title: Brain glucose and acetoacetate metabolism: a comparison of young and older adults.
abstract: The extent to which the age-related decline in regional brain glucose uptake also applies to other important brain fuels is presently unknown. Ketones are the brain's major alternative fuel to glucose, so we developed a dual tracer positron emission tomography protocol to quantify and compare regional cerebral metabolic rates for glucose and the ketone, acetoacetate. Twenty healthy young adults (mean age, 26 years) and 24 healthy older adults (mean age, 74 years) were studied. In comparison with younger adults, older adults had 8 ± 6% (mean ± SD) lower cerebral metabolic rates for glucose in gray matter as a whole (p = 0.035), specifically in several frontal, temporal, and subcortical regions, as well as in the cingulate and insula (p ≤ 0.01, false discovery rate correction). The effect of age on cerebral metabolic rates for acetoacetate in gray matter did not reach significance (p = 0.11). Rate constants (min(-1)) of glucose (Kg) and acetoacetate (Ka) were significantly lower (-11 ± 6%; [p = 0.005], and -19 ± 5%; [p = 0.006], respectively) in older adults compared with younger adults. There were differential effects of age on Kg and Ka as seen by significant interaction effects in the caudate (p = 0.030) and post-central gyrus (p = 0.023). The acetoacetate index, which expresses the scaled residuals of the voxel-wise linear regression of glucose on ketone uptake, identifies regions taking up higher or lower amounts of acetoacetate relative to glucose. The acetoacetate index was higher in the caudate of young adults when compared with older adults (p ≤ 0.05 false discovery rate correction). This study provides new information about glucose and ketone metabolism in the human brain and a comparison of the extent to which their regional use changes during normal aging.
authors.affiliation: Research Center on Aging, Université de Sherbrooke, Sherbrooke, Quebec, Canada; Department of Physiology and Biophysics, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: Scott
authors.initials: S
authors.lastname: Nugent
authors.affiliation: Research Center on Aging, Université de Sherbrooke, Sherbrooke, Quebec, Canada; Sherbrooke Molecular Imaging Center, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Tremblay
authors.affiliation: Banner Alzheimer's Institute, Phoenix, AZ, USA.
authors.forename: Kewei W
authors.initials: KW
authors.lastname: Chen
authors.affiliation: Banner Alzheimer's Institute, Phoenix, AZ, USA.
authors.forename: Napatkamon
authors.initials: N
authors.lastname: Ayutyanont
authors.affiliation: Banner Alzheimer's Institute, Phoenix, AZ, USA.
authors.forename: Auttawut
authors.initials: A
authors.lastname: Roontiva
authors.affiliation: Research Center on Aging, Université de Sherbrooke, Sherbrooke, Quebec, Canada; Department of Physiology and Biophysics, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: Christian-Alexandre
authors.initials: CA
authors.lastname: Castellano
authors.affiliation: Research Center on Aging, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: Melanie
authors.initials: M
authors.lastname: Fortier
authors.affiliation: Research Center on Aging, Université de Sherbrooke, Sherbrooke, Quebec, Canada; Department of Physiology and Biophysics, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: Maggie
authors.initials: M
authors.lastname: Roy
authors.affiliation: Research Center on Aging, Université de Sherbrooke, Sherbrooke, Quebec, Canada; Department of Physiology and Biophysics, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Courchesne-Loyer
authors.affiliation: Research Center on Aging, Université de Sherbrooke, Sherbrooke, Quebec, Canada; Department of Medicine, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: Christian
authors.initials: C
authors.lastname: Bocti
authors.affiliation: Department of Nuclear Medicine and Radiobiology, Université de Sherbrooke, Sherbrooke, Quebec, Canada; Sherbrooke Molecular Imaging Center, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Lepage
authors.affiliation: Department of Nuclear Medicine and Radiobiology, Université de Sherbrooke, Sherbrooke, Quebec, Canada; Sherbrooke Molecular Imaging Center, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Turcotte
authors.affiliation: Research Center on Aging, Université de Sherbrooke, Sherbrooke, Quebec, Canada; Department of Physiology and Biophysics, Université de Sherbrooke, Sherbrooke, Quebec, Canada; Department of Medicine, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: Tamas
authors.initials: T
authors.lastname: Fulop
authors.affiliation: Banner Alzheimer's Institute, Phoenix, AZ, USA.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Reiman
authors.affiliation: Research Center on Aging, Université de Sherbrooke, Sherbrooke, Quebec, Canada; Department of Physiology and Biophysics, Université de Sherbrooke, Sherbrooke, Quebec, Canada; Department of Medicine, Université de Sherbrooke, Sherbrooke, Quebec, Canada. Electronic address: stephen.cunnane@usherbrooke.ca.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Cunnane
mesh_terms: D000090:Acetoacetates / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007659:Ketones / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D049268:Positron-Emission Tomography; D055815:Young Adult
chemical_list: D000090:Acetoacetates; D007659:Ketones; D005947:Glucose
keywords: Acetoacetate; Aging; Brain; FDG; Ketones; Magnetic resonance imaging; Positron emission tomography