ANKLE-BRACHIAL INDEX IS ASSOCIATED WITH CEREBRAL BETA-AMYLOID DEPOSITION IN COGNITIVELY NORMAL ELDERLY INDIVIDUALS

Abstract

Ankle-brachial index (ABI), an indicator of atherosclerosis or arterial stiffness, has been associated with dementia and Alzheimer's disease, no information is yet available for its contribution to AD pathologies. We aimed to investigate the relationship between ABI and in vivo beta-amyloid (Aβ) deposition and AD-specific neurodegeneration in cognitively normal (CN) elderly individuals. Two-hundred fifty five CN elderly subjects who participated in the Korean Brain Aging Study for Early Diagnosis & Prediction of Alzheimer's Disease (KBASE), an ongoing prospective cohort study, were included. All subjects underwent comprehensive clinical and neuropsychological assessment, ABI measurement, apolipoprotein E (APOE) ε4 genotyping, [11C]Pittsburgh Compound B (PiB)-positron emission tomography (PET), and [18F]-fludeoxyglucose (FDG)-PET. Multiple linear regression analysis showed significant positive association between ABI score and global cerebral Aβ deposition even after controlling age, sex, and APOE ε4. When analyses of covariance (ANCOVA) with post-hoc comparison was done for four stratified ABI subgroups (ABI <1.07, 1.07∼1.15, 1.16∼1.24, and >1.24), the highest ABI subgroup (i.e., ABI>1.24) showed significantly higher Aβ deposition than other subgroups. Such associations between Aβ deposition and ABI were significant only in APOE ε4 carriers, but not in non-carriers. There were no significant association between ABI and AD-signature region cerebral glucose metabolism (CMglu). Our findings suggest that arterial stiffness, related to high ABI, may contribute to the occurrence of AD by increasing brain Aβ burden in preclinical stage.