Abstract | BACKGROUND AND OBJECTIVES: 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.
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Authors | Patricia Diaz-Galvan, Scott A Przybelski, Timothy G Lesnick, Christopher G Schwarz, Matthew L Senjem, Jeffrey L Gunter, Clifford R Jack, Hoon-Ki Paul Min, Manoj Jain, Toji Miyagawa, Leah K Forsberg, Julie A Fields, Rodolfo Savica, Jonathan Graff-Radford, David T Jones, Hugo Botha, Erik K St Louis, David S Knopman, Vijay K Ramanan, Owen Ross, Neill Graff-Radford, Gregory S Day, Dennis W Dickson, Tanis J Ferman, Ronald C Petersen, Val J Lowe, Brad F Boeve, Kejal Kantarci |
Journal | Neurology
(Neurology)
Vol. 101
Issue 2
Pg. e178-e188
(07 11 2023)
ISSN: 1526-632X [Electronic] United States |
PMID | 37202168
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | © 2023 American Academy of Neurology. |
Chemical References |
- Amyloid beta-Peptides
- Apolipoprotein E4
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Topics |
- Male
- Humans
- Female
- Lewy Body Disease
(pathology)
- Amyloid beta-Peptides
(analysis)
- Cross-Sectional Studies
- Apolipoprotein E4
(genetics)
- Positron-Emission Tomography
- Alzheimer Disease
(diagnostic imaging)
- Cognitive Dysfunction
(diagnostic imaging)
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