EEG alpha reactivity and cholinergic system integrity in Lewy body dementia and Alzheimer's disease

Julia Schumacher, Alan J Thomas, Luis R Peraza, Michael Firbank, Ruth Cromarty, Calum A Hamilton, Paul C Donaghy, John T O'Brien, John-Paul Taylor, Julia Schumacher, Alan J Thomas, Luis R Peraza, Michael Firbank, Ruth Cromarty, Calum A Hamilton, Paul C Donaghy, John T O'Brien, John-Paul Taylor

Abstract

Background: Lewy body dementia (LBD), which includes dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), is characterised by marked deficits within the cholinergic system which are more severe than in Alzheimer's disease (AD) and are mainly caused by degeneration of the nucleus basalis of Meynert (NBM) whose widespread cholinergic projections provide the main source of cortical cholinergic innervation. EEG alpha reactivity, which refers to the reduction in alpha power over occipital electrodes upon opening the eyes, has been suggested as a potential marker of cholinergic system integrity.

Methods: Eyes-open and eyes-closed resting state EEG data were recorded from 41 LBD patients (including 24 patients with DLB and 17 with PDD), 21 patients with AD, and 40 age-matched healthy controls. Alpha reactivity was calculated as the relative reduction in alpha power over occipital electrodes when opening the eyes. Structural MRI data were used to assess volumetric changes within the NBM using a probabilistic anatomical map.

Results: Alpha reactivity was reduced in AD and LBD patients compared to controls with a significantly greater reduction in LBD compared to AD. Reduced alpha reactivity was associated with smaller volumes of the NBM across all groups (ρ = 0.42, pFDR = 0.0001) and in the PDD group specifically (ρ = 0.66, pFDR = 0.01).

Conclusions: We demonstrate that LBD patients show an impairment in alpha reactivity upon opening the eyes which distinguishes this form of dementia from AD. Furthermore, our results suggest that reduced alpha reactivity might be related to a loss of cholinergic drive from the NBM, specifically in PDD.

Keywords: Dementia with Lewy bodies; Nucleus basalis of Meynert; Parkinson’s disease dementia; Resting state EEG; Structural MRI.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Nucleus basalis of Meynert mask. Region of interest mask for the NBM in MNI space, estimated from the SPM Anatomy Toolbox
Fig. 2
Fig. 2
Alpha reactivity analysis. a Occipital EEG signals of example control and DLB participants in eyes-closed (blue) and eyes-open (red) conditions. b Comparison of mean power spectra for eyes-closed and eyes-open conditions for the different clinical groups. Shaded areas indicate standard errors. AD, Alzheimer’s disease; DLB, dementia with Lewy bodies; HC, healthy controls; PDD, Parkinson’s disease dementia
Fig. 3
Fig. 3
Group comparison. a Group comparison of alpha reactivity. b Group comparison of NBM volumes (normalised with respect to total intracranial volume). In each boxplot, the central line corresponds to the sample median; the upper and lower borders of the box represent the 25th and 75th percentile, respectively; and the length of the whiskers is 1.5 times the interquartile range. Corresponding results from statistical comparisons between the groups are presented in Table 2. AD, Alzheimer’s disease; DLB, dementia with Lewy bodies; HC, healthy controls; NBM, nucleus basalis of Meynert; PDD, Parkinson’s disease dementia
Fig. 4
Fig. 4
Correlations between alpha reactivity and NBM volume. Spearman’s correlations between alpha reactivity and normalised NBM volume across all groups and in each group separately. p values are FDR (false discovery rate)-corrected for multiple comparisons. AD, Alzheimer’s disease; DLB, dementia with Lewy bodies; FDR, false discovery rate; HC, healthy controls; NBM, nucleus basalis of Meynert; PDD, Parkinson’s disease dementia
Fig. 5
Fig. 5
Interpretation of alpha reactivity changes. Illustration of how a reduction in alpha reactivity can be mainly due to a decrease in eyes-closed alpha power (in AD) or an increase in eyes-open alpha power (in LBD) compared to controls. AD, Alzheimer’s disease; LBD, Lewy body dementia; HC, healthy controls

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