, Volume 16, Issue 3, pp 569–579 | Cite as

Blood Pressure Control and Protection of the Aging Brain

  • Nasratullah Wahidi
  • Alan J. LernerEmail author


Hypertension and dementia are both common disorders whose prevalence increases with age. There are multiple mechanisms by which hypertension affects the brain and alters cognition. These include blood flow dynamics, development of large and small vessel pathology and diverse molecular mechanisms including formation of reactive oxygen species and transcriptional cascades. Blood pressure interacts with Alzheimer disease pathology in numerous and unpredictable ways, affecting both β-amyloid and tau deposition, while also interacting with AD genetic risk factors and other metabolic processes. Treatment of hypertension may prevent cognitive decline and dementia, but methodological issues have limited the ability of randomized clinical trials to show this conclusively. Recent studies have raised hope that hypertension treatment may protect the function and structure of the aging brain from advancing to mild cognitive impairment and dementia.


Hypertension Dementia Cognition Aging Alzheimer’s disease Mild cognitive impairment 


Supplementary material

13311_2019_747_MOESM1_ESM.pdf (510 kb)
ESM 1 (PDF 510 kb)


  1. 1.
    Kumar J. Epidemiology of hypertension. Clinical Queries: Nephrology. 2013 Apr 1;2(2):56–61.CrossRefGoogle Scholar
  2. 2.
    Ibrahim MM, Damasceno A. Hypertension in developing countries. The Lancet. 2012 Aug 11;380(9841):611–9.CrossRefGoogle Scholar
  3. 3.
    Fryar CD, Ostchega Y, Hales CM, Zhang G, Kruszon-Moran D. Hypertension prevalence and control among adults: United States, 2015-2016. NCHS data brief. 2017 Oct(289):1–8.Google Scholar
  4. 4.
    Thorin-Trescases N, de Montgolfier O, Pinçon A, Raignault A, Caland L, Labbé P, Thorin E. The impact of pulse pressure on cerebrovascular events leading to age-related cognitive decline. American Journal of Physiology-Heart and Circulatory Physiology. 2018 Feb 16.Google Scholar
  5. 5.
    Cowley Jr AW. Long-term control of arterial blood pressure. Physiological reviews. 1992 Jan 1;72(1):231–300.CrossRefPubMedGoogle Scholar
  6. 6.
    Li X, Lyu P, Ren Y, An J, Dong Y. Arterial stiffness and cognitive impairment. Journal of the neurological sciences. 2017 Sep 15;380:1–0.CrossRefPubMedGoogle Scholar
  7. 7.
    Wagenseil JE, Mecham RP. Elastin in large artery stiffness and hypertension. Journal of cardiovascular translational research. 2012 Jun 1;5(3):264–73.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Zebekakis PE, Nawrot T, Thijs L, Balkestein EJ, van der Heijden-Spek J, Van Bortel LM, Struijker-Boudier HA, Safar ME, Staessen JA. Obesity is associated with increased arterial stiffness from adolescence until old age. Journal of hypertension. 2005 Oct 1;23(10):1839–46.CrossRefPubMedGoogle Scholar
  9. 9.
    SPRINT Research Group. A randomized trial of intensive versus standard blood-pressure control. New England Journal of Medicine. 2015 Nov 26;373(22):2103–16.CrossRefGoogle Scholar
  10. 10.
    Clifford PS. Local control of blood flow. Advances in physiology education. 2011 Mar;35(1):5–15.CrossRefPubMedGoogle Scholar
  11. 11.
    Chopra S, Baby C, Jacob JJ. Neuro-endocrine regulation of blood pressure. Indian journal of endocrinology and metabolism. 2011 Oct;15(Suppl4):S281.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Guzik TJ, Hoch NE, Brown KA, McCann LA, Rahman A, Dikalov S, Goronzy J, Weyand C, Harrison DG. Role of the T cell in the genesis of angiotensin II–induced hypertension and vascular dysfunction. Journal of Experimental Medicine. 2007 Oct 1;204(10):2449–60.CrossRefPubMedGoogle Scholar
  13. 13.
    Schulz E, Gori T, Münzel T. Oxidative stress and endothelial dysfunction in hypertension. Hypertension Research. 2011 Jun;34(6):665–673.CrossRefPubMedGoogle Scholar
  14. 14.
    Montezano AC, Touyz RM. Molecular mechanisms of hypertension—reactive oxygen species and antioxidants: a basic science update for the clinician. Canadian Journal of Cardiology. 2012 May 1;28(3):288–95.CrossRefPubMedGoogle Scholar
  15. 15.
    Harrison DG, Gongora MC. Oxidative stress and hypertension. Medical Clinics. 2009 May 1;93(3):621–35.PubMedGoogle Scholar
  16. 16.
    Bowler JV, Hachinski V. Vascular cognitive impairment: a new approach to vascular dementia. Bailliere's clinical neurology. 1995 Aug;4(2):357–76.PubMedGoogle Scholar
  17. 17.
    Petersen RC. Mild cognitive impairment: transition from aging to Alzheimer's disease. Alzheimer’s disease: advances in etiology, pathogenesis and therapeutics. 2001 Mar 28:141–51.Google Scholar
  18. 18.
    Espeland MA, Probstfield J, Hire D, Redmon JB, Evans GW, Coday M, Lewis CE, Johnson KC, Wilmoth S, Bahnson J, Dulin MF. Systolic blood pressure control among individuals with type 2 diabetes: a comparative effectiveness analysis of three interventions. American journal of hypertension. 2015 Feb 9;28(8):995–1009.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    de Havenon A, Majersik JJ, Tirschwell DL, McNally JS, Stoddard G, Rost NS. Blood pressure, glycemic control, and white matter hyperintensity progression in type 2 diabetics. Neurology. 2019 Mar 12;92(11):e1168–75.PubMedGoogle Scholar
  20. 20.
    Tillema JM, Renaud DL. Leukoencephalopathies in adulthood. In Seminars in neurology 2012 Feb (Vol. 32, No. 01, pp. 085-094). Thieme Medical Publishers.Google Scholar
  21. 21.
    Terry T, Raravikar K, Chokrungvaranon N, Reaven PD. Does aggressive glycemic control benefit macrovascular and microvascular disease in type 2 diabetes?: insights from ACCORD, ADVANCE, and VADT. Current cardiology reports. 2012 Feb 1;14(1):79–88.CrossRefPubMedGoogle Scholar
  22. 22.
    Li G, Rhew IC, Shofer JB, Kukull WA, Breitner JC, Peskind E, Bowen JD, McCormick W, Teri L, Crane PK, Larson EB. Age-varying association between blood pressure and risk of dementia in those aged 65 and older: a community-based prospective cohort study. Journal of the American Geriatrics Society. 2007 Aug;55(8):1161–7.CrossRefPubMedGoogle Scholar
  23. 23.
    Slavin MJ, Brodaty H, Sachdev PS. Challenges of diagnosing dementia in the oldest old population. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences. 2013 May 17;68(9):1103–11.CrossRefGoogle Scholar
  24. 24.
    Forette F, Seux ML, Staessen JA, Thijs L, Babarskiene MR, Babeanu S, Bossini A, Fagard R, Gil-Extremera B, Laks T, Kobalava Z. The prevention of dementia with antihypertensive treatment: new evidence from the systolic hypertension in Europe (Syst-Eur) study. Archives of internal medicine. 2002 Oct 14;162(18):2046–52.CrossRefPubMedGoogle Scholar
  25. 25.
    Peters R, Beckett N, Forette F, Tuomilehto J, Clarke R, Ritchie C, Waldman A, Walton I, Poulter R, Ma S, Comsa M. 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. The Lancet Neurology. 2008 Aug 1;7(8):683–9.CrossRefPubMedGoogle Scholar
  26. 26.
    Williamson JD, Pajewski NM, Auchus AP, Bryan RN, Chelune G, Cheung AK, Cleveland ML, Coker LH, Crowe MG, Cushman WC, Cutler JA. Effect of intensive vs standard blood pressure control on probable dementia: a randomized clinical trial. Jama. 2019 Feb 12;321(6):553–61.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Nasrallah IM. A randomized trial of intensive versus standard systolic blood pressure control on brain structure: results from SPRINT MIND MRI. Alzheimer’s & Dementia: The Journal of the Alzheimer's Association. 2018 Jul 1;14(7):P1666.CrossRefGoogle Scholar
  28. 28.
    Kivipelto M, Ngandu T. Good for the heart and good for the brain?. The Lancet. Neurology. 2019 Apr;18(4):327.CrossRefPubMedGoogle Scholar
  29. 29.
    Sink KM, Leng X, Williamson J, Kritchevsky SB, Yaffe K, Kuller L, Yasar S, Atkinson H, Robbins M, Psaty B, Goff DC. Angiotensin-converting enzyme inhibitors and cognitive decline in older adults with hypertension: results from the Cardiovascular Health Study. Archives of internal medicine. 2009 Jul 13;169(13):1195–202.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    DeKosky ST, Fitzpatrick A, Ives DG, Saxton J, Williamson J, Lopez OL, Burke G, Fried L, Kuller LH, Robbins J, Tracy R. The Ginkgo Evaluation of Memory (GEM) study: design and baseline data of a randomized trial of Ginkgo biloba extract in prevention of dementia. Contemporary clinical trials. 2006 Jun 1;27(3):238–53.CrossRefPubMedGoogle Scholar
  31. 31.
    Hughes TM, Sink KM. Hypertension and its role in cognitive function: current evidence and challenges for the future. American journal of hypertension. 2015 Nov 11;29(2):149–57.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Dufouil C, Chalmers J, Coskun O, Besancon V, Bousser MG, Guillon P, Macmahon S, Mazoyer B, Neal B, Woodward M, Tzourio-Mazoyer N. 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 Sep 13;112(11):1644–50.CrossRefPubMedGoogle Scholar
  33. 33.
    Iadecola C. The pathobiology of vascular dementia. Neuron. 2013 Nov 20;80(4):844–66.CrossRefPubMedGoogle Scholar
  34. 34.
    Schenk C, Wuerz T, Lerner AJ. Small vessel disease and memory loss: what the clinician needs to know to preserve patients’ brain health. Current cardiology reports. 2013 Dec 1;15(12):427.CrossRefPubMedGoogle Scholar
  35. 35.
    Román GC, Erkinjuntti T, Wallin A, Pantoni L, Chui HC. Subcortical ischaemic vascular dementia. The Lancet Neurology. 2002 Nov 1;1(7):426–36.CrossRefPubMedGoogle Scholar
  36. 36.
    Hennessee JP, Reggente N, Cohen MS, Rissman J, Castel AD, Knowlton BJ. White matter integrity in brain structures supporting semantic processing is associated with value-directed remembering in older adults. Neuropsychologia. 2019 Apr 12.Google Scholar
  37. 37.
    van Norden AG, de Laat KF, Gons RA, van Uden IW, van Dijk EJ, van Oudheusden LJ, Esselink RA, Bloem BR, van Engelen BG, Zwarts MJ, Tendolkar I. Causes and consequences of cerebral small vessel disease. The RUN DMC study: a prospective cohort study. Study rationale and protocol. BMC neurology. 2011 Dec;11(1):29.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Kochunov P, Glahn DC, Lancaster J, Winkler A, Karlsgodt K, Olvera RL, Curran JE, Carless MA, Dyer TD, Almasy L, Duggirala R. Blood pressure and cerebral white matter share common genetic factors in Mexican Americans. Hypertension. 2011 Feb 1;57(2):330–5.CrossRefPubMedGoogle Scholar
  39. 39.
    Khan U, Porteous L, Hassan A, Markus H. Risk factor profile of cerebral small vessel disease and its subtypes. Journal of Neurology, Neurosurgery & Psychiatry. 2007 Jan 8.Google Scholar
  40. 40.
    Hassan A, Hunt BJ, O’sullivan M, Bell R, D’souza R, Jeffery S, Bamford JM, Markus HS. Homocysteine is a risk factor for cerebral small vessel disease, acting via endothelial dysfunction. Brain. 2004 Jan 1;127(1):212–9.CrossRefPubMedGoogle Scholar
  41. 41.
    Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. The Lancet Neurology. 2010 Jul 1;9(7):689–701.CrossRefPubMedGoogle Scholar
  42. 42.
    Korczyn AD. Mixed dementia—the most common cause of dementia. Annals of the New York Academy of Sciences. 2002 Nov;977(1):129–34.CrossRefPubMedGoogle Scholar
  43. 43.
    Schmidt R, Schmidt H, Haybaeck J, Loitfelder M, Weis S, Cavalieri M, Seiler S, Enzinger C, Ropele S, Erkinjuntti T, Pantoni L. Heterogeneity in age-related white matter changes. Acta neuropathologica. 2011 Aug 1;122(2):171–85.CrossRefPubMedGoogle Scholar
  44. 44.
    Seiler S, Cavalieri M, Schmidt R. Vascular cognitive impairment—an ill-defined concept with the need to define its vascular component. Journal of the neurological sciences. 2012 Nov 15;322(1–2):11–6.CrossRefPubMedGoogle Scholar
  45. 45.
    Greenberg SM, Vernooij MW, Cordonnier C, Viswanathan A, Salman RA, Warach S, Launer LJ, Van Buchem MA, Breteler MM, Microbleed Study Group. Cerebral microbleeds: a guide to detection and interpretation. The Lancet Neurology. 2009 Feb 1;8(2):165–74.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Sperling RA, Jack Jr CR, Black SE, Frosch MP, Greenberg SM, Hyman BT, Scheltens P, Carrillo MC, Thies W, Bednar MM, Black RS. Amyloid-related imaging abnormalities in amyloid-modifying therapeutic trials: recommendations from the Alzheimer’s Association Research Roundtable Workgroup. Alzheimer's & Dementia. 2011 Jul 1;7(4):367–85.CrossRefGoogle Scholar
  47. 47.
    Jokinen H, Lipsanen J, Schmidt R, Fazekas F, Gouw AA, Van der Flier WM, Barkhof F, Madureira S, Verdelho A, Ferro JM, Wallin A. Brain atrophy accelerates cognitive decline in cerebral small vessel disease The LADIS study. Neurology. 2012 May 29;78(22):1785–92.CrossRefPubMedGoogle Scholar
  48. 48.
    Price CC, Mitchell SM, Brumback B, Tanner JJ, Schmalfuss I, Lamar M, Giovannetti T, Heilman KM, Libon DJ. MRI-leukoaraiosis thresholds and the phenotypic expression of dementia. Neurology. 2012 Aug 21;79(8):734–40.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Monet-Leprêtre M, Haddad I, Baron-Menguy C, Fouillot-Panchal M, Riani M, Domenga-Denier V, Dussaule C, Cognat E, Vinh J, Joutel A. Abnormal recruitment of extracellular matrix proteins by excess Notch3ECD: a new pathomechanism in CADASIL. Brain. 2013 May 6;136(6):1830–45.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Meschia JF. New information on the genetics of stroke. Current neurology and neuroscience reports. 2011 Feb 1;11(1):35–41.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Meschia JF, Worrall BB, Rich SS. Genetic susceptibility to ischemic stroke. Nature Reviews Neurology. 2011 Jul;7(7):369.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Appel LJ. Lifestyle modification as a means to prevent and treat high blood pressure. Journal of the American Society of Nephrology. 2003 Jul 1;14(suppl 2):S99–102.CrossRefPubMedGoogle Scholar
  53. 53.
    Skoog I, Korczyn AD, Guekht A. Neuroprotection in vascular dementia: a future path. Journal of the neurological sciences. 2012 Nov 15;322(1–2):232–6.CrossRefPubMedGoogle Scholar
  54. 54.
    Nithianantharajah J, Hannan AJ. Mechanisms mediating brain and cognitive reserve: experience-dependent neuroprotection and functional compensation in animal models of neurodegenerative diseases. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2011 Mar 30;35(2):331–9.CrossRefPubMedGoogle Scholar
  55. 55.
    Unverzagt FW, Guey LT, Jones RN, Marsiske M, King JW, Wadley VG, Crowe M, Rebok GW, Tennstedt SL. ACTIVE cognitive training and rates of incident dementia. Journal of the International Neuropsychological Society. 2012 Jul;18(4):669–77.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Williams KN, Kemper S. Interventions to reduce cognitive decline in aging. Journal of psychosocial nursing and mental health services. 2010 May 1;48(5):42–51.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Schneider N, Yvon C. A review of multidomain interventions to support healthy cognitive ageing. The journal of nutrition, health & aging. 2013 Mar 1;17(3):252–7.CrossRefGoogle Scholar
  58. 58.
    Eyre H, Baune BT. Neuroimmunological effects of physical exercise in depression. Brain, behavior, and immunity. 2012 Feb 1;26(2):251–66.CrossRefPubMedGoogle Scholar
  59. 59.
    Bridle C, Spanjers K, Patel S, Atherton NM, Lamb SE. Effect of exercise on depression severity in older people: systematic review and meta-analysis of randomised controlled trials. The British Journal of Psychiatry. 2012 Sep;201(3):180–5.CrossRefPubMedGoogle Scholar
  60. 60.
    Karcher HS, Holzwarth R, Mueller HP, Ludolph AC, Huber R, Kassubek J, Pinkhardt EH. Body fat distribution as a risk factor for cerebrovascular disease: an MRI-based body fat quantification study. Cerebrovascular diseases. 2013;35(4):341–8.CrossRefPubMedGoogle Scholar
  61. 61.
    Siervo M, Arnold R, Wells JC, Tagliabue A, Colantuoni A, Albanese E, Brayne C, Stephan BC. Intentional weight loss in overweight and obese individuals and cognitive function: a systematic review and meta-analysis. Obesity Reviews. 2011 Nov;12(11):968–83.CrossRefPubMedGoogle Scholar
  62. 62.
    Chen WW, Zhang X, Huang WJ. Role of physical exercise in Alzheimer’s disease. Biomedical reports. 2016 Apr 1;4(4):403–7.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Rouhl RP, Mertens AE, van Oostenbrugge RJ, Damoiseaux JG, Debrus-Palmans LL, Henskens LH, Kroon AA, de Leeuw PW, Lodder J, Cohen Tervaert JW. Angiogenic T-cells and putative endothelial progenitor cells in hypertension-related cerebral small vessel disease. Stroke. 2012 Jan;43(1):256–8.CrossRefPubMedGoogle Scholar
  64. 64.
    Freitas H, Ferreira G, Trevenzoli I, Oliveira K, de Melo Reis R. Fatty acids, antioxidants and physical activity in brain aging. Nutrients. 2017 Nov;9(11):1263.CrossRefPubMedCentralGoogle Scholar
  65. 65.
    Park HS, Cho HS, Kim TW. Physical exercise promotes memory capability by enhancing hippocampal mitochondrial functions and inhibiting apoptosis in obesity-induced insulin resistance by high fat diet. Metabolic brain disease. 2018 Feb 1;33(1):283–92.CrossRefPubMedGoogle Scholar
  66. 66.
    Musman J, Pons S, Barau C, Caccia C, Leoni V, Berdeaux A, Ghaleh B, Morin D. Regular treadmill exercise inhibits mitochondrial accumulation of cholesterol and oxysterols during myocardial ischemia-reperfusion in wild-type and ob/ob mice. Free Radical Biology and Medicine. 2016 Dec 1;101:317–24.CrossRefPubMedGoogle Scholar
  67. 67.
    Ginty AT, Kraynak TE, Fisher JP, Gianaros PJ. Cardiovascular and autonomic reactivity to psychological stress: neurophysiological substrates and links to cardiovascular disease. Autonomic Neuroscience. 2017 Nov 1;207:2–9.CrossRefPubMedGoogle Scholar
  68. 68.
    Nokia MS, Lensu S, Ahtiainen JP, Johansson PP, Koch LG, Britton SL, Kainulainen H. Physical exercise increases adult hippocampal neurogenesis in male rats provided it is aerobic and sustained. The Journal of physiology. 2016 Apr 1;594(7):1855–73.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Terry RD, Davies P. Dementia of the Alzheimer type. Annual review of neuroscience. 1980 Mar;3(1):77–95.CrossRefPubMedGoogle Scholar
  70. 70.
    Awada A. Early and late-onset Alzheimer’s disease: what are the differences?. Journal of neurosciences in rural practice. 2015 Jul 1;6(3):455.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Petersen RC, Lopez O, Armstrong MJ, Getchius TS, Ganguli M, Gloss D, Gronseth GS, Marson D, Pringsheim T, Day GS, Sager M. Practice guideline update summary: mild cognitive impairment: report of the guideline development, dissemination, and implementation subcommittee of the American Academy of Neurology. Neurology. 2018 Jan 16;90(3):126–35.CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E. Mild cognitive impairment: clinical characterization and outcome. Archives of neurology. 1999 Mar 1;56(3):303–8.CrossRefPubMedGoogle Scholar
  73. 73.
    Faraco G, Park L, Zhou P, Luo W, Paul SM, Anrather J, Iadecola C. Hypertension enhances A β-induced neurovascular dysfunction, promotes β-secretase activity, and leads to amyloidogenic processing of APP. Journal of Cerebral Blood Flow & Metabolism. 2016 Jan;36(1):241–52.CrossRefGoogle Scholar
  74. 74.
    Jeon SY, Byun MS, Yi D, Lee JH, Choe YM, Ko K, Sohn BK, Choi HJ, Lee JY, Lee DY, KBASE Research Group. Influence of hypertension on brain amyloid deposition and Alzheimer’s disease signature neurodegeneration. Neurobiology of aging. 2019 Mar 1;75:62–70.CrossRefPubMedGoogle Scholar
  75. 75.
    Jack Jr CR, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, Holtzman DM, Jagust W, Jessen F, Karlawish J, Liu E. NIA-AA research framework: toward a biological definition of Alzheimer’s disease. Alzheimer's & Dementia. 2018 Apr 1;14(4):535–62.CrossRefGoogle Scholar
  76. 76.
    Cummings J. The National Institute on Aging—Alzheimer’s Association Framework on Alzheimer’s disease: application to clinical trials. Alzheimer's & Dementia. 2019 Jan 1;15(1):172–8.CrossRefGoogle Scholar
  77. 77.
    Gottesman RF, Schneider AL, Zhou Y, Coresh J, Green E, Gupta N, Knopman DS, Mintz A, Rahmim A, Sharrett AR, Wagenknecht LE. Association between midlife vascular risk factors and estimated brain amyloid deposition. JAMA. 2017 Apr 11;317(14):1443–50.CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Clark LR, Koscik RL, Allison SL, Berman SE, Norton D, Carlsson CM, Betthauser TJ, Bendlin BB, Christian BT, Chin NA, Asthana S. Hypertension and obesity moderate the relationship between β-amyloid and cognitive decline in midlife. Alzheimer’s & Dementia. 2018 Oct 25.Google Scholar
  79. 79.
    Yun CH, Lee HY, Lee SK, Kim H, Seo HS, Bang S, Kim SE, Greve DN, Au R, Shin C, Thomas RJ. Amyloid burden in obstructive sleep apnea. Journal of Alzheimer's Disease. 2017 Jan 1;59(1):21–9.CrossRefPubMedGoogle Scholar
  80. 80.
    Ashby EL, Miners JS, Kehoe PG, Love S. Effects of hypertension and anti-hypertensive treatment on amyloid-β (Aβ) plaque load and Aβ-synthesizing and Aβ-degrading enzymes in frontal cortex. Journal of Alzheimer's Disease. 2016 Jan 1;50(4):1191–203.CrossRefPubMedGoogle Scholar
  81. 81.
    Perrotta M, Lembo G, Carnevale D. Hypertension and dementia: epidemiological and experimental evidence revealing a detrimental relationship. International journal of molecular sciences. 2016 Mar 8;17(3):347.CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Montagne A, Zhao Z, Zlokovic BV. Alzheimer’s disease: a matter of blood–brain barrier dysfunction?. Journal of Experimental Medicine. 2017 Nov 6;214(11):3151–69.CrossRefPubMedGoogle Scholar
  83. 83.
    James BD, Bennett DA, Boyle PA, Leurgans S, Schneider JA. Dementia from Alzheimer disease and mixed pathologies in the oldest old. Jama. 2012 May 2;307(17):1798–800.CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Snowdon DA, Greiner LH, Mortimer JA, Riley KP, Greiner PA, Markesbery WR. Brain infarction and the clinical expression of Alzheimer disease: the Nun Study. Jama. 1997 Mar 12;277(10):813–7.CrossRefPubMedGoogle Scholar
  85. 85.
    Zekry D, Hauw JJ, Gold G. Mixed dementia: epidemiology, diagnosis, and treatment. Journal of the American Geriatrics Society. 2002 Aug 1;50(8):1431–8.CrossRefPubMedGoogle Scholar
  86. 86.
    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. Alzheimer's & Dementia: The Journal of the Alzheimer’s Association. 2009 Jul 1;5(4):e17.CrossRefGoogle Scholar
  87. 87.
    Glodzik L, Rusinek H, Pirraglia E, McHugh P, Tsui W, Williams S, Cummings M, Li Y, Rich K, Randall C, Mosconi L. Blood pressure decrease correlates with tau pathology and memory decline in hypertensive elderly. Neurobiology of aging. 2014 Jan 1;35(1):64–71.CrossRefPubMedGoogle Scholar
  88. 88.
    Petrovitch H, White LR, Izmirilian G, Ross GW, Havlik RJ, Markesbery W, Nelson J, Davis DG, Hardman J, Foley DJ, Launer LJ. Midlife blood pressure and neuritic plaques, neurofibrillary tangles, and brain weight at death: the HAAS☆. Neurobiology of aging. 2000 Jan 1;21(1):57–62.CrossRefPubMedGoogle Scholar
  89. 89.
    Moonga I, Niccolini F, Wilson H, Pagano G, Politis M, Alzheimer’s Disease Neuroimaging Initiative. Hypertension is associated with worse cognitive function and hippocampal hypometabolism in Alzheimer’s disease. European journal of neurology. 2017 Sep;24(9):1173–82.CrossRefPubMedGoogle Scholar
  90. 90.
    Whelton PK, Carey RM, Aronow WS, Casey DE, Collins KJ, Himmelfarb CD, DePalma SM, Gidding S, Jamerson KA, Jones DW, MacLaughlin EJ. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Journal of the American College of Cardiology. 2018 May 7;71(19):e127–248.CrossRefPubMedGoogle Scholar
  91. 91.
    Lamprea-Montealegre JA, Zelnick LR, Hall YN, Bansal N, de Boer IH. Prevalence of hypertension and cardiovascular risk according to blood pressure thresholds used for diagnosis. Hypertension. 2018 Sep;72(3):602–9.CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Smith SM, Gurka MJ, Calhoun DA, Gong Y, Pepine CJ, Cooper-DeHoff RM. Optimal systolic blood pressure target in resistant and non-resistant hypertension: a pooled analysis of patient-level data from SPRINT and ACCORD. The American journal of medicine. 2018 Dec 1;131(12):1463–72.CrossRefPubMedGoogle Scholar
  93. 93.
    Sakima A, Satonaka H, Nishida N, Yatsu K, Arima H. Optimal blood pressure targets for patients with hypertension: a systematic review and meta-analysis. Hypertension Research. 2019 Apr;42(4):483.CrossRefPubMedGoogle Scholar
  94. 94.
    Hajjar I, Rosenberger KJ, Kulshreshtha A, Ayonayon HN, Yaffe K, Goldstein FC. Association of JNC-8 and SPRINT systolic blood pressure levels with cognitive function and related racial disparity. JAMA neurology. 2017 Oct 1;74(10):1199–205.CrossRefPubMedPubMedCentralGoogle Scholar
  95. 95.
    Bakris G, Sorrentino M. Redefining hypertension—assessing the new blood-pressure guidelines. New England Journal of Medicine. 2018 Feb 8;378(6):497–9.CrossRefPubMedGoogle Scholar
  96. 96.
    Krishnaswami A, Kim DH, McCulloch CE, Forman DE, Maurer MS, Alexander KP, Rich MW. Individual and joint effects of pulse pressure and blood pressure treatment intensity on serious adverse events in the SPRINT trial. The American Journal of Medicine. 2018 Oct 1;131(10):1220–7.CrossRefPubMedGoogle Scholar
  97. 97.
    Morawski K, Ghazinouri R, Krumme A, McDonough J, Durfee E, Oley L, Mohta N, Juusola J, Choudhry NK. Rationale and design of the Medication adherence Improvement Support App For Engagement—Blood Pressure (MedISAFE-BP) trial. American heart journal. 2017 Apr 1;186:40–7.CrossRefPubMedGoogle Scholar
  98. 98.
    Ciemins, Elizabeth L., Anupama Arora, Nicholas C. Coombs, Barbara Holloway, Elizabeth J. Mullette, Robin Garland, Shannon Bishop-Green, Jerry Penso, and Patricia J. Coon. "Improving blood pressure control using smart technology." Telemedicine and e-Health 24, no. 3 (2018): 222–228.CrossRefPubMedGoogle Scholar
  99. 99.
    Milani RV, Lavie CJ, Bober RM, Milani AR, Ventura HO. Improving hypertension control and patient engagement using digital tools. The American journal of medicine. 2017 Jan 1;130(1):14–20.CrossRefPubMedGoogle Scholar
  100. 100.
    Lu JF, Chen CM, Hsu CY. Effect of home telehealth care on blood pressure control: A public healthcare centre model. Journal of telemedicine and telecare. 2019 Jan;25(1):35–45.CrossRefPubMedGoogle Scholar
  101. 101.
    Hedegaard U, Hallas J, Ravn-Nielsen LV, Kjeldsen LJ. Process-and patient-reported outcomes of a multifaceted medication adherence intervention for hypertensive patients in secondary care. Research in Social and Administrative Pharmacy. 2016 Mar 1;12(2):302–18.CrossRefPubMedGoogle Scholar
  102. 102.
    Green BB, Cook AJ, Ralston JD, Fishman PA, Catz SL, Carlson J, Carrell D, Tyll L, Larson EB, Thompson RS. Effectiveness of home blood pressure monitoring, Web communication, and pharmacist care on hypertension control: a randomized controlled trial. JAMA. 2008 Jun 25;299(24):2857-67.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. 2019

Authors and Affiliations

  1. 1.Department of NeurologyUniversity Hospitals Cleveland Medical CenterClevelandUSA
  2. 2.Case Western Reserve University School of MedicineClevelandUSA

Personalised recommendations