Skip to main content
SpringerLink
Log in

Does the Angiotensin II Receptor Antagonist Losartan Improve Cognitive Function?

  • Current Opinion
  • Published:
Drugs & Aging Aims and scope Submit manuscript

Abstract

Newer classes of antihypertensive agents, such as angiotensin II receptor antagonists, may offer benefits to patients in addition to their ability to lower blood pressure. It is accepted that chronic hypertension contributes to the development of cerebrovascular and cardiovascular disease, and several studies have demonstrated a link between hypertension and reduced cognitive function, especially in patients not receiving antihypertensive medication. In an initial clinical trial, the angiotensin II receptor antagonist losartan was shown to improve cognitive function in patients with hypertension, including in those who were elderly (up to 73 years of age). This effect cannot be explained by a reduction in blood pressure alone and is likely to involve interactions with the diverse biological actions of the renin-angiotensin system.

Improving or maintaining cognitive function in patients with hypertension may translate into economic benefits beyond those expected due to blood pressure control, and would result in considerable quality-of-life benefits for the aging population.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Table II
Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Ferder L, Basso N, De Cacanagh EMV, et al. Aging, the renin system, and angiotensin II receptor antagonists. Cardiovasc Ther Today 2000; 7(3): 1–5

    Google Scholar 

  2. Burnier M, Brunner HR. Angiotensin II receptor antagonists. Lancet 2000;355:637–45

    Article  PubMed  CAS  Google Scholar 

  3. Ferder L, Inserra F, Romano L, et al. Enalapril ameliorates interstitial fibrosis in the aging kidney. J Am Soc Nephrol 1994; 5: 1147–52

    PubMed  CAS  Google Scholar 

  4. Lever AF, Lyall P, Mortin I, et al. Angiotensin II, vascular structure and blood pressure. Kidney Int 1992; 41: 551–5

    Google Scholar 

  5. Haegarty AM. Functional and structural effects of ACE inhibitors on the cardiovascular system. Cardiology 1991; 79Suppl. 1: 3–9

    Article  Google Scholar 

  6. Tedesco MA, Ratti G, Aquino D, et al. Effects of losartan on hypertension and left ventricular mass: a long-term study. J Hum Hypertens 1998; 12: 505–10

    Article  PubMed  CAS  Google Scholar 

  7. Wang DH, Prewitt RL. Captopril reduces aortic and microvascular growth in hypertensive and normotensive rats. Hyper-tension 1990; 15: 68–77

    CAS  Google Scholar 

  8. Tedesco MA, Ratti G, Mennella S, et al. Comparison of losartan and hydrochlorothiazide on cognitive function and quality of life in hypertensive patients. Am J Hypertens 1999; 12: 1130–4

    Article  PubMed  CAS  Google Scholar 

  9. Cacciatore F, Abete P, Ferrara N, et al. The role of blood pressure in cognitive impairment in an elderly population: Os-servatorio Geriatrico Camapano Group. J Hypertens 1997; 15: 135–42

    Article  PubMed  CAS  Google Scholar 

  10. Tzourio C, Dufouil C, Ducimetière P, et al. Cognitive decline in individuals with high blood pressure. Neurology 1999; 53: 1948–52

    Article  PubMed  CAS  Google Scholar 

  11. Glynn RJ, Beckett LA, Hebert LE, et al. Current and remote blood pressure and cognitive decline. JAMA 1999; 281: 438–45

    Article  PubMed  CAS  Google Scholar 

  12. Skoog I, Lernfelt B, Landahl S, et al. A 15-year longitudinal study of blood pressure and dementia. Lancet 1996; 347: 1141–5

    Article  PubMed  CAS  Google Scholar 

  13. Kalmijn S, White L, Ross GW, et al. The metabolic cardiovascular syndrome and the risk of dementia in elderly men: the Honolulu-Asia Aging Study [abstract]. Neurology 2000; 54: A76

    Google Scholar 

  14. Knopman DS, White L, Ross GW, et al. Cardiovascular risk factors and longitudinal cognitive changes in middle-aged adults [abstract]. Neurology 2000; 54: A230

    Article  Google Scholar 

  15. The Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med 2000; 342: 145–53

    Article  Google Scholar 

  16. Forette F, Seux ML, Staessen JA, et al. Prevention of dementia in the randomised double-blind placebo-controlled systolic hypertension in Europe (Syst-Eur) trial. Lancet 1998; 352: 1347–51

    Article  PubMed  CAS  Google Scholar 

  17. Starr JM, Whalley LJ, Deary IJ. The effects of antihypertensive treatment on cognitive function: results from the HOPE study. J Am Geriatr Soc 1996; 44: 411–5

    PubMed  CAS  Google Scholar 

  18. Blumenthal JA, Madden DJ, Pierce TW, et al. Hypertension affects neurobehavioural functioning. Psychosom Med 1993; 55: 44–50

    PubMed  CAS  Google Scholar 

  19. Breteler MM, van Swieten JC, Bots ML, et al. Cerebral white matter lesions, vascular risk factors, and cognitive function in a population-based study: the Rotterdam study. Neurology 1994; 44: 1246–52

    Article  PubMed  CAS  Google Scholar 

  20. Skoog I, Marcusson J, Blennow K. Dementia. It’s getting better all the time. Lancet 1998; 352Suppl. 4: 19–26

    Google Scholar 

  21. Skoog I. Vascular aspects in Alzheimer’s disease. J Neural Transm Suppl 2000; 59: 37–43

    PubMed  CAS  Google Scholar 

  22. Strandgaard S, Paulson OB. Cerebrovascular consequences of hypertension. Lancet 1994; 344: 519–21

    Article  PubMed  CAS  Google Scholar 

  23. Prince M. Vascular risk factors and atherosclerosis as risk factors for cognitive decline and dementia. J Psychosom Res 1995; 39: 525–30

    Article  PubMed  CAS  Google Scholar 

  24. Heckbert SR, Longstreth WT, Psaty BM, et al. The association of antihypertensive agents with MRI white matter findings and with Modified Mini-Mental State Examination in older adults. J Am Geriatr Soc 1997; 45: 1423–33

    PubMed  CAS  Google Scholar 

  25. Kilander L, Nyman H, Boberg M, et al. Hypertension is related to cognitive impairment: a 20-year follow-up of 999 men. Hypertension 1998; 31:780–6

    Article  PubMed  CAS  Google Scholar 

  26. Guo Z, Fratiglioni L, Zhu L, et al. Occurrence and progression of dementia in a community population aged 75 years and older: relationship of antihypertensive medication use. Arch Neurol 1999; 56: 991–6

    Article  PubMed  CAS  Google Scholar 

  27. Richards SS, Emsley CL, Roberts J, et al. The association between vascular risk factor-mediating medications and cognition and dementia diagnosis in a community-based sample of African-Americans. J Am Geriatr Soc 2000; 48: 1035–41

    PubMed  CAS  Google Scholar 

  28. Wright JW, Harding JW. Brain angiotensin receptor subtypes AT1, AT2, and AT4 and their functions. Regul Pept 1995; 59: 269–95

    Article  PubMed  CAS  Google Scholar 

  29. Steckelings UM, Bottari SP, Unger T. Angiotensin receptor subtypes in the brain. Trends Pharmacol Sci 1992; 13: 365–8

    Article  PubMed  CAS  Google Scholar 

  30. Zhuo J, Moeller I, Jenkins, et al. Mapping tissue angiotensin-converting enzyme and angiotensin AT1, AT2, and AT4 receptors. J Hypertens 1998; 16: 2027–37

    Article  PubMed  CAS  Google Scholar 

  31. Li Z, Bains JS, Ferguson AV. Functional evidence that the angiotensin antagonist losartan crosses the blood-brain barrier in the rat. Brain Res Bull 1993; 30: 33–9

    Article  PubMed  CAS  Google Scholar 

  32. Polidori C, Ciccocioppo R, Nisato D, et al. Evaluation of the ability of losartan to cross the blood-brain barrier following acute intragastric treatment. Eur J Pharmacol 1998; 352: 15–21

    Article  PubMed  CAS  Google Scholar 

  33. Barnes NM, Champaneria S, Costall B, et al. Cognitive enhancing actions of DuP 753 detected in a mouse habituation paradigm. Neuroreport 1990; 1: 239–42

    Article  PubMed  CAS  Google Scholar 

  34. Jönsson L, Lindgren P, Wimo A, et al. Costs of mini mental state examination-related cognitive impairment. Pharmaco-economics 1999; 16: 409–16

    Article  Google Scholar 

  35. Jönsson L, Gerth W, Fastbom J. The potential economic consequences of cognitive improvement with losartan. Blood Press 2002; 11: 46–52

    Article  PubMed  Google Scholar 

  36. Rizzo JA, Simons WR. Variations in compliance among hypertensive patients by drug class: implications for health care costs. Clin Ther 1997; 19: 1446–57

    Article  PubMed  CAS  Google Scholar 

  37. Bloom BS. Continuation of initial antihypertensive medication after 1 year of therapy. Clin Ther 1998; 20: 1–10

    Article  Google Scholar 

  38. Düsing R, Lottermoser K, Mengden T, et al. Compliance with antihypertensive therapy: comparison of losartan, amlodip-ine, and metoprolol [abstract]. Dtsch Med Wochenschr 2000; 125Suppl. 3: S50

    Google Scholar 

  39. Moore MA, Edelman JM, Gadick LP, et al. Choice of initial antihypertensive medication may influence the extent to which patients stay on therapy: a community based study of a losartan-based regimen vs usual care. High Blood Press 1998; 7: 156–67

    CAS  Google Scholar 

  40. Morrell RW, Park DC, Kidder DP, et al. Adherence to antihypertensive medications across the life span. Gerontologist 1997; 37: 609–19

    Article  PubMed  CAS  Google Scholar 

  41. Monane M, Bohn RL, Gurwitz JH, et al. The effects of initial drug choice and comorbidity on antihypertensive therapy compliance: results from a population-based study in the elderly. Am J Hypertens 1997; 10: 697–704

    Article  PubMed  CAS  Google Scholar 

  42. Lip GYH, Beever DG. A survey of the current practice of treating hypertension in primary care: the Rational Evaluation and ChoiceinHypertension(REACH)study. Drug Dev Clin Pract 1996; 8: 161–9

    Google Scholar 

Download references

Acknowledgements

The authors wish to thank Michelle Dobson (Complete Medical Communications Limited, UK) for her excellent technical assistance and William Gerth (Merck & Co Inc., USA) for valuable comments on the manuscript. The authors have provided no information on sources of funding or on conflicts of interest directly relevant to the content of this review.

Author information

Authors and Affiliations

  1. Department of Cardio-Thoracic and Respiratory Sciences, Second University of Naples, Naples, Italy

    Michele A. Tedesco, Gennaro Ratti, Giovanni Di Salvo & Francesco Natale

Authors
  1. Michele A. Tedesco
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gennaro Ratti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Giovanni Di Salvo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Francesco Natale
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michele A. Tedesco.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tedesco, M.A., Ratti, G., Di Salvo, G. et al. Does the Angiotensin II Receptor Antagonist Losartan Improve Cognitive Function?. Drugs Aging 19, 723–732 (2002). https://doi.org/10.2165/00002512-200219100-00001

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002512-200219100-00001

Keywords

Search

Navigation