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

J Neurol. 2024 Jul;271(7):4529-4539. doi: 10.1007/s00415-024-12404-2. Epub 2024 May 6.

Abstract

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.

Keywords: Clusters; Cognition; Myopathy; Myotonic dystrophy; Steinert’s disease.

MeSH terms

  • Adult
  • Aged
  • Cluster Analysis
  • Cognitive Dysfunction* / etiology
  • Cognitive Dysfunction* / physiopathology
  • Executive Function / physiology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Myotonic Dystrophy* / complications
  • Myotonic Dystrophy* / physiopathology
  • Myotonic Dystrophy* / psychology
  • Neuropsychological Tests*
  • Young Adult