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Microglial Activation and Progression of Nigrostriatal Dysfunction in Isolated REM Sleep Behavior Disorder

Lookup NU author(s): Emeritus Professor David Brooks, Professor Nicola PaveseORCiD

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Abstract

© 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.Background: Using 11C-(R)-PK11195-PET, we found increased microglia activation in isolated REM sleep behavior disorder (iRBD) patients. Their role remains to be clarified. Objectives: The objective is to assess relationships between activated microglia and progression of nigrostriatal dysfunction in iRBD. Methods: Fifteen iRBD patients previously scanned with 11C-(R)-PK11195 and 18F-DOPA-PET underwent repeat 18F-DOPA-PET after 3 years. 18F-DOPA Ki changes from baseline were evaluated with volumes-of-interest and voxel-based analyses. Results: Significant 18F-DOPA Ki reductions were found in putamen and caudate. Reductions were larger and more widespread in patients with increased nigral microglia activation at baseline. Left nigral 11C-(R)-PK11195 binding at baseline was a predictor of 18F-DOPA Ki reduction in left caudate (coef = −0.0426, P = 0.016). Conclusions: Subjects with increased baseline 11C-(R)-PK11195 binding have greater changes in nigrostriatal function, suggesting a detrimental rather than protective effect of microglial activation. Alternatively, both phenomena occur in patients with prominent nigrostriatal dysfunction without a causative link. The clinical and therapeutic implications of these findings need further elucidation. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Publication metadata

Author(s): Staer K, Iranzo A, Stokholm MG, Hvingelby VS, Danielsen EH, Ostergaard K, Serradell M, Otto M, Svendsen KB, Garrido A, Vilas D, Santamaria J, Moller A, Gaig C, Brooks DJ, Borghammer P, Tolosa E, Pavese N

Publication type: Article

Publication status: Published

Journal: Movement Disorders

Year: 2024

Pages: epub ahead of print

Online publication date: 13/03/2024

Acceptance date: 16/02/2024

ISSN (print): 0885-3185

ISSN (electronic): 1531-8257

Publisher: John Wiley and Sons Inc

URL: https://doi.org/10.1002/mds.29767

DOI: 10.1002/mds.29767

PubMed id: 38477376

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