Older adults with reduced cerebrovascular reactivity exhibit high white matter hyperintensity burden

Arunima Kapoor, Shubir Dutt, John Paul M. Alitin, Isabel J. Sible, Anisa Marshall, Fatemah Shenasa, Allison C. Engstrom, Aimée Gaubert, Xingfeng Shao, David Robert Bradford, Kathleen Rodgers, Mara Mather, Danny J.J. Wang, Daniel A. Nation

Research output: Contribution to journalArticlepeer-review


Cerebrovascular reactivity (CVR) deficits may contribute to small vessel disease, such as white matter hyperintensities (WMH). Moreover, apolipoprotein-e4 (APOE4) carriers at genetic risk for Alzheimer's disease exhibit cerebrovascular dysfunction relative to non-carriers. We examined whether older adults, and APOE4 carriers specifically, with diminished CVR would exhibit higher WMH burden. Independently living older adults (N = 125, mean age = 69.2 years; SD = 7.6; 31.2% male) free of dementia or clinical stroke underwent brain MRI to quantify cerebral perfusion during CVR to hypercapnia and hypocapnia and determine WMH volume. Adjusting for age, sex and intracranial volume, hierarchical regression analysis revealed a significant association between whole brain CVR to hypercapnia and WMH overall [B = −.02, 95% CI (-.04, −.008), p =.003] and in APOE4 carriers [B = −.03, 95% CI (-.06, −.009), p =.009]. Findings suggest deficits in cerebral vasodilatory capacity are associated with WMH burden in older adults and future studies are warranted to further delineate the effect of APOE4 on precipitating WMH.

Original languageEnglish (US)
Pages (from-to)5-10
Number of pages6
JournalNeurobiology of Aging
StatePublished - Jul 2024


  • Cerebrovascular reactivity
  • Small Vessel disease
  • White matter hyperintensities

ASJC Scopus subject areas

  • General Neuroscience
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology


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