β-Amyloid Load on PET Along the Continuum of Dementia With Lewy Bodies

Background:Amyloid-β plaques can co-occur with Lewy-related pathology in patients with dementia with Lewy bodies (DLB), but amyloid-β load at prodromal stages of DLB still needs to be elucidated. We investigated amyloid-β load on PET throughout the DLB continuum, from an early prodromal stage of isolated REM sleep behavior disorder (iRBD) to a stage of mild cognitive impairment with Lewy bodies (MCI-LB), and finally DLB.Methods:We performed a cross-sectional study in patients with a diagnosis of iRBD, MCI-LB, or DLB from the Mayo Clinic Alzheimer’s Disease Research Center. Amyloid-β levels were measured by Pittsburgh compound B (PiB) PET and global cortical standard uptake value ratio (SUVr) was calculated. Global cortical PiB SUVr values from each clinical group were compared to each other and to cognitively unimpaired individuals (CU; n=100) balanced on age and sex using ANCOVA. We used multiple linear regression testing for interaction to study the influences of sex andAPOEε4 status on PiB SUVr along the DLB continuum.Results:Of the 162 patients, 16 had iRBD, 64 had MCI-LB, and 82 had DLB. Compared to CU, global cortical PiB SUVr was higher in DLB (p <0.001) and MCI-LB (p=0.012). The DLB group included the highest proportion of amyloid-β positive patients (60%), followed by MCI-LB (41%), iRBD (25%), and finally CU (19%). Global cortical PiB SUVr was higher inAPOEε4 carriers compared toAPOEε4 non-carriers in MCI-LB (pp=0.049). Women had higher PiB SUVr with older age compared to men across the DLB continuum (βeta estimate=0.014,p=0.02).Conclusion:In this cross-sectional study, levels of amyloid-β load was higher further along the DLB continuum. Whereas amyloid-β levels were comparable to cognitively unimpaired individuals in iRBD, a significant elevation in amyloid-β levels was observed in the pre-dementia stage of MCI-LB and in DLB. Specifically,APOEε4 carriers had higher amyloid-β levels thanAPOEε4 non-carriers and women tended to have higher amyloid-β levels than men as they got older. These findings have important implications in targeting patients within the DLB continuum for clinical trials of disease-modifying therapies.