title: Brain volume and white matter hyperintensities as determinants of cerebral blood flow in Alzheimer's disease.
abstract: To better understand whether decreased cerebral blood flow (CBF) in patients with Alzheimer's disease (AD) reflects neurodegeneration or cerebral small vessel disease, we investigated the associations of normalized brain volume (NBV) and white matter hyperintensity (WMH) volume with CBF. We included 129 patients with AD (66 ± 7 years, 53% female) and 61 age-matched controls (64 ± 5 years, 43% female). CBF was measured with pseudocontinuous arterial spin labeling at 3T in the whole brain and in partial volume corrected cortical maps. When NBV and WMH were simultaneously entered in age and sex adjusted models, smaller NBV was associated with lower whole brain (Stβ: 0.29; p < 0.01) and cortical CBF (Stβ: 0.28; p < 0.01) in patients with AD. Larger WMH volume was also associated with lower whole brain (Stβ: -0.22; p < 0.05) and cortical CBF (Stβ: -0.24; p < 0.05) in AD. Additional adjustments did not change these results. In controls, neither NBV nor WMH was associated with CBF. Our results indicate that in AD, lower CBF as measured using pseudocontinuous arterial spin labeling, reflects the combined disease burden of both neurodegeneration and small vessel disease.
authors.affiliation: Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands. Electronic address: M.Benedictus@vumc.nl.
authors.forename: Marije R
authors.initials: MR
authors.lastname: Benedictus
authors.affiliation: Department of Radiology and Nuclear medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Maja A A
authors.initials: MAA
authors.lastname: Binnewijzend
authors.affiliation: Department of Physics and Medical Technology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Joost P A
authors.initials: JPA
authors.lastname: Kuijer
authors.affiliation: Department of Radiology and Nuclear medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Martijn D
authors.initials: MD
authors.lastname: Steenwijk
authors.affiliation: Department of Radiology and Nuclear medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Adriaan
authors.initials: A
authors.lastname: Versteeg
authors.affiliation: Department of Radiology and Nuclear medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Hugo
authors.initials: H
authors.lastname: Vrenken
authors.affiliation: Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.affiliation: Department of Radiology and Nuclear medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.affiliation: Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands; Department of Epidemiology and Biostatistics, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Wiesje M
authors.initials: WM
authors.lastname: van der Flier
authors.affiliation: Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Niels D
authors.initials: ND
authors.lastname: Prins
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology*; D001921:Brain / Q000098:blood supply* / Q000473:pathology*; D002560:Cerebrovascular Circulation; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D066127:White Matter / Q000473:pathology*
keywords: Alzheimer's disease; Arterial spin labeling; Cerebral blood flow; Cerebral small vessel disease; Neurodegeneration