van der Plas, EllenKoscik, Timothy R.Magnotta, VincentCumming, Sarah A.Monckton, DarrenGutmann, LaurieNopoulos, Peggy2025-03-112025-03-112021-03-18van der Plas E, Koscik TR, Magnotta V, et al. Neurocognitive Features of Motor Premanifest Individuals With Myotonic Dystrophy Type 1. Neurol Genet. 2021;7(2):e577. Published 2021 Mar 18. doi:10.1212/NXG.0000000000000577https://hdl.handle.net/1805/46297Objective: The goal of the study was to identify brain and functional features associated with premanifest phases of adult-onset myotonic dystrophy type 1 (i.e., PreDM1). Methods: This cross-sectional study included 68 healthy adults (mean age = 43.4 years, SD = 12.9), 13 individuals with PreDM1 (mean age: 47.4 years, SD = 16.3), and 37 individuals with manifest DM1 (mean age = 45.2 years, SD = 9.3). The primary outcome measures included fractional anisotropy (FA), motor measures (Muscle Impairment Rating Scale, Grooved Pegboard, Finger-Tapping Test, and grip force), general cognitive abilities (Wechsler Adult Intelligence Scales), sleep quality (Scales for Outcomes in Parkinson's Disease-Sleep), and apathy (Apathy Evaluation Scale). Results: Individuals with PreDM1 exhibited an intermediate level of white matter FA abnormality, where whole-brain FA was lower relative to healthy controls (difference of the estimated marginal mean [EMMdifference] = 0.02, 95% confidence interval (CI) 0.01-0.03, p < 0.001), but the PreDM1 group had significantly higher FA than did individuals with manifest DM1 (EMMdifference = 0.02, 95% CI 0.009-0.03, p < 0.001). Individuals with PreDM1 exhibited reduced performance on the finger-tapping task relative to control peers (EMMdifference = 5.70, 95% CI 0.51-11.00, p = 0.03), but performance of the PreDM1 group was better than that of the manifest DM1 group (EMMdifference = 5.60, 95% CI 0.11-11.00, p = 0.05). Hypersomnolence in PreDM1 was intermediate between controls (EMMdifference = -1.70, 95% CI -3.10-0.35, p = 0.01) and manifest DM1 (EMMdifference = -2.10, 95% CI -3.50-0.60, p = 0.006). Conclusions: Our findings highlight key CNS and functional deficits associated with PreDM1, offering insight in early disease course.en-USAttribution-NonCommercial-NoDerivatives 4.0 InternationalAdult-onset myotonic dystrophy type 1Premanifest phasesWhite matterArticle