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Abstract
Background and Objectives Although alpha-synuclein–related pathology is the hallmark of dementia with Lewy bodies (DLB), cerebrovascular and Alzheimer disease pathologies are common in patients with DLB. Little is known about the contribution of these pathologies to neurodegeneration in DLB. We investigated associations of cerebrovascular, β-amyloid, and tau biomarkers with gray matter (GM) volume in patients with probable DLB.
Methods We assessed patients with probable DLB and cognitively unimpaired (CU) controls with 11C-Pittsburgh compound B (PiB) and 18F-flortaucipir PET as markers of β-amyloid and tau, respectively. MRI was used to assess white matter hyperintensity (WMH) volume (a marker of cerebrovascular lesion load) and regional GM volume (a marker of neurodegeneration). We used correlations and analysis of covariance (ANCOVA) in the entire cohort and structural equation models (SEMs) in patients with DLB to investigate associations of WMH volume and regional β-amyloid and tau PET standardized uptake value ratios (SUVrs) with regional GM volume.
Results We included 30 patients with DLB (69.3 ± 10.2 years, 87% men) and 100 CU controls balanced on age and sex. Compared with CU controls, patients with DLB showed a lower GM volume across all cortical and subcortical regions except for the cuneus, putamen, and pallidum. A larger WMH volume was associated with a lower volume in the medial and orbital frontal cortices, insula, fusiform cortex, and thalamus in patients with DLB. A higher PiB SUVr was associated with a lower volume in the inferior temporal cortex, while flortaucipir SUVr did not correlate with GM volume. SEMs showed that a higher age and absence of the APOE ε4 allele were significant predictors of higher WMH volume, and WMH volume in turn was a significant predictor of GM volume in medial and orbital frontal cortices, insula, and inferior temporal cortex. By contrast, we observed 2 distinct paths for the fusiform cortex, with age having an effect through PiB and flortaucipir SUVr on one path and through WMH volume on the other path.
Discussion Patients with probable DLB have widespread cortical atrophy, most of which is likely influenced by alpha-synuclein–related pathology. Although cerebrovascular, β-amyloid, and tau pathologies often coexist in probable DLB, their contributions to neurodegeneration seem to be region specific.
Glossary
- AD=
- Alzheimer disease;
- ADRC=
- Alzheimer Disease Research Center;
- CU=
- cognitively unimpaired;
- DLB=
- dementia with Lewy bodies;
- FLAIR=
- fluid-attenuated inversion recovery;
- GM=
- gray matter;
- MCALT=
- Mayo Clinic Adult Lifespan Template;
- MMSE=
- Mini-Mental State Examination;
- NFT=
- neurofibrillary tangle;
- PiB=
- Pittsburgh compound B;
- RBD=
- REM sleep behavior disorder;
- SEM=
- structural equation model;
- TIV=
- total intracranial volume;
- UPDRS=
- Unified Parkinson Disease Rating Scale;
- WMH=
- white matter hyperintensity
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 editor was Linda Hershey, MD, PhD, FAAN.
- Received May 12, 2022.
- Accepted in final form October 6, 2022.
- © 2022 American Academy of Neurology
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