Abstract
BACKGROUND AND OBJECTIVES: Mild cognitive impairment (MCI) in isolated REM sleep behavior disorder (iRBD) is a risk factor for subsequent neurodegeneration. We aimed to identify brain metabolism and functional connectivity changes related to MCI in patients with iRBD and the neuroimaging markers' predictive value for phenoconversion. METHODS: This is a prospective cohort study of patients with iRBD with a mean follow-up of 4.2 ± 2.6 years. At baseline, patients with iRBD and age- and sex-matched healthy controls (HCs) underwent (18)F-fluorodeoxyglucose (FDG)-PET and resting-state fMRI scans and a comprehensive neuropsychological test battery. Voxel-wise group comparisons for FDG-PET data were performed using a general linear model. Seed-based connectivity maps were computed using brain regions showing significant hypometabolism associated with MCI in patients with iRBD and compared between groups. A Cox regression analysis was applied to investigate the association between brain metabolism and risk of phenoconversion. RESULTS: Forty patients with iRBD, including 21 with MCI (iRBD-MCI) and 19 with normal cognition (iRBD-NC), and 24 HCs were included in the study. The iRBD-MCI group revealed relative hypometabolism in the inferior parietal lobule, lateral and medial occipital, and middle and inferior temporal cortex bilaterally compared with HC and the iRBD-NC group. In seed-based connectivity analyses, the iRBD-MCI group exhibited decreased functional connectivity of the left angular gyrus with the occipital cortex. Of 40 patients with iRBD, 12 patients converted to Parkinson disease (PD) or dementia with Lewy bodies (DLB). Hypometabolism of the occipital pole (hazard ratio [95% CI] 6.652 [1.387-31.987]), medial occipital (4.450 [1.143-17.327]), and precuneus (3.635 [1.009-13.093]) was associated with higher phenoconversion rate to PD/DLB. DISCUSSION: MCI in iRBD is related to functional and metabolic changes in broad brain areas, particularly the occipital and parietal areas. Moreover, hypometabolism in these brain regions was a predictor of phenoconversion to PD or DLB. Evaluation of cognitive function and neuroimaging characteristics could be useful for risk stratification in patients with iRBD.