Carotid Stiffness is Associated with Brain Amyloid-β Burden in Amnestic Mild Cognitive Impairment

Background: Vascular dysfunction has been implicated in the onset and progression of Alzheimer's disease (AD), yet the relationship of arterial stiffening with brain amyloid-β (Aβ) burden in at risk patients is unclear. Objective: We aimed to determine the relationship of aortic and carotid arterial stiffening with Aβ burden in patients with amnestic mild cognitive impairment (aMCI), a proposed transitional stage between normal aging and AD. Methods: Thirty-two older adults with aMCI underwent ¹⁸Florbetapir PET amyloid imaging to ascertain Aβ burden via standardized uptake value ratio (SUVR). Carotid-femoral pulse wave velocity (cfPWV), which reflects aortic stiffness, and carotid β stiffness index and distensibility, which reflect local cerebral arterial stiffness, thus having direct impact on the cerebral circulation, were measured using applanation tonometry and ultrasonography. Results: Region-of-interest based analysis showed that precuneus and mean cortex Aβ SUVR were correlated positively with carotid β stiffness index and negatively with carotid distensibility after adjusting for age, sex, mean arterial pressure (MAP), pulse pressure (PP), and APOE4 status. Whole-brain voxel-wise analysis showed that Aβ SUVR was positively correlated with carotid β stiffness index, and negatively with carotid distensibility at the precuneus/cingulate gyrus after multiple comparison correction. cfPWV was not correlated with Aβ SUVR. Conclusions: Carotid rather than aortic stiffening was independently associated with brain Aβ burden in patients with aMCI after adjusting for age, sex, MAP, PP, and APOE4 status. These findings provide evidence that arterial stiffening, particularly carotid artery stiffening, may contribute to AD pathology in patients with aMCI.