Abstract
ObjectivesTo investigate in vivo degeneration of the cholinergic system in mild cognitive impairment with Lewy bodies (MCI-LB), we studied nucleus basalis of Meynert (NBM) volumes from structural MR images and its relation to EEG slowing and cognitive impairment. MethodsWe studied the NBM using structural MR images in 37 patients with MCI-LB, 34 patients with MCI with Alzheimer’s disease (MCI-AD), and 31 healthy control participants. We also tested correlations between NBM volumes and measures of overall cognition and measures of EEG slowing in the MCI groups. ResultsOverall NBM volume was reduced in MCI-LB compared to controls with no significant difference between MCI-AD and controls or between the two MCI groups. The voxel-wise analysis revealed bilateral clusters of reduced NBM volume in MCI-LB compared to controls and smaller clusters in MCI-AD compared to controls. There was a significant association between overall NBM volume and measures of overall cognition in MCI-LB, but not in MCI-AD. In both MCI groups, reduced NBM volume was correlated with more severe EEG slowing. ConclusionsThis study provides in vivo evidence that early cholinergic degeneration in DLB occurs at the MCI stage and is related to the severity of cognitive impairment. Furthermore, the results suggest that early EEG slowing in MCI-LB might be in part cholinergically driven. Importantly, these findings suggest an early cholinergic deficit in MCI-LB that may motivate further testing of the effectiveness of cholinesterase inhibitors in this group.
Highlights
While post-mortem studies suggest that cholinergic deficits in dementia with Lewy bodies (DLB) might occur earlier in the course of the disease compared to Alzheimer’s disease (AD) (Tiraboschi et al, 2002), no previous study has investigated early cholinergic changes in DLB in vivo and how these relate to cognitive impairment in patients with mild cognitive impairment (MCI) with Lewy bodies (MCI-LB)
Adden brooke’s Cognitive Examination - Revised (ACE-R), Addenbrooke’s Cognitive Examination – Revised; dominant frequency (DF), dominant fre quency; MCI with Alzheimer’s disease (MCI-AD), mild cognitive impairment with Alzheimer’s disease; MCI-LB, mild cognitive impairment with Lewy bodies; Mini Mental State Examination (MMSE), Mini-Mental State Examination frequency were positively correlated with nucleus basalis of Meynert (NBM) volume (Table 3 and Fig. 3B)
There was no significant correlation between NBM volume and alpha reactivity in either group
Summary
Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) are characterized by marked cholinergic deficits (Lippa et al, 1999; Tira boschi et al, 2002) which have been shown to be more severe in DLB compared to AD (Colloby et al, 2017; Hanyu et al, 2007; Kim et al, 2011; Whitwell et al, 2007) and are mainly caused by degeneration of the nucleus basalis of Meynert (NBM) (Erskine et al, 2019; Lippa et al, 1999; Perry et al, 1993). While post-mortem studies suggest that cholinergic deficits in DLB might occur earlier in the course of the disease compared to AD (Tiraboschi et al, 2002), no previous study has investigated early cholinergic changes in DLB in vivo and how these relate to cognitive impairment in patients with MCI with Lewy bodies (MCI-LB). While early EEG abnormalities seem to be specific to Lewy body disease – they are much less severe in patients with MCI-AD – these changes are not observed in all MCI-LB patients (Schumacher et al, 2020a). The second aim of this study was to investigate whether early changes in quantitative EEG measures – including measures of EEG slowing and alpha reactivity – are related to early NBM degeneration in MCI-LB
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