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

Jun Hua | SeungWook 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
Neurobiology of aging | 2019

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.

Pubmed ID: 30738323

Research resources used in this publication

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Associated grants

  • Agency: NIA NIH HHS, United States
    Id: P30 AG066507
  • Agency: NIBIB NIH HHS, United States
    Id: P41 EB015909
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS108452

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MATLAB (tool)

RRID:SCR_001622

Multi paradigm numerical computing environment and fourth generation programming language developed by MathWorks. Allows matrix manipulations, plotting of functions and data, implementation of algorithms, creation of user interfaces, and interfacing with programs written in other languages, including C, C++, Java, Fortran and Python. Used to explore and visualize ideas and collaborate across disciplines including signal and image processing, communications, control systems, and computational finance.

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SPM (tool)

RRID:SCR_007037

Software package for analysis of brain imaging data sequences. Sequences can be a series of images from different cohorts, or time-series from same subject. Current release is designed for analysis of fMRI, PET, SPECT, EEG and MEG.

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