Plasma β-amyloid and MRI markers of cerebral small vessel disease: Three-City Dijon Study

Objective: We investigated the relation of circulating plasma β-amyloid (Aβ) with MRI markers of small vessel disease (SVD) in dementia-free community persons. Methods: Participants were 1,690 individuals aged 65 to 80 years from the Three-City Dijon Study. Plasma Aβ measurement and MRI examination were performed at baseline and after a 4-year follow-up. MRI markers of SVD included white matter hyperintensities (WMH), lacunes, and enlarged perivascular spaces. We examined the relation of plasma Aβ levels with MRI markers of SVD at baseline and with progression of WMH over follow-up (n = 1,057). We also assessed whether these relations were modified by vascular risk factors, notably blood pressure. Results: Low plasma Aβ 1–40 levels were associated with increased progression of WMH, and low Aβ 1–42 with higher odds of extensive WMH progression over the follow-up (odds ratio = 1.66, 95% confidence interval = 1.16–2.38). Consistently low Aβ 1–40 and Aβ 1–42 levels on both measurements were associated with accelerated progression of WMH. These associations were modified by blood pressure levels but not the APOE e4 genotype. Conclusions: Progression of WMH volume in dementia-free older persons is associated with levels of circulating plasma Aβ. These results reinforce the notion of an interrelation of vascular and neurodegenerative mechanisms in cerebral aging.