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Structural Brain Correlates of Sleep Microstructure in Spinocerebellar Ataxia Type 2 and its Role on Clinical Phenotype

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Abstract

The influence of brain atrophy on sleep microstructure in Spinocerebellar Ataxias (SCAs) has not been extensively explored limiting the use of these sleep traits as surrogate biomarkers of neurodegeneration and clinical phenotype. The objective of the study is to explore the relationship between sleep microstructure and brain atrophy in SCA2 and its role in the clinical phenotype. Fourteen SCA2 mutation carriers (7 pre-manifest and 7 manifest subjects) underwent polysomnographic, structural MRI, and clinical assessments. Particularly, markers of REM and non-REM sleep microstructure, measures of cerebellar and brainstem atrophy, and clinical scores were analyzed through correlation and mediation analyses. The sleep spindle activity exhibited a negative correlation with the number of trials required to complete the verbal memory test (VMT), and a positive correlation with the cerebellar volume, but the significance of the latter correlation did not survive multiple testing corrections. However, the causal mediation analyses unveiled that sleep spindle activity significantly mediates the association between cerebellar atrophy and VMT performance. Regarding REM sleep, both phasic EMG activity and REM sleep without atonia exhibited significant associations with pontine atrophy and disease severity measures. However, they did not demonstrate a causal mediation effect between the atrophy measures and disease severity. Our study provides evidence about the association of the pontocerebellar atrophy with sleep microstructure in SCA2 offering insights into the cerebellar involvement in cognition via the control of the sleep spindle activity. Therefore, our findings may help to understand the disease pathogenesis and to better characterize sleep microstructure parameters as disease biomarkers.

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Data Availability

This dataset is not publicly available and can be asked from the Cuban authors directly upon reasonable request.

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Acknowledgements

The authors thank all SCA2 subjects for their cooperation. We also thank the Cuban Ministry of Public Health and the Federal Ministry of Education and Research of Germany (BMBF 01DN18022) for providing the funds used in the present study.

Funding

This work was supported by the Cuban Ministry of Public Health and the Federal Ministry of Education and Research of Germany (BMBF 01DN18022).

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Authors and Affiliations

  1. Centre for the Research and Rehabilitation of Hereditary Ataxias, Libertad St 16 between 12 St & 16 St. 80100, Holguin, Cuba

    Roberto Rodríguez-Labrada, Nalia Canales-Ochoa, Arnoy Peña-Acosta, Annelié Estupiñán-Rodríguez & Luis Velázquez-Pérez

  2. Cuban Centre for Neurosciences, 190 St, between 25 St & 27 St, 11300, Playa, Havana, Cuba

    Roberto Rodríguez-Labrada & Yaimeé Vázquez-Mojena

  3. Department of Imaging, Clinical-Surgical Hospital “Lucía Iñiguez”, Avenue Celia Sanchez 1, Holguín, Cuba

    Maria de Lourdes Galicia-Polo

  4. Clinic of Sleep Medicine, UNAM, Cuauhtémoc, Mexico

    Edilia Cruz-Rivas

  5. Department of Neurology, RWTH Aachen University, Pauwelsstr. 3052074, Aachen, Germany

    Sandro Romanzetti, Imis Dogan & Kathrin Reetz

  6. JARA-BRAIN Institute Molecular Neuroscience and Neuroimaging, Forschungszentrum Jülich GmbH, RWTH Aachen University, 52074, Aachen, Germany

    Sandro Romanzetti, Imis Dogan & Kathrin Reetz

  7. Clinic of Neurology, Experimental Neurology, Goethe University Frankfurt, University Hospital, 60590, Frankfurt, Germany

    Georg Auburger

  8. Cuban Academy of Sciences, Cuba St 460, Between Teniente Rey & Amargura , 10100, Habana Vieja, Havana, Cuba

    Luis Velázquez-Pérez

  9. Department of Human Physiology, Medical University of Havana, 146 St, 3102, 11300, Playa, Havana, Cuba

    Luis Velázquez-Pérez

  10. Faculty of Chemistry, University of Havana, Zapata St Between G St & Carlitos Aguirre St., 10400, Plaza de La Revolución, Havana, Cuba

    Luis Velázquez-Pérez

Authors
  1. Roberto Rodríguez-Labrada
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  2. Nalia Canales-Ochoa
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Contributions

RRL and LVP: Conceptualization and study design.

RRL, LVP and GA: Literature search.

RRL, NCO, ECR, APA, AER, YVM: Data collection.

RRL, MLGP, SR: Data analysis.

RRL, LVP, SR, ID, GA, KR: Data interpretation.

RRL: Writing-original draft.

LVP, SR, ID, KR and GA: Writing-review & editing.

Corresponding authors

Correspondence to Roberto Rodríguez-Labrada or Luis Velázquez-Pérez.

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Ethical Approval

The study was approved by the ethics committee of the Centre for the Research and Rehabilitation of Hereditary Ataxias (Holguin, Cuba), and was conducted according to the Declaration of Helsinki. Written informed consent was obtained from each participant.

Competing Interests

The authors declare no competing interests.

Financial Disclosure

All Cuban authors received funding from the Cuban Ministry of Public Health, whereas RRL, SR, ID, KR and LVP received funding from the Federal Ministry of Education and Research of Germany (BMBF 01DN18022). None has received any other funding for the last 12 months relevant or not for this manuscript.

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Luis Velázquez-Pérez is a senior author.

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Rodríguez-Labrada, R., Canales-Ochoa, N., Galicia-Polo, M.d.L. et al. Structural Brain Correlates of Sleep Microstructure in Spinocerebellar Ataxia Type 2 and its Role on Clinical Phenotype. Cerebellum (2024). https://doi.org/10.1007/s12311-024-01674-1

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