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

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) and 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.

Structural and metabolic brain correlates of arithmetic word‐problem solving in Huntington's disease

“…Arithmetic performance was assessed using the recently developed arithmetic word-problem solving task (HD-WPA) (Horta-Barba et al, 2021). The HD-WPA consists of six-word, written arithmetic operations requiring addition, subtraction, multiplication, or division of increasing difficulty.…”

“…The HD-WPA consists of six-word, written arithmetic operations requiring addition, subtraction, multiplication, or division of increasing difficulty. A detailed description of the task can be found in our previous work (Horta-Barba et al, 2021). All arithmetic problems were presented in a written sentence.…”

“…These findings support previous reports in the healthy population and in the context of various diseases (Bellon et al, 2020; Rosselli et al, 1998; Zamarian, Ischebeck, et al, 2009). Arithmetic reasoning requires the deployment of several cognitive processes subserved by a complex interaction of different brain systems (Horta‐Barba et al, 2021). This includes attention and working memory, executive functions, and visuospatial reasoning (Andersson, 2008; Menon, 2008; Träff et al, 2018).…”

“…Deficits in arithmetic word‐problem solving are evident in both premanifest and manifest HD (Allain et al, 2005; Horta‐Barba et al, 2021; Nanetti et al, 2018). It was recently demonstrated in a large sample of participants that arithmetic performance is not only associated with planning, sustained attention, and working memory but also with more posterior‐cortical‐related processes such as visuoconstructive and mental rotation abilities (Horta‐Barba et al, 2021; Nanetti et al, 2018; Teichmann et al, 2008). These findings support previous reports in the healthy population and in the context of various diseases (Bellon et al, 2020; Rosselli et al, 1998; Zamarian, Ischebeck, et al, 2009).…”

“…Arithmetic reasoning requires the deployment of several cognitive processes subserved by a complex interaction of different brain systems (Horta-Barba et al, 2021). This includes attention and working memory, executive functions, and visuospatial reasoning (Andersson, 2008;Menon, 2008;Träff et al, 2018).…”