Objective: To investigate the presence of a brain signature able to predict the development of dementia in patients with idiopathic REM sleep behavior disorder (iRBD).

Background: Idiopathic RBD is associated with dementia with Lewy bodies and Parkinson’s disease. Clinical features in iRBD include motor, cognitive, sensory, autonomic, and psychiatric changes. Structural brain changes have been reported but are inconsistent. In this study, we investigated a brain-clinical signature of iRBD and investigated if its expression predicted the development of a synucleinopathy in these patients.

Method: Forty-eight iRBD patients followed longitudinally underwent polysomnography, neurological and neuropsychological assessments, and MRI structural acquisition. Brain tissue deformation was measured using deformation-based morphometry in CAT12 and Jacobian determinants maps were standardized to those generated in 41 matched controls. Clinical variables included 27 measures covering cognitive, motor, sleep, autonomic, and psychiatric features. Partial least squares correlation was used to derive latent variables that maximized covariance between brain and clinical features. Logistic regressions were used to study if the pattern predicted conversion during follow-up. The pattern expression was tested in independent cohorts of 45 patients with an overt synucleinopathy (i.e., dementia with Lewy bodies or Parkinson’s disease).

Results: A single latent variable explained 31.1% of the covariance between brain deformation and clinical features of iRBD. This variable was related to cognitive and motor variables, particularly mild cognitive impairment and UPDRS-III, with worse clinical scores associating with more brain deformation. The brain pattern was characterized by contraction in the basal ganglia, substantia nigra, and white matter and by expansion of the ventricular system and the subarachnoid cisterns. The baseline expression of this pattern predicted conversion to a synucleinopathy in iRBD, specifically dementia with Lewy bodies. When applied to MRI data from patients with an overt synucleinopathy, a higher expression was seen in patients with Dementia with Lewy Bodies compared to patients with Parkinson’s disease.

Conclusion: Using longitudinal and cross-sectional data, we identified a brain signature that predicts conversion to Dementia with Lewy Bodies in iRBD. Future studies should apply this signature on a wider sample of iRBD patients followed longitudinally.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-brain-signature-of-prodromal-lewy-body-dementia/