Cognitive enhancement following acute losartan in normotensive young adults
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Losartan, an angiotensin II receptor antagonist (AIIA), is an antihypertensive that has previously been suggested to have cognitive-enhancing potential for older adults. The objective indices for such effects are equivocal, however, and if these drugs do offer dual advantages of hypertension control plus cognitive-enhancing potential, there exists a clear need to establish this directly.
This work examines the potential of losartan administered as a single dose to healthy young adults to improve cognitive performance alone or to reverse scopolamine-induced cognitive decrements.
In two placebo-controlled, double-blind studies, participants completed a cognitive test battery once before and once after drug absorption. In experiment 1, participants were randomly allocated to receive placebo, losartan 50 mg or losartan 100 mg. In experiment 2, participants were randomly allocated to one of four treatment groups: placebo/placebo, placebo/scopolamine, losartan/scopolamine and losartan/placebo (50 mg losartan p.o. and 1.2 mg scopolamine hydrochloride p.o.).
Losartan 50 mg improved performance on a task of prospective memory when administered alone and reversed the detrimental effects of scopolamine both in a standard lexical decision paradigm (p < 0.01) and when the task incorporated a prospective memory component (p < 0.008).
The findings highlight a cognitive-enhancing potential for losartan on compromised cognitive systems and emphasise the potential of AIIAs to produce benefits over and above hypertension control.
KeywordsCognition Ageing Antihypertensive Angiotensin Angiotensin receptor antagonists Losartan Scopolamine
The first author was funded on a PhD studentship from Biotechnology & Biological Sciences Research Council. Medical cover was provided by the following doctors during their employment with Brighton & Sussex Medical School: Ahmed O, Echlin K, Grice J, Hussein A, Lewis M, Naqvi S, Pepple R, Pressney I, Young A and Yu D.
- Albiston AL, Morton CJ, Ng HL, Pham V, Yeatman HR, Holly R, Ye S, Fernando RN, De Bundel D, Ascher DB, Mendelsohn FAO, Parker MW, Chai SY (2008) Identification and characterization of a new cognitive enhancer based on inhibition of insulin-regulated aminopeptidase. FASEB J 22:4209–4217PubMedCrossRefGoogle Scholar
- Brandimonte MA, Ferrante D, Feresin C, Delbello R (2001) Dissociating prospective memory from vigilance processes. Psychologica 22:97–113Google Scholar
- Fogari R, Mugellini A, Zoppi A, Lazzari P, Destro M, Rinaldi A et al (2006) Effect of telmisartan/hydrochlorothiazide vs lisinopril/hydrochlorothiazide combination on ambulatory blood pressure and cognitive function in elderly hypertensive patients. J Hum Hypertens 20(3):177–185PubMedCrossRefGoogle Scholar
- Hanon F, Berrou J, Negre-Pages L, Goch JH, Nadhazi Z, Petrella R, Sedefdjian A et al (2008) Effects of hypertension therapy based on eprosartan on systolic arterial blood pressure and cognitive function: primary results of the observational study on cognitive function and systolic blood pressure reduction open-label study. J Hypertens 26(8):1642–1650PubMedCrossRefGoogle Scholar
- McMurray JJ, Ostergren J, Swedberg K, Granger CB, Held P, Michelson EL et al (2003) Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: The charm-added trial. Lancet 362:767–771CrossRefGoogle Scholar
- Nelson HE (1982) National Adult Reading Test (NART): test manual. NFER-Nelson, WindsorGoogle Scholar
- Rey A (1941) L'examen psychologique dans les cas d'encephalopathie traumatique. Archives de Psychologie 28(112):112–164Google Scholar
- Spielberger CD, Gorsuch RL, Lushene RE (1970) STAI: manual for the state-trait anxiety inventory. Consulting Psychologists Press, Palo Alto, pp 23–49Google Scholar