Electroencephalographic prodromal markers of dementia across conscious states in Parkinson's disease.

In Parkinson's disease, electroencephalographic abnormalities during wakefulness and non-rapid eye movement sleep (spindles) were found to be predictive biomarkers of dementia. Because rapid eye movement sleep is regulated by the cholinergic system, which shows early degeneration in Parkinson's disease with cognitive impairment, anomalies during this sleep stage might mirror dementia development. In this prospective study, we examined baseline electroencephalographic absolute spectral power across three states of consciousness (non-rapid eye movement sleep, rapid eye movement sleep, and wakefulness) in 68 non-demented patients with Parkinson's disease and 44 healthy controls. All participants underwent baseline polysomnographic recordings and a comprehensive neuropsychological assessment. Power spectral analyses were performed on standard frequency bands. Dominant occipital frequency during wakefulness and ratios of slow-to-fast frequencies during rapid eye movement sleep and wakefulness were also computed. At follow-up (an average 4.5 years after baseline), 18 patients with Parkinson's disease had developed dementia and 50 patients remained dementia-free. In rapid eye movement sleep, patients with Parkinson's disease who later developed dementia showed, at baseline, higher absolute power in delta and theta bands and a higher slowing ratio, especially in temporal, parietal, and occipital regions, compared to patients who remained dementia-free and controls. In non-rapid eye movement sleep, lower baseline sigma power in parietal cortical regions also predicted development of dementia. During wakefulness, patients with Parkinson's disease who later developed dementia showed lower dominant occipital frequency as well as higher delta and slowing ratio compared to patients who remained dementia-free and controls. At baseline, higher slowing ratios in temporo-occipital regions during rapid eye movement sleep were associated with poor performance on visuospatial tests in patients with Parkinson's disease. Using receiver operating characteristic curves, we found that best predictors of dementia in Parkinson's disease were rapid eye movement sleep slowing ratios in posterior regions, wakefulness slowing ratios in temporal areas, and lower dominant occipital frequency. These results suggest that electroencephalographic slowing during sleep is a new promising predictive biomarker for Parkinson's disease dementia, perhaps as a marker of cholinergic denervation.

Electroencephalogram slowing predicts neurodegeneration in rapid eye movement sleep behavior disorder.

A large proportion of patients with idiopathic rapid eye movement sleep behavior disorder (iRBD) develop a synucleinopathy, mostly Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Therefore, identifying markers of neurodegeneration in iRBD could have major implications. We aimed to assess the usefulness of electroencephalography (EEG) spectral analysis performed during wakefulness for predicting the development of a neurodegenerative disease in iRBD. Fifty-four iRBD patients, 28 of whom developed Parkinson's disease, multiple system atrophy, or dementia with Lewy bodies (mean follow-up: 3.5 years), and 30 healthy controls underwent at baseline a resting-state waking EEG recording, neurological exam, and neuropsychological assessment. Absolute and relative spectral powers were analyzed for 5 frequency bands in frontal, central, parietal, temporal, and occipital regions. The slow-to-fast [(δ + θ)/(ß1 + ß2)] power ratio for each of the 5 cortical regions and the dominant occipital frequency were calculated as an index of cortical slowing. Patients who developed disease showed higher absolute delta and theta power in all 5 cortical regions compared to disease-free patients and controls. The slow-to-fast power ratio was higher in all regions in patients who developed disease than in the 2 other groups. Moreover, patients who developed disease had a slower dominant occipital frequency compared to controls. The only significant difference observed between disease-free iRBD patients and controls was higher absolute delta power in frontal and occipital regions in iRBD patients. Specific EEG abnormalities were identified during wakefulness in iRBD patients who later developed a synucleinopathy. EEG slowing is a promising marker of neurodegeneration in iRBD patients.

Electroencephalogram slowing in rapid eye movement sleep behavior disorder is associated with mild cognitive impairment.

BACKGROUND: Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is a well-documented risk factor for synucleinopathies such as Parkinson disease (PD) and dementia with Lewy bodies (DLB). Moreover, approximately 50% of iRBD patients have mild cognitive impairment (MCI). The purpose of our study was to investigate waking electroencephalogram (EEG) abnormalities specific to iRBD patients with MCI. METHODS: Forty-two polysomnographically confirmed iRBD patients, including 23 iRBD [+]MCI patients 19 patients without MCI (iRBD [-]MCI), and 37 healthy subjects participated in the study. All participants underwent a complete neuropsychologic assessment for MCI diagnosis and a waking quantitative EEG recording. RESULTS: iRBD [+]MCI patients had a higher slow-to-fast frequency ratio than iRBD [-]MCI patients and controls in the parietal, temporal, and occipital regions. iRBD [+]MCI patients also had higher relative θ power in the parietal, temporal, and occipital regions and lower relative α power in the occipital region compared to iRBD [-]MCI patients and controls. Moreover, iRBD [+]MCI patients had higher relative θ power in the frontal and central areas and lower relative ß power in the central, parietal, and temporal regions compared to controls. The dominant occipital frequency also was slower in iRBD [+]MCI patients compared to controls. No between-group differences were observed between iRBD [-]MCI patients and controls. CONCLUSION: In iRBD patients, only those with concomitant MCI showed waking EEG slowing in the posterior cortical regions, providing a potential marker for an increased risk for developing DLB or PD.

Validity of the Mattis Dementia Rating Scale to detect mild cognitive impairment in Parkinson's disease and REM sleep behavior disorder.

BACKGROUND/AIMS: Mild cognitive impairment (MCI) is frequent in Parkinson's disease (PD) and idiopathic REM sleep behavior disorder (iRBD). However, only a few studies have evaluated the validity of brief cognitive measures to detect MCI in PD or iRBD using standard diagnostic criteria for MCI. Our aim was to evaluate the validity of the Mini-Mental State Examination (MMSE) and the Mattis Dementia Rating Scale (DRS-2) to detect MCI in PD and iRBD. METHODS: Forty PD patients and 34 iRBD patients were studied. Receiver operating characteristic curves were created for both tests to assess their effectiveness in identifying MCI in PD and iRBD. RESULTS: In PD, a normality cutoff of 138 on the DRS-2 yielded the best balance between sensitivity (72%) and specificity (86%) with a correct classification of 80%. In iRBD, the optimal normality cutoff was 141 on the DRS-2, with a sensitivity of 90%, a specificity of 71% and a correct classification of 82%. No cutoff for the MMSE was found to have acceptable sensitivity or specificity. CONCLUSION: The DRS-2 has satisfactory validity to detect MCI in PD or iRBD. The MMSE proved to be invalid as a screening test for MCI in both populations.