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

Objective:We investigated the relation of circulating plasma -amyloid (A) 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 A 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 A 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 A(1-40) levels were associated with increased progression of WMH, and low A(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 A(1-40) and A(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 epsilon 4 genotype.Conclusions:Progression of WMH volume in dementia-free older persons is associated with levels of circulating plasma A. These results reinforce the notion of an interrelation of vascular and neurodegenerative mechanisms in cerebral aging.