Association of Plasma Aβ Levels with MRI Markers of Cerebral Small Vessel Disease (S38.005)

BACKGROUND MRI-markers of cerebral small vessel disease (SVD) including white matter hyperintensities (WMH) are associated with an increased risk of dementia, including Alzheimer disease (AD). Age and hypertension are the main known risk factors for SVD, but in older persons extensive WMH may also reflect underlying cerebral amyloid angiopathy, due to amyloid β (Aβ) deposits in cerebral artery walls. The objective of this study was to determine whether plasma levels of Aβ are associated with MRI markers of SVD in dementia-free older community persons. METHODS Plasma Aβ concentrations (Aβ1-40, Aβ1-42, and Aβ1-42 /Aβ1-40 ratio) and MRI markers of SVD (WMH, lacunar infarcts, and perivascular spaces [PVS]) were evaluated in participants aged >65 years from the French 3C-Dijon cohort, at baseline (n=1,693) and after a 4-year follow-up (n=1,057). WMHs were measured using an automated method of tissue segmentation and quantification of lesion size. The association of baseline plasma Aβ with baseline MRI markers and WHM progression were examined. Using repeated Aβ measures we also tested the association of Aβ variability with progression of WMH volumes. RESULTS Lower plasma Aβ1-42, and Aβ1-42/Aβ1-40 ratio were associated with increased odds of having a large burden of PVS in the white matter (蠅10 PVS in the section containing greatest number of PVS) (OR=0.65, 95% CI=0.49-0.88, p=0.03; for Aβ1-42/Aβ1-40 OR=0.73, 95% CI=0.54-0.98, p=0.04). Lower Aβ1-40 at baseline (β±SE=-0.02±0.01, p=0.02), and consistently low Aβ1-42 over the follow up (β±SE=-0.03±0.01, p=0.03) were associated with accelerated progression of WMHs. CONCLUSION Plasma Aβ levels were associated with baseline more PVS and with accelerated WMH progression in dementia-free older community persons. Additional investigations are needed to explore whether cerebral amyloid angiopathy, AD-related neurodegenerative processes, or both, contribute to these associations. Disclosure: Dr. Kaffashian has nothing to disclose. Dr. Tzourio has received personal compensation for activities with Abbott, and Servier. Dr. Soumare has nothing to disclose. Dr. Dufouil has received personal compensation for activities with Eisai Inc. as a consultant. Dr. Crivello has nothing to disclose. Dr. Zhu has nothing to disclose. Dr. Schraen-Maschke has nothing to disclose. Dr. Mazoyer has nothing to disclose. Dr. Buee has received personal compensation for activities with reMYND. Dr. Buee has received personal compensation in an editorial capacity for Abstract Alzheimer. Dr. Debette has nothing to disclose.