Sildenafil Improves Vascular and Metabolic Function in Patients with Alzheimer’s Disease

Article type: Research Article

Authors: Sheng, Min^{a; b; 1} | Lu, Hanzhang^{a; c; 1} | Liu, Peiying^{a; c} | Li, Yang^{a; c} | Ravi, Harshan^{a; c} | Peng, Shin-Lei^{a; c; g} | Diaz-Arrastia, Ramon^d | Devous, Michael D.^e | Womack, Kyle B.^{e; f; *}

Affiliations: [a] Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA | [b] Department of Radiology, Beijing Eden Hospital, Beijing, China | [c] Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA | [d] Department of Neurology, University of Pennsylvania Perelman School of Medicine, Penn Presbyterian Medical Center, Philadelphia, PA, USA | [e] Department of Neurology and Neurotherapeutics, The University of Texas Southwestern Medical Center, Dallas, TX, USA | [f] Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX, USA | [g] Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, Taiwan

Correspondence: [*] Correspondence to: Kyle B. Womack, MD, Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9129, USA. Tel.: +1 214 648 0315; Fax: +1 214 648 2031; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: 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.

Keywords: Cerebral blood flow, cerebral metabolic rate of oxygen, cerebrovascular reactivity, magnetic resonance imaging, Montreal Cognitive Assessment, sildenafil

DOI: 10.3233/JAD-161006

Journal: Journal of Alzheimer's Disease, vol. 60, no. 4, pp. 1351-1364, 2017