Genetic, vascular and amyloid components of cerebral blood flow in a preclinical population

J Cereb Blood Flow Metab. 2023 Oct;43(10):1726-1736. doi: 10.1177/0271678X231178993. Epub 2023 May 26.

Abstract

Aging-related cognitive decline can be accelerated by a combination of genetic factors, cardiovascular and cerebrovascular dysfunction, and amyloid-β burden. Whereas cerebral blood flow (CBF) has been studied as a potential early biomarker of cognitive decline, its normal variability in healthy elderly is less known. In this study, we investigated the contribution of genetic, vascular, and amyloid-β components of CBF in a cognitively unimpaired (CU) population of monozygotic older twins. We included 134 participants who underwent arterial spin labeling (ASL) MRI and [18F]flutemetamol amyloid-PET imaging at baseline and after a four-year follow-up. Generalized estimating equations were used to investigate the associations of amyloid burden and white matter hyperintensities with CBF. We showed that, in CU individuals, CBF: 1) has a genetic component, as within-pair similarities in CBF values were moderate and significant (ICC > 0.40); 2) is negatively associated with cerebrovascular damage; and 3) is positively associated with the interaction between cardiovascular risk scores and early amyloid-β burden, which may reflect a vascular compensatory response of CBF to early amyloid-β accumulation. These findings encourage future studies to account for multiple interactions with CBF in disease trajectory analyses.

Keywords: Alzheimer’s disease; Arterial spin labeling (ASL); cerebral blood flow (CBF); twin analysis; white matter hyperintensities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease* / complications
  • Alzheimer Disease* / diagnostic imaging
  • Alzheimer Disease* / genetics
  • Amyloid / genetics
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / metabolism
  • Cerebrovascular Circulation / genetics
  • Cognitive Dysfunction*
  • Humans
  • Magnetic Resonance Imaging / methods
  • Positron-Emission Tomography

Substances

  • Amyloid beta-Peptides
  • Amyloid