Joint effect of the APOE gene and midlife systolic blood pressure on late-life cognitive impairment: the Honolulu-Asia aging study.
OBJECTIVE
The aim of this study was to explore the joint effect of the APOE epsilon4 allele and midlife systolic blood pressure (SBP) on the risk for poor cognitive function in late life.


METHODS
The study includes 3605 surviving members of the cohort of the Japanese-American men followed prospectively over 26 years (1965-1991) as a part of the Honolulu Heart Program. In 1965 men were aged 45 to 68 years and were living in the island of Oahu, Hawaii. For this study the sample was divided into 4 categories: normal SBP (<160 mm Hg)/No epsilon4, as the reference category; normal SBP/epsilon4; high SBP/no epsilon4; high SBP/epsilon4. The relative risk (RR) of late-life intermediate and poor cognitive function relative to good function was measured by the Cognitive Abilities Screening Instrument (CASI) test.


RESULTS
After adjusting for age, education, smoking, alcohol use, and body mass index, the RR for poor cognitive function (CASI <74) compared with good cognitive function (CASI >/=82) in never-treated subjects was 1.3 (95% CI 0.9 to 1.9) for the normal SBP/epsilon4 category, 2.6 (0.7 to 10.0) for the high SBP/no epsilon4, and 13.0 (1.9 to 83.8) for the high SBP/epsilon4. Adjustment for diabetes, prevalent stroke, coronary disease, and ankle-brachial index reduced the RR of poor cognition by 25.5% (RR 13.0 to 10.8) in those with both risk factors. In the treated group, the RR was 1.9 (0.7 to 4.5) for those with both risk factors.


CONCLUSIONS
The results suggest that midlife high SBP has a stronger adverse effect on cognitive function in persons with higher genetic susceptibility, but this effect may be modified by antihypertensive treatment.
Peila
R
R
Epidemiology, Demography and Biometry Program, National Institute on Aging, National Institutes of Health, Bethesda, Md, USA.
White
L R
LR
Petrovich
H
H
Masaki
K
K
Ross
G W
GW
Havlik
R J
RJ
Launer
L J
LJ
D000368:Aged; D000375:Aging; D000483:Alleles; D000959:Antihypertensive Agents / Q000627:therapeutic use; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics*; D003072:Cognition Disorders / Q000453:epidemiology / Q000235:genetics*; D015331:Cohort Studies; D015897:Comorbidity; D003710:Demography; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006254:Hawaii / Q000453:epidemiology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D007564:Japan / Q000208:ethnology; D008297:Male; D012306:Risk; D018570:Risk Assessment; D012307:Risk Factors
D000959:Antihypertensive Agents; D053327:Apolipoprotein E4; D001057:Apolipoproteins E