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

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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.

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Data availability

Data of this study can be shared upon request to the corresponding author.

Abbreviations

ANOVA:

Analysis of variance

BECS-GRECO:

Groupe de réflexion sur les évaluations cognitives—neuropsychological semantic battery

CSCT:

Computerized Speed Cognitive Test

DM1:

Myotonic dystrophy type 1

HADS:

Hospital Anxiety and Depression Scale

HVLT:

Hopkins Verbal Learning Test

IQ:

Intellectual quotient

LARS:

Lille Apathy Rating Scale

MASC:

Movie for the Assessment of Social Cognition

MIRS:

Muscular Impairment Rating Scale

N-LST:

Number–letter sequence task

QFS:

Questionnaire de Fonctionnement Social

TMT:

Trail Making Test

ToM:

Theory of mind

VOSP:

Visual Object and Space Perception

WAIS:

Wechsler Adult Intelligence Scale

WHOQOL-BREF:

World Health Organization Quality of Life Brief Version

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Acknowledgements

We thank the team of the neuromuscular center of the university hospital of Lille, which each day helps us to organize the patients’ follow-up. We also thank Sebastian Sorger Brock for the English proofreading.

Funding

This work was funded by the Centre Hospitalier Universitaire de Lille, F-59000, Lille, France; by the association Santélys, 59120, Loos, France; and by the Projet Fédératif Hospitalo-Universitaire-VasCog, F-59000, Lille, France.

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Authors and Affiliations

  1. U1172-LilNCog-Lille Neuroscience & Cognition, Univ. Lille, Inserm, CHU Lille, 59000, Lille, France

    Jean-Baptiste Davion, Céline Tard, Luc Defebvre & Xavier Delbeuck

  2. Department of Neurology, CHU Lille, 59000, Lille, France

    Jean-Baptiste Davion, Céline Tard, Luc Defebvre & Xavier Delbeuck

  3. Reference Center for Neuromuscular Diseases Nord/Est/Ile-de-France, CHU Lille, 59000, Lille, France

    Jean-Baptiste Davion, Céline Tard, Loren Fragoso & Amina Wilu-Wilu

  4. Department of Pediatric Neurology, CHU Lille, 59000, Lille, France

    Jean-Baptiste Davion

  5. Lille University Hospital Centre, DISTALZ, Development of Innovative Strategies for a Transdisciplinary Approach to Alzheimer’s Disease, Lille, France

    Emilie Skrobala

  6. Lille-Paris National Resource and Resilience Center (CN2R), 59000, Lille, France

    Xavier Delbeuck

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  1. Jean-Baptiste Davion
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Correspondence to Jean-Baptiste Davion.

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Davion, JB., Tard, C., Fragoso, L. et al. Heterogeneity of cognitive impairments in myotonic dystrophy type 1 explained by three distinct cognitive profiles. J Neurol (2024). https://doi.org/10.1007/s00415-024-12404-2

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