Disappearing metabolic youthfulness in the cognitively impaired female brain

Neurobiol Aging. 2021 May;101:224-229. doi: 10.1016/j.neurobiolaging.2021.01.026. Epub 2021 Feb 3.


Sex differences play a vital role in human brain structure and physiology. Previous reports have proposed evidence hinting at a metabolic advantage in female brains across adulthood. It remained to be determined whether this advantage would be maintained across the spectrum of cognitive impairment, up to and including dementia due to Alzheimer's disease (AD). Here, using a machine-learning algorithm, we explore sex differences in metabolic brain-age derived from fluorodeoxyglucose positron emission tomography imaging among cognitively healthy individuals and those affected by mild cognitive impairment and clinically probable AD. First, we report that cognitively healthy male participants showed a persistently "older" looking brains when compared to healthy female participants in term of metabolic brain age, confirming earlier reports. However, this distinction disappeared among MCI individuals and probable AD patients, and this loss could not be explained by an accompanying neurodegeneration. This would seem to indicate that females have a higher rate of decline in brain glucose metabolism when cognitively impaired to negate their prior advantage.

Keywords: Alzheimer's disease; Fluorodeoxyglucose; Metabolic brain-age; Mild cognitive impairment; Positron emission tomography; Sex difference.

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

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / complications
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Brain / pathology
  • Cognitive Dysfunction / diagnostic imaging
  • Cognitive Dysfunction / metabolism*
  • Cognitive Dysfunction / pathology
  • Dementia / diagnostic imaging
  • Dementia / etiology
  • Dementia / metabolism*
  • Dementia / pathology
  • Female
  • Glucose / metabolism*
  • Humans
  • Machine Learning
  • Male
  • Middle Aged
  • Nerve Degeneration
  • Positron-Emission Tomography
  • Sex Characteristics*


  • Glucose