Heterogeneity of cognitive impairments in myotonic dystrophy type 1 explained by three distinct cognitive profiles.

BACKGROUND: Severity and nature of cognitive impairments in Myotonic dystrophy type 1 (DM1) are heterogeneous among studies. We hypothesized that this heterogeneity is explained by different cognitive profiles in DM1, with different clinical, biological and behavioral features. METHODS: Adult patients with genetically proven DM1 underwent a clinical, neuropsychological and behavioral assessment. We conducted a k-means clustering analysis on 9 cognitive tests representative of different domains (verbal/non-verbal episodic memory, visuo-constructive abilities, visual gnosis, executive functions, information processing speed). RESULTS: We included 124 DM1 patients. Mean age was 45.1 ± 13.5 years [19.8-73.2], mean age of onset was 30.4 ± 15.7 years [5-72], and mean CTG triplets' expansion size was 489.7 ± 351.8 [50-1600]. We found 3 cognitive clusters, including, respectively, 84, 29 and 11 patients. The first cluster included patients with more preserved cognitive functions; the second included patients with worse cognitive performances which predominate on executive functions; and the third even more pronounced and diffuse cognitive deficits. Younger patients, with a more recent DM1 clinical onset, higher educational level were more frequently classified in the cluster with more preserved cognitive functions. There were no significant differences between clusters regarding CTG triplets' expansion, neither age at DM1 onset, nor most of behavioral measures. CONCLUSIONS: We found different cognitive profiles in our DM1 population, which seem influenced by age and DM1 duration. Our findings may explain the heterogeneity of studies about cognition in DM1, and suggest a potential neurodegenerative mechanism in DM1 adults.

Characterization of theory of mind performance in patients with myotonic dystrophy type 1.

INTRODUCTION: Myotonic dystrophy type 1 (DM1) is associated with motor dysfunction as well as psychological and cognitive impairments, including altered social cognition. Theory of mind (ToM) impairments have been reported in this disease but their nature and their cognitive/cerebral correlates have yet to be determined. METHODS: Fifty DM1 patients and 50 healthy controls were assessed using the Movie for the Assessment of Social Cognition, which quantifies impairments in affective and cognitive components of ToM through the depiction of everyday situations. We also measured the study participants' cognitive, behavioral and social abilities, quality of life, and brain MRI characteristics. RESULTS: DM1 patients presented a significant impairment in ToM performance compared to controls (p < .001). The patients' errors were related to hypomentalizations (p < .001 vs controls) but not to hypermentalizations (p = .95). The affective component was affected (p < .001 vs controls) but not the cognitive component (p = .09). The ToM impairment was associated with demographic variables (older age and a lower educational level), genetic findings (a larger CTG triplets repeat expansion) and cognitive scores (slower information processing speed). Associations were also found with brain MRI variables (lower white matter and supratentorial volumes) but not with behavioral or social variables. DISCUSSION: DM1 patients display a ToM impairment, characterized by predominant hypomentalizations concerning the affective component. This impairment might result from structural brain abnormalities observed in DM1.