TY - JOUR
T1 - Atorvastatin therapy is associated with greater and faster cerebral hemodynamic response
AU - Xu, Guofan
AU - Fitzgerald, Michele E.
AU - Wen, Zhifei
AU - Fain, Sean B.
AU - Alsop, David C.
AU - Carroll, Timothy
AU - Ries, Michele L.
AU - Rowley, Howard A.
AU - Sager, Mark A.
AU - Asthana, Sanjay
AU - Johnson, Sterling C.
AU - Carlsson, Cynthia M.
N1 - Funding Information:
Acknowledgement This study was supported by a Wisconsin Comprehensive Memory Program Alzheimer’s Disease Pilot Study Award with funds from the State of Wisconsin and the University of Wisconsin General Clinical Research Center (NCRR grant M01 RR03186). Dr. Carlsson was supported by a Beeson Career Development Award (1K23 AG026752–01, a grant jointly funded by NIA, the John A. Hartford Foundation, Atlantic Philanthropies, and the Starr Foundation). Portions of this study were supported by the NIA (R01 AG21155) and a Merit Review Grant from the Department of Veterans Affairs. The authors would like to sincerely thank all of the dedicated research participants. This is Madison VA GRECC manuscript number 2007–11.
PY - 2008/5
Y1 - 2008/5
N2 - Hypercholesterolemia in midlife increases the risk of subsequent cognitive decline, neurovascular disease, and Alzheimer's disease (AD), and statin use is associated with reduced prevalence of these outcomes. While statins improve vasoreactivity in peripheral arteries and large cerebral arteries, little is known about the effects of statins on cerebral hemodynamic responses and cognition in healthy asymptomatic adults. At the final visit of a 4-month randomized, controlled, double-blind study comparing atorvastatin 40 mg daily to placebo, 16 asymptomatic middle-aged adults (15 had useable data) underwent blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI), arterial spin labeling (ASL) quantitative cerebral blood flow (qCBF), dynamic susceptibility contrast (DSC) and structural imaging of the brain. Using a memory recognition task requiring discrimination of previously viewed (PV) and novel (NV) human faces, fMRI was used to elicit activation from brain regions known to be vulnerable to changes associated with AD. The BOLD signal amplitude (PV > NV) and latency to each stimulus were tested on a voxel basis between the atorvastatin (n = 8) and placebo (n = 7) groups. Persons randomized to atorvastatin not only showed significantly greater BOLD amplitude in the right angular gyrus, left superior parietal lobule, right middle temporal and superior sulcus than the placebo group, but also decreased hemodynamic response latencies in the right middle frontal gyrus, left precentral gyrus, left cuneus and right posterior middle frontal gyrus. However, neither the resting cerebral blood flow (CBF) measured with ASL nor the mean transit time (MTT) of cerebral perfusion calculated from DSC showed differences in these regions in either group. The drug related BOLD differences during memory recognition suggest that atorvastatin may have improved cerebral small vessel vasoreactivity, possibly through an effect on endothelial function. Furthermore, these results suggest that the effect of atorvastatin on the task-induced BOLD signal may not be a simple consequence of baseline flow change.
AB - Hypercholesterolemia in midlife increases the risk of subsequent cognitive decline, neurovascular disease, and Alzheimer's disease (AD), and statin use is associated with reduced prevalence of these outcomes. While statins improve vasoreactivity in peripheral arteries and large cerebral arteries, little is known about the effects of statins on cerebral hemodynamic responses and cognition in healthy asymptomatic adults. At the final visit of a 4-month randomized, controlled, double-blind study comparing atorvastatin 40 mg daily to placebo, 16 asymptomatic middle-aged adults (15 had useable data) underwent blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI), arterial spin labeling (ASL) quantitative cerebral blood flow (qCBF), dynamic susceptibility contrast (DSC) and structural imaging of the brain. Using a memory recognition task requiring discrimination of previously viewed (PV) and novel (NV) human faces, fMRI was used to elicit activation from brain regions known to be vulnerable to changes associated with AD. The BOLD signal amplitude (PV > NV) and latency to each stimulus were tested on a voxel basis between the atorvastatin (n = 8) and placebo (n = 7) groups. Persons randomized to atorvastatin not only showed significantly greater BOLD amplitude in the right angular gyrus, left superior parietal lobule, right middle temporal and superior sulcus than the placebo group, but also decreased hemodynamic response latencies in the right middle frontal gyrus, left precentral gyrus, left cuneus and right posterior middle frontal gyrus. However, neither the resting cerebral blood flow (CBF) measured with ASL nor the mean transit time (MTT) of cerebral perfusion calculated from DSC showed differences in these regions in either group. The drug related BOLD differences during memory recognition suggest that atorvastatin may have improved cerebral small vessel vasoreactivity, possibly through an effect on endothelial function. Furthermore, these results suggest that the effect of atorvastatin on the task-induced BOLD signal may not be a simple consequence of baseline flow change.
KW - Alzheimer's disease
KW - Arterial spin labeling
KW - BOLD
KW - Dynamic susceptibility contrast
KW - Event-related fMRI
KW - Hemodynamic response
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U2 - 10.1007/s11682-007-9019-7
DO - 10.1007/s11682-007-9019-7
M3 - Article
C2 - 20157644
AN - SCOPUS:77949581293
SN - 1931-7557
VL - 2
SP - 94
EP - 104
JO - Brain Imaging and Behavior
JF - Brain Imaging and Behavior
IS - 2
ER -
