Effects of Hypoperfusion in Alzheimer's Disease

Issue title: Imaging the Alzheimer Brain

Guest editors: J. Wesson Ashford, Allyson Rosen, Maheen Adamson, Peter Bayley, Osama Sabri, Ansgar Furst, Sandra E. Black and Michael Weiner

Article type: Research Article

Authors: Austin, Benjamin P.^{a; b; c} | Nair, Veena A.^c | Meier, Timothy B.^d | Xu, Guofan^b | Rowley, Howard A.^{c; f} | Carlsson, Cynthia M.^{b; e; f} | Johnson, Sterling C.^{b; e; f} | Prabhakaran, Vivek^{c; d; *}

Affiliations: [a] UW Cardiovascular Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA | [b] Department of Veterans Affairs (VA) Geriatric Research, Education and Clinical Center (GRECC), Madison, WI, USA | [c] Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA | [d] Neuroscience Training Program, University of Wisconsin-Madison, Madison, WI, USA | [e] Department of Medicine, Division of Geriatrics and Gerontology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA | [f] Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

Correspondence: [*] Correspondence to: Vivek Prabhakaran, MD, PhD, Department of Radiology, University of Wisconsin, School of Medicine and Public Health, 600 Highland Avenue, Madison, WI 53792-3252, USA. Tel.: +1 608 265 5269; Fax: +1 608 265 4152; E-mail: [email protected].

Abstract: The role of hypoperfusion in Alzheimer's disease (AD) is a vital component to understanding the pathogenesis of this disease. Disrupted perfusion is not only evident throughout disease manifestation, it is also demonstrated during the pre-clinical phase of AD (i.e., mild cognitive impairment) as well as in cognitively healthy persons at high-risk for developing AD due to family history or genetic factors. Studies have used a variety of imaging modalities (e.g., SPECT, MRI, PET) to investigate AD, but with its recent technological advancements and non-invasive use of blood water as an endogenous tracer, arterial spin labeling (ASL) MRI has become an imaging technique of growing popularity. Through numerous ASL studies, it is now known that AD is associated with both global and regional cerebral hypoperfusion and that there is considerable overlap between the regions implicated in the disease state (consistently reported in precuneus/posterior cingulate and lateral parietal cortex) and those implicated in disease risk. Debate exists as to whether decreased blood flow in AD is a cause or consequence of the disease. Nonetheless, hypoperfusion in AD is associated with both structural and functional changes in the brain and offers a promising putative biomarker that could potentially identify AD in its pre-clinical state and be used to explore treatments to prevent, or at least slow, the progression of the disease. Finally, given that perfusion is a vascular phenomenon, we provide insights from a vascular lesion model (i.e., stroke) and illustrate the influence of disrupted perfusion on brain structure and function and, ultimately, cognition in AD.

Keywords: Alzheimer's disease, hypoperfusion, perfusion, stroke, mild cognitive impairment, ASL, MRI, vascular risk factors

DOI: 10.3233/JAD-2011-0010

Journal: Journal of Alzheimer's Disease, vol. 26, no. s3, pp. 123-133, 2011