Objective: To examine the relationship between cognitive decline and atrophy across cholinergic basal forebrain (BF) subregions in advanced Parkinson’s disease (PD).

Background: Recent studies show gray matter (GM) atrophy of the Nucleus Basalis of Meynert (Ch.4/4p), a posterior BF subregion, in PD Mild Cognitive Impairment (PD-MCI) compared to healthy older adults. Smaller GM volumes in area Ch.4/4p were also associated with reduced attention, memory and visuospatial skills.

Method: Cognitive data and 3T T1-weigthed MRI scans from 185 individuals with advanced PD (duration mean=9.96yrs, SD=3.84) were included. Cognitive diagnoses (PD-Intact n=65, PD-MCI n=120) were determined using the MDS level 2 criteria. Cognitive data were reduced in 5 components (memory, executive, attention, visuospatial, language) using Principal Component Analyses. MRI scans were preprocessed in SPM12. Segmented GM images were registered to a population-specific DARTEL template using non-linear modulation. Regions of interest (ROIs) include the total BF volume and volumes of 4 subregions: Ch.1-2, Ch.3, Ch.4, Ch.4p. GM volume in each ROI is the sum of the intensity of voxels within the ROI divided by the number of voxels and a scaling factor for GM concentration. Age and total intracranial volume were regressed out of ROI volumes.

Results: Total BF volume was reduced in PD-MCI relative to PD-Intact (t=2.23, p=.02). This difference was driven by atrophy in Ch.1-2 (t=2.69, p=.008). Area Ch.4 exhibited a trend level difference (t=1.69, p=.09), while the remaining regions did not differentiate the groups. In the full sample, smaller total BF volume was significantly correlated with memory (r=.19, p=.01) and executive function (r=.19, p=.008), but not with other abilities (p >.20). As for subregions, Ch.1-2 correlated significantly with memory (r=.24, p=.002) and Ch.4 with executive function (r=.22, p=.003).

Conclusion: It is increasingly understood that BF atrophy is a feature of PD closely related to cognitive impairment. Our findings build on this evidence by comparing subregional BF atrophy in advanced PD with and without PD-MCI. We show that Ch1-2 volume is smaller in PD-MCI and is associated with memory, which is consistent with its known septohippocampal cholinergic projection. Group differences in Ch.4 volumes were less pronounced, but were related to executive function, in keeping with its broad neocortical projections.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cholinergic-basal-forebrain-atrophy-and-cognitive-decline-in-advanced-parkinsons-disease/