title: Impaired cerebral vasoreactivity to CO2 in Alzheimer's disease using BOLD fMRI.
abstract: OBJECTIVE
  To evaluate the cerebral vasoreactivity using blood oxygenation level dependent functional MRI during carbogen inhalation with 7% CO(2) in Alzheimer's disease and amnestic mild cognitive impairment.
  
  
  METHODS
  Thirty nine subjects were included to be investigated using blood oxygenation level dependent (BOLD) functional MRI at 1.5T during a block-design carbogen inhalation paradigm, with a high concentration face-mask under physiological monitoring. Basal cerebral perfusion was measured using pulsed arterial spin labeling. Image analyses were conducted using Matlab® and SPM5 with physiological regressors and corrected for partial volume effect.
  
  
  RESULTS
  Among selected participants, 12 subjects were excluded because of incomplete protocol, leaving for analysis 27 subjects without significant microangiopathy diagnosed for Alzheimer's disease (n=9), amnestic mild cognitive impairment (n=7), and matched controls (n=11). No adverse reaction related to the CO(2) challenge was reported. Carbogen inhalation induced a whole-brain signal increase, predominant in the gray matter. In patients, signal changes corrected for gray matter partial volume were decreased (0.36±0.13% BOLD/mmHg in Alzheimer's disease, 0.36±0.12 in patients with mild cognitive impairment, 0.62±0.20 in controls). Cerebral vasoreactivity impairments were diffuse but seemed predominant in posterior areas. The basal hypoperfusion in Alzheimer's disease was not significantly different from patients with mild cognitive impairment and controls. Among clinical and biological parameters, no effect of apoE4 genotype was detected. Cerebral vasoreactivity values were correlated with cognitive performances and hippocampal volumes. Among age and hippocampal atrophy, mean CVR was the best predictor of the mini-mental status examination.
  
  
  CONCLUSIONS
  This BOLD functional MRI study on CO(2) challenge shows impaired cerebral vasoreactivity in patients with Alzheimer's disease and amnestic mild cognitive impairment at the individual level. These preliminary findings using a new MRI approach may help to better characterize patients with cognitive disorders in clinical practice and further investigate vaso-protective therapeutics.
authors: Inserm, U836, Grenoble, France.
authors: S
authors: S
authors: Cantin
authors: M
authors: M
authors: Villien
authors: O
authors: O
authors: Moreaud
authors: I
authors: I
authors: Tropres
authors: S
authors: S
authors: Keignart
authors: E
authors: E
authors: Chipon
authors: J-F
authors: JF
authors: Le Bas
authors: J
authors: J
authors: Warnking
authors: A
authors: A
authors: Krainik
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology*; D001284:Atrophy; D002245:Carbon Dioxide / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D060825:Cognitive Dysfunction; D003627:Data Interpretation, Statistical; D005260:Female; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood*; D012044:Regression Analysis; D013113:Spin Labels
chemical_list: D013113:Spin Labels; D002245:Carbon Dioxide; D010100:Oxygen