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

Andrea Horta-Barba, Saul Martinez-Horta, Jesús Perez-Perez, Frederic Sampedro, Natascia De Lucia, Giuseppe De Michele, Elena Salvatore, Stefanie Kehrer, Josef Priller, Simone Migliore, Ferdinando Squitieri, Anna Castaldo, Caterina Mariotti, Veronica Mañanes, Jose Luis Lopez-Sendon, Noelia Rodriguez, Asunción Martinez-Descals, Filipa Júlio, Cristina Janurio, Marianna DelussiMarina De Tommaso, Sandra Noguera, Jesus Ruiz-Idiago, Emilia J. Sitek, Renata Wallner, Angela Nuzzi, Javier Pagonabarraga, Jaime Kulisevsky

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


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.

Original languageEnglish
Pages (from-to)459-468
Number of pages10
JournalJournal of Huntington's Disease
Issue number4
StatePublished - 2021
Externally publishedYes


  • Huntington's disease
  • acalculia
  • arithmetic
  • cognition
  • neuropsychology
  • word-problem solving


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