Hyperinsulinemia and risk of Alzheimer disease.
OBJECTIVE
To explore the association between fasting insulin levels and dementia.


METHODS
Fasting insulin levels were measured from frozen sera using solid-phase chemiluminescent enzyme immunoassay in a sample of elderly subjects chosen at random from a cohort of persons aged 65 years and older from northern Manhattan. Dementia was diagnosed using standard methods. Neuropsychiatric testing was available on all subjects at each follow-up interval.


RESULTS
A total of 683 subjects without prevalent dementia were followed for 3,691 person-years and 149 persons developed dementia (137 Alzheimer disease [AD], 6 dementia associated with stroke, 6 other). The risk of AD doubled in the 39% of the sample with hyperinsulinemia (HR = 2.1; 95% CI: 1.5, 2.9) and was highest in people without diabetes. The HR relating presence of hyperinsulinemia or diabetes in 50% of our sample to AD was 2.2 (95% CI: 1.5, 3.1). The risk of AD attributable to the presence of hyperinsulinemia or diabetes was 39%. The HR of AD for the highest quartile of insulin compared to the lowest was 1.7 (95% CI: 1.0, 2.7; p for trend = 0.009). Hyperinsulinemia was also related to a significant decline in memory-related cognitive scores, but not to decline in other cognitive domains.


CONCLUSIONS
Hyperinsulinemia is associated with a higher risk of AD and decline in memory.
Taub Institute for Research of Alzheimer's Disease and the Aging Brain, Joseph P. Mailman School of Public Health, Columbia University, New York, USA.
Jose A
JA
Luchsinger
Ming-Xin
MX
Tang
Steven
S
Shea
Richard
R
Mayeux
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000208:ethnology / Q000209:etiology; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000097:blood; D003071:Cognition; D003430:Cross-Sectional Studies; D003704:Dementia / Q000097:blood / Q000209:etiology; D003920:Diabetes Mellitus / Q000523:psychology; D005260:Female; D006801:Humans; D006946:Hyperinsulinism / Q000523:psychology*; D008137:Longitudinal Studies; D008297:Male; D016017:Odds Ratio; D015995:Prevalence; D016016:Proportional Hazards Models; D012307:Risk Factors; D020521:Stroke / Q000150:complications
D053327:Apolipoprotein E4; D001057:Apolipoproteins E