Association of Carotid Intima Media Thickening with Future Brain Region Specific Amyloid-beta Burden

Background: Carotid atherosclerosis is associated with cognitive impairment and dementia, though there is limited evidence of a direct link between carotid disease and amyloid-beta (A beta) burden. Objective: We studied the association of baseline and progressive carotid intima media thickness (CIMT) with A beta on 11C-Pittsburgh Compound B (PiB) to determine if those with carotid atherosclerosis would have higher A beta burden. Methods: We studied 47 participants from the Framingham Offspring cohort with carotid ultrasounds measuring CIMT at their 6th clinic examination (aged 49.5 +/- 5.7 years) and an average of 9.6 years later, and PiB imaging measuring A beta on average 22.1 years post baseline. We used multivariate linear regression analyses to relate baseline, follow-up, mean, and progression of internal carotid artery (ICA) and common carotid artery (CCA) CIMT to A beta in brain regions associated with Alzheimer's disease (AD) and related dementias (ADRD), adjusting for age, sex, and other vascular risk factors. Results: Participants with higher mean ICA IMT had more A beta in the precuneus (beta +/- standard error [beta +/- SE]: 0.466 +/- 0.171 mm, p = 0.01) and the frontal, lateral, and retrosplenial regions (beta +/- SE: 0.392 +/- 0.164 mm, p = 0.022) after adjusting for age, sex, vascular risk factors, and medication use. We did not find an association between any CCA IMT measures and A beta or progression of ICA or CCA IMT and A beta. Conclusion: Carotid atherosclerosis, as measured by ICA IMT, is associated with increased A beta burden later in life. These findings support a link between vascular disease and AD/ADRD pathophysiology.