The distribution of brain aerobic glycolysis (AG) in normal young adults correlates spatially with amyloid-beta (Aâ) deposition in individuals with symptomatic and preclinical Alzheimer disease (AD). Brain AG decreases with age, but the functional significance of this decrease with regard to the development of AD symptomatology is poorly understood. Using PET measurements of regional blood flow, oxygen consumption, and glucose utilization-from which we derive AG-we find that cognitive impairment is strongly associated with loss of the typical youthful pattern of AG. In contrast, amyloid positivity without cognitive impairment was associated with preservation of youthful brain AG, which was even higher than that seen in cognitively unimpaired, amyloid negative adults. Similar findings were not seen for blood flow nor oxygen consumption. Finally, in cognitively unimpaired adults, white matter hyperintensity burden was found to be specifically associated with decreased youthful brain AG. Our results suggest that AG may have a role in the resilience and/or response to early stages of amyloid pathology and that age-related white matter disease may impair this process.

Original languageEnglish
Article numbere2212256120
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number7
StatePublished - Feb 14 2023


  • Alzheimer's disease
  • aerobic glycolysis
  • aging
  • resilience
  • white matter hyperintensities


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