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Cognitive and Brain Metabolism Profiles of Mild Cognitive Impairment in Prodromal Alpha-Synucleinopathy
Pietro Mattioli1, Matteo Pardini1,2, Nicola Girtler1,3
1Department of Neuroscience, University of Genoa, Genoa, Italy.
Background:
Mild cognitive impairment (MCI) is a heterogeneous condition. Idiopathic REM sleep behavior disorder (iRBD) can be associated with MCI (MCI-RBD).
Objective:
To investigate neuropsychological and brain metabolism features of patients with MCI-RBD by comparison with matched MCI-AD patients. To explore their predictive value toward conversion to a full-blown neurodegenerative disease.
Methods:
Seventeen MCI-RBD patients (73.6±6.5 years) were enrolled. Thirty-four patients with MCI-AD were matched for age (74.8±4.4 years), Mini-Mental State Exam score and education with a case-control criterion. All patients underwent a neuropsychological assessment and brain 18F-FDG-PET. Images were compared between groups to identify hypometabolic volumes of interest (MCI-RBD-VOI and MCI-AD-VOI). The dependency of whole-brain scaled metabolism levels in MCI-RBD-VOI and MCI-AD-VOI on neuropsychological test scores was explored with linear regression analyses in both groups, adjusting for age and education. Survival analysis was performed to investigate VOIs phenoconversion prediction power.
Results:
MCI-RBD group scored lower in executive functions and higher in verbal memory compared to MCI-AD group. Also, compared with MCI-AD, MCI-RBD group showed relative hypometabolism in a posterior brain area including cuneus, precuneus, and occipital regions while the inverse comparison revealed relative hypometabolism in the hippocampus/parahippocampal areas in MCI-AD group. MCI-RBD-VOI metabolism directly correlated with executive functions in MCI-RBD (p = 0.04). MCI-AD-VOI metabolism directly correlated with verbal memory in MCI-AD (p = 0.001). MCI-RBD-VOI metabolism predicted (p = 0.03) phenoconversion to an alpha-synucleinopathy. MCI-AD-VOI metabolism showed a trend (p = 0.07) in predicting phenoconversion to dementia.
Conclusion:
MCI-RBD and MCI-AD showed distinct neuropsychological and brain metabolism profiles, that may be helpful for both diagnosis and prognosis purposes.
Insights
Mild cognitive impairment with REM sleep behavior disorder (MCI-RBD) and Alzheimer's disease (MCI-AD) show distinct cognitive and brain metabolism patterns. These differences aid in diagnosing MCI-RBD and predicting neurodegenerative disease progression.
Area of Science:
- Neuroscience
- Neurology
- Cognitive Science
Background:
- Mild cognitive impairment (MCI) is a complex condition with varied underlying causes.
- Idiopathic REM sleep behavior disorder (iRBD) is increasingly recognized as a potential prodromal marker for neurodegenerative diseases, leading to MCI with iRBD (MCI-RBD).
Purpose of the Study:
- To delineate the distinct neuropsychological and brain metabolism characteristics of patients with MCI-RBD compared to those with MCI due to Alzheimer's disease (MCI-AD).
- To assess the predictive value of these identified features for the conversion to overt neurodegenerative conditions.
Main Methods:
- Seventeen MCI-RBD patients and thirty-four age-, Mini-Mental State Exam-, and education-matched MCI-AD patients underwent comprehensive neuropsychological assessments.
- Brain 18F-FDG-PET scans were performed to identify hypometabolic volumes of interest (VOIs) in both groups: MCI-RBD-VOI and MCI-AD-VOI.
- Linear regression and survival analyses explored the relationship between VOI metabolism, neuropsychological scores, and phenoconversion to neurodegenerative diseases.
Main Results:
- MCI-RBD patients exhibited lower executive function and higher verbal memory scores than MCI-AD patients.
- Relative hypometabolism in posterior brain regions (cuneus, precuneus, occipital) was observed in MCI-RBD, whereas MCI-AD showed hippocampal/parahippocampal hypometabolism.
- MCI-RBD-VOI metabolism correlated with executive function and predicted phenoconversion to alpha-synucleinopathy, while MCI-AD-VOI metabolism trended towards predicting dementia conversion.
Conclusions:
- MCI-RBD and MCI-AD present with distinct neuropsychological profiles and distinct patterns of brain glucose metabolism.
- These identified differences hold potential utility for improving the diagnostic accuracy and prognostic assessment of patients with mild cognitive impairment.
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