Arithmetic Word-Problem Solving as Cognitive Marker of Progression in Pre-Manifest and Manifest Huntington’s Disease

Article type: Research Article

Authors: Horta-Barba, Andrea^{a; b; c; d; e} | Martinez-Horta, Saul^{a; b; c; d; e} | Perez-Perez, Jesús^{a; b; c; d; e} | Sampedro, Frederic^{a; b; c} | de Lucia, Natascia^{e; f} | De Michele, Giuseppe^{e; f} | Salvatore, Elena^{e; f} | Kehrer, Stefanie^{e; g} | Priller, Josef^{e; g} | Migliore, Simone^h | Squitieri, Ferdinando^h | Castaldo, Anna^{e; i} | Mariotti, Caterina^{e; i} | Mañanes, Veronica^{e; j} | Lopez-Sendon, Jose Luis^{e; j} | Rodriguez, Noelia^{e; k} | Martinez-Descals, Asunción^{e; k} | Júlio, Filipa^{e; l; m} | Janurio, Cristina^{e; l; m} | Delussi, Marianna^{e; n} | de Tommaso, Marina^{e; n} | Noguera, Sandra^{e; o} | Ruiz-Idiago, Jesus^{e; o} | Sitek, Emilia J.^{e; p; q} | Wallner, Renata^r | Nuzzi, Angela^e | Pagonabarraga, Javier^{a; b; c; d; e} | Kulisevsky, Jaime^{a; b; c; d; e; *} | on behalf the Cognitive Phenotype Working Group of the European Huntington’s Disease Network

Affiliations: [a] Movement Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain | [b] Biomedical Research Institute (IIB-Sant Pau), Barcelona, Spain | [c] Centro de Investigación en Red-Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain | [d] Department of Medicine, Autonomous University of Barcelona (UAB), Barcelona, Spain | [e] European Huntington’s Disease Network (EHDN) | [f] University of Naples “Federico II”, Naples, Italy | [g] Department of Neuropsychiatry, Charité – Universitätsmedizin, Berlin, Germany | [h] Huntington and Rare Diseases Unit, Fondazione IRCCS Casa Sollievo della, Sofferenza Research Hospital, San Giovanni Rotondo, Italy | [i] Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy | [j] Department of Neurology, Hospital Universitario Ramon y Cajal, Madrid, Spain | [k] Department of Neurology. Fundación Jimenez Diaz, Madrid, Spain | [l] Coimbra Institute for Biomedical Imaging and Translational Research - CIBIT, University of Coimbra, Coimbra, Portugal | [m] Neurology Department, Coimbra University Hospital, Coimbra, Portugal | [n] Applied Neurophysiology and Pain Unit, Apulian Center for Huntington’s Disease SMBNOS Department, “Aldo Moro” University, Bari, Italy | [o] Hospital Mare de Deu de la Mercè, Barcelona, Spain | [p] Department of Neurological and Psychiatric Nursing, Faculty of Health Science, Medical University of Gdansk, Gdańsk, Poland | [q] Department of Neurology, St. Adalbert Hospital, Gdańsk, Poland | [r] Department of Psychiatry, Medical University of Wroclaw, Wroclaw, Poland

Correspondence: [*] Correspondence to: Jaime Kulisevsky, Movement Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Mas Casanovas 90 –08041 Barcelona, Spain. Tel.: +34 93 5565986; Fax: +34 93 5565748; E-mail: jkulisevsky@santpau.cat.

Abstract: Background:Arithmetic word-problem solving depends on the interaction of several cognitive processes that may be affected early in the disease in gene-mutation carriers for Huntington’s disease (HD). Objective:Our goal was to examine the pattern of performance of arithmetic tasks in premanifest and manifest HD, and to examine correlations between arithmetic task performance and other neuropsychological tasks. Methods:We collected data from a multicenter cohort of 165 HD gene-mutation carriers. The sample consisted of 31 premanifest participants: 16 far-from (>12 years estimated time to diagnosis; preHD-A) and 15 close-to (≤12 years estimated time to diagnosis; preHD-B), 134 symptomatic patients (early-mild HD), and 37 healthy controls (HC). We compared performance between groups and explored the associations between arithmetic word-problem solving and neuropsychological and clinical variables. Results:Total arithmetic word-problem solving scores were lower in preHD-B patients than in preHD-A (p < 0.05) patients and HC (p < 0.01). Early-mild HD patients had lower scores than preHD patients (p < 0.001) and HC (p < 0.001). Compared to HC, preHD and early-mild HD participants made more errors as trial complexity increased. Moreover, arithmetic word-problem solving scores were significantly associated with measures of global cognition (p < 0.001), frontal-executive functions (p < 0.001), attention (p < 0.001) visual working memory (p < 0.001), mental rotation (p < 0.001), and confrontation naming (p < 0.05). Conclusion:Arithmetic word-problem solving is affected early in the course of HD and is related to deficient processes in frontal-executive and mentalizing-related processes.

Keywords: Huntington’s disease, cognition, arithmetic, neuropsychology, word-problem solving, acalculia

DOI: 10.3233/JHD-210480

Journal: Journal of Huntington's Disease, vol. 10, no. 4, pp. 459-468, 2021