Journal of the International Neuropsychological Society

Brief Communication

Neuropsychological Features of Asymptomatic c.709-1G>A Progranulin Mutation Carriers  *

Myriam Barandiarana1a2a3 c1, Ainara Estangaa2a3a4, Fermín Morenoa1a2a3a4, Begoña Indakoetxeaa1a2a3a4, Ainhoa Alzualdea2a3a4, Nekane Balluerkaa5, José Félix Martí Massóa1a2a3a4 and Adolfo López de Munaina1a2a3a4

a1 Department of Neurology, Hospital Donostia, San Sebastián, Gipuzkoa, Spain

a2 Centro de Investigación en Red sobre Enfermedades Neurodegenerativas (CIBERNED, area 6), Gipuzkoa, Spain

a3 Neurogenetics Research Unit, Ilundain Fundazioa, Gipuzkoa, Spain

a4 Neurociences Area, Institute Biodonostia, San Sebastián, Gipuzkoa, Spain

a5 Department of Social Psychology and Methodology of Behavioral Sciences, University of the Basque Country, San Sebastián, Spain


Mutations in the progranulin (PGRN) gene have been identified as a cause of frontotemporal dementia (FTD). However, little is known about the neuropsychological abilities of asymptomatic carriers of these mutations. The aim of the study was to assess cognitive functioning in asymptomatic c.709-1G>A PGRN mutation carriers. We hypothesized that poorer neuropsychological performance could be present before the development of clinically significant FTD symptoms. Thirty-two asymptomatic first-degree relatives of FTD patients carrying the c.709-1G>A mutation served as study participants, including 13 PGRN mutation carriers (A-PGRN+) and 19 non-carriers (PGRN-). A neuropsychological battery was administered. We found that the A-PGRN+ participants obtained significantly poorer scores than PGRN- individuals on tests of attention (Trail-Making Test Part A), mental flexibility (Trail-Making Test Part B), and language (Boston Naming Test). Poorer performance on these tests in asymptomatic PGRN mutation carriers may reflect a prodromal phase preceding the onset of clinically significant symptoms of FTD. (JINS, 2012, 18, 1086–1090)

(Received September 23 2011)

(Revised May 16 2012)

(Accepted May 16 2012)


  • Frontotemporal dementia;
  • Cognition;
  • Executive function;
  • Attention;
  • Primary progressive aphasia;
  • Early diagnosis


c1 Correspondence and reprint requests to: Myriam Barandiaran, Department of Neurology, Hospital Donostia, Paseo Dr Begiristain sn, CP 20014, San Sebastian, Gipuzkoa, Spain. E-mail:


*  Authors’ Disclosure and Study Funding: This work was supported by Diputación Foral de Gipuzkoa (dossier 76/08) and the Basque Government (SAIOTEK program). Dr. López de Munain is a PhD with funding from the Instituto de Salud Carlos III. Authors report no disclosures.