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NeuroImage 2011, Vol. 58 (2) :579 -587 doi:10.1016/j.neuroimage.2011.06.070 <<-上一篇 下一篇 ->>
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% CO2 in Alzheimer's disease and amnestic mild cognitive impairment.

Participants and methods

Thirty nine subjects were included to be investigated using blood oxygenation level dependent (BOLD) functional MRI at 1.5 T 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.


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 CO2 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.


This BOLD functional MRI study on CO2 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.


? BOLD fMRI of CO2 challenge, a new method to test vasoreactivity in clinical practice. ? Impaired vasoreactivity detected in patients with AD or MCI without microangiopathy. ? BOLD fMRI of CO2 challenge may help for diagnosis at the individual level.

Keywords: Alzheimer's disease Mild cognitive impairment Cerebral vasoreactivity Carbon dioxide BOLD fMRI
收稿日期:31 January 2011     修回日期:13 May 2011     发布日期: 1 July 2011    
A: Regressors used for fMRI analyses based on EtCO2 time courses during carbogen inhalation. The baseline was lower in AD compared to controls. Carbogen inhalation raised EtCO2 in all groups. Under carbogen, EtCO2 was lower in AD compared to MCI. Mean EtCO2 were not significantly different across groups (Table 4). B: EtCO2 temporal profiles with standard error after normalization for the amplitude show similar onset over blocks.
Mean CBF at rest evaluated using ASL with standard deviation. Mean values in mL/100 g/min were lower in AD although intergroup differences were not significant.
Cerebral vasoreactivity (m ± sd, corrected for gray matter partial volume) was decreased in AD and MCI (*p < 0.001) in all ROIs.
Individual values of cerebral vasoreactivity (corrected for gray matter partial volume) were decreased in AD and MCI. Values did not overlap in cingulum, occipital, and temporal lobes.
A: percentage of BOLD signal (corrected for gray matter partial volume change) averaged over three blocks with standard error. Amplitudes of both AD and MCI were decreased. B: Normalized BOLD signal changes, averaged over three blocks and corrected for timing (onset and ending) of the per-group average hypercapnia response. Slopes of the response during hypercapnic transition (1) and steady-state (2) showed in controls a rapid signal increase followed by a “plateau” during hypercapnic steady-state. In AD, the signal profile was closer to a long-lasting increase to reach maximum.
Intergroup comparison of cerebral vasoreactivity shows significant decrease in AD when compared to controls (p < 0.05). Warm colors indicate areas with significant higher CVR in controls than in AD.
Illustrative individual T maps, representing BOLD response to carbogen inhalation, without partial volume effect correction. Compared to control (58 yo man; MMSE = 29; hippocampal atrophy = 0; mean CVR without EtCO2 scaling = 2.38% BOLD; mean CVR with EtCO2 scaling = 0.58% BOLD/mmHg), CVR responses of patients with MCI (76 yo man; MMSE = 27; hippocampal atrophy = 3; mean CVR without EtCO2 scaling = 1.81% BOLD; mean CVR with EtCO2 scaling = 0.33% BOLD/mmHg) and AD (81 yo woman; MMSE = 22; hippocampal atrophy = 4; mean CVR without EtCO2 scaling = 1.30% BOLD; mean CVR with EtCO2 scaling = 0.30% BOLD/mmHg) were diffusely decreased.
Table 1.Demographic, clinical and biological data for each group (m ± sd).
Table 2.Scores for hippocampal atrophy (Scheltens et al., 1992) and microangiopathy (Inzitari et al., 2009) (m ± sd).
Table 3.Pearson's correlation coefficients between basal perfusion measured by ASL, age, and hippocampal atrophy.
Table 4.Physiological parameters (m ± sd) during air and carbogen inhalation. End tidal CO2 (EtCO2) is expressed in mmHg, heart rate in beats per minute, respiratory rate in breaths per minute, and arterial oxygen saturation (SaO2) in %. Significant intergroup differences under air (*) and carbogen (**).
Table 5.Pearson's correlation coefficients between CVR, MMSE, and hippocampal atrophy.
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