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Biomarkers for Insulin Resistance and Inflammation and the Risk for All-Cause Dementia and Alzheimer Disease: Results From the Framingham Heart Study

TM van Himbergen, AS Beiser, M Ai... - Archives of ..., 2012 - Am Med Assoc Objective 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 ...

The population distributions of plasma adiponectin, insulin, glycated albumin, glucose, and hs CRP levels were positively skewed. The use of natural-log–transformed values provided the best-fitting model for analyses, in which these markers were treated as a continuous variable. Cox proportional hazards regression models were used to examine the relation between the study marker levels and the incidence of all-cause dementia and AD. The risk of dementia is more likely to change as a function of age than of time; we thus used age as the time scale, adjusting for left truncation at entry. Survival age was defined as age at diagnosis of dementia if the individual had dementia or age at death if the individual did not have dementia at death; the remaining participants were censored at the last age known to not have dementia. In analyses of AD, participants with incident non-AD dementia were censored at the date of diagnosis of dementia. Primary analyses were adjusted for age and sex. Supplementary analyses were additionally adjusted for BMI, weight change, APOE genotype (with or without an APOE ϵ4 allele), DHA concentrations, and educational level. An additional subset analysis was performed in 550 subjects who also had serum creatinine and plasma homocysteine measurements available. Plasma adiponectin levels were also evaluated with a median cutoff–based analysis. Testosterone selectively inhibits the secretion of adiponectin from adipocytes resulting in lower levels of circulating adiponectin in men. To take this into account, we investigated interactions by sex and additionally performed analyses stratified by sex. Subjects who had a stroke during the study period were not excluded, since such an event could lie along the causal pathway between elevated plasma levels of the study markers and the development of dementia. All statistical analyses were performed with the use of SAS software (SAS Institute).