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

Marine Lunven (1, 2, 3, 4, 5, 6) , Jennifer Hamet Bagnou (7) , Katia Youssov (1, 2, 3, 4, 5, 6) , Alexis Gabadinho (1, 2, 3, 4, 5, 6) , Rafika Fliss (1, 2, 3, 4, 5, 6) , Justine Montillot (1, 2, 3, 4, 5, 6) , Etienne Audureau (8) , Blanche Bapst (9, 10) , Graça Morgado (11) , Ralf Reilmann (12, 13) , Robin Schubert , Monica Busse (14) , David Craufurd (15, 16) , Renaud Massart (1, 2, 3, 4, 5, 6) , Anne Rosser (14) , Anne-Catherine Bachoud-Lévi (6, 9, 17, 3)

1 Hôpital Albert Chenevier
2 IMRB - Institut Mondor de Recherche Biomédicale
3 CHU Trousseau [APHP]
4 CHU Henri Mondor [Créteil]
5 NeurATRIS - IHU-A-ICM - Institut de neurosciences translationnelles de Paris
6 DEC - Département d'Etudes Cognitives - ENS Paris
7 CPU - Cognition, Perception et Usages - LISN
8 AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP)
9 UPEC Médecine - Université Paris-Est Créteil Val-de-Marne - Faculté de médecine
10 Service de Neuroradiologie
11 CIC Henri Mondor - Centre d'Investigation Clinique Henri Mondor
12 WWU - Westfälische Wilhelms-Universität Münster = University of Münster
13 Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen
14 Cardiff University
15 University of Manchester [Manchester]
16 Saint Mary's Hospital [London]
17 U955 Inserm - UPEC - IMRB - "NeuroPsychologie Interventionnelle" [Créteil]

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 disease

Domaines: Neurosciences; Médecine humaine et pathologie

Marine Lunven, Jennifer Hamet Bagnou, Katia Youssov, Alexis Gabadinho, Rafika Fliss, et al.. Cognitive decline in Huntington’s disease in the Digitalized Arithmetic Task (DAT). PLoS ONE, 2021, 16 (8), pp.e0253064. ⟨10.1371/journal.pone.0253064⟩. ⟨hal-04387041⟩