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

Min Sheng, Hanzhang Lu, Peiying Liu, Yang Li, Harshan Ravi, Shin Lei Peng, Ramon Diaz-Arrastia, Michael D. Devous, Kyle B. Womack

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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 (CMRO 2), and cerebrovascular reactivity (CVR) after a single dose of sildenafil administration in order to assess its physiological effects in patients with AD. CBF, CMRO 2, 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 CMRO 2 data were obtained in twelve patients. Complete CVR data were obtained in eight patients. Global CBF and CMRO 2 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.

Original languageEnglish (US)
Pages (from-to)1351-1364
Number of pages14
JournalJournal of Alzheimer's Disease
Volume60
Issue number4
DOIs
StatePublished - 2017

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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