title: The Utility of Cerebral Blood Flow as a Biomarker of Preclinical Alzheimer's Disease.
abstract: There is accumulating evidence suggesting that changes in brain perfusion are present long before the clinical symptoms of Alzheimer's disease (AD), perhaps even before amyloid-β accumulation or brain atrophy. This evidence, consistent with the vascular hypothesis of AD, implicates cerebral blood flow (CBF) in the pathogenesis of AD and suggests its utility as a biomarker of preclinical AD. The extended preclinical phase of AD holds particular significance for disease modification, as treatment would likely be most effective in this early asymptomatic stage of disease. This highlights the importance of identifying reliable and accurate biomarkers of AD that can differentiate normal aging from preclinical AD prior to clinical symptom manifestation. Cerebral perfusion, as measured by arterial spin labeling magnetic resonance imaging (ASL-MRI), has been shown to distinguish between normal controls and adults with AD. In addition to demonstrating diagnostic utility, CBF has shown usefulness as a tool for identifying those who are at risk for AD and for predicting subtle cognitive decline and conversion to mild cognitive impairment and AD. Taken together, this evidence not only implicates CBF as a useful biomarker for tracking disease severity and progression, but also suggests that ASL-measured CBF may be useful for identifying candidates for future AD treatment trials, especially in the preclinical, asymptomatic phases of the disease.
authors.affiliation: VA San Diego Healthcare System, 3350 La Jolla Village Dr., MC 151B, San Diego, CA, 92161, USA.|SDSU/UC San Diego Joint Doctoral Program in Clinical Psychology, 6363 Alvarado Court, Suite 103, San Diego, CA, 92120, USA.
authors.forename: Chelsea C
authors.initials: CC
authors.lastname: Hays
authors.affiliation: VA San Diego Healthcare System, 3350 La Jolla Village Dr., MC 151B, San Diego, CA, 92161, USA.|Department of Psychiatry, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA.
authors.forename: Zvinka Z
authors.initials: ZZ
authors.lastname: Zlatar
authors.affiliation: VA San Diego Healthcare System, 3350 La Jolla Village Dr., MC 151B, San Diego, CA, 92161, USA. cwierenga@ucsd.edu.|Department of Psychiatry, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA. cwierenga@ucsd.edu.
authors.forename: Christina E
authors.initials: CE
authors.lastname: Wierenga
mesh_terms: D000375:Aging / Q000502:physiology; D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology*; D015415:Biomarkers / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D006801:Humans; D012307:Risk Factors
chemical_list: D015415:Biomarkers
keywords: Alzheimer’s disease; Arterial spin labeling; Cerebral blood flow; Mild cognitive impairment; Neuroimaging; Perfusion