The Ankle-Brachial Index Is Associated with Cerebral β-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 β-amyloid (Aβ) 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, [11C]Pittsburgh Compound B (PiB)-positron emission tomography (PET), [18F]-fludeoxyglucose PET, and magnetic resonance imaging.

Results: A significant positive association was found between the ABI and global cerebral Aβ retention measured by PiB-PET, even after controlling for age, sex, and APOE ε4. 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 Aβ deposition than that of the other subgroups. This relationship between Aβ deposition and the ABI was significant only in APOE ε4 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 Aβ burden in cognitively healthy elderly individuals, particularly in APOE ε4 carriers.

Keywords: Alzheimer’s disease; apolipoprotein E ε4; cerebral Aβ deposition; cerebral glucose metabolism.