Objective: To investigate the relationship between amyloid burden measured by PET and white matter microstructural alterations assessed by advanced diffusion MRI in individuals with Parkinson’s disease with dementia (PDD) and dementia with Lewy bodies (DLB).

Background: The clinical significance of amyloid burden in PDD and DLB remains unclear despite frequent mixed alpha-synuclein and amyloid pathology. The relationship between regional amyloid deposition and white matter microstructural changes associated with cognitive impairment is particularly unknown. Advanced dMRI techniques such as DTI and DKI enable detailed evaluation of white matter microstructure and may clarify the impact of amyloid pathology in PDD/DLB.

Method: Amyloid PET using ¹⁸F-flutemetamol and dMRI data, including DTI and DKI, were obtained from 20 individuals with PDD and 24 with DLB at Juntendo University Hospital between July 2022 and October 2024.

Results: Among the 44 participants, 23 were amyloid-PET positive. No significant differences were found in age (70.2±8.83, 75.2±5.94, p=0.0673), disease duration (9.14±4.13, 9.76±5.46, p=0.667), or Hoehn & Yahr stage (3.13±0.99, 3.00±1.10, p=0.727) between amyloid positive and negative group. Tract-wise analyses showed higher free-water–corrected axial diffusivity (ADt) and lower axial kurtosis (AK) in many major white matter tracts in the amyloid-positive group indicating chronic axonal degeneration. The centiloid scale correlated positively with ADt and free-water–corrected mean diffusivity (MDt), and negatively with AK. Voxel-wise analyses identified significant differences between groups in several major tracts associated with cognitive function, including the cingulum, anterior limb of the internal capsule, and corpus callosum. Regional SUVr in precuneus and posterior cingulate gyrus associated with cognitive scores, including Mini Mental State Examination, The Montreal Cognitive Assessment, and Pareidolia test. SUVr values of precuneus and posterior cingulate gyrus correlated with DTI and DKI metrics in the connected tracts including cingulum and corpus callosum.

Conclusion: Amyloid burden is significantly associated with microstructural alterations in white matter tracts in individuals with PDD/DLB.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/amyloid-burden-in-the-precuneus-and-posterior-cingulate-gyrus-is-associated-with-cognitive-function-and-white-matter-microstructure-in-lewy-body-dementia/