Testing the cognitive effects of tadalafil. Neuropsychological secondary outcomes from the PASTIS trial

Pauls, M. M.H. et al. (2023) Testing the cognitive effects of tadalafil. Neuropsychological secondary outcomes from the PASTIS trial. Cerebral Circulation - Cognition and Behavior, 5, 100187. (doi: 10.1016/j.cccb.2023.100187) (PMID:37811523) (PMCID:PMC10550803)

Abstract

Cerebral small vessel disease (SVD) is a major cause of cognitive impairment in older people. As secondary endpoints in a phase-2 randomised clinical trial, we tested the effects of single administration of a widely-used PDE5 inhibitor, tadalafil, on cognitive performance in older people with SVD. In a double-blinded, placebo-controlled, cross-over trial, participants received tadalafil (20 mg) and placebo on two visits ≥ 7 days apart (randomised to order of treatment). The Montreal Cognitive Assessment (MOCA) was administered at baseline, alongside a measure to estimate optimal intellectual ability (Test of Premorbid Function). Then, before and after treatment, a battery of neuropsychological tests was administered, assessing aspects of attention, information processing speed, working memory and executive function. Sixty-five participants were recruited and 55 completed the protocol (N = 55, age: 66.8 (8.6) years, range 52–87; 15/40 female/male). Median MOCA score was 26 (IQR: 23, 27], range 15–30). No significant treatment effects were seen in any of the neuropsychological tests. There was a trend towards improved performance on Digit Span Forward (treatment effect 0.37, C.I. 0.01, 0.72; P = 0.0521). We did not identify significant treatment effects of single-administration tadalafil on neuropsychological performance in older people with SVD. The trend observed on Digit Span Forward may help to inform future studies.

• Item Type: Articles
• Additional Information: This study was joint-funded by UK Alzheimer's Society and Alzheimer's Drug Discovery Foundation (Grant Ref. 20140901, PI: AH Hainsworth). ABY Shtaya was supported by a National Institute for Health and Research Clinical Lectureship (CL-2015–16–001).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Young, Dr Robin and Fish, Dr Jessica
• Authors: Pauls, M. M.H., Fish, J., Binnie, L. R., Benjamin, P., Betteridge, S., Clarke, B., Dhillon, M.-P. K., Ghatala, R., Hainsworth, F. A.H., Howe, F. A., Khan, U., Kruuse, C., Madigan, J. B., Moynihan, B., Patel, B., Pereira, A. C., Rostrup, E., Shtaya, A. B.Y., Spilling, C. A.,, Trippier, S., Williams, R., Young, R., Barrick, T. R., Isaacs, J. D., and Hainsworth, A. H.
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Mental Health and Wellbeing; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
• Journal Name: Cerebral Circulation - Cognition and Behavior
• Publisher: Elsevier
• ISSN: 2666-2450
• ISSN (Online): 2666-2450
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in Cerebral Circulation - Cognition and Behavior 5:100187
• Publisher Policy: Reproduced under a Creative Commons licence