations between APOE major isoforms, rs405509 promoter and rs440446 intron-1 polymorphisms, and nonpathologic cognitive aging. Men from the Helsinki Birth Cohort Study took the Finnish Defence Forces Basic Intellectual Ability Test twice, at age 20.1 (n = 404) and 67.6 years (n = 247). APOE major isoforms did not associate with cognitive ability. In the APOE major isoform-adjusted analyses, the number of rs405509 minor alleles was associated with a higher cognitive ability total and verbal, arithmetic, and visuospatial subtest scores at 67.6 years (p-values < 0.004). In the analyses of cognitive change, the visuospatial subtest score increased across time in rs440446 minor allele carriers but decreased in noncarriers (p = 0.007). Associations in the APOE major isoform-stratified analyses were significant in the APOE ε3/3 homozygotes only. The APOE locus harbors additional modifying alleles, independent of APOE major isoforms that are associated with better preserved general cognitive ability in nondemented elderly men and change in visuospatial ability across 5 decades. These results suggest that at least 2 distinct mechanisms link the APOE locus with cognitive ability.
Institute of Behavioral Sciences, University of Helsinki, Finland; Folkhälsan Research Center, Helsinki, Finland. Electronic address: ville.rantalainen@helsinki.fi.
Ville
V
Rantalainen
Institute of Behavioral Sciences, University of Helsinki, Finland; Folkhälsan Research Center, Helsinki, Finland.
Jari
J
Lahti
National Supervisory Authority on Welfare and Health, Department of Health Care Supervision; Center of Military Medicine, Helsinki, Finland.
Markus
M
Henriksson
Division of Welfare and Health Promotion, Department of Chronic Disease Prevention, Diabetes Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland; Hospital for Children and Adolescents, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland; Department of Obstetrics and Gynaecology, Oulu University Hospital and University of Oulu, Oulu, Finland.
Eero
E
Kajantie
Department of Neurology, Helsinki University Central Hospital; Molecular Neurology, Research Programs Unit, Biomedicum, University of Helsinki, Finland.
Pentti
P
Tienari
Department of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Unit of General Practice, Helsinki, Finland; Folkhälsan Research Center, Helsinki, Finland; Vasa Central Hospital, Vasa, Finland.
Johan G
JG
Eriksson
Institute of Behavioral Sciences, University of Helsinki, Finland.
Katri
K
Raikkonen
D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics* / Q000523:psychology*; D000483:Alleles; D001057:Apolipoproteins E / Q000235:genetics*; D003071:Cognition; D015331:Cohort Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020033:Protein Isoforms; D055815:Young Adult
D001057:Apolipoproteins E; D020033:Protein Isoforms
APOE; Normal cognitive aging; longitudinal studies