Brain Metabolism Related to Mild Cognitive Impairment and Phenoconversion in Patients With Isolated REM Sleep
Eun Jin Yoon1, Jee-Young Lee1, Heejung Kim2
1From the Memory Network (E.J.Y.) and Institute of Radiation Medicine (H.K.), Medical Research Center, Seoul National University; Departments of Nuclear Medicine (E.J.Y., H.K., Y.K.K.) and Neurology (J.-Y.L., D.Y., J.H.S., H.N.), Seoul National University-Seoul Metropolitan Government Boramae Medical Center, and Department of Neurology (B.J.), Seoul National University College of Medicine; and Department of Neurology (D.Y.), Kyung Hee University Hospital, Seoul, Korea.
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 18F-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.
Insights
Mild cognitive impairment in isolated REM sleep behavior disorder is linked to brain metabolism changes. Occipital and parietal hypometabolism predicts conversion to Parkinson
Area of Science:
- Neuroscience
- Neurology
- Sleep Medicine
Background:
- Mild cognitive impairment (MCI) in patients with isolated REM sleep behavior disorder (iRBD) is a significant risk factor for developing neurodegenerative diseases.
- Understanding the underlying brain changes in iRBD with MCI is crucial for predicting disease progression and neurodegeneration.
Purpose of the Study:
- To identify specific brain metabolism and functional connectivity alterations associated with MCI in iRBD patients.
- To evaluate the predictive value of neuroimaging markers for phenoconversion to neurodegenerative conditions like Parkinson's disease (PD) or dementia with Lewy bodies (DLB).
Main Methods:
- A prospective cohort study involving 40 iRBD patients (21 with MCI, 19 with normal cognition) and 24 healthy controls (HCs).
- Baseline assessments included 18F-fluorodeoxyglucose (FDG)-PET, resting-state fMRI, and comprehensive neuropsychological testing.
- Statistical analyses involved voxel-wise group comparisons, seed-based functional connectivity mapping, and Cox regression for phenoconversion risk.
Main Results:
- The iRBD-MCI group showed significant hypometabolism in the inferior parietal lobule, occipital cortex, and temporal cortex compared to HCs and iRBD-normal cognition groups.
- Decreased functional connectivity was observed between the left angular gyrus and the occipital cortex in iRBD-MCI patients.
- Hypometabolism in the occipital pole, medial occipital cortex, and precuneus significantly predicted a higher rate of phenoconversion to PD or DLB.
Conclusions:
- MCI in iRBD is associated with widespread functional and metabolic brain changes, particularly in occipital and parietal regions.
- Neuroimaging markers of hypometabolism in these areas serve as predictors for phenoconversion to PD or DLB.
- Cognitive function assessment combined with neuroimaging offers a valuable tool for risk stratification in iRBD patients.
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