Developmental and vascular risk factors for Alzheimer's disease.
To investigate developmental and vascular risk factors for Alzheimer's disease (AD), we examined 90 incident cases of probable AD in a cohort of 1859 individuals followed prospectively for six years. The presence of the APOE-epsilon4 allele was the strongest risk factor, and with increasing survival age, the effect of epsilon4 diminished. Among epsilon4 positives, developmental risk factors such as smaller head circumference (< or =54.4 cm) and having more than four children in the household at age 2-3 were independently associated with incident AD (hazard ratio (HR)=2.6 (95% CI 1.04-6.3) and 3.3 (1.2-9.2), respectively). Among epsilon4 negatives, vascular risk factors were related to AD risk (self-reported diagnoses of transient ischemic attack and diabetes (HR=5.1, 95% CI 1.7-15.5; HR 3.3, 95% CI 1.4-8.1)). These findings indicate that clinical AD is a result of early life as well as later life risk factors, and that genetic predisposition to the disease may modify the constellation of predictors.
Borenstein
Amy R
AR
Department of Epidemiology and Biostatistics, College of Public Health, University of South Florida, 13201 Bruce B. Downs Blvd., Tampa, FL 33612-3805, USA. aborenst@hsc.usf.edu
Wu
Yougui
Y
Mortimer
James A
JA
Schellenberg
Gerard D
GD
McCormick
Wayne C
WC
Bowen
James D
JD
McCurry
Susan
S
Larson
Eric B
EB
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000208:ethnology* / Q000235:genetics* / Q000473:pathology; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D001213:Asian / Q000235:genetics*; D001794:Blood Pressure; D001921:Brain / Q000473:pathology; D002318:Cardiovascular Diseases / Q000208:ethnology; D015331:Cohort Studies; D015897:Comorbidity; D003920:Diabetes Mellitus / Q000208:ethnology; D004522:Educational Status; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006801:Humans; D006973:Hypertension / Q000208:ethnology; D007564:Japan / Q000208:ethnology; D008297:Male; D009929:Organ Size; D011446:Prospective Studies; D012307:Risk Factors; D035781:Siblings; D012959:Socioeconomic Factors; D014861:Washington / Q000453:epidemiology
D053327:Apolipoprotein E4; D001057:Apolipoproteins E