18F-fluorodeoxyglucose positron emission tomography, aging, and apolipoprotein E genotype in cognitively normal persons.
Our objective was to examine associations between glucose metabolism, as measured by (18)F-fluorodeoxyglucose positron emission tomography (FDG PET), and age and to evaluate the impact of carriage of an apolipoprotein E (APOE) ε4 allele on glucose metabolism and on the associations between glucose metabolism and age. We studied 806 cognitively normal (CN) and 70 amyloid-imaging-positive cognitively impaired participants (35 with mild cognitive impairment and 35 with Alzheimer's disease [AD] dementia) from the Mayo Clinic Study of Aging, Mayo Alzheimer's Disease Research Center and an ancillary study who had undergone structural MRI, FDG PET, and (11)C-Pittsburgh compound B (PiB) PET. Using partial volume corrected and uncorrected FDG PET glucose uptake ratios, we evaluated associations of regional FDG ratios with age and carriage of an APOE ε4 allele in CN participants between the ages of 30 and 95 years, and compared those findings with the cognitively impaired participants. In region-of-interest (ROI) analyses, we found modest but statistically significant declines in FDG ratio in most cortical and subcortical regions as a function of age. We also found a main effect of APOE ε4 genotype on FDG ratio, with greater uptake in ε4 noncarriers compared with carriers but only in the posterior cingulate and/or precuneus, lateral parietal, and AD-signature meta-ROI. The latter consisted of voxels from posterior cingulate and/or precuneus, lateral parietal, and inferior temporal. In age- and sex-matched CN participants the magnitude of the difference in partial volume corrected FDG ratio in the AD-signature meta-ROI for APOE ε4 carriers compared with noncarriers was about 4 times smaller than the magnitude of the difference between age- and sex-matched elderly APOE ε4 carrier CN compared with AD dementia participants. In an analysis in participants older than 70 years (31.3% of whom had elevated PiB), there was no interaction between PiB status and APOE ε4 genotype with respect to glucose metabolism. Glucose metabolism declines with age in many brain regions. Carriage of an APOE ε4 allele was associated with reductions in FDG ratio in the posterior cingulate and/or precuneus, lateral parietal, and AD-signature ROIs, and there was no interaction between age and APOE ε4 status. The posterior cingulate and/or precuneus and lateral parietal regions have a unique vulnerability to reductions in glucose metabolic rate as a function both of age and carriage of an APOE ε4 allele.
Department of Neurology, Mayo Clinic and Foundation, Rochester, MN, USA; Mayo Clinic Alzheimer's Disease Research Center, Mayo Clinic and Foundation, Rochester, MN, USA. Electronic address: knopman@mayo.edu.
David S
DS
Knopman
Mayo Clinic Alzheimer's Disease Research Center, Mayo Clinic and Foundation, Rochester, MN, USA; Department of Radiology, Mayo Clinic and Foundation, Rochester, MN, USA.
Clifford R
CR
Jack
Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, MN, USA.
Heather J
HJ
Wiste
Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, MN, USA.
Emily S
ES
Lundt
Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, MN, USA.
Stephen D
SD
Weigand
Department of Neurology, Mayo Clinic and Foundation, Rochester, MN, USA.
Prashanthi
P
Vemuri
Department of Radiology, Mayo Clinic and Foundation, Rochester, MN, USA.
Val J
VJ
Lowe
Department of Radiology, Mayo Clinic and Foundation, Rochester, MN, USA.
Kejal
K
Kantarci
Department of Radiology, Mayo Clinic and Foundation, Rochester, MN, USA.
Jeffrey L
JL
Gunter
Department of Radiology, Mayo Clinic and Foundation, Rochester, MN, USA.
Matthew L
ML
Senjem
Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, MN, USA.
Michelle M
MM
Mielke
Department of Neurology, Mayo Clinic and Foundation, Rochester, MN, USA; Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, MN, USA.
Rosebud O
RO
Roberts
Department of Neurology, Mayo Clinic and Foundation, Rochester, MN, USA; Mayo Clinic Alzheimer's Disease Research Center, Mayo Clinic and Foundation, Rochester, MN, USA.
Bradley F
BF
Boeve
Department of Neurology, Mayo Clinic and Foundation, Rochester, MN, USA; Mayo Clinic Alzheimer's Disease Research Center, Mayo Clinic and Foundation, Rochester, MN, USA; Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, MN, USA.
Ronald C
RC
Petersen
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000378:metabolism*; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D053327:Apolipoprotein E4 / Q000235:genetics*; D001921:Brain / Q000378:metabolism*; D060825:Cognitive Dysfunction / Q000235:genetics / Q000378:metabolism; D005260:Female; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D005838:Genotype; D005947:Glucose / Q000378:metabolism*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals
D053327:Apolipoprotein E4; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D005947:Glucose
Aging; Alzheimer's disease; Apolipoprotein E; FDG positron emission tomography