Background <p>Myotonic dystrophy type 1 (DM1) is a complex, multisystemic neuromuscular disorder that affects various systems, including the muscular and central nervous systems. The natural history of DM1 includes a cognitive decline over time across multiple cognitive functions. However, the course of the cognitive profile remains unknown over short follow-up intervals. The study aimed to document the course of the neuropsychological profile in adults with DM1 over 12 months using classic paper-pencil tests and computerized cognitive tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB^®).</p> Methods <p>Adult participants with a genetically confirmed diagnosis of juvenile, adult, or late-onset phenotype of myotonic dystrophy type 1 (DM1) underwent a battery of traditional paper-and-pencil tests alongside four assessments from the computerized cognitive battery, CANTAB^®. Cognitive functions were evaluated at baseline and at two follow-up points, each 6 months apart. Repeated measures ANOVAs were conducted, followed by post hoc analyses to compare results across the different time points. Significant changes were interpreted in relation to the measurement error.</p> Results <p>Forty-four participants with DM1 (m = 45.5 ± 11.2 years) were assessed (50% juvenile, 38.6% adult, 11.4% late-onset). Results showed an overall stability in cognitive functions at both 6 and 12 months. However, verbal memory (California Verbal Learning Test) and multitasking skills (CANTAB^®) exhibited an improvement outside of the measurement error, likely reflecting a learning effect.</p> Conclusions <p>Short-term progression studies are essential to improve trial readiness by documenting the best outcome measures to assess treatment effectiveness and gathering a comprehensive overview of the cognitive profile progression in DM1.</p>