title: Forebrain-dominant deficit in cerebrovascular reactivity in Alzheimer's disease.
abstract: Epidemiologic evidence and postmortem studies of cerebral amyloid angiopathy suggest that vascular dysfunction may play an important role in the pathogenesis of Alzheimer's disease (AD). However, alterations in vascular function under in vivo conditions are poorly understood. In this study, we assessed cerebrovascular-reactivity (CVR) in AD patients and age-matched controls using CO(2)-inhalation while simultaneously acquiring Blood-Oxygenation-Level-Dependent (BOLD) MR images. Compared with controls, AD patients had widespread reduction in CVR in the rostral brain including prefrontal, anterior cingulate, and insular cortex (p < 0.01). The deficits could not be explained by cardiovascular risk factors. The spatial distribution of the CVR deficits differed drastically from the regions of cerebral blood flow (CBF) deficits, which were found in temporal and parietal cortices. Individuals with greater CVR deficit tended to have a greater volume of leukoaraiosis as seen on FLAIR MRI (p = 0.004). Our data suggest that early AD subjects have evidence of significant forebrain vascular contractility deficits. The localization, while differing from CBF findings, appears to be spatially similar to PIB amyloid imaging findings.
authors.affiliation: Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Uma S
authors.initials: US
authors.lastname: Yezhuvath
authors.forename: Jinsoo
authors.initials: J
authors.lastname: Uh
authors.forename: Yamei
authors.initials: Y
authors.lastname: Cheng
authors.forename: Kristin
authors.initials: K
authors.lastname: Martin-Cook
authors.forename: Myron
authors.initials: M
authors.lastname: Weiner
authors.forename: Ramon
authors.initials: R
authors.lastname: Diaz-Arrastia
authors.forename: Matthias
authors.initials: M
authors.lastname: van Osch
authors.forename: Hanzhang
authors.initials: H
authors.lastname: Lu
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000503:physiopathology*; D016229:Amyloid beta-Peptides; D002245:Carbon Dioxide; D002560:Cerebrovascular Circulation; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D016548:Prosencephalon / Q000098:blood supply*; D014661:Vasoconstriction
chemical_list: D016229:Amyloid beta-Peptides; D002245:Carbon Dioxide