Increased cerebral blood volume in small arterial vessels is a correlate of amyloid-β–related cognitive decline

Jun Hua, Seung Wook Lee, Nicholas I.S. Blair, Michael Wyss, Jiri M.G. van Bergen, Simon J. Schreiner, Sonja M. Kagerer, Sandra E. Leh, Anton F. Gietl, Valerie Treyer, Alfred Buck, Roger M. Nitsch, Klaas P. Pruessmann, Hanzhang Lu, Peter C.M. Van Zijl, Marilyn Albert, Christoph Hock, Paul G. Unschuld

Research output: Contribution to journalArticlepeer-review

Abstract

The protracted accumulation of amyloid-β (Aβ) is a major pathologic hallmark of Alzheimer's disease and may trigger secondary pathological processes that include neurovascular damage. This study was aimed at investigating long-term effects of Aβ burden on cerebral blood volume of arterioles and pial arteries (CBVa), possibly present before manifestation of dementia. Aβ burden was assessed by 11C Pittsburgh compound-B positron emission tomography in 22 controls and 18 persons with mild cognitive impairment (MCI), [ages: 75(±6) years]. After 2 years, inflow-based vascular space occupancy at ultra-high field strength of 7-Tesla was administered for measuring CBVa, and neuropsychological testing for cognitive decline. Crushing gradients were incorporated during MR-imaging to suppress signals from fast-flowing blood in large arteries, and thereby sensitize inflow-based vascular space occupancy to CBVa in pial arteries and arterioles. CBVa was significantly elevated in MCI compared to cognitively normal controls and regional CBVa related to local Aβ deposition. For both MCI and controls, Aβ burden and follow-up CBVa in several brain regions synergistically predicted cognitive decline over 2 years. Orbitofrontal CBVa was positively associated with apolipoprotein E e4 carrier status. Increased CBVa may reflect long-term effects of region-specific pathology associated with Aβ deposition. Additional studies are needed to clarify the role of the arteriolar system and the potential of CBVa as a biomarker for Aβ-related vascular downstream pathology.

Original languageEnglish (US)
Pages (from-to)181-193
Number of pages13
JournalNeurobiology of aging
Volume76
DOIs
StatePublished - Apr 2019

Keywords

  • 7 Tesla
  • Aging
  • Alzheimer's disease
  • Biomarker
  • CBV
  • Cerebral autoregulation
  • High field
  • Imaging
  • MRI
  • PET
  • Perfusion
  • Vascular

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Clinical Neurology
  • Geriatrics and Gerontology

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