Enlarged perivascular spaces and their association with motor, cognition, MRI markers and cerebrovascular risk factors in male fragile X premutation carriers.

Autor: Elias-Mas A; Radiology Department, Hospital Universitari Mútua de Terrassa, Terrassa, Barcelona, Spain; Institute for Research and Innovation Parc Taulí (I3PT), Sabadell, Spain; Genetics Doctorate Program, Universitat de Barcelona (UB), Barcelona, Spain. Electronic address: aelias@mutuaterrassa.cat., Wang JY; Center for Mind and Brain, University of California Davis, CA, United States. Electronic address: jyiwang@ucdavis.edu., Rodríguez-Revenga L; Biochemistry and Molecular Genetics Department, Hospital Clinic of Barcelona, Barcelona, Spain; CIBER of Rare Diseases (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain; Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. Electronic address: lbodi@clinic.cat., Kim K; Department of Public Health Sciences, University of California Davis School of Medicine, Sacramento, CA, United States. Electronic address: kmkim@ucdavis.edu., Tassone F; MIND Institute, University of California Davis, Sacramento, CA, United States; Department of Biochemistry and Molecular Medicine, University of California Davis School of Medicine, Sacramento, CA, United States. Electronic address: ftassone@ucdavis.edu., Hessl D; MIND Institute, University of California Davis, Sacramento, CA, United States; Department of Psychiatry and Behavioral Sciences, University of California Davis School of Medicine, Sacramento, CA, United States. Electronic address: drhessl@ucdavis.edu., Rivera SM; Center for Mind and Brain, University of California Davis, CA, United States; MIND Institute, University of California Davis, Sacramento, CA, United States; Department of Psychology, University of Maryland, College Park, MD, United States. Electronic address: smrivera@umd.edu., Hagerman R; MIND Institute, University of California Davis, Sacramento, CA, United States; Department of Pediatrics, University of California Davis Medical Center, Sacramento, CA, United States. Electronic address: rjhagerman@ucdavis.edu.
Jazyk: angličtina
Zdroj: Journal of the neurological sciences [J Neurol Sci] 2024 Jun 15; Vol. 461, pp. 123056. Date of Electronic Publication: 2024 May 17.
DOI: 10.1016/j.jns.2024.123056
Abstrakt: FMR1 premutation carriers (55-200 CGG repeats) are at risk of developing fragile X-associated tremor/ataxia syndrome (FXTAS), a neurodegenerative disorder associated with motor and cognitive impairment. Bilateral hyperintensities of the middle cerebellar peduncles (MCP sign) are the major radiological hallmarks of FXTAS. In the general population, enlarged perivascular spaces (PVS) are biomarkers of small vessel disease and glymphatic dysfunction and are associated with cognitive decline. Our aim was to determine if premutation carriers show higher ratings of PVS than controls and whether enlarged PVS are associated with motor and cognitive impairment, MRI features of neurodegeneration, cerebrovascular risk factors and CGG repeat length. We evaluated 655 MRIs (1-10 visits/participant) from 229 carriers (164 with FXTAS and 65 without FXTAS) and 133 controls. PVS in the basal ganglia (BG-EPVS), centrum semiovale, and midbrain were evaluated with a semiquantitative scale. Mixed-effects models were used for statistical analysis adjusting for age. In carriers with FXTAS, we revealed that (1) BG-PVS ratings were higher than those of controls and carriers without FXTAS; (2) BG-PVS severity was associated with brain atrophy, white matter hyperintensities, enlarged ventricles, FXTAS stage and abnormal gait; (3) age-related increase in BG-PVS was associated with cognitive dysfunction; and (4) PVS ratings of all three regions showed robust associations with CGG repeat length and were higher in carriers with the MCP sign than carriers without the sign. This study demonstrates clinical relevance of PVS in FXTAS especially in the basal ganglia region and suggests microangiopathy and dysfunctional cerebrospinal fluid circulation in FXTAS physiopathology.
Competing Interests: Declaration of competing interest R.J.H. has received funding from Zynerba,Tetra Pharma and the Azrieli Foundation to carry out treatment studies in fragile X syndrome and has also consulted with Zynerba regarding treatment studies in fragile X syndrome. D.H. has received funding from the following, all of which are directed to the UC Davis, in support of fragile X treatment programs, and he receives no personal funds and has no relevant financial interest in any of the commercial entities listed: Autifony, Ovid, Tetra/Shionogi, Healx, and Zynerba pharmaceutical companies to consult on outcome measures and clinical trial design. F.T. has received funding from Zynerba and the Azrieli Foundation to carry out molecular studies in fragile X syndrome. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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