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Early Neuropsychological Characteristics of Progranulin Mutation Carriers

Published online by Cambridge University Press:  04 July 2014

Bradley J. Hallam ,
Claudia Jacova ,
Ging-Yuek R. Hsiung ,
Dana Wittenberg ,
Pheth Sengdy ,
Phoenix Bouchard-Kerr ,
Penny Slack ,
Rosa Rademakers ,
Matthew Baker  and
Tiffany W. Chow
...Show all authors
Bradley J. Hallam*
Affiliation:
Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, British Columbia, Canada
Claudia Jacova
Affiliation:
Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, British Columbia, Canada
Ging-Yuek R. Hsiung
Affiliation:
Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, British Columbia, Canada
Dana Wittenberg
Affiliation:
Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, British Columbia, Canada
Pheth Sengdy
Affiliation:
Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, British Columbia, Canada
Phoenix Bouchard-Kerr
Affiliation:
Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, British Columbia, Canada
Penny Slack
Affiliation:
Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, British Columbia, Canada
Rosa Rademakers
Affiliation:
Department of Neuroscience, Mayo Clinic, Jacksonville, Florida
Matthew Baker
Affiliation:
Department of Neuroscience, Mayo Clinic, Jacksonville, Florida
Tiffany W. Chow
Affiliation:
Department of Medicine, Division of Neurology, University of Toronto, Toronto, Ontario, Canada
Brian Levine
Affiliation:
Rotman Research Institute at Baycrest Health Sciences, Toronto, Ontario, Canada
Howard H. Feldman
Affiliation:
Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, British Columbia, Canada
Ian R. Mackenzie
Affiliation:
Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada
*
Correspondence and reprint requests to: Bradley J. Hallam, GF Strong Rehabilitation Centre, 4255 Laurel Street, Vancouver, British Columbia V5Z 2G9, Canada. E-mail: brad.hallam@vch.ca
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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. (JINS, 2014, 20, 1–10)

Keywords

Ubiquitin positive frontotemporal dementiaGranulinFTLD with TDP-43 PathologyHereditary neurodegenerative diseaseCognitive symptomNeuropsychology
Type
Research Articles
Information
Journal of the International Neuropsychological Society , Volume 20 , Issue 7 , August 2014 , pp. 694 - 703
Copyright
Copyright © The International Neuropsychological Society 2014 

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