Lower neurovascular coupling response despite higher cerebral blood flow at rest in apolipoprotein ɛ4 positive adults

PLoS One. 2024 Dec 3;19(12):e0314744. doi: 10.1371/journal.pone.0314744. eCollection 2024.

Abstract

Cerebral blood flow at rest declines with age. However, age-related changes in functional measures of cerebrovascular health including cerebrovascular reactivity and neurovascular coupling are not well understood. Additionally, the effect of apolipoprotein E (APOE) ε4, a strong genetic risk factor for Alzheimer's disease, on cerebral blood flow and cerebrovascular function remains unclear. APOEε4 positive (APOEε4+; n = 37, age = 63±4y) and APOEε4 negative (APOEε4-; n = 50, age = 63±4y) cognitively unimpaired adults participated in this study. Macrovascular cerebral blood flow and microvascular cerebral perfusion were measured using 4D flow MRI and pseudo-continuous arterial spin labeling MRI, respectively. Cerebrovascular reactivity and neurovascular coupling were assessed by measuring middle cerebral artery blood velocity in response to hypercapnia and the n-back test, respectively. Neurovascular coupling was lower in APOEε4+ compared with APOEε4- adults (P<0.05), despite higher cerebral blood flow and cerebrovascular reactivity to hypercapnia. Alterations in neurovascular coupling may occur early, prior to changes in cognition, in aging APOEε4 carriers.

MeSH terms

  • Aged
  • Apolipoprotein E4* / genetics
  • Blood Flow Velocity
  • Cerebrovascular Circulation* / physiology
  • Female
  • Humans
  • Hypercapnia / physiopathology
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neurovascular Coupling* / physiology
  • Rest / physiology

Substances

  • Apolipoprotein E4

Grants and funding

This research was supported by the Wisconsin Alzheimer's Disease Research Center (P30-AG062715). This research was also supported by the National Institutes of Health grants HL118154 (to JB) and HL007936 (to KM, T32 award to University of Wisconsin–Madison Cardiovascular Research Center), and an Alzheimer's Association Research Grant (#17-499398 to JB).