ABSTRACT
The distribution of brain aerobic glycolysis (AG) in normal young adults correlates spatially with amyloid-beta (Aβ) deposition in individuals with dementia of the Alzheimer type (DAT) and asymptomatic individuals with brain amyloid deposition. Brain AG decreases with age but the functional significance of this decrease with regard to the development of DAT 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 typical, 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 implicate preserved AG as a factor in brain resilience to amyloid pathology and suggest that white matter disease may be a cause and/or consequence of this impaired resilience.
Competing Interest Statement
Andrei Vlassenko: NIH research grants R01-AG057536, R01-AG053503, RF1-AG073210 Manu Goyal: NIH research grants R01-AG057536, R01-AG053503, RF1-AG073210; Stock equity in IBM, Kyndryl, Moderna and BioNTech Marcus Raichle: NIH research grant R01-AG053503 John Morris: NIH research grants P30-AG066444, P01-AG003991, P01-AG026276, U19-AG032438; consulting fees: Barcelona Brain Research Center (BBRC), TS Srinivasan Advisory Board, Chennai, India Tammie Benzinger: Avid Pharmaceuticals (a subsidiary of Eli Lilly and Company) provides precursor and technology transfer to Washington University for use of Florbetapir-F18.