Hyperinsulinemia and Cognitive Decline in a Middle-Aged Cohort

  1. Sara E. Young, MD12,
  2. Arch G. Mainous III, PHD1 and
  3. Mark Carnemolla, BS1
  1. 1Department of Family Medicine, Medical University of South Carolina, Charleston, South Carolina
  2. 2Department of Family Medicine, Medical College of Georgia, Augusta, Georgia
  1. Address correspondence and reprint requests to Sara E. Young, MD, Department of Family Medicine, Medical College of Georgia, HB-3032, Augusta, GA 30912-3500. E-mail: sayoung{at}


OBJECTIVE—Determining modifiable risks factors for cognitive decline and dementia are a public health priority as we seek to prevent dementia. Type 2 diabetes and related disorders such as hyperinsulinemia increase with aging and are increasing in the U.S. population. Our objective was to determine whether hyperinsulinemia is associated with cognitive decline among middle-aged adults without type 2 diabetes, dementia, or stroke in the Atherosclerosis Risk in Communities (ARIC) cohort.

RESEARCH DESIGN AND METHODS—Middle-aged adults (aged 45–64 years at baseline) in the ARIC cohort had fasting insulin and glucose assessed between 1987 and 1989. Subjects with dementia, type 2 diabetes, or stroke at baseline were excluded from analysis. Three tests of cognitive function available at baseline and 6 years later were delayed word recall (DWR), digit symbol subtest (DSS), and first letter word fluency (WF). Cross-sectional comparisons and linear regression models were computed for cognitive tests at baseline and change in cognitive test scores to determine whether cognitive function was associated with two measures of insulin resistance, fasting insulin and homeostasis model assessment (HOMA). Linear regression models controlled for age, sex, race, marital status, education level, smoking status, alcohol use, depression, hypertension, and hyperlipidemia.

RESULTS—In unadjusted and adjusted analyses, hyperinsulinemia based on fasting insulin and HOMA at baseline was associated with significantly lower baseline DWR, DSS, and WF scores and a greater decline over 6 years in DWR and WF.

CONCLUSIONS—Insulin resistance is a potentially modifiable midlife risk factor for cognitive decline and dementia.


  • A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

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    • Accepted September 17, 2006.
    • Received May 4, 2006.
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