Potential utility of longitudinal 123I‐FP‐CIT SPECT imaging in predicting phenoconversion to overt synucleinopathy in isolated REM sleep behavior disorder. (31st December 2021)

• Record Type: Journal Article
• Authors: Miyagawa, Toji; Przybelski, Scott A.; Maltais, Daniela D.; Min, Hoon‐Ki; Jordan, Lennon; Lesnick, Timothy G.; St. Louis, Erik K.; Silber, Michael H.; Graff‐Radford, Jonathan; Jones, David T.; Savica, Rodolfo; Knopman, David S.; Petersen, Ronald C.; Kremers, Walter K.; Forsberg, Leah K.; Fields, Julie A.; Ferman, Tanis J.; Allen, Laura A.; Kantarci, Kejal; Lowe, Val J.; Boeve, Bradley F.
• Is Part Of: Alzheimer's & dementia. Volume 17(2021)Supplement 5
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-12-31
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.056563
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Isolated REM Sleep Behavior Disorder (iRBD) patients are known to be at high risk for developing an overt synucleinopathy – particularly Dementia with Lewy Bodies (DLB) and Parkinson's Disease (PD). Reduced nigrostriatal uptake on 123 I‐FP‐CIT SPECT reflects dopamine deficiency, which is common in the overt synucleinopathies. We sought to assess how 123 I‐FP‐CIT SPECT imaging in iRBD changes longitudinally and whether an abnormal 123 I‐FP‐CIT SPECT scan precedes and predicts future transition to an overt synucleinopathy. Method: Participants with polysomnography‐confirmed iRBD from the Mayo Clinic Alzheimer's Disease Research Center database +/‐ North American Prodromal Synucleinopathy (NAPS) Consortium who had two or more longitudinal 123 I‐FP‐CIT SPECT scans and been followed prospectively for at least 24 months were included in this analysis. Striatonigral dopamine transporter uptake was evaluated semi‐quantitatively with 123 I‐FP‐CIT SPECT using DaTQUANT software (GE Healthcare) to calculate z‐scores of putamen uptake. Result: Thirty‐five iRBD participants (86% male) were evaluated prospectively (mean 62.5 ± 19.4 months) and underwent two or more 123 I‐FP‐CIT SPECT scans at a minimum of 12 months intervals. Thirteen participants (37%) developed an overt synucleinopathy (11 DLB and 2 PD; phenoconverters) and 22 participants (63%) remained as iRBD (stable iRBD). Phenoconverters were older (mean 70.8 ± 7.0 vs 63.4 ± 6.0 years old) and had more negative DaTQUANT putamen z‐scores (mean ‐1.68 ± 1.42 vs ‐0.33 ± 1.52) than stable iRBD participants at baseline. Among phenoconverters, nine participants (69%) had one or more 123 I‐FP‐CIT SPECT scans with DaTQUANT putamen z‐score of <‐2.0 prior to phenoconversion, and mean time from initial DaTQUANT putamen z‐score of <‐2.0 to phenoconversion was 36.8 ± 28.7 months. In stable RBD participants, eight participants (36%) showed a decline in DaTQUANT putamen z‐score of >1 between the most recent and the baseline scan, and four participants (18%) presented DaTQUANT putamen z‐score of <‐2.0 at the most recent scan. Conclusion: These findings suggest that a decline in putamen uptake on 123 I‐FP‐CIT SPECT in iRBD serves as a predictor and a surrogate biomarker for progression of iRBD to an overt synucleinopathy.