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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 104; no. 48; pp. 19067 - 19072
• Main Authors: Mosconi, Lisa, Brys, Miroslaw, Switalski, Remigiusz, Mistur, Rachel, Glodzik, Lidia, Pirraglia, Elizabeth, Tsui, Wai, De Santi, Susan, de Leon, Mony J
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 27.11.2007; National Acad Sciences
• Series: From the Cover
• Subjects: Aged; Aged, 80 and over; Alzheimer disease; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - epidemiology; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer's disease; Alzheimers disease; apolipoprotein E; Apolipoprotein E4 - genetics; Biological Sciences; brain; Brain Mapping; Cerebral Cortex - diagnostic imaging; Cerebral Cortex - metabolism; Cognition & reasoning; cortex; Dementia; education; Effects; Family history; Female; Fluorine Radioisotopes - pharmacokinetics; Fluorodeoxyglucose F18 - pharmacokinetics; gender; Genes, Mitochondrial; Genetic Heterogeneity; Genetic Predisposition to Disease; Genetics; Genomic Imprinting; genotype; Genotypes; Glucose; Glucose - metabolism; Humans; Magnetic Resonance Imaging; Male; memory; Metabolism; Middle Aged; Mitochondrial DNA; Mothers; Neurology; Parents; Parietal lobe; patients; Positron emission tomography; Predisposing factors; Retrospective Studies; Risk; Risk factors; tomography
• DOI: 10.1073/pnas.0705036104
• ISSN: 0027-8424; 1091-6490

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-[¹⁸F]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.