Dataset Information

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

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, p_FDR = 0.0001) and in the PDD group specifically (ρ = 0.66, p_FDR = 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.

SUBMITTER: Schumacher J

PROVIDER: S-EPMC7178985 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Patients who have dementia with Lewy bodies and Alzheimer's disease show early degeneration of the cholinergic nucleus basalis of Meynert. However, how white matter projections between the nucleus basalis of Meynert and the cortex are altered in neurodegenerative disease is unknown. Tractography of white matter pathways originating from the nucleus basalis of Meynert was performed using diffusion-weighted imaging in 46 patients with Alzheimer's disease dementia, 48 with dementia with Lewy bodies, 35 with mild cognitive impairment with Alzheimer's disease, 38 with mild cognitive impairment with Lewy bodies and 71 control participants. Mean diffusivity of the resulting pathways was compared between groups and related to cognition, attention, functional EEG changes and dementia conversion in the mild cognitive impairment groups. We successfully tracked a medial and a lateral pathway from the nucleus basalis of Meynert. Mean diffusivity of the lateral pathway was higher in both dementia and mild cognitive impairment groups than controls (all P < 0.03). In the patient groups, increased mean diffusivity of this pathway was related to more impaired global cognition (β = -0.22, P = 0.06) and worse performance on an attention task (β = 0.30, P = 0.03). In patients with mild cognitive impairment, loss of integrity of both nucleus basalis of Meynert pathways was associated with increased risk of dementia progression [hazard ratio (95% confidence interval), medial pathway: 2.51 (1.24-5.09); lateral pathway: 2.54 (1.24-5.19)]. Nucleus basalis of Meynert volume was reduced in all clinical groups compared to controls (all P < 0.001), but contributed less strongly to cognitive impairment and was not associated with attention or dementia conversion. EEG slowing in the patient groups as assessed by a decrease in dominant frequency was associated with smaller nucleus basalis of Meynert volumes (β = 0.22, P = 0.02) and increased mean diffusivity of the lateral pathway (β = -0.47, P = 0.003). We show that degeneration of the cholinergic nucleus basalis of Meynert in Alzheimer's disease and dementia with Lewy bodies is accompanied by an early reduction in integrity of white matter projections that originate from this structure. This is more strongly associated with cognition and attention than the volume of the nucleus basalis of Meynert itself and might be an early indicator of increased risk of dementia conversion in people with mild cognitive impairment.

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