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Multimodal MRI Characterization of Nucleus Basalis of Meynert Degeneration: Structural Atrophy and Free-water Diffusion in Parkinson's Disease Cognitive Impairment

· 2026-06-09

DOI: 10.21203/rs.3.rs-9971780/v1

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Abstract Background Cognitive impairment in Parkinson's disease (PD) is linked to degeneration of the cholinergic basal forebrain, particularly cholinergic nucleus 4 (Ch4) in the nucleus basalis of Meynert. Structural and diffusion MRI separately detect this degeneration, but few studies have combined these modalities across the PD cognitive spectrum. Methods We analyzed 92 participants: 14 healthy controls (HC), 35 PD with normal cognition (PD-NC), 33 with mild cognitive impairment (PD-MCI), and 10 with dementia (PDD). For Ch4 and cholinergic nuclei 1, 2, and 3 (Ch1-3) in the medial septal/diagonal band complex, we determined TIV-normalized gray matter density (GMD) and free-water (FW) fraction. We evaluated group differences, cognitive correlations, adjusted multivariable regression, and exploratory ROC discrimination. Results Ch4 GMD was significantly lower in PDD compared to PD-MCI (p = 0.007), PD-NC (p 

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