© 2009 Psychology Press, an imprint of the Taylor & Francis Group, an Informa business http://www.psypress.com/jcen DOI: 10.1080/13803390903337878 JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY 2010, 32 (6), 590–598 NCEN A double blind evaluation of cognitive decline in a Norwegian cohort of asymptomatic carriers of Huntington’s disease Cognition In asymptomatic huntington’S disease Marleen R. van Walsem, 1 Kjetil Sundet, 2 Lars Retterstøl, 3 and Øyvind Sundseth 4 1 Oslo University Hospital, Rikshospitalet, Centre for Rare Disorders, Oslo, Norway 2 Institute of Psychology, University of Oslo, Oslo, Norway 3 Department of Medical Genetics, Oslo University Hospital, Ullevål, Norway 4 Department of Neuropsychology and Rehabilitation, Oslo University Hospital, Ullevål, Norway Previous studies investigating subclinical signs of cognitive decline in presymptomatic carriers of Huntington’s disease (HD) have shown conflicting results. The current study examines cognition in 105 at-risk individuals, using a broad neuropsychological test battery and adopting strict inclusion criteria for attaining a homogeneous sample. Results obtained by analyses of variance and effect size calculations indicate no clinical evidence of significant cognitive decline in asymptomatic HD carriers very far from onset of illness compared to noncarriers. Closeness to disease onset amongst gene carriers influenced cognition negatively whereas cytosine–adenine– guanine (CAG) repeat size did not. The findings call for longitudinal follow-up studies using a combination of clinical instruments and experimental paradigms to pinpoint when subtle cognitive deficits occur and within which of the cognitive domains. Keywords: Huntington’s disease; Cognition; Asymptomatic; Cytosine–adenine–guanine; Proximity to disease onset. INTRODUCTION Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder, which develops progressively and with great variability in disease onset. The disease is caused by a cytosine–adenine–guanine (CAG) repeat expansion of the gene IT15 on the short arm of chromo- some 4 (Gusella, Wexler, & Conneally, 1983; Huntington’s Disease Collaborative Research Group, 1993). Healthy individuals typically have a CAG repeat expansion vary- ing from 6 to 27. A CAG repeat expansion of 36 or more indicates a diagnosis of HD, while those individuals with 29–35 CAG repeats are unlikely to develop the disease themselves; they do, however, give a small risk to their children (Levin, Richie, & Jakupciak, 2006). The onset and development of symptoms (motor, cognitive and behavioral) are characterized by great diversity as well as severity. This makes it difficult to determine the start of clinical HD accurately. By conven- tion, HD is diagnosed when an individual has a positive family history of HD and unequivocal motor signs. However, less distinctive symptoms such as behavioral alterations and cognitive decline may appear earlier than involuntary movements. Healthy individuals who are gene carriers provide a unique opportunity to examine the earliest signs and progression of HD. Insight into subclinical signs of neurodegeneration will be critical for the design of future clinical trials of prophylactic and early treatment. Investigations of asymptomatic gene carriers by means of brain imaging techniques provide evidence for physical changes in brain regions that are involved in cognitive functions well before the onset of clinical HD. For example, Ciarmiello et al. (2006) found significant The authors would like to thank Olga Solberg and Kristin Eiklind for their help with obtaining and documenting the results of the predictive test procedure and Jenny Keylock for her help in language editing. Preliminary results of this study were presented during the Annual Plenary meeting of the European Huntington’s Disease Network (EHDN) 2009 in Lisbon, Portugal. Address correspondence to Marleen R. van Walsem, Oslo University Hospital, Rikshospitalet, Centre for Rare Disorders, Oslo, Norway (E-mail: marleen.walsem@rikshospitalet.no or marleenvanwalsem@yahoo.com).