title: Influence of family history of dementia in the development and progression of late-onset Alzheimer's disease.
abstract: Family history of dementia (FH) is a recognized risk factor for developing late-onset Alzheimer's disease (AD). We asked whether having FH increases AD risk and influences disease severity (age at onset and cognitive impairment) in 420 AD patients and 109 controls with (FH+) or without (FH-). The relationships of APOE and other AD risk genes with FH were analyzed as well. The proportion of APOE e4 allele carriers was higher among the FH+ than the FH- AD patients (49.6% vs. 38.9%; P = 0.04). The distribution of the risk genotypes of nine AD susceptibility genes previously examined (CHAT, CYP17, CYP19, ESR1, FSHR, P53, P73, P21, PPARG) did not differ between the FH+ and the FH- AD patients, indicating that none contributed significantly to familial clustering of disease. FH was associated with an increased AD risk (odds ratio [OR] 2.71, 95% confidence interval [CI] 1.44-5.09; P = 0.002) independent of carrying the APOE e4 allele (OR 2.61, 95%CI 1.53-4.44; P = 0.0004). Having a first-degree relative or a parent with dementia was significantly associated with AD risk (OR 2.9, 95%CI 1.3-6.4; P = 0.009 and OR 2.7, 95%CI 1.1-6.2; P = 0.02) but having a sibling with dementia was not (OR 1.7, 95%CI 0.2 to 14.7; P = 0.6). Among the FH+ AD patients, having one or both parents affected seemed to raise the risk of earlier onset age (P = 0.02) and greater cognitive impairment (P = 0.02) than having only an affected sibling, whereas having two or more affected relatives did not.
authors.affiliation: CNR Institute of Cellular Biology and Neurobiology, Monterotondo Scalo, Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Scarabino
authors.affiliation: Department of Neuroscience, Alzheimer's Disease Center, University and Hospital of Verona, Verona, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gambina
authors.affiliation: Department of Neuroscience, Alzheimer's Disease Center, University and Hospital of Verona, Verona, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Broggio
authors.affiliation: Department of Biology and Biotechnology "Charles Darwin," Sapienza University, Rome, Italy.
authors.forename: Franca
authors.initials: F
authors.lastname: Pelliccia
authors.affiliation: Department of Biology and Biotechnology "Charles Darwin," Sapienza University, Rome, Italy.|Department of Biology and Biotechnology "Charles Darwin," CNR Institute of Molecular Biology and Pathology, Sapienza University, Rome, Italy.
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Corbo
mesh_terms: D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000209:etiology*; D001057:Apolipoproteins E / Q000235:genetics; D016022:Case-Control Studies; D060825:Cognitive Dysfunction / Q000150:complications / Q000235:genetics; D003704:Dementia / Q000150:complications*; D018450:Disease Progression; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D012307:Risk Factors
chemical_list: D001057:Apolipoproteins E
keywords: Alzheimer's disease; family history; first degree relatives