Movement disorders : official journal of the Movement Disorder Society · 2026
Cortical Cholinergic Pathway Degeneration Reflects Cognitive Impairment and Dementia in Parkinson's Disease.
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Slater Nicola M, Myall Daniel J, Shoorangiz Reza, Meissner Wassilios G, Kirk Ian J, Keenan Ross J, Lee Rebecca M, Horne Kyla-Louise, MacAskill Michael R, Le Heron Campbell J, Pitcher Toni L, Anderson Tim J, Melzer Tracy R, Dalrymple-Alford John C
Аннотация
BACKGROUND: Cognitive impairment is a prevalent and debilitating feature of Parkinson's disease (PD). Increasing evidence from postmortem and in vivo positron emission tomography imaging studies supports cholinergic dysfunction in PD. There is, however, little evidence regarding the influence of the structural integrity of cortical cholinergic pathways that emanate from the nucleus basalis of Meynert (NBM).
OBJECTIVES: To investigate the association between cognition and the structural integrity of medial and lateral cortical cholinergic projection pathways in PD.
METHODS: Neuropsychological assessment, T1 imaging, and high angular resolution diffusion imaging (HARDI) were acquired from 108 participants with PD (41 female, mean age 71.3 years) and 41 control participants (22 female, mean age 70.6 years). Streamlines representing three cortical cholinergic pathways (one medial and two lateral) from the NBM were extracted from anatomically constrained tractography. Structural integrity was compared across controls and cognitive subgroups (PD with normal cognition [PD-N], with mild cognitive impairment [PD-MCI], and with dementia [PDD]) and using a continuous global measure of cognition.
RESULTS: In PD, we found evidence that lower cognitive performance was associated with increased mean diffusivity across all pathways, especially the perisylvian component of the lateral pathway. In those individuals with dementia, increased free water fraction and decreased fractional anisotropy and fiber density and cross-section was detected across all pathways.
CONCLUSIONS: Degeneration of the cortical cholinergic system is associated with cognitive decline in PD. Future work should determine whether pathway degeneration predicts future cognitive decline and dementia. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
OBJECTIVES: To investigate the association between cognition and the structural integrity of medial and lateral cortical cholinergic projection pathways in PD.
METHODS: Neuropsychological assessment, T1 imaging, and high angular resolution diffusion imaging (HARDI) were acquired from 108 participants with PD (41 female, mean age 71.3 years) and 41 control participants (22 female, mean age 70.6 years). Streamlines representing three cortical cholinergic pathways (one medial and two lateral) from the NBM were extracted from anatomically constrained tractography. Structural integrity was compared across controls and cognitive subgroups (PD with normal cognition [PD-N], with mild cognitive impairment [PD-MCI], and with dementia [PDD]) and using a continuous global measure of cognition.
RESULTS: In PD, we found evidence that lower cognitive performance was associated with increased mean diffusivity across all pathways, especially the perisylvian component of the lateral pathway. In those individuals with dementia, increased free water fraction and decreased fractional anisotropy and fiber density and cross-section was detected across all pathways.
CONCLUSIONS: Degeneration of the cortical cholinergic system is associated with cognitive decline in PD. Future work should determine whether pathway degeneration predicts future cognitive decline and dementia. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.