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Cross-sectional Associations of β-Amyloid, Tau, and Cerebrovascular Biomarkers With Neurodegeneration in Probable Dementia With Lewy Bodies. | LitMetric

Cross-sectional Associations of β-Amyloid, Tau, and Cerebrovascular Biomarkers With Neurodegeneration in Probable Dementia With Lewy Bodies.

Neurology

From the Division of Clinical Geriatrics (D.F., P.D.-G., E.W.), Center for Alzheimer's Research, Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet, Stockholm, Sweden; Departments of Radiology (D.F., C.G.S., P.D.-G., M.L.S., V.J.L., C.R.J., K.K.), Quantitative Health Sciences (S.A.P., T.G.L.), Neurology (J.G.-R., D.S.K., D.T.J., R.S., R.C.P., B.F.B.), Information Technology (M.L.S.), and Psychiatry and Psychology (J.A.F.), Mayo Clinic, Rochester, MN; Departments of Psychiatry and Psychology (T.J.F.) and Neurology (N.G.-R.), Mayo Clinic, Jacksonville, FL; and Department of Neuroimaging (E.W.), Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom.

Published: February 2023

AI Article Synopsis

  • The study investigates how cerebrovascular, β-amyloid, and tau pathologies affect gray matter volume in patients with dementia with Lewy bodies (DLB), who also often have Alzheimer's and cerebrovascular issues.
  • Researchers used PET imaging and MRI to assess the relationships between these biomarkers and gray matter volume in patients with DLB compared to cognitively unimpaired controls.
  • Results showed that DLB patients had significantly lower gray matter volume, with associations found between larger cerebrovascular damage (indicated by white matter hyperintensity) and reduced volume in specific brain regions, while β-amyloid levels affected certain areas but tau levels did not correlate with gray matter

Article 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 C-Pittsburgh compound B (PiB) and F-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 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9984215PMC
http://dx.doi.org/10.1212/WNL.0000000000201579DOI Listing

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