Increased plasma adiponectin is an independent risk factor for all-cause dementia and Alzheimer’s disease in women, according to findings from the Framingham Heart Study.
In 840 dementia-free subjects from the prospective cohort study who had sera levels of biomarkers for glucose homeostasis and inflammation that were measured at a biennial examination between 1985 and 1988, and who were followed for a median of 13 years, 159 developed dementia, including 125 with Alzheimer’s disease (AD).
Adiponectin, a hormone derived from visceral fat, was the only biomarker tested to be linked with the development of all-cause dementia (hazard ratio, 1.29 per 1 standard deviation increase in adiponectin level) or AD (HR, 1.33 per 1 SD increase) after adjustment for age, education, body mass index, recent weight change, apolipoprotein E epsilon 4 allele status, and plasma docosahexaenoic acid levels, Thomas M. van Himbergen, Ph.D., of Tufts University, Boston, and his colleagues reported online in the Jan. 2 issue of Archives of Neurology.
Those with baseline adiponectin levels greater than the sex-specific median had a greater risk of both dementia and AD, compared with those with baseline values less than the median (HR, 1.63 and 1.87, respectively), the investigators found (Arch. Neurol. 2012 Jan. 2 [doi:10.1001/archneurol.2011.670]).
"We hypothesized that adiponectin contributes to or serves as a risk marker for the development of all-cause dementia and AD."
Other biomarkers of glucose homeostasis that were evaluated in this study were glucose, glycated albumin, and insulin levels. Biomarkers of inflammation that were evaluated included hsCRP (high-sensitivity C-reactive protein) and Lp-PLA2 (lipoprotein-associated phospholipase A2) levels. Because data suggest that the management of cardiovascular risk factors (such as type 2 diabetes, high blood pressure, and obesity) might reduce cognitive decline, the investigators hypothesized that factors that underlie type 2 diabetes, such as insulin signaling and inflammation, also might contribute to the development of all-cause dementia and AD.
"Furthermore, based on the role adiponectin plays in insulin signaling and the presence of adiponectin receptors in neurological tissue, we hypothesized that adiponectin contributes to or serves as a risk marker for the development of all-cause dementia and AD," the investigators wrote.
They found no indications that plasma insulin, glucose, glycated albumin, and levels of Lp-PLA2 were associated with either. Although higher plasma levels of hsCRP initially appeared to be associated with a reduced risk for Alzheimer’s and dementia, the association was no longer significant in the fully adjusted model.
Although the finding of an association between elevated adiponectin and an increased risk of dementia and AD in women supported the investigators’ hypothesis, it also raises questions.
"It is well established that insulin signaling is dysfunctional in the brains of patients with AD, and since adiponectin enhances insulin sensitivity, one would also expect beneficial actions protecting against cognitive decline," they wrote.
It is possible that adiponectin levels in the study participants might have risen as a protective response to vascular damage or unidentified changes in brain morphology; thus, studies that evaluate the correlation between adiponectin and cognitive decline over time – as well as mendelian randomization studies linking genetic variation in the adiponectin gene to plasma adiponectin levels and cognitive decline – will be of particular interest, the investigators said, noting that the results of the current study require confirmation in other samples.
In addition, Dr. van Himbergen and his colleagues reported, one limitation of the study is the "predominantly white nature" of the study sample. "Hence, our results require verification in other racial and ethnic samples," they wrote.
Funding for this study was provided by multiple sources, including Mahidol University in Bangkok, Thailand; the U.S. National Institutes of Health; the U.S. Department of Agriculture; the U.S. National Heart, Lung, and Blood Institute; the U.S. National Institute of Neurological Disorders and Stroke; and the U.S. National Institute on Aging. Dr. van Himbergen was supported by a research grant from the Unilever Food and Health Research Institute in the Netherlands.