Differential effects of blood insulin and HbA1c on cerebral amyloid burden and neurodegeneration in nondiabetic cognitively normal older adults

Neurobiol Aging. 2017 Nov;59:15-21. doi: 10.1016/j.neurobiolaging.2017.07.004. Epub 2017 Jul 20.


We tested the hypothesis that lower insulin or higher glycated hemoglobin (HbA1c) levels in blood are associated with increased cerebral beta amyloid (Aβ) deposition and neurodegeneration in nondiabetic cognitively normal (CN) older adults. A total of 205 nondiabetic CN older adults underwent comprehensive clinical assessment, [11C]Pittsburgh compound B (PiB)-positron emission tomography (PET), [18F]fluorodeoxyglucose-PET, magnetic resonance imaging, and blood sampling for fasting insulin and HbA1c measurement. Lower blood insulin was significantly associated with increased Aβ positivity rates and decreased cerebral glucose metabolism in the AD-signature region. In contrast, higher HbA1c levels were not associated with Aβ positivity rates but were significantly associated with higher rates of having neurodegeneration in the AD-signature regions. Our results suggest different roles of insulin and HbA1c in AD pathogenesis, in that decreased blood insulin below optimal levels may contribute to increasing cerebral Aβ deposition and neurodegeneration whereas impaired glycemic control may aggravate neurodegeneration through a nonamyloid mechanism in nondiabetic CN older adults.

Keywords: Cerebral amyloid burden; Glycated hemoglobin; Insulin; Neurodegeneration; Preclinical Alzheimer's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / etiology
  • Amyloid beta-Peptides / metabolism*
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Female
  • Glycated Hemoglobin A / metabolism*
  • Humans
  • Insulin / blood*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neurodegenerative Diseases / diagnosis*
  • Neurodegenerative Diseases / diagnostic imaging
  • Neurodegenerative Diseases / etiology*
  • Neuroimaging
  • Positron-Emission Tomography


  • Amyloid beta-Peptides
  • Biomarkers
  • Glycated Hemoglobin A
  • Insulin
  • hemoglobin A1c protein, human