Cognitive decline over time in myotonic dystrophy type 1: a systematic review of longitudinal studies.

BACKGROUND: Myotonic Dystrophy Type 1 (DM1) is a multisystem genetic disorder and the most common muscular dystrophy in adults. Central nervous system involvement is well-documented in DM1, including cognitive impairment. Cross-sectional studies have described a heterogeneous neuropsychological profile; however, the trajectory of cognitive functioning over time remains unclear, highlighting the need to focus on longitudinal studies. This systematic review aimed to examine longitudinal evidence on cognitive progression in DM1 and to analyze patterns of decline across clinical phenotypes. METHODS: Following PRISMA 2020 guidelines, a systematic search was conducted in three databases: PubMed, Web of Science, and Scopus. Eligible studies were original longitudinal investigations assessing cognitive performance in DM1 using standardized measures. Risk of bias was assessed using an adapted Newcastle-Ottawa Scale. RESULTS: Sixteen studies met the inclusion criteria, with follow-up periods ranging from 1 to 20 years. In pediatric phenotypes, intellectual disability and global cognitive impairment were evident at baseline, with largely stable trajectories over time. In contrast, adult- and late-onset phenotypes reported a pattern of slow, progressive, domain-specific cognitive decline, particularly in visuoconstruction and processing speed. Age and disease duration emerged as the most consistent predictors of decline over time. CONCLUSION: The available evidence supports a dual-process model of cognitive dysfunction in DM1, combining early neurodevelopmental impairment with later domain-specific neurodegenerative decline. These findings highlight the importance of longitudinal cognitive monitoring and suggest that specific cognitive domains may serve as sensitive markers for disease progression and potential endpoints in clinical trials. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251148417, identifier (CRD420251148417).