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Maternal family history of Alzheimer's disease predisposes to reduced brain glucose metabolism.

TitleMaternal family history of Alzheimer's disease predisposes to reduced brain glucose metabolism.
Publication TypeJournal Article
Year of Publication2007
AuthorsMosconi L, Brys M, Switalski R, Mistur R, Glodzik L, Pirraglia E, Tsui W, De Santi S, de Leon MJ
JournalProc Natl Acad Sci U S A
Volume104
Issue48
Pagination19067-72
Date Published2007 Nov 27
ISSN1091-6490
KeywordsAged, Aged, 80 and over, Alzheimer Disease, Apolipoprotein E4, Brain Mapping, Cerebral Cortex, Female, Fluorine Radioisotopes, Fluorodeoxyglucose F18, Genes, Mitochondrial, Genetic Heterogeneity, Genetic Predisposition to Disease, Genomic Imprinting, Glucose, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Mothers, Positron-Emission Tomography, Retrospective Studies, Risk
Abstract

Having a parent affected with late-onset Alzheimer's disease (AD) is a risk factor for developing AD among cognitively normal subjects. We examined whether cognitively normal subjects with a parental family history of AD show cerebral metabolic rate of glucose (CMRglc) reductions consistent with AD as compared with those without a family history and whether there are parent gender effects. Forty-nine 50- to 80-year-old normal subjects were examined who received clinical, neuropsychological, and 2-[(18)F]fluoro-2-deoxy-d-glucose-positron emission tomography examinations, including 16 subjects with a maternal (FHm) and eight with a paternal (FHp) family history of AD and 25 with no family history (FH(-)). FH groups were comparable for demographic and neuropsychological measures. As compared with both FH(-) and FHp groups, FHm subjects showed CMRglc reductions in the same regions as clinically affected AD patients, involving the posterior cingulate cortex/precuneus, parietotemporal and frontal cortices, and medial temporal lobes (P < 0.05, corrected for multiple comparisons). These effects remained significant after accounting for possible risk factors for AD, including age, gender, education, apolipoprotein E genotype, and subjective memory complaints. No CMRglc differences were found between FHp and FH(-) subjects. This study shows a relationship between reduced CMRglc in AD-vulnerable brain regions and a maternal family history of AD in cognitively normal individuals.

DOI10.1073/pnas.0705036104
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID18003925
PubMed Central IDPMC2141909
Grant ListR01 AG022374 / AG / NIA NIH HHS / United States
M01 RR000096 / RR / NCRR NIH HHS / United States
R01 AG013616 / AG / NIA NIH HHS / United States
P30 AG008051 / AG / NIA NIH HHS / United States
R01 AG012101 / AG / NIA NIH HHS / United States
M01-RR0096 / RR / NCRR NIH HHS / United States
AG022374 / AG / NIA NIH HHS / United States
AG13616 / AG / NIA NIH HHS / United States
AG08051 / AG / NIA NIH HHS / United States
AG12101 / AG / NIA NIH HHS / United States

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