Biomarkers for insulin resistance and inflammation and the risk for all-cause dementia and alzheimer disease: results from the Framingham Heart Study

Arch Neurol. 2012 May;69(5):594-600. doi: 10.1001/archneurol.2011.670.


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 Alzheimer disease (AD) and all-cause dementia.

Design: Prospective cohort study.

Setting: 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.

Participants: Eight hundred forty (541 women, median age of 76 years) subjects participated in the study.

Main outcome measures: We used sex-pooled and sex-specific multivariable Cox proportional hazards models adjusted for age, education, body mass index, recent change in weight, APOE ε4 allele status, and plasma docosahexaenoic acid levels to determine association of these biomarkers with the development of all-cause dementia and AD.

Results: 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.

Conclusion: In women, increased plasma adiponectin levels are an independent risk factor for the development of both all-cause dementia and AD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 1-Alkyl-2-acetylglycerophosphocholine Esterase / blood
  • Adiponectin / blood
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / blood*
  • Alzheimer Disease / epidemiology
  • Alzheimer Disease / etiology
  • Alzheimer Disease / genetics
  • Apolipoproteins E / genetics
  • Blood Glucose*
  • C-Reactive Protein / metabolism
  • Chromatography, High Pressure Liquid
  • Cohort Studies
  • Dementia / blood*
  • Dementia / epidemiology
  • Dementia / etiology
  • Dementia / genetics
  • Female
  • Fluorometry
  • Humans
  • Inflammation / blood
  • Inflammation / complications*
  • Insulin / blood
  • Insulin Resistance*
  • Male
  • Middle Aged
  • Peptide Fragments / genetics
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Factors
  • Serum Albumin / metabolism
  • Sex Factors


  • Adiponectin
  • Apolipoproteins E
  • Blood Glucose
  • Insulin
  • Peptide Fragments
  • Serum Albumin
  • apolipoprotein E (141-155)
  • glycosylated serum albumin
  • C-Reactive Protein
  • 1-Alkyl-2-acetylglycerophosphocholine Esterase