Objective: To investigate the association between Aβ accumulation and clinical characteristics across the Lewy body disease (LBD) spectrum, with a specific focus on global and domain-specific cognitive profiles.

Background: Cognitive impairment can emerge throughout LBD. Early executive deficits can arise in isolated REM sleep behavior disorder (iRBD), a shared prodromal phase to Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). β-amyloid (Aβ) co-pathology is frequently detected in autopsies of LBD.

Method: Participants diagnosed with iRBD, PD, and DLB underwent 18F-florbetaben PET scan, neuropsychological test, APOE genotyping, and the MDS-UPDRS evaluation. Subjects were categorized based on global cognitive status. Generalized linear models examined Aβ levels, quantified by standardized uptake value ratios (SUVRs) from PET, in relation to global and domain-specific cognitive decline, as well as Lewy body-related clinical features. Additionally, we investigated a distinct subgroup named the iRBD-cohort continuum, consisting of individuals with iRBD and phenoconverters.

Results: A total of 86 participants with LBD, including 14 normal cognition (NC-LB), 54 with mild cognitive impairment (MCI-LB), and 18 with dementia (Dementia-LB), were included. The likelihood of a positive Aβ scan increased with advancing cognitive stages. Female participants and APOE e4 allele carriers exhibited higher global cortical SUVRs compared to males and non-carriers, respectively. Voxel-wise comparisons revealed clusters of elevated Aβ in the Dementia-LB individuals across the prefrontal, parietal, precentral cortices, the SMA, and the lingual gyrus. Global cortical SUVRs positively correlated with increasing MDS-UPDRS motor scores in Dementia-LB (p = 0.011). Participants with impaired performance (z-score < –1.0) on the Trail Making Test Part B (TMT-B) displayed elevated Aβ signals, particularly in the SMA and precentral cortex. No such association was found for other neuropsychological test items. Notably, within the iRBD-cohort continuum, there was a clear linear relationship between TMT-B impairment and increased Aβ signals.

Conclusion: Across the LBD spectrum, there is a progressive accumulation of cortical Aβ that correlates with worsening cognition, particularly executive function. Individuals within the iRBD-continuum may experience a distinct evolution and cognitive impact of Aβ co-pathology.

Demographics and Clinical Characteristics

Voxel-based comparison of Aβ PET in LBD

Aβ load and cognitive profiles in LBD

Aβ load and clinical features

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MDS Abstracts - https://www.mdsabstracts.org/abstract/association-of-%ce%b2-amyloid-load-on-pet-with-cognitive-profiles-across-the-lewy-body-diseases-continuum/