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

Published online by Cambridge University Press:  16 November 2012

Myriam Barandiaran ,
Ainara Estanga ,
Fermín Moreno ,
Begoña Indakoetxea ,
Ainhoa Alzualde ,
Nekane Balluerka ,
José Félix Martí Massó  and
Adolfo López de Munain
Myriam Barandiaran*
Affiliation:
Department of Neurology, Hospital Donostia, San Sebastián, Gipuzkoa, Spain Centro de Investigación en Red sobre Enfermedades Neurodegenerativas (CIBERNED, area 6), Gipuzkoa, Spain Neurogenetics Research Unit, Ilundain Fundazioa, Gipuzkoa, Spain
Ainara Estanga
Affiliation:
Centro de Investigación en Red sobre Enfermedades Neurodegenerativas (CIBERNED, area 6), Gipuzkoa, Spain Neurogenetics Research Unit, Ilundain Fundazioa, Gipuzkoa, Spain Neurociences Area, Institute Biodonostia, San Sebastián, Gipuzkoa, Spain
Fermín Moreno
Affiliation:
Department of Neurology, Hospital Donostia, San Sebastián, Gipuzkoa, Spain Centro de Investigación en Red sobre Enfermedades Neurodegenerativas (CIBERNED, area 6), Gipuzkoa, Spain Neurogenetics Research Unit, Ilundain Fundazioa, Gipuzkoa, Spain Neurociences Area, Institute Biodonostia, San Sebastián, Gipuzkoa, Spain
Begoña Indakoetxea
Affiliation:
Department of Neurology, Hospital Donostia, San Sebastián, Gipuzkoa, Spain Centro de Investigación en Red sobre Enfermedades Neurodegenerativas (CIBERNED, area 6), Gipuzkoa, Spain Neurogenetics Research Unit, Ilundain Fundazioa, Gipuzkoa, Spain Neurociences Area, Institute Biodonostia, San Sebastián, Gipuzkoa, Spain
Ainhoa Alzualde
Affiliation:
Centro de Investigación en Red sobre Enfermedades Neurodegenerativas (CIBERNED, area 6), Gipuzkoa, Spain Neurogenetics Research Unit, Ilundain Fundazioa, Gipuzkoa, Spain Neurociences Area, Institute Biodonostia, San Sebastián, Gipuzkoa, Spain
Nekane Balluerka
Affiliation:
Department of Social Psychology and Methodology of Behavioral Sciences, University of the Basque Country, San Sebastián, Spain
José Félix Martí Massó
Affiliation:
Department of Neurology, Hospital Donostia, San Sebastián, Gipuzkoa, Spain Centro de Investigación en Red sobre Enfermedades Neurodegenerativas (CIBERNED, area 6), Gipuzkoa, Spain Neurogenetics Research Unit, Ilundain Fundazioa, Gipuzkoa, Spain Neurociences Area, Institute Biodonostia, San Sebastián, Gipuzkoa, Spain
Adolfo López de Munain
Affiliation:
Department of Neurology, Hospital Donostia, San Sebastián, Gipuzkoa, Spain Centro de Investigación en Red sobre Enfermedades Neurodegenerativas (CIBERNED, area 6), Gipuzkoa, Spain Neurogenetics Research Unit, Ilundain Fundazioa, Gipuzkoa, Spain Neurociences Area, Institute Biodonostia, San Sebastián, Gipuzkoa, Spain
*
Correspondence and reprint requests to: Myriam Barandiaran, Department of Neurology, Hospital Donostia, Paseo Dr Begiristain sn, CP 20014, San Sebastian, Gipuzkoa, Spain. E-mail: [email protected]
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Abstract

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)

Keywords

Frontotemporal dementiaCognitionExecutive functionAttentionPrimary progressive aphasiaEarly diagnosis
Type
Brief Communication
Information
Journal of the International Neuropsychological Society , Volume 18 , Issue 6 , November 2012 , pp. 1086 - 1090
Copyright
Copyright © The International Neuropsychological Society 2012

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Footnotes

*

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.

References

Baker, M., Mackenzie, I.R., Pickering-Brown, S.M., Gass, J., Rademarkers, R., Lindholm, C., Hutton, M. (2006). Mutation in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature, 442, 916–919.CrossRefGoogle ScholarPubMed
Bateman, A., Bennett, H.P. (2009). The granulin gene family: From cancer to dementia. Bioessays, 31, 1245–1254.CrossRefGoogle ScholarPubMed
Bechara, A. (2007). Iowa Gambling Task. Lutz, FL: Psychological Assessment Resources.Google Scholar
Conners, C.K. (2000). Continuous Performance Test II. Toronto: Multi-Health Systems.Google Scholar
Cruts, M., Gijselinck, I., van der Zee, J., Engelborghs, S., Wils, H., Pirici, D., Van, B.C. (2006). Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21. Nature, 442, 920–924.CrossRefGoogle ScholarPubMed
Fisher, N.J., Tierney, M.C., Snow, W.G., Szalai, J.P. (1999). Odd/Even short forms of the Boston Naming test: Preliminary geriatric norms. Clinical Neuropsychology, 13(3), 359–364.CrossRefGoogle ScholarPubMed
Geschwind, D.H., Robidoux, J., Alarcon, M., Miller, B.L., Wilhelmsen, K.C., Cummings, J.L., Nasreddine, Z.S. (2001). Dementia and neurodevelopmental predisposition: Cognitive dysfunction in presymptomatic subjects precedes dementia by decades in frontotemporal dementia. Annals of Neurology, 50, 741–746.CrossRefGoogle ScholarPubMed
Ghidoni, R., Benussi, L., Glionna, M., Franzoni, M., Binetti, G. (2008). Low plasma progranulin levels predict progranulin mutations in frontotemporal lobar degeneration. Neurology, 71, 1235–1239.CrossRefGoogle ScholarPubMed
Heaton, R.K. (1981). Wisconsin Card Sorting Test (WCST). Odessa, FL: Psychological Assessment Resources.Google Scholar
López, M.J., Rodríguez, J.M., Santín, C., Torrico, E. (2003). Utilidad de las formas cortas de la Escala de Inteligencia de Wechsler para Adultos (WAIS). Anales de Psicología, 19, 53–63.Google Scholar
López de Munain, A., Alzualde, A., Gorostidi, A., Otaegui, D., Ruiz-Martínez, J., Indakoetxea, B., Martí Massó, J.F. (2008). Mutations in progranulin gene: Clinical, pathological, and ribonucleic acid expression findings. Biological Psychiatry, 63, 946–952.CrossRefGoogle ScholarPubMed
Moreno, F., Indakoetxea, B., Barandiaran, M., Alzualde, A., Gabilondo, A., Estanga, A., López de Munain, A. (2009). “Frontotemporoparietal” dementia: Clinical phenotype associated with the c.709-1G>A PGRN mutation. Neurology, 73, 1367–1374.CrossRefGoogle ScholarPubMed
Morris, J.C., Mohs, R.C., Rogers, H., Fillenbaum, G., Heyman, A. (1988). CERAD: Clinical and neuropsychological assessment of Alzheimer's disease. Psychopharmacological Bulletin, 24, 641–652.Google ScholarPubMed
Peña-Casanova, J., Blesa, R., Aguilar, M., Gramunt-Fombuena, N., Gómez-Ansón, B., Oliva, R., Sol, J.M., for the NEURONORMA Study Team (2009). Spanish multicenter normative studies (NEURONORMA Project): Methods and simple characteristics. Archives of Clinical Neuropsychology, 24, 307–319.CrossRefGoogle Scholar
Reitan, R.M. (1958). Validity of the Trail Making Test as an indicator of organic brain damage. Perceptual and Motor Skills, 8, 271–276.CrossRefGoogle Scholar
Rohrer, J.D., Crutch, S.J., Warrington, E.K., Warren, J.D. (2010). Progranulin-associated primary progressive aphasia: A distinct phenotype? Neuropsychologia, 48, 288–297.CrossRefGoogle ScholarPubMed
Rhorer, J.D., Warren, J.D. (2011). Phenotypic signatures of genetic frontotemporal dementia. Current Opinion in Neurology, 24, 542–549.CrossRefGoogle Scholar
Sawrie, S., Martin, R.C., Gillian, F.G., Faught, R.E., Maton, B., Hugg, J.W., Kuzniecky, R.I. (2000). Visual confrontation naming and hippocampal function. A neural network study using quantitative 1 H magnetic resonance spectroscopy. Brain, 123, 770–780.CrossRefGoogle ScholarPubMed
Tam, F., Churchill, N.W., Strother, S.C., Graham, S.J. (2011). A new tablet for writing and drawing during functional MRI. Human Brain Mapping, 32, 240–248.CrossRefGoogle ScholarPubMed
Torralva, T., Roca, M., Gleichgerrcht, E., Bekinschtein, T., Manes, F. (2009). A neuropsychological battery to detect specific executive and social cognitive impairments in early frontotemporal dementia. Brain, 132, 1299–1309.CrossRefGoogle ScholarPubMed
Wechsler, D. (1997). Wechsler Adult Intelligence Scale-III. San Antonio: The Psychological Corporation.Google Scholar
Zimmerman, P., Leclercq, M. (2002). Neuropsychological aspects of attentional functions and disturbances. In M. Leclercq & P. Zimmerman (Eds.), Applied neuropsychology of attention: Theory, diagnosis and rehabilitation. New York: Psychology Press.Google Scholar