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Title: Biomarkers for insulin resistance and inflammation and the risk for all-cause dementia and Alzheimer disease

Author
item VAN HIMBERGEN, THOMAS M. - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item BEISER, ALEXA S. - Boston University
item AI, MASUMI - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item SESHADRI, SUDHA - Boston University
item OTOKOZAWA, SEIKO - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item AU, RHODA - Boston University
item THONGTANG, NUNTAKORN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item WOLF, PHILIP A. - Boston University
item SCHAEFER, ERNST J. - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Archives of Neurology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/30/2011
Publication Date: 1/2/2012
Citation: Van Himbergen, T., Beiser, A., Ai, M., Seshadri, S., Otokozawa, S., Au, R., Thongtang, N., Wolf, P., Schaefer, E. 2012. Biomarkers for insulin resistance and inflammation and the risk for all-cause dementia and Alzheimer disease. Archives of Neurology. DOI: 10.1001/archneurol.2011.670.

Interpretive Summary: Loss of mental and cognitive function increases with aging and often progresses to dementia in the elderly. Our goal was to assess various predictors of who would develop dementia over time in the Framingham Heart Study. At baseline we measured various parameters using blood samples, and then determined which would predict dementia. In our prior studies we showed that a certain genetic factor apoE genotype was strongly associated with increased risk as were high levels of homocysteine (linked to decreased intake of folate and vitamins B12 and B6) and low levels of plasma phospholipid docosahexaenoic acid or DHA (linked to decreased intake of oily fish or fish oil capsules). In this study we examined other factors including markers of diabetes (insulin, glucose, glycated albumin) and whole body inflammation (C reactive protein, adiponectin, and lipoprotein associated phospholipase A2). Of all these latter parameters only high levels of adiponectin, a protein produced in fat, were significantly associated with an increased risk of all-cause dementia and Alzheimer’s disease in women, but not men. Adiponectin levels are strongly linked to low body mass index. Our data indicate that high levels of adiponectin in women, often linked to being underweight, are a significant predictor of developing all cause dementia and Alzheimer’s disease in the elderly. This research is of interest to those people interested in preventing dementia with aging.

Technical Abstract: Our aim was to investigate the contribution of biomarkers of glucose homeostasis (adiponectin, glucose, glycated albumin, and insulin levels) and inflammation (high-sensitivity C-reactive protein and lipoprotein-associated phospholipase A(2) levels) to the risk of developing Alzheimer disease (AD) and all-cause dementia in a prospective cohort study. Dementia-free Framingham Heart Study participants had sera measured for these biomarkers at the 19th biennial examination (1985-1988) and were followed up prospectively for the development of AD and all-cause dementia. Eight hundred forty (541 women, median age of 76 years) subjects participated in the study. We used sex-pooled and sex-specific multivariable Cox proportional hazards models adjusted for age, education, body mass index, recent change in weight, APOE e4 allele status, and plasma docosahexaenoic acid levels to determine association of these biomarkers with the development of all-cause dementia and AD. We found that over a mean follow-up period of 13 years, 159 persons developed dementia (including 125 with AD). After adjustment for other risk factors, only adiponectin in women was associated with an increased risk of all-cause dementia (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.00-1.66; P = .054) and AD (HR, 1.33; 95% CI, 1.00-1.76; P = .050) per 1-SD increase in adiponectin level. Women with baseline adiponectin values more than the median had a higher risk of all-cause dementia (HR, 1.63; 95% CI, 1.03-2.56; P = .04) and AD (HR, 1.87; 95% CI, 1.13-3.10; P = .01) as compared with those with values less than the median. In conclusion in women, increased plasma adiponectin levels are an independent risk factor for the development of both all-cause dementia and AD.