EEG alpha peak frequency: cognitive impairment severity marker in isolated REM sleep behavior disorder

Abstract

Isolated REM sleep behavior disorder (iRBD) is a prodrome of α-synucleinopathies like Parkinson's disease (PD) and dementia with Lewy bodies (DLB). The best marker for prediction of lead time to phenoconversion is reduced striatal dopamine transporter (DaT)-binding, unavailable for most patients. This study investigated EEG alpha peak frequency (APF) slowing - an established marker of cognitive deterioration - as a severity marker in iRBD patients. In 320 patients clinically suspected of RBD 3-night-polysomnography was performed. After exclusion of 131 patients, mainly due to psychotropic medication, three groups were studied: Non-Syn - motor behavior unrelated to RBD (n = 34); iRBD (n = 122); RBD converted to overt α-synucleinopathies (PD = 19; DLB = 14). Data show in patients with iRBD significant correlations between APF, DaT-binding ratios and cognition. The strong correlation of APF < 8 Hz with caudate DaT-binding (r = 0.50-0.65) suggests, APF could be an easy-to-use severity marker for counseling patients on lead time until possible conversion to overt α-synucleinopathy especially in DLB.

Fig. 1

Flowchart of patient inclusion and exclusion.

Fig. 2. Correlation between APF and DaT-binding in RBD patients.

In 118 included RBD patients DaT-SPECT was performed. APF correlated significantly with all DaT-SPECT regions (SBR-values): left and right a caudate; b anterior putamen; c posterior putamen.

Fig. 3. APF vs DaT-binding in advanced RBD patients.

APF showed strongest correlation in advanced RBD patients who had a z-value of ≤−1.5 SD in one or both caudate regions (n = 45) in the a most affected caudate and b least affected caudate.

Fig. 4. APF vs. cognition.

APF correlated significantly with TMT-A and TMT-B in a/c RBD patients (n = 131), b/d patients with most affected caudate ≤−2 (n = 27).

Fig. 5. Gradual correlation of APF vs DaT-binding.

Starting on the left with all RBD patients included, this figure shows the Spearman´s rank coefficients of the correlation between APF and DaT-SPECT right caudate, left caudate, in subgroups of RBD patients by excluding patients based on their APF with increments of 0.1 Hz. Gray bars show the number of RBD patients included in the correlation. *significant correlation (p < 0.05).