The Ankle-Brachial Index Is Associated with Cerebral beta-Amyloid Deposition in Cognitively Normal Older Adults

Abstract

Background: Although ankle-brachial index (ABI), an indicator of atherosclerosis or arterial stiffness, has been associated with dementia and Alzheimer's disease (AD), no information is yet available for its contribution to AD pathologies. We investigated the relationship between the ABI and in vivo beta-amyloid (A) deposition and AD-specific neurodegeneration in cognitively normal (CN) elderly individuals. Methods: A total of 256 CN elderly subjects who participated in the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE), an ongoing prospective cohort study, were included. All subjects underwent comprehensive clinical and neuropsychological assessments, ABI measurement, apolipoprotein E (APOE) genotyping, [C-11]Pittsburgh Compound B (PiB)-positron emission tomography (PEI), [F-18]-fludeoxyglucose PET, and magnetic resonance imaging. Results: A significant positive association was found between the ABI and global cerebral A beta retention measured by PiB-PET, even after controlling for age, sex, and APOE epsilon 4. When three stratified ABI subgroups (ABI < 1.00, 1.00-1.29, and >= 1.30) were compared, the highest ABI subgroup (ie, ABI >= 1.30) showed significantly higher A beta deposition than that of the other subgroups. This relationship between A beta deposition and the ABI was significant only in APOE epsilon 4 carriers, but not in noncarriers. No significant association was observed between the ABI and neurodegeneration in the AD-signature regions. Conclusion: Our findings suggest that a high ABI, possibly related to arterial stiffness, is associated with elevated brain A beta burden in cognitively healthy elderly individuals, particularly in APOE epsilon 4 carriers.