title: Dynamic relationships between age, amyloid-β deposition, and glucose metabolism link to the regional vulnerability to Alzheimer's disease.
abstract: SEE HANSSON AND GOURAS DOI101093/AWW146 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Although some brain regions such as precuneus and lateral temporo-parietal cortex have been shown to be more vulnerable to Alzheimer's disease than other areas, a mechanism underlying the differential regional vulnerability to Alzheimer's disease remains to be elucidated. Using fluorodeoxyglucose and Pittsburgh compound B positron emission tomography imaging glucose metabolism and amyloid-β deposition, we tested whether and how life-long changes in glucose metabolism relate to amyloid-β deposition and Alzheimer's disease-related hypometabolism. Nine healthy young adults (age range: 20-30), 96 cognitively normal older adults (age range: 61-96), and 20 patients with Alzheimer's disease (age range: 50-90) were scanned using fluorodeoxyglucose and Pittsburgh compound B positron emission tomography. Among cognitively normal older subjects, 32 were further classified as amyloid-positive, with 64 as amyloid-negative. To assess the contribution of glucose metabolism to the regional vulnerability to amyloid-β deposition, we defined the highest and lowest metabolic regions in young adults and examined differences in amyloid deposition between these regions across groups. Two-way analyses of variance were conducted to assess regional differences in age and amyloid-β-related changes in glucose metabolism. Multiple regressions were applied to examine the association between amyloid-β deposition and regional glucose metabolism. Both region of interest and whole-brain voxelwise analyses were conducted to complement and confirm the results derived from the other approach. Regional differences in glucose metabolism between the highest and lowest metabolism regions defined in young adults (T = 12.85, P < 0.001) were maintained both in Pittsburgh compound B-negative cognitively normal older subjects (T = 6.66, P < 0.001) and Pittsburgh compound B-positive cognitively normal older subjects (T = 10.62, P < 0.001), but, only the Pittsburgh compound B-positive cognitively normal older subjects group showed significantly higher Pittsburgh compound B retention in the highest compared to the lowest glucose metabolism regions defined in young adults (T = 2.05, P < 0.05). Regional differences in age and amyloid-β-dependent changes in glucose metabolism were found such that frontal glucose metabolism was reduced with age, while glucose metabolism in the precuneus was maintained across the lifespan (right hemisphere: F = 7.69, P < 0.001; left hemisphere: F = 8.69, P < 0.001). Greater Alzheimer's disease-related hypometabolism was observed in brain regions that showed both age-invariance and amyloid-β-related increases in glucose metabolism. Our results indicate that although early and life-long regional variation in glucose metabolism relates to the regional vulnerability to amyloid-β accumulation, Alzheimer's disease-related hypometabolism is more specific to brain regions showing age-invariant glucose metabolism and amyloid-β-related hypermetabolism.
authors.affiliation: 1 Helen Wills Neuroscience Institute, University of California-Berkeley, Berkeley, CA 94720, USA hwamee.oh@columbia.edu.
authors.forename: Hwamee
authors.initials: H
authors.lastname: Oh
authors.affiliation: 1 Helen Wills Neuroscience Institute, University of California-Berkeley, Berkeley, CA 94720, USA.
authors.forename: Cindee
authors.initials: C
authors.lastname: Madison
authors.affiliation: 2 Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Baker
authors.affiliation: 1 Helen Wills Neuroscience Institute, University of California-Berkeley, Berkeley, CA 94720, USA 2 Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA 3 Memory and Aging Center and Department of Neurology, University of California-San Francisco, San Francisco, CA 94117, USA.
authors.forename: Gil
authors.initials: G
authors.lastname: Rabinovici
authors.affiliation: 1 Helen Wills Neuroscience Institute, University of California-Berkeley, Berkeley, CA 94720, USA 2 Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors.forename: William
authors.initials: W
authors.lastname: Jagust
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D013844:Thiazoles; D055815:Young Adult
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D019275:Radiopharmaceuticals; D013844:Thiazoles; D019788:Fluorodeoxyglucose F18; D005947:Glucose
keywords: Alzheimer’s disease pathology; beta-amyloid deposition; cognitively normal older adults; glucose metabolism; regional vulnerability