Amyloid-Beta Deposition Patterns in Dementia with Lewy Bodies: Voxel-Wise Spatial Covariance Analysis and Associations with Core Clinical Features

Abstract Background Amyloid co-pathology is common in Lewy body dementia, yet its spatial distribution and relationship to clinical heterogeneity remain unclear. Prior studies have focused on global burden or between-group comparisons rather than variation within Lewy body dementia. Objectives To determine whether Lewy body dementia exhibits a distinct spatial pattern of amyloid deposition relative to Alzheimer disease and controls, and to identify symptom-specific covariance patterns associated with its core features. Methods We performed voxel-wise principal component analysis of F-18 Florbetapir positron emission tomography scans from 77 participants (Lewy body dementia n = 35, Alzheimer disease n = 22, controls n = 20) to derive spatial covariance patterns. Spatial covariance analysis within the Lewy body dementia subgroup investigated patterns related to cognitive fluctuations, parkinsonism, rapid eye movement sleep behavior disorder and visual hallucinations. Results No distinct amyloid deposition pattern specific to Lewy body dementia was identified. Within the Lewy body dementia subgroup, covariance patterns were observed for cognitive fluctuations, characterized by left-lateralized frontal-temporal-striatal involvement; parkinsonism, demonstrating an anterior-posterior gradient; and rapid eye movement sleep behavior disorder, showing medial temporal involvement with frontal-parietal sparing. No pattern was identified for visual hallucinations. Conclusions Lewy body dementia does not exhibit a distinct amyloid deposition pattern, but regional variation in amyloid distribution may be associated with clinical heterogeneity. These findings suggest that cortical-network symptoms, particularly cognitive fluctuations, may relate to greater cortical amyloid co-pathology, whereas features linked to subcortical substrates, including parkinsonism and rapid eye movement sleep behavior disorder, may relate to cortical amyloid sparing.