Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Cognitive function and hypertension

Abstract

The importance of lowering blood pressure (BP) in hypertensive subjects is well known but the relationship between hypertension and cognitive function is controversial. This article reviews the role of hypertension in the aetiology of cognitive impairment and the relationships between BP, cerebral perfusion and cognition. It also summarizes findings of studies addressing the effect of antihypertensive therapy and cognition. An electronic database search of MEDLINE, EMBASE and the Cochrane Library and extensive manual searching of articles were conducted to identify studies that have used objective measurements of BP and neuropsychological tests to investigate the relationship among hypertension, cognitive function and/or antihypertensive treatment. In total, 28 cross-sectional studies, 22 longitudinal studies and 8 randomized placebo-controlled trials met the inclusion criteria. Cross-sectional studies showed mixed relationships between higher BP and cognition, with many studies showing no correlation or even J- or U-shaped associations. The majority of longitudinal studies demonstrated elevated BP to be associated with cognitive decline. Randomized studies demonstrated heterogeneous and, sometimes conflicting, effects of BP lowering on cognitive function. Suggested reasons for this heterogeneity include multiple mechanisms by which hypertension affects the brain, the variety of cognitive instruments used for assessment and differences in antihypertensive treatments. Although lowering the BP is beneficial in most patients with vascular risk factors, the effects of BP reduction on cognition remain unclear. Given the predicted upswing in people with cognitive impairments, the time is right for randomized clinical trials with specific cognitive end points to examine the relationship between cognitive function and hypertension and guide practice.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Collins R, Peto R, MacMahon S, Hebert P, Fiebach NH, Eberlein KA et al. Blood pressure, stroke and coronary heart disease. Part 2, short-term reduction in blood pressure: overview of randomised drug trials in their epidemiological context. Lancet 1990; 335: 827–838.

    Article  CAS  Google Scholar 

  2. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R, Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002; 360: 1903–1913.

    Article  PubMed  Google Scholar 

  3. PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood pressure-lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack. Lancet 2001; 358: 1033–1041.

    Article  Google Scholar 

  4. Dufouil C, Chalmers C, Coskun O, Besancon V, Bousser M-G, Guillon P et al. Effects of blood pressure lowering on cerebral white matter hyperintensities in patients with stroke. The PROGRESS (Perindopril Protection against Recurrent Stroke Study) magnetic resonance imaging substudy. Circulation 2005; 112: 1644–1650.

    Article  Google Scholar 

  5. Spence JD . Cerebral consequences of hypertension: where do they lead? J Hypertens Suppl 1996; 14: S139–S145.

    CAS  Google Scholar 

  6. Skoog I . A review on blood pressure and ischaemic white matter lesions. Dement Geriatr Cogn Disord 1998; 9 (Suppl 1): 13–19.

    Article  Google Scholar 

  7. O’Sullivan M, Morris RG, Huckstep B, Jones DK, Williams SC, Markus HS . Diffusion tensor MRI correlates with executive dysfunction in patients with ischaemic leukoaraiosis. J Neurol Neurosurg Psychiatry 2004; 75: 441–447.

    Article  PubMed  Google Scholar 

  8. de la Torre JC, Fortin T . A chronic physiological rat model of Alzheimer's disease. Behav Brain Res 1994; 63: 35–40.

    Article  CAS  Google Scholar 

  9. Sparks DL, Scheff SW, Liu H, Landers TM, Coyne CM, Hunsaker III JC . Increased incidence of neurofibrillary tangles (NFT) in non-demented individuals with hypertension. J Neurol Sci 1995; 131: 162–169.

    Article  CAS  Google Scholar 

  10. Kalaria RN, Kenny RA, Ballard CG, Perry R, Ince P, Polvikoski T . Towards defining the neuropathological substrates of vascular dementia. J Neurol Sci 2004; 226: 75–80.

    Article  Google Scholar 

  11. O’Brien JT, Erkinjuntii E, Reisberg B, Roman G, Sawada T, Pantoni L et al. Vascular cognitive impairment. Lancet Neurol 2003; 2: 89–93.

    Article  Google Scholar 

  12. Qiu C, Winblad B, Fratiglioni L . The age-dependent relation of blood pressure to cognitive function and dementia. Lancet Neurol 2005; 4: 487–499.

    Article  Google Scholar 

  13. Cummings JL . Frontal–subcortical circuits and human behavior. J Psychosom Res 1998; 44: 627–628.

    Article  CAS  Google Scholar 

  14. Birns J, Markus H, Kalra L . Blood pressure reduction for vascular risk: is there a price to be paid? Stroke 2005; 36: 1308–1313.

    Article  Google Scholar 

  15. Shi J, Yang SH, Stubley L, Day AL, Simpkins JW . Hypoperfusion induces overexpression of beta-amyloid precursor protein mRNA in a focal ischemic rodent model. Brain Res 2000; 853: 1–4.

    Article  CAS  Google Scholar 

  16. Tanaka M, Fukuyama H, Yamauchi H, Narita M, Nabatame H, Yokode M et al. Regional cerebral blood flow abnormalities in nondemented patients with memory impairment. J Neuroimag 2002; 12: 112–118.

    Article  Google Scholar 

  17. Verghese J, Lipton RB, Hall CB, Kuslansky G, Katz MJ . Low blood pressure and the risk of dementia in very old individuals. Neurology 2003; 61: 1667–1672.

    Article  CAS  Google Scholar 

  18. Wallace RB, Lemke JH, Morris MC, Goodenberger M, Kohout F, Hinrichs JV . Relationship of free-recall memory to hypertension in the elderly: the Iowa 65+ Rural Health Study. J Chronic Dis 1985; 38: 475–481.

    Article  CAS  Google Scholar 

  19. Farmer ME, White LR, Abbott RD, Wolz MM, Wolf PA . Blood pressure and cognitive performance: the Framingham Study. Am J Epidemiol 1987; 126: 1103–1114.

    Article  CAS  Google Scholar 

  20. Elias MF, Robbins MA, Schultz Jr NR, Pierce TW . Is blood pressure an important variable in research on aging and neuropsychological test performance? J Gerontol 1990; 45: P128–P135.

    Article  CAS  Google Scholar 

  21. Scherr PA, Hebert LE, Smith IA, Evans DA . Relation of blood pressure to cognitive functions in the elderly. Am J Epidemiol 1991; 134: 1303–1315.

    Article  CAS  Google Scholar 

  22. Starr JM, Whalley LJ, Inch S, Schering PA . Blood pressure and cognitive function in healthy old people. J Am Geriatr Soc 1993; 41: 753–756.

    Article  CAS  Google Scholar 

  23. Desmond DW, Tatemichi TK, Paik M, Stern Y . Risk factors for cerebrovascular disease as correlates of cognitive function in a stroke-free cohort. Arch Neurol 1993; 50: 162–166.

    Article  CAS  Google Scholar 

  24. Kuusisto J, Koivisto K, Mykkanen L, Helkala EL, Vanhanen M, Hänninen T et al. Essential hypertension and cognitive function: the role of hyperinsulinemia. Hypertension 1993; 22: 771–779.

    Article  CAS  Google Scholar 

  25. Launer LJ, Masaki K, Petrovitch H, Foley D, Havlik RJ . The association between midlife blood pressure levels and late-life cognitive function. The Honolulu-Asia Aging Study. JAMA 1995; 274: 1846–1851.

    Article  CAS  Google Scholar 

  26. Gale CR, Martyn CN, Cooper C . Cognitive impairment and mortality in a cohort of elderly people. Br Med J 1996; 312: 608–611.

    Article  CAS  Google Scholar 

  27. Guo Z, Fratiglioni L, Winblad B, Viitanen M . Blood pressure and performance on the Mini-Mental State Examination in the very old: cross-sectional and longitudinal data from the Kungsholmen Project. Am J Epidemiol 1997; 145: 1106–1113.

    Article  CAS  Google Scholar 

  28. Cacciatore F, Abete P, Ferrera N, Paolisso G, Amato L, Canonico S et al. The role of blood pressure in cognitive impairment in an elderly population. J Hypertens 1997; 15: 135–142.

    Article  CAS  Google Scholar 

  29. van Boxtel MPJ, Gaillard C, Houx PJ, Buntinx F, de Leeuw PW, Jolles J . Can the blood pressure predict task performance in a healthy population sample? J Hypertens 1997; 15: 1069–1076.

    Article  CAS  Google Scholar 

  30. Cerhan JR, Folsom AR, Mortimer JA, Shahar E, Knopman DS, McGovern PG et al. Correlates of cognitive function in middle-aged adults. Atherosclerosis Risk in Communities (ARIC) Study Investigators. Gerontology 1998; 44: 95–105.

    Article  CAS  Google Scholar 

  31. Kilander L, Nyman H, Boberg M, Hansson L, Lithell H . Hypertension is related to cognitive impairment: a 20-year follow-up of 999 men. Hypertension 1998; 31: 780–786.

    Article  CAS  Google Scholar 

  32. Seux M-L, Thijs L, Forette F, Staessen JA, Birkenhäger WH, Bulpitt CJ et al. Correlates of cognitive status of old patients with isolated systolic hypertension: the Syst-Eur Vascular Dementia Project. J Hypertens 1998; 16: 963–969.

    Article  CAS  Google Scholar 

  33. Glynn RJ, Beckett LA, Hebert LE, Morris MC, Scherr PA, Evans DA . Current and remote blood pressure and cognitive decline. JAMA 1999; 281: 438–445.

    Article  CAS  PubMed  Google Scholar 

  34. Harrington F, Saxby BK, McKeith IG, Wesnes K, Ford GA . Cognitive performance in hypertensive and normotensive older subjects. Hypertension 2000; 36: 1079–1082.

    Article  CAS  PubMed  Google Scholar 

  35. Di Carlo A, Baldereschi M, Amaducci L, Maggi S, Grigoletto F, Scarlato G et al. Cognitive impairment without dementia in older people: prevalence, vascular risk factors, impact on disability. The Italian Longitudinal Study on Aging. J Am Geriatr Soc 2000; 48: 775–782.

    Article  CAS  PubMed  Google Scholar 

  36. Stewart R, Richards M, Brayne C, Mann A . Vascular risk and cognitive impairment in an older, British, African-Caribbean population. J Am Geriatr Soc 2001; 49: 263–269.

    Article  CAS  Google Scholar 

  37. André-Petersson L, Hagberg B, Janzon L, Steen G . A comparison of cognitive ability in normotensive and hypertensive 68-year-old men: results from population study ‘men born in 1914’, in Malmö, Sweden. Exp Aging Res 2001; 27: 319–340.

    Article  Google Scholar 

  38. Izquierdo-Porrera AM, Waldstein SR . Cardiovascular risk factors and cognitive function in African Americans. J Gerontol B Psychol Sci Soc Sci 2002; 57: P377–P380.

    Article  Google Scholar 

  39. Morris MC, Scherr PA, Hebert LE, Bennett DA, Wilson RS, Glynn RJ et al. Association between blood pressure and cognitive function in a biracial community population of older persons. Neuroepidemiology 2002; 21: 123–130.

    Article  Google Scholar 

  40. Budge MM, de Jager C, Hogervorst E, Smith AD, Oxford Project To Investigate Memory and Ageing (OPTIMA). Total plasma homocysteine, age, systolic blood pressure, and cognitive performance in older people. J Am Geriatr Soc 2002; 50: 2014–2018.

    Article  Google Scholar 

  41. Paran E, Anson O, Reuveni H . Blood pressure and cognitive functioning among independent elderly. Am J Hypertens 2003; 16: 818–826.

    Article  Google Scholar 

  42. Pandav R, Dodge HH, DeKosky ST, Ganguli M . Blood pressure and cognitive impairment in India and the United States: a cross-national epidemiological study. Arch Neurol 2003; 60: 1123–1128.

    Article  Google Scholar 

  43. Kähönen-Väre M, Brunni-Hakala S, Lindroos M, Pitkala K, Strandberg T, Tilvis R . Left ventricular hypertrophy and blood pressure as predictors of cognitive decline in old age. Aging Clin Exp Res 2004; 16: 147–152.

    Article  Google Scholar 

  44. Kuo HK, Sorond F, Iloputaife I, Gagnon M, Milberg W, Lipsitz LA . Effect of blood pressure on cognitive functions in elderly persons. J Gerontol A Biol Sci Med Sci 2004; 59: 1191–1194.

    Article  PubMed  Google Scholar 

  45. Waldstein SR, Giggey PP, Thayer JF, Zonderman AB . Nonlinear relations of blood pressure to cognitive function: the Baltimore Longitudinal Study of Aging. Hypertension 2005; 45: 374–379.

    Article  CAS  Google Scholar 

  46. Wilkie F, Eisdorfer C . Intelligence and blood pressure in the aged. Science 1971; 172: 959–962.

    Article  CAS  Google Scholar 

  47. Elias MF, Wolf PA, D’Agostino RB, Cobb J, White LR . Untreated blood pressure level is inversely related to cognitive functioning: the Framingham Study. Am J Epidemiol 1993; 138: 353–364.

    Article  CAS  Google Scholar 

  48. Swan GE, DeCarli C, Miller BL, Reed T, Wolf PA, Jack LM et al. Association of midlife blood pressure to late-life cognitive decline and brain morphology. Neurology 1998; 51: 986–993.

    Article  CAS  Google Scholar 

  49. Swan GE, Carmelli D, Larue A . Systolic blood pressure tracking over 25 to 30 years and cognitive performance in older adults. Stroke 1998; 29: 2334–2340.

    Article  CAS  Google Scholar 

  50. Sacktor N, Gray S, Kawas C, Herbst J, Costa P, Fleg J . Systolic blood pressure within an intermediate range may reduce memory loss in an elderly hypertensive cohort. J Geriatr Psychiatry Neurol 1999; 12: 1–6.

    Article  CAS  Google Scholar 

  51. Haan MN, Shemanski L, Jagust WJ, Manolio TA, Kuller L . The role of APOE epsilon4 in modulating effects of other risk factors for cognitive decline in elderly persons. JAMA 1999; 282: 40–46.

    Article  CAS  Google Scholar 

  52. Tzourio C, Dufouil C, Ducimetière P, Alpérovitch A . Cognitive decline in individuals with high blood pressure: a longitudinal study in the elderly. EVA Study Group. Epidemiology of Vascular Aging. Neurology 1999; 53: 1948–1952.

    Article  CAS  Google Scholar 

  53. Kilander L, Nyman H, Boberg M, Lithell H . The association between low diastolic blood pressure in middle age and cognitive function in old age. A population-based study. Age Ageing 2000; 29: 243–248.

    Article  CAS  Google Scholar 

  54. Knopman D, Boland LL, Mosley T, Howard G, Liao D, Szklo M et al. Cardiovascular risk factors and cognitive decline in middle-aged adults. Neurology 2001; 56: 42–48.

    Article  CAS  Google Scholar 

  55. Reinprecht F, Elmståhl S, Janzon L, André-Petersson L . Hypertension and changes of cognitive function in 81-year-old men: a 13-year follow-up of the population study ‘men born in 1914’, Sweden. J Hypertens 2003; 21: 57–66.

    Article  CAS  Google Scholar 

  56. Elias MF, Elias PK, Sullivan LM, Wolf PA, D’Agostino RB . Lower cognitive function in the presence of obesity and hypertension: the Framingham Heart Study. Int J Obes Relat Metab Disord 2003; 27: 260–268.

    Article  CAS  Google Scholar 

  57. Piguet O, Grayson DA, Creasey H, Bennett HP, Brooks WS, Waite LM et al. Vascular risk factors, cognition and dementia incidence over 6 years in the Sydney Older Persons Study. Neuroepidemiology 2003; 22: 165–171.

    Article  Google Scholar 

  58. Elias PK, Elias MF, Robbins MA, Budge MM . Blood pressure-related cognitive decline: does age make a difference? Hypertension 2004; 44: 631–636.

    Article  CAS  Google Scholar 

  59. Okumiya K, Matsubayashi K, Wada T, Osaki Y, Doi Y, Ozawa T . J-curve relation between blood pressure and decline in cognitive function in older people living in community, Japan. J Am Geriatr Soc 1997; 45: 1032–1033.

    Article  CAS  Google Scholar 

  60. Bohannon AD, Fillenbaum GG, Pieper CF, Hanlon JT, Blazer DG . Relationship of race/ethnicity and blood pressure to change in cognitive function. J Am Geriatr Soc 2002; 50: 424–429.

    Article  Google Scholar 

  61. Hebert LE, Scherr PA, Bennett DA, Bienias JL, Wilson RS, Morris MC et al. Blood pressure and late-life cognitive function change: a biracial longitudinal population study. Neurology 2004; 62: 2021–2024.

    Article  CAS  Google Scholar 

  62. Gorelick PB . Risk factors for vascular dementia and Alzheimer disease. Stroke 2004; 35 (11 Suppl 1): 2620–2622.

    Article  Google Scholar 

  63. Birns J, Morris R, Jarosz J, Markus H, Kalra L . Ethnic differences in the cerebrovascular impact of hypertension. Cerebrovasc Dis 2008; 25: 408–416.

    Article  Google Scholar 

  64. Luchsinger JA, Tang MX, Shea S, Mayeux R . Hyperinsulinemia and risk of Alzheimer disease. Neurology 2004; 63: 1187–1192.

    Article  Google Scholar 

  65. Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D’Agostino RB et al. Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N Engl J Med 2002; 346: 476–483.

    Article  CAS  Google Scholar 

  66. Birns J, Morris R, Donaldson N, Kalra L . The effects of blood pressure reduction on cognitive function: a review of effects based on pooled data from clinical trials. J Hypertens 2006; 24: 1907–1914.

    Article  CAS  Google Scholar 

  67. Lasser NL, Nash J, Lasser VI, Hamill SJ, Batey DM . Effects of antihypertensive therapy on blood pressure control, cognition, and reactivity. A placebo-controlled comparison of prazosin, propranolol, and hydrochlorothiazide. Am J Med 1989; 86: 98–103.

    Article  CAS  Google Scholar 

  68. McCorvey Jr E, Wright Jr JT, Culbert JP, McKenney JM, Proctor JD, Annett MP . Effect of hydrochlorothiazide, enalapril, and propranolol on quality of life and cognitive and motor function in hypertensive patients. Clin Pharm 1993; 12: 300–305.

    Google Scholar 

  69. Applegate WB, Pressels S, Wittes J, Luhr J, Shekelle RB, Camel GH et al. Impact of the treatment of isolated systolic hypertension on behavioural variables: results from the Systolic Hypertension in the Elderly Program. Arch Intern Med 1994; 154: 2154–2160.

    Article  CAS  Google Scholar 

  70. Prince M, Bird AS, Blizard RA, Mann AH . Is the cognitive function of older patients affected by antihypertensive treatment? Results from 54 months of the Medical Research Council's trial of hypertension in older adults. Br Med J 1996; 312: 801–805.

    Article  CAS  Google Scholar 

  71. Forette F, Seux ML, Staessen JA, Thijs L, Birkenhager WH, Babarskiene MR et al. Prevention of dementia in randomised double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial. Lancet 1998; 352: 2046–2052.

    Article  Google Scholar 

  72. Denolle T, Sassano P, Allain H, Bentue-Ferrer D, Breton S, Cimarosti I et al. Effects of nicardipine and clonidine on cognitive functions and electroencephalography in hypertensive patients. Fundam Clin Pharmacol 2002; 16: 527–535.

    Article  CAS  Google Scholar 

  73. Tzourio C, Anderson C, Chapman N, Woodward M, Neal B, MacMahon S et al. Effects of blood pressure lowering with perindopril and indapamide therapy on dementia and cognitive decline in patients with cerebrovascular disease. Arch Inter Med 2003; 163: 1069–1075.

    Article  CAS  Google Scholar 

  74. Lithell H, Hansson L, Skoog I, Elmfeldt D, Hofman A, Olofsson B et al. The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double-blind intervention trial. J Hypertens 2003; 21: 875–886.

    Article  CAS  PubMed  Google Scholar 

  75. Dimsdale JE, Newton RP, Joist T . Neuropsychological side-effects of beta blockers. Arch Intern Med 1989; 149: 514–525.

    Article  CAS  Google Scholar 

  76. Twamley EW, Ropacki SA, Bondi MW . Neuropsychological and neuroimaging changes in preclinical Alzheimer's disease. J Int Neuropsychol Soc 2006; 12: 707–735.

    Article  PubMed  Google Scholar 

  77. Roman GC, Erkinjuntti T, Wallin A, Pantoni L, Chui HC . Subcortical ischaemic vascular dementia. Lancet Neurol 2002; 1: 426–436.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to L Kalra.

Additional information

Disclosure

The authors report no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Birns, J., Kalra, L. Cognitive function and hypertension. J Hum Hypertens 23, 86–96 (2009). https://doi.org/10.1038/jhh.2008.80

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jhh.2008.80

Keywords

This article is cited by

Search

Quick links