{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T18:21:52Z","timestamp":1794075712292,"version":"4.8.0"},"reference-count":41,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2021,8,23]],"date-time":"2021-08-23T00:00:00Z","timestamp":1629676800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Efficient cognitive tasks sensitive to longitudinal deterioration in small cohorts of Huntington\u2019s disease (HD) patients are lacking in HD research. We thus developed and assessed the digitized arithmetic task (DAT), which combines inner language and executive functions in approximately 4 minutes.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We assessed the psychometric properties of DAT in three languages, across four European sites, in 77 early-stage HD patients (age: 52 \u00b1 11 years; 27 females), and 57 controls (age: 50 \u00b1 10, 31 females). Forty-eight HD patients and 34 controls were followed up to one year with 96 participants who underwent MRI brain imaging (HD patients = 46) at baseline and 50 participants (HD patients = 22) at one year. Linear mixed models and Pearson correlations were used to assess associations with clinical assessment.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>At baseline, HD patients were less accurate (p = 0.0002) with increased response time (p&lt;0.0001) when compared to DAT in controls. Test-retest reliability in HD patients ranged from good to excellent for response time (range: 0.63\u20130.79) and from questionable to acceptable for accuracy (range: r = 0.52\u20130.69). Only DAT, the Mattis Dementia Rating Scale, the Symbol Digit Modalities Test, and Total Functional Capacity scores were able to detect a decline within a one-year follow-up in HD patients (all p&lt; 0.05). In contrast with all the other cognitive tasks, DAT correlated with striatal atrophy over time (p = 0.037) but not with motor impairment.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>DAT is fast, reliable, motor-free, applicable in several languages, and able to unmask cognitive decline correlated with striatal atrophy in small cohorts of HD patients. This likely makes it a useful endpoint in future trials for HD and other neurodegenerative diseases.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0253064","type":"journal-article","created":{"date-parts":[[2021,8,23]],"date-time":"2021-08-23T17:46:56Z","timestamp":1629740816000},"page":"e0253064","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Cognitive decline in Huntington\u2019s disease in the Digitalized Arithmetic Task (DAT)"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9431-5980","authenticated-orcid":true,"given":"Marine","family":"Lunven","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Hamet Bagnou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia","family":"Youssov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Gabadinho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafika","family":"Fliss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justine","family":"Montillot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etienne","family":"Audureau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blanche","family":"Bapst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gra\u00e7a","family":"Morgado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5904-9517","authenticated-orcid":true,"given":"Ralf","family":"Reilmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Schubert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Busse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Craufurd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renaud","family":"Massart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4716-4753","authenticated-orcid":true,"given":"Anne","family":"Rosser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Catherine","family":"Bachoud-L\u00e9vi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,8,23]]},"reference":[{"key":"pone.0253064.ref001","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/0092-8674(93)90585-E","article-title":"A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington\u2019s disease chromosomes","volume":"72","author":"ME MacDonald","year":"1993","journal-title":"Cell"},{"key":"pone.0253064.ref002","article-title":"Targeting Huntingtin Expression in Patients with Huntington\u2019s Disease","author":"SJ Tabrizi","year":"2019","journal-title":"N Engl J Med"},{"key":"pone.0253064.ref003","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/S1474-4422(17)30280-6","article-title":"Therapies targeting DNA and RNA in Huntington\u2019s disease","volume":"16","author":"EJ Wild","year":"2017","journal-title":"Lancet Neurol"},{"key":"pone.0253064.ref004","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1002\/mds.26011","article-title":"Diagnostic criteria for Huntington\u2019s disease based on natural history","volume":"29","author":"R Reilmann","year":"2014","journal-title":"Mov Disord Off J Mov Disord Soc"},{"key":"pone.0253064.ref005","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1002\/mds.27227","article-title":"Rating scales for cognition in Huntington\u2019s disease: Critique and recommendations","volume":"33","author":"TA Mestre","year":"2018","journal-title":"Mov Disord Off J Mov Disord Soc"},{"key":"pone.0253064.ref006","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/S1474-4422(14)70262-5","article-title":"Safety, tolerability, and efficacy of PBT2 in Huntington\u2019s disease: a phase 2, randomised, double-blind, placebo-controlled trial","volume":"14","author":"Huntington Study Group Reach2HD Investigators","year":"2015","journal-title":"Lancet Neurol"},{"key":"pone.0253064.ref007","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1002\/mds.870110204","article-title":"Unified Huntington\u2019s Disease Rating Scale: reliability and consistency","volume":"11","author":"Huntington Study Group","year":"1996","journal-title":"Huntington Study Group. Mov Disord Off J Mov Disord Soc"},{"key":"pone.0253064.ref008","first-page":"1520","article-title":"Natural history of Huntington disease","volume":"70","author":"ER Dorsey","year":"2013","journal-title":"JAMA Neurol"},{"key":"pone.0253064.ref009","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1136\/jnnp-2011-301940","article-title":"Evaluation of longitudinal 12 and 24 month cognitive outcomes in premanifest and early Huntington\u2019s disease","volume":"83","author":"JC Stout","year":"2012","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"pone.0253064.ref010","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/S1474-4422(13)70088-7","article-title":"Predictors of phenotypic progression and disease onset in premanifest and early-stage Huntington\u2019s disease in the TRACK-HD study: analysis of 36-month observational data","volume":"12","author":"SJ Tabrizi","year":"2013","journal-title":"Lancet Neurol"},{"key":"pone.0253064.ref011","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1002\/mds.25964","article-title":"HD-CAB: A cognitive assessment battery for clinical trials in Huntington\u2019s disease 1,2,3: HD-Cab in Huntington\u2019s Disease","volume":"29","author":"JC Stout","year":"2014","journal-title":"Mov Disord"},{"key":"pone.0253064.ref012","doi-asserted-by":"crossref","first-page":"e0145842","DOI":"10.1371\/journal.pone.0145842","article-title":"How to Capitalize on the Retest Effect in Future Trials on Huntington\u2019s Disease","volume":"10","author":"C Schramm","year":"2015","journal-title":"PloS One"},{"key":"pone.0253064.ref013","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1136\/jnnp-2012-302441","article-title":"The long-term safety and efficacy of bilateral transplantation of human fetal striatal tissue in patients with mild to moderate Huntington\u2019s disease","volume":"84","author":"RA Barker","year":"2013","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"pone.0253064.ref014","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1212\/01.WNL.0000098878.47789.BD","article-title":"Profile of cognitive progression in early Huntington\u2019s disease","volume":"61","author":"AK Ho","year":"2003","journal-title":"Neurology"},{"key":"pone.0253064.ref015","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/S1474-4422(20)30143-5","article-title":"Biological and clinical characteristics of gene carriers far from predicted onset in the Huntington\u2019s disease Young Adult Study (HD-YAS): a cross-sectional analysis","volume":"19","author":"RI Scahill","year":"2020","journal-title":"Lancet Neurol"},{"key":"pone.0253064.ref016","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.cortex.2017.07.022","article-title":"A systematic linguistic profile of spontaneous narrative speech in pre-symptomatic and early stage Huntington\u2019s disease","volume":"100","author":"W Hinzen","year":"2018","journal-title":"Cortex J Devoted Study Nerv Syst Behav"},{"key":"pone.0253064.ref017","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1007\/s11910-011-0215-x","article-title":"Cognitive Impairment in Huntington Disease: Diagnosis and Treatment","volume":"11","author":"JS Paulsen","year":"2011","journal-title":"Curr Neurol Neurosci Rep"},{"key":"pone.0253064.ref018","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1093\/brain\/awn036","article-title":"Language processing within the striatum: evidence from a PET correlation study in Huntington\u2019s disease","volume":"131","author":"M Teichmann","year":"2008","journal-title":"Brain"},{"key":"pone.0253064.ref019","doi-asserted-by":"crossref","DOI":"10.1371\/currents.RRN1288","article-title":"Seven-year clinical follow-up of premanifest carriers of Huntington\u2019s disease","volume":"3","author":"E Hart","year":"2011","journal-title":"PLoS Curr"},{"key":"pone.0253064.ref020","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.bandl.2015.02.004","article-title":"Phonology and arithmetic in the language-calculation network","volume":"143","author":"J Andin","year":"2015","journal-title":"Brain Lang"},{"key":"pone.0253064.ref021","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1093\/brain\/awh472","article-title":"The role of the striatum in rule application: the model of Huntington\u2019s disease at early stage","volume":"128","author":"M Teichmann","year":"2005","journal-title":"Brain J Neurol"},{"key":"pone.0253064.ref022","article-title":"Cortical thickness, stance control, and arithmetic skill: An exploratory study in premanifest Huntington disease","author":"L Nanetti","year":"2018","journal-title":"Parkinsonism Relat Disord"},{"key":"pone.0253064.ref023","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1212\/WNL.31.10.1333","article-title":"Huntington disease: functional capacities in patients treated with neuroleptic and antidepressant drugs","volume":"31","author":"I. Shoulson","year":"1981","journal-title":"Neurology"},{"key":"pone.0253064.ref024","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1002\/ana.410410521","article-title":"CAG repeat number governs the development rate of pathology in Huntington\u2019s disease","volume":"41","author":"JB Penney","year":"1997","journal-title":"Ann Neurol"},{"key":"pone.0253064.ref025","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/S0010-9452(86)80030-2","article-title":"An assessment of verbal recall, recognition and fluency abilities in patients with Huntington\u2019s disease","volume":"22","author":"N Butters","year":"1986","journal-title":"Cortex J Devoted Study Nerv Syst Behav"},{"key":"pone.0253064.ref026","article-title":"Mental status examination for organic mental syndrome in the elderly patients","author":"S. Mattis","year":"1976","journal-title":"Geriatr Psychiatry Hand Book Psychiatr Prim Care Physicians"},{"key":"pone.0253064.ref027","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1080\/13854049108403297","article-title":"The Hopkins Verbal Learning Test: Development of a new memory test with six equivalent forms","volume":"5","author":"J. Brandt","year":"1991","journal-title":"Clin Neuropsychol"},{"key":"pone.0253064.ref028","doi-asserted-by":"crossref","first-page":"5","DOI":"10.5334\/pb-51-1-5","article-title":"Combining Speed and Accuracy in Cognitive Psychology: Is the Inverse Efficiency Score (IES) a Better Dependent Variable than the Mean Reaction Time (RT) and the Percentage Of Errors (PE)?","volume":"51","author":"R Bruyer","year":"2011","journal-title":"Psychol Belg"},{"key":"pone.0253064.ref029","doi-asserted-by":"crossref","first-page":"40","DOI":"10.3758\/s13428-018-1076-x","article-title":"Combining speed and accuracy to control for speed-accuracy trade-offs(?).","volume":"51","author":"HR Liesefeld","year":"2019","journal-title":"Behav Res Methods"},{"key":"pone.0253064.ref030","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/S0896-6273(02)00569-X","article-title":"Whole Brain Segmentation: Automated Labeling of Neuroanatomical Structures in the Human Brain","volume":"33","author":"B Fischl","year":"2002","journal-title":"Neuron"},{"key":"pone.0253064.ref031","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v067.i01","article-title":"Fitting Linear Mixed-Effects Models Using lme4","volume":"67","author":"D Bates","year":"2015","journal-title":"J Stat Softw"},{"key":"pone.0253064.ref032","doi-asserted-by":"crossref","first-page":"2495","DOI":"10.1212\/WNL.0000000000004743","article-title":"Motor, cognitive, and functional declines contribute to a single progressive factor in early HD","volume":"89","author":"SA Schobel","year":"2017","journal-title":"Neurology"},{"key":"pone.0253064.ref033","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/bs.pbr.2016.12.011","article-title":"From open to large-scale randomized cell transplantation trials in Huntington\u2019s disease: Lessons from the multicentric intracerebral grafting in Huntington\u2019s disease trial (MIG-HD) and previous pilot studies","volume":"230","author":"A-C Bachoud-L\u00e9vi","year":"2017","journal-title":"Prog Brain Res"},{"key":"pone.0253064.ref034","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/j.neuron.2019.05.001","article-title":"Huntingtin Lowering Strategies for Disease Modification in Huntington\u2019s Disease","volume":"102","author":"SJ Tabrizi","year":"2019","journal-title":"Neuron"},{"key":"pone.0253064.ref035","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1212\/01.wnl.0000261918.90053.96","article-title":"Predictors of diagnosis in Huntington disease","volume":"68","author":"Huntington Study Group","year":"2007","journal-title":"Neurology"},{"key":"pone.0253064.ref036","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1212\/WNL.45.5.951","article-title":"Distinct cognitive profiles of cortical and subcortical dementia in advanced illness","volume":"45","author":"JS Paulsen","year":"1995","journal-title":"Neurology"},{"key":"pone.0253064.ref037","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1001\/archneur.1989.00520470060028","article-title":"Differentiation of Alzheimer\u2019s disease and Huntington\u2019s disease with the Dementia Rating Scale","volume":"46","author":"DP Salmon","year":"1989","journal-title":"Arch Neurol"},{"key":"pone.0253064.ref038","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1212\/WNL.56.8.1052","article-title":"Retest effects and cognitive decline in longitudinal follow-up of patients with early HD","volume":"56","author":"AC Bachoud-L\u00e9vi","year":"2001","journal-title":"Neurology"},{"key":"pone.0253064.ref039","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1002\/ana.25862","article-title":"Alertness Training Improves Spatial Bias and Functional Ability in Spatial Neglect","volume":"88","author":"T Van Vleet","year":"2020","journal-title":"Ann Neurol"},{"key":"pone.0253064.ref040","doi-asserted-by":"crossref","first-page":"104125","DOI":"10.1016\/j.cognition.2019.104125","article-title":"Delayed disengagement of attention from distractors signalling reward","volume":"195","author":"P Watson","year":"2020","journal-title":"Cognition"},{"key":"pone.0253064.ref041","volume-title":"Cambridge Cambridgeshire","author":"JT Townsend","year":"1984"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0253064","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,23]],"date-time":"2021-08-23T17:47:36Z","timestamp":1629740856000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0253064"}},"subtitle":[],"editor":[{"given":"Gianluigi","family":"Forloni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,8,23]]},"references-count":41,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8,23]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0253064","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,23]]}}}