title: Early neuropsychological characteristics of progranulin mutation carriers.
abstract: Mutations in the progranulin gene (GRN) are a common cause of familial frontotemporal dementia. We used a comprehensive neuropsychological battery to investigate whether early cognitive changes could be detected in GRN mutation carriers before dementia onset. Twenty-four at-risk members from six families with known GRN mutations underwent detailed neuropsychological testing. Group differences were investigated by domains of attention, language, visuospatial function, verbal memory, non-verbal memory, working memory and executive function. There was a trend for mutation carriers (n=8) to perform more poorly than non-carriers (n=16) across neuropsychological domains, with significant between group differences for visuospatial function (p<.04; d=0.92) and working memory function (p<.02; d=1.10). Measurable cognitive differences exist before the development of frontotemporal dementia in subjects with GRN mutations. The neuropsychological profile of mutation carriers suggests early asymmetric, right hemisphere brain dysfunction that is consistent with recent functional imaging data from our research group and the broader literature.
authors.affiliation: 1Department of Medicine,Division of Neurology,University of British Columbia,Vancouver,British Columbia,Canada.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Hallam
authors.affiliation: 1Department of Medicine,Division of Neurology,University of British Columbia,Vancouver,British Columbia,Canada.
authors.forename: Claudia
authors.initials: C
authors.lastname: Jacova
authors.affiliation: 1Department of Medicine,Division of Neurology,University of British Columbia,Vancouver,British Columbia,Canada.
authors.forename: Ging-Yuek R
authors.initials: GY
authors.lastname: Hsiung
authors.affiliation: 1Department of Medicine,Division of Neurology,University of British Columbia,Vancouver,British Columbia,Canada.
authors.forename: Dana
authors.initials: D
authors.lastname: Wittenberg
authors.affiliation: 1Department of Medicine,Division of Neurology,University of British Columbia,Vancouver,British Columbia,Canada.
authors.forename: Pheth
authors.initials: P
authors.lastname: Sengdy
authors.affiliation: 1Department of Medicine,Division of Neurology,University of British Columbia,Vancouver,British Columbia,Canada.
authors.forename: Phoenix
authors.initials: P
authors.lastname: Bouchard-Kerr
authors.affiliation: 1Department of Medicine,Division of Neurology,University of British Columbia,Vancouver,British Columbia,Canada.
authors.forename: Penny
authors.initials: P
authors.lastname: Slack
authors.affiliation: 2Department of Neuroscience,Mayo Clinic,Jacksonville,Florida.
authors.forename: Rosa
authors.initials: R
authors.lastname: Rademakers
authors.affiliation: 2Department of Neuroscience,Mayo Clinic,Jacksonville,Florida.
authors.forename: Matthew
authors.initials: M
authors.lastname: Baker
authors.affiliation: 3Department of Medicine,Division of Neurology,University of Toronto,Toronto,Ontario,Canada.
authors.forename: Tiffany W
authors.initials: TW
authors.lastname: Chow
authors.affiliation: 4Rotman Research Institute at Baycrest Health Sciences,Toronto,Ontario,Canada.
authors.forename: Brian
authors.initials: B
authors.lastname: Levine
authors.affiliation: 1Department of Medicine,Division of Neurology,University of British Columbia,Vancouver,British Columbia,Canada.
authors.forename: Howard H
authors.initials: HH
authors.lastname: Feldman
authors.affiliation: 5Department of Pathology,University of British Columbia,Vancouver,British Columbia,Canada.
authors.forename: Ian R
authors.initials: IR
authors.lastname: Mackenzie
mesh_terms: D000328:Adult; D000368:Aged; D001288:Attention; D003072:Cognition Disorders / Q000209:etiology*; D004252:DNA Mutational Analysis; D005260:Female; D057180:Frontotemporal Dementia / Q000150:complications* / Q000235:genetics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D007802:Language; D008297:Male; D008568:Memory; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009483:Neuropsychological Tests; D000077153:Progranulins; D012372:ROC Curve; D018709:Statistics, Nonparametric; D014706:Verbal Learning
chemical_list: C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins