Background: Alzheimer's disease (AD) is the leading cause of degenerative dementia in the aging population. Patients with AD have alterations in cerebral hemodynamic function including reduced cerebral blood flow (CBF) and cerebral metabolic rate. Therefore, improved cerebrovascular function may be an attractive goal for pharmaceutical intervention in AD.
Objective: We wished to observe the acute effects of sildenafil on cerebrovascular function and brain metabolism in patients with AD.
Methods: We used several novel non-invasive MRI techniques to investigate the alterations of CBF, cerebral metabolic rate of oxygen (CMRO2), and cerebrovascular reactivity (CVR) after a single dose of sildenafil administration in order to assess its physiological effects in patients with AD. CBF, CMRO2, and CVR measurements using MRI were performed before and one hour after the oral administration of 50 mg sildenafil. Baseline Montreal Cognitive Assessment score was also obtained.
Results: Complete CBF and CMRO2 data were obtained in twelve patients. Complete CVR data were obtained in eight patients. Global CBF and CMRO2 significantly increased (p = 0.03, p = 0.05, respectively) following sildenafil administration. Voxel-wise analyses of CBF maps showed that increased CBF was most pronounced in the bilateral medial temporal lobes. CVR significantly decreased after administration of sildenafil.
Conclusion: Our data suggest that a single dose of sildenafil improves cerebral hemodynamic function and increases cerebral oxygen metabolism in patients with AD.
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http://dx.doi.org/10.3233/JAD-161006 | DOI Listing |
Eur Radiol Exp
December 2024
Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China.
Background: To investigate the accuracy of quantitative blood oxygen level-dependent (qBOLD) magnetic resonance imaging (MRI) in identifying hypoxia within glioblastoma and explore dynamic changes in oxygenation status of glioblastoma with and without metformin administration.
Methods: Three healthy and seven C6-bearing rats underwent 7-T qBOLD MRI. Oxygen extraction fraction (OEF) and cerebral metabolism rate of O (CMRO) were calculated from qBOLD data.
Am J Hematol
January 2025
Department of Clinical Hematology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Sickle cell disease (SCD) is complicated by silent cerebral infarcts (SCIs), for which anemia is an important risk factor. Despite normal oxygen delivery (OD), cerebral vascular reserve (CVR), and cerebral metabolic rate of oxygen (CMRO) are diminished in SCD, possibly causing the formation of SCIs. Voxelotor inhibits polymerization by increasing the hemoglobin oxygen binding, ameliorating hemolytic anemia.
View Article and Find Full Text PDFNMR Biomed
January 2025
Center for Magnetic Resonance Research (CMRR), Department of Radiology, University of Minnesota, Minneapolis, Minnesota, USA.
Cerebral glucose and oxygen metabolism and blood perfusion play key roles in neuroenergetics and oxidative phosphorylation to produce adenosine triphosphate (ATP) energy molecules in supporting cellular activity and brain function. Their impairments have been linked to numerous brain disorders. This study aimed to develop an in vivo magnetic resonance spectroscopy (MRS) method capable of simultaneously assessing and quantifying the major cerebral metabolic rates of glucose (CMR) and oxygen (CMRO) consumption, lactate formation (CMR), and tricarboxylic acid (TCA) cycle (V); cerebral blood flow (CBF); and oxygen extraction fraction (OEF) via a single dynamic MRS measurement using an interleaved deuterium (H) and oxygen-17 (O) MRS approach.
View Article and Find Full Text PDFJ Cereb Blood Flow Metab
November 2024
Department of Biomedical Engineering, University at Buffalo, Buffalo, NY, USA.
The study investigated the sensitivity of a novel MRI-based OEF mapping, quantitative susceptibility mapping plus quantitative blood oxygen level-dependent imaging (QSM+qBOLD or QQ), to physiological changes, particularly increased oxygen extraction fraction (OEF) by using hyperventilation as a vasoconstrictive stimulus. While QQ's sensitivity to decreased OEF during hypercapnia has been demonstrated, its sensitivity to increased OEF levels, crucial for cerebrovascular disorders like vascular dementia and Parkinson's disease, remains unexplored. In comparison with a previous QSM-based OEF, we evaluated QQ's sensitivity to high OEF values.
View Article and Find Full Text PDFNeuroimage
November 2024
Department of Radiology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong 519000, China. Electronic address:
Background: Brain structure, oxygenation and perfusion are important factors in aging. Coupling between regional cerebral oxygen consumption and perfusion also reflects functions of neurovascular unit (NVU). Their trajectories and sex differences during normal aging important for clinical interpretation are still not well defined.
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