Low Ankle-Brachial Index Relates to Alzheimer-Signature Cerebral Glucose Metabolism in Cognitively Impaired Older Adults

J Alzheimers Dis. 2023;93(1):87-95. doi: 10.3233/JAD-220911.

Abstract

Background: Ankle-brachial index (ABI), an indicator of atherosclerosis or arterial stiffness, has been associated with Alzheimer's disease (AD) dementia and related cognitive impairment. Nevertheless, only limited information is available regarding its contribution to brain alterations leading to cognitive decline in late-life.

Objective: We aimed to investigate the relationship of ABI with in vivo AD pathologies and cerebrovascular injury in cognitively impaired older adults.

Methods: Total 127 cognitively impaired (70 mild cognitive impairment and 57 AD dementia) individuals, who participated in an ongoing prospective cohort study, were included. All participants underwent comprehensive clinical and neuropsychological assessment, ABI measurement, apolipoprotein E (APOE) ɛ4 genotyping, and multi-modal brain imaging including [11C] Pittsburgh Compound B (PiB)-positron emission tomography (PET) and [18F] fludeoxyglucose (FDG)-PET, and MRI.

Results: General linear model analysis showed significant relationship between ABI strata (low ABI: <1.00, normal ABI: 1.00-1.29, and high ABI: ≥1.30) and AD-signature region cerebral glucose metabolism (AD-CM), even after controlling age, sex, clinical dementia rating-sum of box, and APOE ɛ4 positivity (p = 0.029). Post hoc comparison revealed that low ABI had significantly lower AD-CM than middle and high ABI, while no difference of AD-CM was found between middle and high ABI. There was no significant difference of global Aβ deposition, AD-signature region cortical thickness, and white matter hyperintensity volume between the three ABI strata.

Conclusion: Our findings suggest that lower ABI, likely related to atherosclerosis, may contribute to the aggravation of AD-related regional neurodegeneration in cognitively impaired older adults.

Keywords: Alzheimer’s disease; ankle-brachial index; cerebral Aβ deposition; mild cognitive impairment; neurodegeneration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease* / diagnostic imaging
  • Alzheimer Disease* / genetics
  • Alzheimer Disease* / metabolism
  • Amyloid beta-Peptides / metabolism
  • Ankle Brachial Index
  • Apolipoproteins E / metabolism
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Cognitive Dysfunction* / diagnostic imaging
  • Cognitive Dysfunction* / genetics
  • Cognitive Dysfunction* / metabolism
  • Glucose / metabolism
  • Humans
  • Magnetic Resonance Imaging
  • Positron-Emission Tomography / methods
  • Prospective Studies

Substances

  • Amyloid beta-Peptides
  • Apolipoproteins E
  • Glucose