title: Visual Working Memory Impairment in Premanifest Gene-Carriers and Early Huntington's Disease.
abstract: Working memory deficits have been found in Huntington's disease (HD) and in a small group of premanifest (PreHD) gene-carriers. However, the nature and extent of these deficits are unknown. In a large cross-sectional study, we aimed to determine the degree of visuospatial working memory dysfunction across multiple stages of HD. Specifically, visuospatial working memory capacity and response times across various degrees of difficulty were examined, as well as the relationship between visuospatial working memory and motor dysfunction. We examined 62 PreHD-A gene-carriers (>10.8 years from estimated disease onset), 58 PreHD-B gene-carriers (<10.8 years from estimated disease onset), 77 stage-1 HD patients (HD1), 44 stage-2 HD patients (HD2), and 122 healthy controls. Participants viewed coloured squares (in sets of 3, 5 and 7) on a screen and were to decide whether on a subsequent screen the encircled square has changed colour. Accuracy and response times were recorded. Compared to controls, significant group differences in visuospatial working memory capacity (accuracy) were seen in PreHD-B, HD1 and HD2 groups across the difficulty levels. Significant group differences on response times were found for all groups (PreHD-A to HD2) compared to controls; the most difficult level producing the only group difference in speed between PreHD-A and controls. Accuracy and speed were positively correlated only in the HD groups. These findings suggest that visuospatial working memory impairments are detectable in both premanifest and manifest HD; the manifest HD showed evidence for a "worse-worse phenomenon" whereby reductions were present in both motor speed and accuracy.
authors: Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands.
authors: Eve M
authors: EM
authors: Dumas
authors: UCL Institute of Neurology, University College London, Queen Square, London, UK.
authors: Miranda J
authors: MJ
authors: Say
authors: Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK.
authors: Rebecca
authors: R
authors: Jones
authors: School of Psychology and Psychiatry, Monash University, Clayton Campus, VIC, Australia.
authors: Izelle
authors: I
authors: Labuschagne
authors: School of Psychology and Psychiatry, Monash University, Clayton Campus, VIC, Australia.
authors: Alison M
authors: AM
authors: O'Regan
authors: Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands.
authors: Ellen P
authors: EP
authors: Hart
authors: Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands.
authors: Simon J A
authors: SJ
authors: van den Bogaard
authors: Queller Consulting, Dunedin, FL, USA.
authors: Sarah
authors: S
authors: Queller
authors: Department of Genetics and Cytogenetics, and INSERM UMR S679, APHP Hôpital de la Salpêtrière, Paris, France.
authors: Damian
authors: D
authors: Justo
authors: Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
authors: Allison
authors: A
authors: Coleman
authors: Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
authors: Rachelle C
authors: RC
authors: Dar Santos
authors: Department of Genetics and Cytogenetics, and INSERM UMR S679, APHP Hôpital de la Salpêtrière, Paris, France.
authors: Alexandra
authors: A
authors: Dürr
authors: Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
authors: Blair R
authors: BR
authors: Leavitt
authors: UCL Institute of Neurology, University College London, Queen Square, London, UK.
authors: Sarah J
authors: SJ
authors: Tabrizi
authors: Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands.
authors: Raymund A C
authors: RA
authors: Roos
authors: School of Psychology and Psychiatry, Monash University, Clayton Campus, VIC, Australia.
authors: Julie C
authors: JC
authors: Stout
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D006816:Huntington Disease / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D008570:Memory, Short-Term; D008875:Middle Aged; D009483:Neuropsychological Tests
keywords: Huntington's disease; cognitive dysfunction; premanifest gene-carriers; visual working memory