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    Free water imaging of the cholinergic system in dementia with Lewy bodies and Alzheimer's disease

    Schumacher, Julia, Ray, Nicola J, Hamilton, Calum A, Bergamino, Maurizio, Donaghy, Paul C, Firbank, Michael, Watson, Rosie, Roberts, Gemma, Allan, Louise, Barnett, Nicola, O'Brien, John T, Thomas, Alan J and Taylor, John-Paul (2023) Free water imaging of the cholinergic system in dementia with Lewy bodies and Alzheimer's disease. Alzheimer's and Dementia, 19 (10). pp. 4549-4563. ISSN 1552-5260

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    INTRODUCTION: Degeneration of cortical cholinergic projections from the nucleus basalis of Meynert (NBM) is characteristic of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), whereas involvement of cholinergic projections from the pedunculopontine nucleus (PPN) to the thalamus is less clear. METHODS: We studied both cholinergic projection systems using a free water-corrected diffusion tensor imaging (DTI) model in the following cases: 46 AD, 48 DLB, 35 mild cognitive impairment (MCI) with AD, 38 MCI with Lewy bodies, and 71 controls. RESULTS: Free water in the NBM-cortical pathway was increased in both dementia and MCI groups compared to controls and associated with cognition. Free water along the PPN-thalamus tract was increased only in DLB and related to visual hallucinations. Results were largely replicated in an independent cohort. DISCUSSION: While NBM-cortical projections degenerate early in AD and DLB, the thalamic cholinergic input from the PPN appears to be more selectively affected in DLB and might associate with visual hallucinations. Highlights: Free water in the NBM-cortical cholinergic pathways is increased in AD and DLB. NBM-cortical pathway integrity is related to overall cognitive performance. Free water in the PPN-thalamus cholinergic pathway is only increased in DLB, not AD. PPN-thalamus pathway integrity might be related to visual hallucinations in DLB.

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