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Abstract
Background and Objectives β-Amyloid (Aβ) plaques can co-occur with Lewy-related pathology in patients with dementia with Lewy bodies (DLB), but Aβ load at prodromal stages of DLB still needs to be elucidated. We investigated Aβ 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 Disease Research Center. Aβ levels were measured by Pittsburgh compound B (PiB) PET, and global cortical standardized uptake value ratio (SUVR) was calculated. Global cortical PiB SUVR values from each clinical group were compared with each other and with those of cognitively unimpaired (CU) individuals (n = 100) balanced on age and sex using analysis of covariance. We used multiple linear regression testing for interaction to study the influences of sex and APOE ε4 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 with CU individuals, global cortical PiB SUVR was higher in those with DLB (p < 0.001) and MCI-LB (p = 0.012). The DLB group included the highest proportion of Aβ-positive patients (60%), followed by MCI-LB (41%), iRBD (25%), and finally CU (19%). Global cortical PiB SUVR was higher in APOE ε4 carriers compared with that in APOE ε4 noncarriers in MCI-LB (p < 0.001) and DLB groups (p = 0.049). Women had higher PiB SUVR with older age compared with men across the DLB continuum (β estimate = 0.014, p = 0.02).
Discussion In this cross-sectional study, levels of Aβ load was higher further along the DLB continuum. Whereas Aβ levels were comparable with those in CU individuals in iRBD, a significant elevation in Aβ levels was observed in the predementia stage of MCI-LB and in DLB. Specifically, APOE ε4 carriers had higher Aβ levels than APOE ε4 noncarriers, and women tended to have higher Aβ 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.
Glossary
- Aβ=
- β-amyloid;
- AD=
- Alzheimer disease;
- ANCOVA=
- analysis of covariance;
- CDR=
- Clinical Dementia Rating;
- CDR-SOB=
- CDR Sum of Boxes;
- CU=
- cognitively unimpaired;
- DaTscan=
- 123I-FP-CIT SPECT;
- DLB=
- dementia with Lewy bodies;
- FDR=
- false discovery rate;
- iRBD=
- isolated REM sleep behavior disorder;
- MCALT=
- Mayo Clinic Adult Lifespan Template;
- MCI-LB=
- mild cognitive impairment with Lewy bodies;
- MCSA=
- Mayo Clinic Study of Aging;
- MMSE=
- Mini-Mental State Examination;
- PiB=
- Pittsburgh compound B;
- PSG=
- polysomnography;
- SPM=
- statistical parametric mapping;
- SUVR=
- standardized uptake value ratio
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Submitted and externally peer reviewed. The handling editors were Deputy Editor Bradford Worrall, MD, MSc, FAAN, and Assistant Editor Andrea Schneider, MD, PhD.
- Received August 8, 2022.
- Accepted in final form March 23, 2023.
- © 2023 American Academy of Neurology
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