Cognitive decline in Huntington's disease in the Digitalized Arithmetic Task (DAT)

Lunven, Marine, Bagnou, Jennifer Hamet, Youssov, Katia, Gabadinho, Alex, Fliss, Rafika, Montillot, Justine, Audureau, Etienne, Bapst, Blanche, Morgado, Graca, Reilmann, Ralf, Schubert, Robin, Busse, Monica ORCID: https://orcid.org/0000-0002-5331-5909, Craufurd, David, Massart, Renaud, Rosser, Anne ORCID: https://orcid.org/0000-0002-4716-4753 and Bachoud-Levi, Anne-Catherine 2021. Cognitive decline in Huntington's disease in the Digitalized Arithmetic Task (DAT). PLoS ONE 16 (8) , e0253064. 10.1371/journal.pone.0253064

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Abstract

Background Efficient cognitive tasks sensitive to longitudinal deterioration in small cohorts of Huntington’s 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. Methods We assessed the psychometric properties of DAT in three languages, across four European sites, in 77 early-stage HD patients (age: 52 ± 11 years; 27 females), and 57 controls (age: 50 ± 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. Results At baseline, HD patients were less accurate (p = 0.0002) with increased response time (p<0.0001) when compared to DAT in controls. Test-retest reliability in HD patients ranged from good to excellent for response time (range: 0.63–0.79) and from questionable to acceptable for accuracy (range: r = 0.52–0.69). 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< 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. Conclusions 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Centre for Trials Research (CNTRR)
Additional Information:	This is an open access article distributed under the terms of the Creative Commons Attribution License
Publisher:	Public Library of Science
ISSN:	1932-6203
Date of First Compliant Deposit:	11 June 2021
Date of Acceptance:	25 May 2021
Last Modified:	05 May 2023 18:50
URI:	https://orca.cardiff.ac.uk/id/eprint/141872

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