Objective: To assess relationships between the structural status of the cholinergic basal forebrain (cBF), hippocampus (HPC) and multi-domain cognitive function in Parkinson’s disease (PD).

Background: Visuospatial impairment in PD is associated with posterior cortical deficits suggested to result from, among other pathologies, degeneration of the cBF. Such deficits might herald the onset of a progressing dementia syndrome. However, whether degeneration of the cBF in PD is associated with a decline in specific cognitive domains is untested in datasets with fine-grained neuropsychological assessment. Further, it is not clear if any influence of the cBF on cognitive health is independent of coexisting degeneration in the wider brain. In particular, the HPC is known to support visuospatial function, is intimately connected with the cBF, and undergoes significant degeneration in PD.

Methods: Twenty-seven PD patients without dementia and 20 controls underwent cognitive assessment and MRI. Relationships between sub-regional cBF volumes (Ch12, Ch4, Ch4p), the whole HPC and its subfields were related with cognitive scores. We applied the a priori prediction that there would be significant relationships between cBF and HPC volumes and visuospatial function. Regions showing significant correlations with cognitive scores were entered into a linear regression model to assess their combined relationships.

Results: In PD, but not controls, performance on the Rey-Osterrieth complex figure (ROCF) test, a test of visuospatial function, was associated with the volume of Ch4p (p=.04) and the whole HPC volume (p=.02). Further exploratory correlations within the HPC subfields revealed that only the CA3 region was significantly associated with scores on the task (p=.005 FWE-corrected). Volumetric measures did not correlate with episodic memory or executive function. Linear regression analysis to further investigate if Ch4p and CA3 are uniquely associated with visuospatial function revealed that only CA3 is uniquely associated with ROCF scores, explaining 40% of their variability.

Conclusions: Both the cBF and the CA3 region of the HPC are implicated in visuospatial impairment in PD. Variations in CA3 volume mediate the relationship between the cBF and visuospatial cognition. Our results support the view that cholinergic system is involved in visuospatial dysfunction in PD and highlight the role of cholinergic input to the HPC.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cholinergic-basal-forebrain-and-hippocampal-structure-influence-visuospatial-function-in-parkinsons-disease/