title: Glucose hypometabolism is highly localized, but lower cortical thickness and brain atrophy are widespread in cognitively normal older adults.
abstract: Several studies have suggested that glucose hypometabolism may be present in specific brain regions in cognitively normal older adults and could contribute to the risk of subsequent cognitive decline. However, certain methodological shortcomings, including a lack of partial volume effect (PVE) correction or insufficient cognitive testing, confound the interpretation of most studies on this topic. We combined [(18)F]fluorodeoxyglucose ([(18)F]FDG) positron emission tomography (PET) and magnetic resonance (MR) imaging to quantify cerebral metabolic rate of glucose (CMRg) as well as cortical volume and thickness in 43 anatomically defined brain regions from a group of cognitively normal younger (25 ± 3 yr old; n = 25) and older adults (71 ± 9 yr old; n = 31). After correcting for PVE, we observed 11-17% lower CMRg in three specific brain regions of the older group: the superior frontal cortex, the caudal middle frontal cortex, and the caudate (P ≤ 0.01 false discovery rate-corrected). In the older group, cortical volumes and cortical thickness were 13-33 and 7-18% lower, respectively, in multiple brain regions (P ≤ 0.01 FDR correction). There were no differences in CMRg between individuals who were or were not prescribed antihypertensive medication. There were no significant correlations between CMRg and cognitive performance or metabolic parameters measured in fasting plasma. We conclude that highly localized glucose hypometabolism and widespread cortical thinning and atrophy can be present in older adults who are cognitively normal, as assessed using age-normed neuropsychological testing measures.
authors.affiliation: Research Center on Aging, Departments of Physiology and Biophysics, Scott.Nugent@USherbrooke.ca.
authors.forename: Scott
authors.initials: S
authors.lastname: Nugent
authors.affiliation: Research Center on Aging, Medicine.
authors.forename: Christian-Alexandre
authors.initials: CA
authors.lastname: Castellano
authors.affiliation: Centre Hospitalier Universitaire de Sherbrooke Research Center, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: Philippe
authors.initials: P
authors.lastname: Goffaux
authors.affiliation: Nuclear Medicine and Radiobiology, and Sherbrooke Molecular Imaging Center, and.
authors.forename: Kevin
authors.initials: K
authors.lastname: Whittingstall
authors.affiliation: Nuclear Medicine and Radiobiology, and Sherbrooke Molecular Imaging Center, and.
authors.forename: Martin
authors.initials: M
authors.lastname: Lepage
authors.affiliation: Nuclear Medicine and Radiobiology, and.
authors.forename: Nancy
authors.initials: N
authors.lastname: Paquet
authors.affiliation: Research Center on Aging, Medicine.
authors.forename: Christian
authors.initials: C
authors.lastname: Bocti
authors.affiliation: Research Center on Aging, Medicine.
authors.forename: Tamas
authors.initials: T
authors.lastname: Fulop
authors.affiliation: Research Center on Aging, Departments of Physiology and Biophysics, Medicine.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Cunnane
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism / Q000473:pathology*; D000959:Antihypertensive Agents / Q000009:adverse effects; D001284:Atrophy; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000473:pathology*; D001923:Brain Chemistry / Q000502:physiology; D002540:Cerebral Cortex / Q000473:pathology*; D003071:Cognition / Q000502:physiology; D056344:Executive Function / Q000502:physiology; D005260:Female; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007700:Kinetics; D008279:Magnetic Resonance Imaging; D008297:Male; D057567:Memory, Long-Term / Q000502:physiology; D008570:Memory, Short-Term / Q000502:physiology; D008875:Middle Aged; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents; D001786:Blood Glucose; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D005947:Glucose
keywords: aging; cerebral glucose metabolism; cortical thickness; cortical volume; positron emission tomography