Journal of Yeungnam Medical Science

Yeungnam University College of Medicine, Yeungnam University Institute Medical Science (영남대 의대 학술지 편집위원회)
권호 표지
DOI QR코드

DOI QR Code

Hypertension and cognitive dysfunction: a narrative review

  • Eun-Jin Cheon (Department of Psychiatry, Yeungnam University College of Medicine)
  • Received : 2022.08.31
  • Accepted : 2022.10.07
  • Published : 2023.07.31
Download PDF
⟨ Previous Next ⟩

Abstract

Cognitive dysfunction is relatively less considered a complication of hypertension. However, there is sufficient evidence to show that high blood pressure in middle age increases the risk of cognitive decline and dementia in old age. The greatest impact on cognitive function in those with hypertension is on executive or frontal lobe function, similar to the area most damaged in vascular dementia. Possible cognitive disorders associated with hypertension are vascular dementia, Alzheimer disease, and Lewy body dementia, listed in decreasing strength of association. The pathophysiology of cognitive dysfunction in individuals with hypertension includes brain atrophy, microinfarcts, microbleeds, neuronal loss, white matter lesions, network disruption, neurovascular unit damage, reduced cerebral blood flow, blood-brain barrier damage, enlarged perivascular damage, and proteinopathy. Antihypertensive drugs may reduce the risk of cognitive decline and dementia. Given the high prevalence of dementia and its impact on quality of life, treatment of hypertension to reduce cognitive decline may be a clinically relevant intervention.

Keywords

References

  1. Lackland DT, Weber MA. Global burden of cardiovascular disease and stroke: hypertension at the core. Can J Cardiol 2015;31:569-71.  https://doi.org/10.1016/j.cjca.2015.01.009
  2. Manolio TA, Olson J, Longstreth WT. Hypertension and cognitive function: pathophysiologic effects of hypertension on the brain. Curr Hypertens Rep 2003;5:255-61.  https://doi.org/10.1007/s11906-003-0029-6
  3. Fratiglioni L, De Ronchi D, Aguero-Torres H. Worldwide prevalence and incidence of dementia. Drugs Aging 1999;15:365-75.  https://doi.org/10.2165/00002512-199915050-00004
  4. Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet 2005;365:217-23.  https://doi.org/10.1016/S0140-6736(05)17741-1
  5. Farmer ME, Kittner SJ, Abbott RD, Wolz MM, Wolf PA, White LR. Longitudinally measured blood pressure, antihypertensive medication use, and cognitive performance: the Framingham Study. J Clin Epidemiol 1990;43:475-80.  https://doi.org/10.1016/0895-4356(90)90136-D
  6. Gottesman RF, Schneider AL, Albert M, Alonso A, Bandeen-Roche K, Coker L, et al. Midlife hypertension and 20-year cognitive change: the atherosclerosis risk in communities neurocognitive study. JAMA Neurol 2014;71:1218-27.  https://doi.org/10.1001/jamaneurol.2014.1646
  7. 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;51:986-93.  https://doi.org/10.1212/WNL.51.4.986
  8. 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;274:1846-51.  https://doi.org/10.1001/jama.1995.03530230032026
  9. Gottesman RF, Albert MS, Alonso A, Coker LH, Coresh J, Davis SM, et al. Associations between midlife vascular risk factors and 25-year incident dementia in the Atherosclerosis Risk in Communities (ARIC) Cohort. JAMA Neurol 2017;74:1246-54.  https://doi.org/10.1001/jamaneurol.2017.1658
  10. Whitmer RA, Sidney S, Selby J, Johnston SC, Yaffe K. Midlife cardiovascular risk factors and risk of dementia in late life. Neurology 2005;64:277-81.  https://doi.org/10.1212/01.WNL.0000149519.47454.F2
  11. Kivipelto M, Ngandu T, Fratiglioni L, Viitanen M, Kareholt I, Winblad B, et al. Obesity and vascular risk factors at midlife and the risk of dementia and Alzheimer disease. Arch Neurol 2005;62:1556-60.  https://doi.org/10.1001/archneur.62.10.1556
  12. Kivipelto M, Helkala EL, Hanninen T, Laakso MP, Hallikainen M, Alhainen K, et al. Midlife vascular risk factors and late-life mild cognitive impairment: a population-based study. Neurology 2001;56:1683-9.  https://doi.org/10.1212/WNL.56.12.1683
  13. Launer LJ, Ross GW, Petrovitch H, Masaki K, Foley D, White LR, et al. Midlife blood pressure and dementia: the Honolulu-Asia aging study. Neurobiol Aging 2000;21:49-55.  https://doi.org/10.1016/S0197-4580(00)00096-8
  14. Ou YN, Tan CC, Shen XN, Xu W, Hou XH, Dong Q, et al. Blood pressure and risks of cognitive impairment and dementia: a systematic review and meta-analysis of 209 prospective studies. Hypertension 2020;76:217-25.  https://doi.org/10.1161/HYPERTENSIONAHA.120.14993
  15. Freitag MH, Peila R, Masaki K, Petrovitch H, Ross GW, White LR, et al. Midlife pulse pressure and incidence of dementia: the Honolulu-Asia Aging Study. Stroke 2006;37:33-7.  https://doi.org/10.1161/01.STR.0000196941.58869.2d
  16. Nation DA, Preis SR, Beiser A, Bangen KJ, Delano-Wood L, Lamar M, et al. Pulse pressure is associated with early brain atrophy and cognitive decline: modifying effects of APOE-ε4. Alzheimer Dis Assoc Disord 2016;30:210-5.  https://doi.org/10.1097/WAD.0000000000000127
  17. Kivipelto M, Helkala EL, Laakso MP, Hanninen T, Hallikainen M, Alhainen K, et al. Midlife vascular risk factors and Alzheimer's disease in later life: longitudinal, population based study. BMJ 2001;322:1447-51.  https://doi.org/10.1136/bmj.322.7300.1447
  18. Kennelly SP, Lawlor BA, Kenny RA. Blood pressure and the risk for dementia: a double edged sword. Ageing Res Rev 2009;8:61-70.  https://doi.org/10.1016/j.arr.2008.11.001
  19. Waldstein SR, Jennings JR, Ryan CM, Muldoon MF, Shapiro AP, Polefrone JM, et al. Hypertension and neuropsychological performance in men: interactive effects of age. Health Psychol 1996;15:102-9.  https://doi.org/10.1037//0278-6133.15.2.102
  20. Goldstein FC, Hajjar IM, Dunn CB, Levey AI, Wharton W. The relationship between cognitive functioning and the JNC-8 guidelines for hypertension in older adults. J Gerontol A Biol Sci Med Sci 2017;72:121-6.  https://doi.org/10.1093/gerona/glw181
  21. Erkinjuntti T. Subcortical vascular dementia. Cerebrovasc Dis 2002;13(Suppl 2):58-60.  https://doi.org/10.1159/000049152
  22. Desmond DW. Cognition and white matter lesions. Cerebrovasc Dis 2002;13(Suppl 2):53-7.  https://doi.org/10.1159/000049151
  23. Iadecola C, Gottesman RF. Neurovascular and cognitive dysfunction in hypertension. Circ Res 2019;124:1025-44.  https://doi.org/10.1161/CIRCRESAHA.118.313260
  24. Smith EE, Muzikansky A, McCreary CR, Batool S, Viswanathan A, Dickerson BC, et al. Impaired memory is more closely associated with brain beta-amyloid than leukoaraiosis in hypertensive patients with cognitive symptoms. PLoS One 2018;13:e0191345. 
  25. Alexander GE, Crutcher MD. Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends Neurosci 1990;13:266-71.  https://doi.org/10.1016/0166-2236(90)90107-L
  26. Reed BR, Mungas DM, Kramer JH, Ellis W, Vinters HV, Zarow C, et al. Profiles of neuropsychological impairment in autopsy-defined Alzheimer's disease and cerebrovascular disease. Brain 2007;130(Pt 3):731-9.  https://doi.org/10.1093/brain/awl385
  27. Hestad K, Engedal K, Horndalsveen P, Strand BH. Blood pressure in different dementia disorders, mild cognitive impairment, and subjective cognitive decline. Front Aging Neurosci 2020;12:257. 
  28. Barba R, Martinez-Espinosa S, Rodriguez-Garcia E, Pondal M, Vivancos J, Del Ser T. Poststroke dementia: clinical features and risk factors. Stroke 2000;31:1494-501.  https://doi.org/10.1161/01.STR.31.7.1494
  29. Phelps EB, Swantek S. Meta-analysis of modifiable risk factors of Alzheimer's disease. In: Tampi RR, Tampi DJ, Young JJ, Balasubramaniam M, Joshi P, editors. Essential reviews in geriatric psychiatry. New York: Springer Cham; 2022. p. 349-53. 
  30. Power MC, Weuve J, Gagne JJ, McQueen MB, Viswanathan A, Blacker D. The association between blood pressure and incident Alzheimer disease: a systematic review and meta-analysis. Epidemiology 2011;22:646-59. https://doi.org/10.1097/EDE.0b013e31822708b5
  31. Goldstein FC, Levey AI, Steenland NK. High blood pressure and cognitive decline in mild cognitive impairment. J Am Geriatr Soc 2013;61:67-73.  https://doi.org/10.1111/jgs.12067
  32. Reitz C, Tang MX, Manly J, Mayeux R, Luchsinger JA. Hypertension and the risk of mild cognitive impairment. Arch Neurol 2007;64:1734-40.  https://doi.org/10.1001/archneur.64.12.1734
  33. Golimstok A, Campora N, Rojas JI, Fernandez MC, Elizondo C, Soriano E, et al. Cardiovascular risk factors and frontotemporal dementia: a case-control study. Transl Neurodegener 2014;3:13. 
  34. Atkins ER, Bulsara MK, Panegyres PK. Cerebrovascular risk factors in early-onset dementia. J Neurol Neurosurg Psychiatry 2012;83:666-7.  https://doi.org/10.1136/jnnp.2009.202846
  35. Cheng CK, Tsao YC, Su YC, Sung FC, Tai HC, Kung WM. Metabolic risk factors of Alzheimer's disease, dementia with Lewy bodies, and normal elderly: a population-based study. Behav Neurol 2018;2018:8312346. 
  36. Hu X, De Silva TM, Chen J, Faraci FM. Cerebral vascular disease and neurovascular injury in ischemic stroke. Circ Res 2017;120:449-71.  https://doi.org/10.1161/CIRCRESAHA.116.308427
  37. Watase H, Sun J, Hippe DS, Balu N, Li F, Zhao X, et al. Carotid artery remodeling is segment specific: an in vivo study by cardiovascular magnetic resonance imaging. Circulation 2015;132(Suppl 3):A18848. 
  38. Iulita MF, Noriega de la Colina A, Girouard H. Arterial stiffness, cognitive impairment and dementia: confounding factor or real risk? J Neurochem 2018;144:527-48.  https://doi.org/10.1111/jnc.14235
  39. Ogola BO, Zimmerman MA, Clark GL, Abshire CM, Gentry KM, Miller KS, et al. New insights into arterial stiffening: does sex matter? Am J Physiol Heart Circ Physiol 2018;315:H1073-87.  https://doi.org/10.1152/ajpheart.00132.2018
  40. Benarroch EE. Neuroscience for clinicians: basic processes, circuits, disease mechanisms, and therapeutic implications. New York: Oxford University Press; 2021. 
  41. Iadecola C. The neurovascular unit coming of age: a journey through neurovascular coupling in health and disease. Neuron 2017;96:17-42. 
  42. Back SA, Tuohy TM, Chen H, Wallingford N, Craig A, Struve J, et al. Hyaluronan accumulates in demyelinated lesions and inhibits oligodendrocyte progenitor maturation. Nat Med 2005;11:966-72.  https://doi.org/10.1038/nm1279
  43. Joutel A, Chabriat H. Pathogenesis of white matter changes in cerebral small vessel diseases: beyond vessel-intrinsic mechanisms. Clin Sci (Lond) 2017;131:635-51.  https://doi.org/10.1042/CS20160380
  44. Simpson JE, Fernando MS, Clark L, Ince PG, Matthews F, Forster G, et al. White matter lesions in an unselected cohort of the elderly: astrocytic, microglial and oligodendrocyte precursor cell responses. Neuropathol Appl Neurobiol 2007;33:410-9.  https://doi.org/10.1111/j.1365-2990.2007.00828.x
  45. Munoz Maniega S, Chappell FM, Valdes Hernandez MC, Armitage PA, Makin SD, Heye AK, et al. Integrity of normal-appearing white matter: influence of age, visible lesion burden and hypertension in patients with small-vessel disease. J Cereb Blood Flow Metab 2017;37:644-56.  https://doi.org/10.1177/0271678X16635657
  46. Kusano Y, Echeverry G, Miekisiak G, Kulik TB, Aronhime SN, Chen JF, et al. Role of adenosine A2 receptors in regulation of cerebral blood flow during induced hypotension. J Cereb Blood Flow Metab 2010;30:808-15.  https://doi.org/10.1038/jcbfm.2009.244
  47. Appelman AP, Exalto LG, van der Graaf Y, Biessels GJ, Mali WP, Geerlings MI. White matter lesions and brain atrophy: more than shared risk factors?: a systematic review. Cerebrovasc Dis 2009;28:227-42.  https://doi.org/10.1159/000226774
  48. Gottesman RF, Schneider AL, Zhou Y, Coresh J, Green E, Gupta N, et al. Association between midlife vascular risk factors and estimated brain amyloid deposition. JAMA 2017;317:1443-50.  https://doi.org/10.1001/jama.2017.3090
  49. Vemuri P, Lesnick TG, Przybelski SA, Knopman DS, Lowe VJ, Graff-Radford J, et al. Age, vascular health, and Alzheimer disease biomarkers in an elderly sample. Ann Neurol 2017;82:706-18.  https://doi.org/10.1002/ana.25071
  50. Arvanitakis Z, Capuano AW. Author response: late-life blood pressure association with cerebrovascular and Alzheimer disease pathology. Neurology 2019;92:732. 
  51. Kester MI, van der Flier WM, Mandic G, Blankenstein MA, Scheltens P, Muller M. Joint effect of hypertension and APOE genotype on CSF biomarkers for Alzheimer's disease. J Alzheimers Dis 2010;20:1083-90.  https://doi.org/10.3233/JAD-2010-091198
  52. Faraco G, Park L, Zhou P, Luo W, Paul SM, Anrather J, et al. Hypertension enhances Aβ-induced neurovascular dysfunction, promotes β-secretase activity, and leads to amyloidogenic processing of APP. J Cereb Blood Flow Metab 2016;36:241-52.  https://doi.org/10.1038/jcbfm.2015.79
  53. Azarpazhooh MR, Avan A, Cipriano LE, Munoz DG, Sposato LA, Hachinski V. Concomitant vascular and neurodegenerative pathologies double the risk of dementia. Alzheimers Dement 2018;14:148-56.  https://doi.org/10.1016/j.jalz.2017.07.755
  54. Austin SA, Katusic ZS. Loss of endothelial nitric oxide synthase promotes p25 generation and tau phosphorylation in a murine model of Alzheimer's disease. Circ Res 2016;119:1128-34.  https://doi.org/10.1161/CIRCRESAHA.116.309686
  55. Tian M, Zhu D, Xie W, Shi J. Central angiotensin II-induced Alzheimer-like tau phosphorylation in normal rat brains. FEBS Lett 2012;586:3737-45.  https://doi.org/10.1016/j.febslet.2012.09.004
  56. Korf ES, White LR, Scheltens P, Launer LJ. Midlife blood pressure and the risk of hippocampal atrophy: the Honolulu Asia Aging Study. Hypertension 2004;44:29-34.  https://doi.org/10.1161/01.HYP.0000132475.32317.bb
  57. Applegate WB, Pressel S, Wittes J, Luhr J, Shekelle RB, Camel GH, et al. Impact of the treatment of isolated systolic hypertension on behavioral variables. Results from the systolic hypertension in the elderly program. Arch Intern Med 1994;154:2154-60.  https://doi.org/10.1001/archinte.1994.00420190047006
  58. 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;352:1347-51.  https://doi.org/10.1016/S0140-6736(98)03086-4
  59. Forette F, Seux ML, Staessen JA, Thijs L, Babarskiene MR, Babeanu S, et al. The prevention of dementia with antihypertensive treatment: new evidence from the Systolic Hypertension in Europe (Syst-Eur) study. Arch Intern Med 2002;162:2046-52.  https://doi.org/10.1001/archinte.162.18.2046
  60. 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 Intern Med 2003;163:1069-75.  https://doi.org/10.1001/archinte.163.9.1069
  61. Peters R, Beckett N, Forette F, Tuomilehto J, Clarke R, Ritchie C, et al. Incident dementia and blood pressure lowering in the Hypertension in the Very Elderly Trial cognitive function assessment (HYVET-COG): a double-blind, placebo controlled trial. Lancet Neurol 2008;7:683-9.  https://doi.org/10.1016/S1474-4422(08)70143-1
  62. Bosch J, Yusuf S, Pogue J, Sleight P, Lonn E, Rangoonwala B, et al. Heart outcomes prevention evaluation: use of ramipril in preventing stroke: double blind randomised trial. BMJ 2002;324:699-702.  https://doi.org/10.1136/bmj.324.7339.699
  63. Aronow WS. Hypertension and cognitive impairment. Ann Transl Med 2017;5:259. 
  64. Gupta A, Perdomo S, Billinger S, Beddhu S, Burns J, Gronseth G. Treatment of hypertension reduces cognitive decline in older adults: a systematic review and meta-analysis. BMJ Open 2020;10:e038971. 
  65. Hughes D, Judge C, Murphy R, Loughlin E, Costello M, Whiteley W, et al. Association of blood pressure lowering with incident dementia or cognitive impairment: a systematic review and meta-analysis. JAMA 2020;323:1934-44.  https://doi.org/10.1001/jama.2020.4249
  66. Mossello E, Pieraccioli M, Nesti N, Bulgaresi M, Lorenzi C, Caleri V, et al. Effects of low blood pressure in cognitively impaired elderly patients treated with antihypertensive drugs. JAMA Intern Med 2015;175:578-85.  https://doi.org/10.1001/jamainternmed.2014.8164
  67. Yang W, Luo H, Ma Y, Si S, Zhao H. Effects of antihypertensive drugs on cognitive function in elderly patients with hypertension: a review. Aging Dis 2021;12:841-51.  https://doi.org/10.14336/AD.2020.1111
  68. Dufouil C, Chalmers J, Coskun O, Besancon V, Bousser MG, 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;112:1644-50.  https://doi.org/10.1161/CIRCULATIONAHA.104.501163
  69. Chuang YF, Breitner JC, Chiu YL, Khachaturian A, Hayden K, Corcoran C, et al. Use of diuretics is associated with reduced risk of Alzheimer's disease: the Cache County Study. Neurobiol Aging 2014;35:2429-35.  https://doi.org/10.1016/j.neurobiolaging.2014.05.002
  70. Peters R, Yasar S, Anderson CS, Andrews S, Antikainen R, Arima H, et al. Investigation of antihypertensive class, dementia, and cognitive decline: a meta-analysis. Neurology 2020;94:e267-81.  https://doi.org/10.1212/WNL.0000000000008732
  71. Hanon O, Berrou JP, Negre-Pages L, Goch JH, Nadhazi Z, Petrella R, et al. 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 2008;26:1642-50.  https://doi.org/10.1097/HJH.0b013e328301a280
  72. Radaideh GA, Choueiry P, Ismail A, Eid E, Berrou JP, Sedefdjian A, et al. Eprosartan-based hypertension therapy, systolic arterial blood pressure and cognitive function: analysis of Middle East data from the OSCAR study. Vasc Health Risk Manag 2011;7:491-5.  https://doi.org/10.2147/VHRM.S19699
  73. Kalra L. Antihypertensive drugs decrease risk of Alzheimer disease: Ginkgo Evaluation of Memory Study. Neurology 2014;82:1192. 
  74. Gelber RP, Ross GW, Petrovitch H, Masaki KH, Launer LJ, White LR. Antihypertensive medication use and risk of cognitive impairment: the Honolulu-Asia Aging Study. Neurology 2013;81:888-95.  https://doi.org/10.1212/WNL.0b013e3182a351d4
  75. Xu W, Tan L, Wang HF, Jiang T, Tan MS, Tan L, et al. Meta-analysis of modifiable risk factors for Alzheimer's disease. J Neurol Neurosurg Psychiatry 2015;86:1299-306. https://doi.org/10.1136/jnnp-2015-310548