Impact of Hypertension on Cognitive Function: A Scientific Statement from the American Heart Association

Hypertension

Volumn 68, Issue 6, 2016, Pages e67-e94

  Iadecola, Costantino ^a   Yaffe, Kristine ^b   Biller, José ^d   Bratzke, Lisa C ^e   Faraci, Frank M ^f   Gorelick, Philip B ^g   Gulati, Martha ^h   Kamel, Hooman ^a   Knopman, David S ⁱ   Launer, Lenore J ^j   Saczynski, Jane S ^k   Seshadri, Sudha ^l   Al Hazzouri, Adina Zeki ^c  

^a WEILL CORNELL MEDICAL COLLEGE   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c UNIVERSITY OF MIAMI   (United States)

^d LOYOLA UNIVERSITY CHICAGO   (United States)

^e UNIVERSITY OF WISCONSIN MADISON SCHOOL OF NURSING   (United States)

^f UNIVERSITY OF IOWA   (United States)

^g MICHIGAN STATE UNIVERSITY   (United States)

^h UNIVERSITY OF ARIZONA   (United States)

ⁱ Mayo Clinic   (United States)

^j NIA LEPS   (United States)

^k UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

^l FRAMINGHAM HEART STUDY   (United States)

more..

Author keywords

AHA Scientific Statements; Alzheimer disease; biomarkers; blood pressure; clinical trials; neuroimaging; therapy; vascular cognitive impairment

Indexed keywords

AMYLOID BETA PROTEIN; ANGIOTENSIN RECEPTOR ANTAGONIST; ANTIHYPERTENSIVE AGENT; BIOLOGICAL MARKER; CALCIUM CHANNEL BLOCKING AGENT; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; RAMIPRIL; TELMISARTAN;

AGE; ALZHEIMER DISEASE; ARTICLE; AUTOREGULATION; BLOOD BRAIN BARRIER; BLOOD PRESSURE; BLOOD PRESSURE MEASUREMENT; BLOOD VESSEL FUNCTION; BRAIN ATROPHY; BRAIN BLOOD VESSEL; BRAIN CIRCULATION; BRAIN FUNCTION; BRAIN HEMORRHAGE; BRAIN ISCHEMIA; CEREBROSPINAL FLUID; CEREBROVASCULAR DISEASE; COGNITION; COGNITIVE DEFECT; ELEVATED BLOOD PRESSURE; EXECUTIVE FUNCTION; GENETIC MARKER; HUMAN; HYPERTENSION; MEDICAL SOCIETY; MEMORY; META ANALYSIS (TOPIC); NEUROPATHOLOGY; NEUROVASCULAR COUPLING; NONHUMAN; OBSERVATIONAL STUDY; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); RISK FACTOR; SEX; VASCULAR ENDOTHELIUM; WHITE MATTER LESION; AGED; COGNITION DISORDERS; COMPLICATION; DEMENTIA, VASCULAR; DISEASE COURSE; EVIDENCE BASED MEDICINE; FEMALE; FOLLOW UP; MALE; PATHOPHYSIOLOGY; PRACTICE GUIDELINE; RISK ASSESSMENT; SEVERITY OF ILLNESS INDEX; SEX DIFFERENCE; UNITED STATES; VERY ELDERLY;

AGE FACTORS; AGED; AGED, 80 AND OVER; ALZHEIMER DISEASE; AMERICAN HEART ASSOCIATION; ANTIHYPERTENSIVE AGENTS; COGNITION DISORDERS; DEMENTIA, VASCULAR; DISEASE PROGRESSION; EVIDENCE-BASED MEDICINE; FEMALE; FOLLOW-UP STUDIES; HUMANS; HYPERTENSION; MALE; PRACTICE GUIDELINES AS TOPIC; RISK ASSESSMENT; SEVERITY OF ILLNESS INDEX; SEX FACTORS; UNITED STATES;

EID: 84994824011     PISSN: 0194911X     EISSN: 15244563     Source Type: Journal    
DOI: 10.1161/HYP.0000000000000053     Document Type: Article

References (326)

1. Dementia: A Public Health Priority. Geneva, Switzerland: World Health Organization; 2012.
2. Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP. The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement. 2013;9:63-75.e2. doi: 10.1016/j.jalz.2012.11.007.
3. Gorelick PB, Scuteri A, Black SE, Decarli C, Greenberg SM, Iadecola C, Launer LJ, Laurent S, Lopez OL, Nyenhuis D, Petersen RC, Schneider JA, Tzourio C, Arnett DK, Bennett DA, Chui HC, Higashida RT, Lindquist R, Nilsson PM, Roman GC, Sellke FW, Seshadri S; on behalf of the American Heart Association Stroke Council, Council on Epidemiology and Prevention, Council on Cardiovascular Nursing, Council on Cardiovascular Radiology and Intervention, and Council on Cardiovascular Surgery and Anesthesia. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011;42:2672-2713. doi: 10.1161/STR.0b013e3182299496.
4. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, de Ferranti S, Després JP, Fullerton HJ, Howard VJ, Huffman MD, Judd SE, Kissela BM, Lackland DT, Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Matchar DB, McGuire DK, Mohler ER 3rd, Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Willey JZ, Woo D, Yeh RW, Turner MB; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics-2015 update: a report from the American Heart Association [published corrections appear in Circulation. 2015;131:e535 and Circulation. 2016;133:e417]. Circulation. 2015;131:e29-e322. doi: 10.1161/CIR.0000000000000152.
5. Lim SS, Vos T, Flaxman AD, Danaei G, Shibuya K, Adair-Rohani H, Amann M, Anderson HR, Andrews KG, Aryee M, Atkinson C, Bacchus LJ, Bahalim AN, Balakrishnan K, Balmes J, Barker-Collo S, Baxter A, Bell ML, Blore JD, Blyth F, Bonner C, Borges G, Bourne R, Boussinesq M, Brauer M, Brooks P, Bruce NG, Brunekreef B, Bryan-Hancock C, Bucello C, Buchbinder R, Bull F, Burnett RT, Byers TE, Calabria B, Carapetis J, Carnahan E, Chafe Z, Charlson F, Chen H, Chen JS, Cheng AT, Child JC, Cohen A, Colson KE, Cowie BC, Darby S, Darling S, Davis A, Degenhardt L, Dentener F, Des Jarlais DC, Devries K, Dherani M, Ding EL, Dorsey ER, Driscoll T, Edmond K, Ali SE, Engell RE, Erwin PJ, Fahimi S, Falder G, Farzadfar F, Ferrari A, Finucane MM, Flaxman S, Fowkes FG, Freedman G, Freeman MK, Gakidou E, Ghosh S, Giovannucci E, Gmel G, Graham K, Grainger R, Grant B, Gunnell D, Gutierrez HR, Hall W, Hoek HW, Hogan A, Hosgood HD 3rd, Hoy D, Hu H, Hubbell BJ, Hutchings SJ, Ibeanusi SE, Jacklyn GL, Jasrasaria R, Jonas JB, Kan H, Kanis JA, Kassebaum N, Kawakami N, Khang YH, Khatibzadeh S, Khoo JP, Kok C, Laden F, Lalloo R, Lan Q, Lathlean T, Leasher JL, Leigh J, Li Y, Lin JK, Lipshultz SE, London S, Lozano R, Lu Y, Mak J, Malekzadeh R, Mallinger L, Marcenes W, March L, Marks R, Martin R, McGale P, McGrath J, Mehta S, Mensah GA, Merriman TR, Micha R, Michaud C, Mishra V, Mohd Hanafiah K, Mokdad AA, Morawska L, Mozaffarian D, Murphy T, Naghavi M, Neal B, Nelson PK, Nolla JM, Norman R, Olives C, Omer SB, Orchard J, Osborne R, Ostro B, Page A, Pandey KD, Parry CD, Passmore E, Patra J, Pearce N, Pelizzari PM, Petzold M, Phillips MR, Pope D, Pope CA 3rd, Powles J, Rao M, Razavi H, Rehfuess EA, Rehm JT, Ritz B, Rivara FP, Roberts T, Robinson C, Rodriguez-Portales JA, Romieu I, Room R, Rosenfeld LC, Roy A, Rushton L, Salomon JA, Sampson U, Sanchez-Riera L, Sanman E, Sapkota A, Seedat S, Shi P, Shield K, Shivakoti R, Singh GM, Sleet DA, Smith E, Smith KR, Stapelberg NJ, Steenland K, Stöckl H, Stovner LJ, Straif K, Straney L, Thurston GD, Tran JH, Van Dingenen R, van Donkelaar A, Veerman JL, Vijayakumar L, Weintraub R, Weissman MM, White RA, Whiteford H, Wiersma ST, Wilkinson JD, Williams HC, Williams W, Wilson N, Woolf AD, Yip P, Zielinski JM, Lopez AD, Murray CJ, Ezzati M, AlMazroa MA, Memish ZA. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010 [published corrections appear in Lancet. 2013;381:628 and Lancet. 2013;381:1276]. Lancet. 2012;380:2224-2260. doi: 10.1016/S0140-6736(12)61766-8.
6. Elias MF, Goodell AL, Dore GA. Hypertension and cognitive functioning: a perspective in historical context. Hypertension. 2012;60:260-268. doi: 10.1161/HYPERTENSIONAHA.111.186429.
7. Gąsecki D, Kwarciany M, Nyka W, Narkiewicz K. Hypertension, brain damage and cognitive decline. Curr Hypertens Rep. 2013;15:547-558. doi: 10.1007/s11906-013-0398-4.
8. Iadecola C, Gorelick PB. Converging pathogenic mechanisms in vascular and neurodegenerative dementia. Stroke. 2003;34:335-337.
9. Attems J, Jellinger KA. The overlap between vascular disease and Alzheimer's disease: lessons from pathology. BMC Med. 2014;12:206. doi: 10.1186/s12916-014-0206-2.
10. Toledo JB, Arnold SE, Raible K, Brettschneider J, Xie SX, Grossman M, Monsell SE, Kukull WA, Trojanowski JQ. Contribution of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer's Coordinating Centre. Brain. 2013;136(pt 9):2697-2706. doi: 10.1093/brain/awt188.
11. Schneider JA, Arvanitakis Z, Leurgans SE, Bennett DA. The neuropathology of probable Alzheimer disease and mild cognitive impairment. Ann Neurol. 2009;66:200-208. doi: 10.1002/ana.21706.
12. 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;277:813-817.
13. Chui HC, Zarow C, Mack WJ, Ellis WG, Zheng L, Jagust WJ, Mungas D, Reed BR, Kramer JH, Decarli CC, Weiner MW, Vinters HV. Cognitive impact of subcortical vascular and Alzheimer's disease pathology. Ann Neurol. 2006;60:677-687. doi: 10.1002/ana.21009.
14. Chui HC, Ramirez-Gomez L. Clinical and imaging features of mixed Alzheimer and vascular pathologies. Alzheimers Res Ther. 2015;7:21. doi: 10.1186/s13195-015-0104-7.
15. Norton S, Matthews FE, Barnes DE, Yaffe K, Brayne C. Potential for primary prevention of Alzheimer's disease: an analysis of population-based data [published correction appears in Lancet Neurol. 2014;13:1020]. Lancet Neurol. 2014;13:788-794. doi: 10.1016/S1474-4422(14)70136-X.
16. Faraco G, Iadecola C. Hypertension: a harbinger of stroke and dementia. Hypertension. 2013;62:810-817. doi: 10.1161/HYPERTENSIONAHA. 113.01063.
17. Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol. 2010;9:689-701. doi: 10.1016/S1474-4422(10)70104-6.
18. Moser M, Roccella EJ. The treatment of hypertension: a remarkable success story. J Clin Hypertens (Greenwich). 2013;15:88-91. doi: 10.1111/ jch.12033.
19. Lackland DT, Roccella EJ, Deutsch AF, Fornage M, George MG, Howard G, Kissela BM, Kittner SJ, Lichtman JH, Lisabeth LD, Schwamm LH, Smith EE, Towfighi A; on behalf of the American Heart Association Stroke Council; Council on Cardiovascular and Stroke Nursing; Council on Quality of Care and Outcomes Research; Council on Functional Genomics and Translational Biology. Factors influencing the decline in stroke mortality: a statement from the American Heart Association/ American Stroke Association. Stroke. 2014;45:315-353. doi: 10.1161/01. str.0000437068.30550.cf.
20. Iadecola C. Neurovascular regulation in the normal brain and in Alzheimer's disease. Nat Rev Neurosci. 2004;5:347-360. doi: 10.1038/nrn1387.
21. Ritz K, Denswil NP, Stam OC, van Lieshout JJ, Daemen MJ. Cause and mechanisms of intracranial atherosclerosis. Circulation. 2014;130:1407-1414. doi: 10.1161/CIRCULATIONAHA.114.011147.
22. Faraci FM. Protecting against vascular disease in brain. Am J Physiol Heart Circ Physiol. 2011;300:H1566-H1582. doi: 10.1152/ ajpheart.01310.2010.
23. Laurent S, Boutouyrie P. The structural factor of hypertension: large and small artery alterations. Circ Res. 2015;116:1007-1021. doi: 10.1161/ CIRCRESAHA.116.303596.
24. Baumbach GL, Heistad DD. Remodeling of cerebral arterioles in chronic hypertension. Hypertension. 1989;13(pt 2):968-972.
25. Rizzoni D, De Ciuceis C, Porteri E, Paiardi S, Boari GE, Mortini P, Cornali C, Cenzato M, Rodella LF, Borsani E, Rizzardi N, Platto C, Rezzani R, Rosei EA. Altered structure of small cerebral arteries in patients with essential hypertension. J Hypertens. 2009;27:838-845. doi: 10.1097/ HJH.0b013e32832401ea.
26. Faconti L, Bruno RM, Ghiadoni L, Taddei S, Virdis A. Ventricular and vascular stiffening in aging and hypertension. Curr Hypertens Rev. 2015;11:100-109.
27. Iadecola C. The pathobiology of vascular dementia. Neuron. 2013;80:844-866. doi: 10.1016/j.neuron.2013.10.008.
28. Henskens LH, Kroon AA, van Oostenbrugge RJ, Gronenschild EH, Fuss-Lejeune MM, Hofman PA, Lodder J, de Leeuw PW. Increased aortic pulse wave velocity is associated with silent cerebral small-vessel disease in hypertensive patients. Hypertension. 2008;52:1120-1126. doi: 10.1161/ HYPERTENSIONAHA.108.119024.
29. Yang EY, Chambless L, Sharrett AR, Virani SS, Liu X, Tang Z, Boerwinkle E, Ballantyne CM, Nambi V. Carotid arterial wall characteristics are associated with incident ischemic stroke but not coronary heart disease in the Atherosclerosis Risk in Communities (ARIC) study. Stroke. 2012;43:103-108. doi: 10.1161/STROKEAHA.111.626200.
30. Zeki Al Hazzouri A, Newman AB, Simonsick E, Sink KM, Sutton Tyrrell K, Watson N, Satterfield S, Harris T, Yaffe K, Health ABCS. Pulse wave velocity and cognitive decline in elders: the Health, Aging, and Body Composition Study. Stroke. 2013;44:388-393. doi: 10.1161/ STROKEAHA.112.673533.
31. Mitchell GF. Cerebral small vessel disease: role of aortic stiffness and pulsatile hemodynamics. J Hypertens. 2015;33:2025-2028. doi: 10.1097/ HJH.0000000000000717.
32. Moore SM, Zhang H, Maeda N, Doerschuk CM, Faber JE. Cardiovascular risk factors cause premature rarefaction of the collateral circulation and greater ischemic tissue injury. Angiogenesis. 2015;18:265-281. doi: 10.1007/s10456-015-9465-6.
33. Faber JE, Zhang H, Lassance-Soares RM, Prabhakar P, Najafi AH, Burnett MS, Epstein SE. Aging causes collateral rarefaction and increased severity of ischemic injury in multiple tissues. Arterioscler Thromb Vasc Biol. 2011;31:1748-1756. doi: 10.1161/ATVBAHA.111.227314.
34. Li Y, Shen Q, Huang S, Li W, Muir ER, Long JA, Duong TQ. Cerebral angiography, blood flow and vascular reactivity in progressive hypertension. Neuroimage. 2015;111:329-337. doi: 10.1016/j.neuroimage.2015.02.053.
35. Muller M, van der Graaf Y, Visseren FL, Mali WP, Geerlings MI; SMART Study Group. Hypertension and longitudinal changes in cerebral blood flow: the SMART-MR study. Ann Neurol. 2012;71:825-833. doi: 10.1002/ ana.23554.
36. De Ciuceis C, Cornali C, Porteri E, Mardighian D, Pinardi C, Fontanella MM, Rodella LF, Rezzani R, Rizzoni D, Boari GE, Rosei EA, Gasparotti R. Cerebral small-resistance artery structure and cerebral blood flow in normotensive subjects and hypertensive patients. Neuroradiology. 2014;56:1103-1111. doi: 10.1007/s00234-014-1423-2.
37. Te Riet L, van Esch JH, Roks AJ, van den Meiracker AH, Danser AH. Hypertension: renin-angiotensin-aldosterone system alterations. Circ Res. 2015;116:960-975. doi: 10.1161/CIRCRESAHA.116.303587.
38. Hall JE, do Carmo JM, da Silva AA, Wang Z, Hall ME. Obesity-induced hypertension: interaction of neurohumoral and renal mechanisms. Circ Res. 2015;116:991-1006. doi: 10.1161/CIRCRESAHA.116.305697.
39. Romero JC, Reckelhoff JF. State-of-the-art lecture: role of angiotensin and oxidative stress in essential hypertension. Hypertension. 1999;34(pt 2):943-949.
40. Young CN, Davisson RL. Angiotensin-II, the brain, and hypertension: an update. Hypertension. 2015;66:920-926. doi: 10.1161/ HYPERTENSIONAHA.115.03624.
41. Daugherty A, Rateri DL, Lu H, Inagami T, Cassis LA. Hypercholesterolemia stimulates angiotensin peptide synthesis and contributes to atherosclerosis through the AT1A receptor. Circulation. 2004;110:3849-3857. doi: 10.1161/01.CIR.0000150540.54220.C4.
42. Aono J, Suzuki J, Iwai M, Horiuchi M, Nagai T, Nishimura K, Inoue K, Ogimoto A, Okayama H, Higaki J. Deletion of the angiotensin II type 1a receptor prevents atherosclerotic plaque rupture in apolipoprotein E-/-mice [published correction appears in Arterioscler Thromb Vasc Biol. 2014;34:e18]. Arterioscler Thromb Vasc Biol. 2012;32:1453-1459. doi: 10.1161/ATVBAHA.112.249516.
43. Gupta A, Iadecola C. Impaired Aβ clearance: a potential link between atherosclerosis and Alzheimer's disease. Front Aging Neurosci. 2015;7:115. doi: 10.3389/fnagi.2015.00115.
44. Liu J, Liu S, Matsumoto Y, Murakami S, Sugakawa Y, Kami A, Tanabe C, Maeda T, Michikawa M, Komano H, Zou K. Angiotensin type 1a receptor deficiency decreases amyloid β-protein generation and ameliorates brain amyloid pathology. Sci Rep. 2015;5:12059. doi: 10.1038/ srep12059.
45. Faraco G, Park L, Zhou P, Luo W, Paul SM, Anrather J, Iadecola C. Hypertension enhances Aβ-induced neurovascular dysfunction, promotes β-secretase activity, and leads to amyloidogenic processing of APP. J Cereb Blood Flow Metab. 2016;36:241-252. doi: 10.1038/jcbfm.2015.79.
46. Chan SL, Baumbach GL. Deficiency of Nox2 prevents angiotensin II-induced inward remodeling in cerebral arterioles. Front Physiol. 2013;4:133. doi: 10.3389/fphys.2013.00133.
47. Chan SL, Umesalma S, Baumbach GL. Epidermal growth factor receptor is critical for angiotensin II-mediated hypertrophy in cerebral arterioles. Hypertension. 2015;65:806-812. doi: 10.1161/ HYPERTENSIONAHA.114.04794.
48. Wu J, Thabet SR, Kirabo A, Trott DW, Saleh MA, Xiao L, Madhur MS, Chen W, Harrison DG. Inflammation and mechanical stretch promote aortic stiffening in hypertension through activation of p38 mitogen-activated protein kinase. Circ Res. 2014;114:616-625. doi: 10.1161/CIRCRESAHA.114.302157.
49. Katusic ZS, Austin SA. Endothelial nitric oxide: protector of a healthy mind. Eur Heart J. 2014;35:888-894. doi: 10.1093/eurheartj/eht544.
50. Cipolla MJ. The Cerebral Circulation. San Rafael, CA: Morgan & Claypool Life Sciences; 2009:1-59.
51. Andresen J, Shafi NI, Bryan RM Jr. Endothelial influences on cerebrovascular tone. J Appl Physiol (1985). 2006;100:318-327. doi: 10.1152/ japplphysiol.00937.2005.
52. Chen BR, Kozberg MG, Bouchard MB, Shaik MA, Hillman EM. A critical role for the vascular endothelium in functional neurovascular coupling in the brain. J Am Heart Assoc. 2014;3:e000787. doi: 10.1161/ JAHA.114.000787.
53. Di Marco LY, Venneri A, Farkas E, Evans PC, Marzo A, Frangi AF. Vascular dysfunction in the pathogenesis of Alzheimer's disease: a review of endothelium-mediated mechanisms and ensuing vicious circles. Neurobiol Dis. 2015;82:593-606. doi: 10.1016/j.nbd.2015.08.014.
54. Madden JA. Role of the vascular endothelium and plaque in acute ischemic stroke. Neurology. 2012;79(suppl 1):S58-S62. doi: 10.1212/ WNL.0b013e3182695836.
55. Poggesi A, Pasi M, Pescini F, Pantoni L, Inzitari D. Circulating biologic markers of endothelial dysfunction in cerebral small vessel disease: a review. J Cereb Blood Flow Metab. 2016;36:72-94. doi: 10.1038/ jcbfm.2015.116.
56. Hoth KF, Tate DF, Poppas A, Forman DE, Gunstad J, Moser DJ, Paul RH, Jefferson AL, Haley AP, Cohen RA. Endothelial function and white matter hyperintensities in older adults with cardiovascular disease. Stroke. 2007;38:308-312. doi: 10.1161/01.STR.0000254517.04275.3f.
57. Hillman EM. Coupling mechanism and significance of the BOLD signal: a status report. Annu Rev Neurosci. 2014;37:161-181. doi: 10.1146/ annurev-neuro-071013-014111.
58. Jennings JR, Muldoon MF, Ryan C, Price JC, Greer P, Sutton-Tyrrell K, van der Veen FM, Meltzer CC. Reduced cerebral blood flow response and compensation among patients with untreated hypertension. Neurology. 2005;64:1358-1365. doi: 10.1212/01.WNL.0000158283.28251.3C.
59. van Beek AH, Claassen JA, Rikkert MG, Jansen RW. Cerebral autoregulation: an overview of current concepts and methodology with special focus on the elderly. J Cereb Blood Flow Metab. 2008;28:1071-1085. doi: 10.1038/jcbfm.2008.13.
60. Jordan JD, Powers WJ. Cerebral autoregulation and acute ischemic stroke. Am J Hypertens. 2012;25:946-950. doi: 10.1038/ajh.2012.53.
61. Traon AP, Costes-Salon MC, Galinier M, Fourcade J, Larrue V. Dynamics of cerebral blood flow autoregulation in hypertensive patients [published correction appears in J Neurol Sci. 2002;201:91]. J Neurol Sci. 2002;195:139-144.
62. Fugate JE, Rabinstein AA. Posterior reversible encephalopathy syndrome: clinical and radiological manifestations, pathophysiology, and outstanding questions [published correction appears in Lancet Neurol. 2014;14:874]. Lancet Neurol. 2015;14:914-925. doi: 10.1016/S1474-4422(15)00111-8.
63. Price RS, Kasner SE. Hypertension and hypertensive encephalopathy. Handb Clin Neurol. 2014;119:161-167. doi: 10.1016/ B978-0-7020-4086-3.00012-6.
64. Varon J, Marik PE. Clinical review: the management of hypertensive crises. Crit Care. 2003;7:374-384. doi: 10.1186/cc2351.
65. Back SA, Kroenke CD, Sherman LS, Lawrence G, Gong X, Taber EN, Sonnen JA, Larson EB, Montine TJ. White matter lesions defined by diffusion tensor imaging in older adults. Ann Neurol. 2011;70:465-476. doi: 10.1002/ana.22484.
66. Feekes JA, Cassell MD. The vascular supply of the functional compartments of the human striatum. Brain. 2006;129(pt 8):2189-2201. doi: 10.1093/brain/awl158.
67. Feekes JA, Hsu SW, Chaloupka JC, Cassell MD. Tertiary microvascular territories define lacunar infarcts in the basal ganglia. Ann Neurol. 2005;58:18-30. doi: 10.1002/ana.20505.
68. Purkayastha S, Fadar O, Mehregan A, Salat DH, Moscufo N, Meier DS, Guttmann CR, Fisher ND, Lipsitz LA, Sorond FA. Impaired cerebrovascular hemodynamics are associated with cerebral white matter damage. J Cereb Blood Flow Metab. 2014;34:228-234. doi: 10.1038/ jcbfm.2013.180.
69. Pires PW, Dams Ramos CM, Matin N, Dorrance AM. The effects of hypertension on the cerebral circulation. Am J Physiol Heart Circ Physiol. 2013;304:H1598-H1614. doi: 10.1152/ajpheart.00490.2012.
70. Tietz S, Engelhardt B. Brain barriers: crosstalk between complex tight junctions and adherens junctions. J Cell Biol. 2015;209:493-506. doi: 10.1083/jcb.201412147.
71. Zhao Z, Nelson AR, Betsholtz C, Zlokovic BV. Establishment and dysfunction of the blood-brain barrier. Cell. 2015;163:1064-1078. doi: 10.1016/j.cell.2015.10.067.
72. Winkler EA, Sagare AP, Zlokovic BV. The pericyte: a forgotten cell type with important implications for Alzheimer's disease? Brain Pathol. 2014;24:371-386. doi: 10.1111/bpa.12152.
73. Rosenberg GA. Neurological diseases in relation to the blood-brain barrier. J Cereb Blood Flow Metab. 2012;32:1139-1151. doi: 10.1038/ jcbfm.2011.197.
74. Huisa BN, Caprihan A, Thompson J, Prestopnik J, Qualls CR, Rosenberg GA. Long-term blood-brain barrier permeability changes in Binswanger disease. Stroke. 2015;46:2413-2418. doi: 10.1161/STROKEAHA.115.009589.
75. Wardlaw JM, Smith C, Dichgans M. Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging [published correction appears in Lancet. 2013;12:532]. Lancet Neurol. 2013;12:483-497. doi: 10.1016/S1474-4422(13)70060-7.
76. Joutel A, Faraci FM. Cerebral small vessel disease: insights and opportunities from mouse models of collagen IV-related small vessel disease and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Stroke. 2014;45:1215-1221. doi: 10.1161/ STROKEAHA.113.002878.
77. Nakagawa T, Hasegawa Y, Uekawa K, Ma M, Katayama T, Sueta D, Toyama K, Kataoka K, Koibuchi N, Maeda M, Kuratsu J, Kim-Mitsuyama S. Renal denervation prevents stroke and brain injury via attenuation of oxidative stress in hypertensive rats. J Am Heart Assoc. 2013;2:e000375. doi: 10.1161/JAHA.113.000375.
78. Toth P, Tucsek Z, Sosnowska D, Gautam T, Mitschelen M, Tarantini S, Deak F, Koller A, Sonntag WE, Csiszar A, Ungvari Z. Age-related autoregulatory dysfunction and cerebromicrovascular injury in mice with angiotensin II-induced hypertension. J Cereb Blood Flow Metab. 2013;33:1732-1742. doi: 10.1038/jcbfm.2013.143.
79. Akiguchi I, Tomimoto H, Suenaga T, Wakita H, Budka H. Blood-brain barrier dysfunction in Binswanger's disease; an immunohistochemical study. Acta Neuropathol. 1998;95:78-84.
80. Dankbaar JW, Hom J, Schneider T, Cheng SC, Lau BC, van der Schaaf I, Virmani S, Pohlman S, Wintermark M. Age-and anatomy-related values of blood-brain barrier permeability measured by perfusion-CT in non-stroke patients. J Neuroradiol. 2009;36:219-227. doi: 10.1016/j. neurad.2009.01.001.
81. Rosenberg GA, Wallin A, Wardlaw JM, Markus HS, Montaner J, Wolfson L, Iadecola C, Zlokovic BV, Joutel A, Dichgans M, Duering M, Schmidt R, Korczyn AD, Grinberg LT, Chui HC, Hachinski V. Consensus statement for diagnosis of subcortical small vessel disease. J Cereb Blood Flow Metab. 2016;36:6-25. doi: 10.1038/jcbfm.2015.172.
82. Armulik A, Genové G, Betsholtz C. Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. Dev Cell. 2011;21:193-215. doi: 10.1016/j.devcel.2011.07.001.
83. Suzuki K, Masawa N, Sakata N, Takatama M. Pathologic evidence of microvascular rarefaction in the brain of renal hypertensive rats. J Stroke Cerebrovasc Dis. 2003;12:8-16. doi: 10.1053/jscd.2003.1.
84. Wechsler D. Wechsler Adult Intelligence Scale-Revised. New York, NY: Psychological Corp; 1981.
85. Schmidt M. Rey Auditory Verbal Learning Test: A Handbook. Los Angeles, CA: Western Psychological Services; 1996.
86. Rosenberg SJ, Ryan JJ, Prifitera A. Rey Auditory-Verbal Learning Test performance of patients with and without memory impairment. J Clin Psychol. 1984;40:785-787.
87. Knopman DS, Ryberg S. A verbal memory test with high predictive accuracy for dementia of the Alzheimer type. Arch Neurol. 1989;46:141-145.
88. Benton AL, Hamsher JDS, Sivan AB. Multilingual Aphasia Examination. Iowa City, IA: AJA Associates; 1989.
89. Lezak M. Neuropsychological Assessment. New York, NY: Oxford University Press; 2004.
90. Morris JC, Heyman A, Mohs RC, Hughes JP, van Belle G, Fillenbaum G, Mellits ED, Clark C. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD), part I: clinical and neuropsychological assessment of Alzheimer's disease. Neurology. 1989;39:1159-1165.
91. Army Individual Test Battery: Manual of Directions and Scoring. Washington, DC: War Department, Adjutant General's Office; 1944.
92. Reitan R. Validity of the Trail Making Test as an indicator of organic brain damage. Perceptual and Motor Skills. 1958;18:271-276
93. Yaffe K, Vittinghoff E, Pletcher MJ, Hoang TD, Launer LJ, Whitmer R, Coker LH, Sidney S. Early adult to midlife cardiovascular risk factors and cognitive function. Circulation. 2014;129:1560-1567. doi: 10.1161/ CIRCULATIONAHA.113.004798.
94. Gottesman RF, Schneider AL, Albert M, Alonso A, Bandeen-Roche K, Coker L, Coresh J, Knopman D, Power MC, Rawlings A, Sharrett AR, Wruck LM, Mosley TH. Midlife hypertension and 20-year cognitive change: the Atherosclerosis Risk in Communities neurocognitive study. JAMA Neurol. 2014;71:1218-1227. doi: 10.1001/jamaneurol.2014.1646.
95. Knopman D, Boland LL, Mosley T, Howard G, Liao D, Szklo M, McGovern P, Folsom AR; Atherosclerosis Risk in Communities (ARIC) Study Investigators. Cardiovascular risk factors and cognitive decline in middle-aged adults. Neurology. 2001;56:42-48.
96. Köhler S, Baars MA, Spauwen P, Schievink S, Verhey FR, van Boxtel MJ. Temporal evolution of cognitive changes in incident hypertension: prospective cohort study across the adult age span. Hypertension. 2014;63:245-251. doi: 10.1161/HYPERTENSIONAHA.113.02096.
97. Cerhan JR, Folsom AR, Mortimer JA, Shahar E, Knopman DS, McGovern PG, Hays MA, Crum LD, Heiss G. Correlates of cognitive function in middle-aged adults: Atherosclerosis Risk in Communities (ARIC) Study Investigators. Gerontology. 1998;44:95-105.
98. 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.
99. Debette S, Seshadri S, Beiser A, Au R, Himali JJ, Palumbo C, Wolf PA, DeCarli C. Midlife vascular risk factor exposure accelerates structural brain aging and cognitive decline. Neurology. 2011;77:461-468. doi: 10.1212/WNL.0b013e318227b227.
100. Knopman DS, Mosley TH, Catellier DJ, Coker LH; Atherosclerosis Risk in Communities Study Brain MRI Study. Fourteen-year longitudinal study of vascular risk factors, APOE genotype, and cognition: the ARIC MRI Study. Alzheimers Dement. 2009;5:207-214. doi: 10.1016/j. jalz.2009.01.027.
101. Hachinski V, Iadecola C, Petersen RC, Breteler MM, Nyenhuis DL, Black SE, Powers WJ, DeCarli C, Merino JG, Kalaria RN, Vinters HV, Holtzman DM, Rosenberg GA, Wallin A, Dichgans M, Marler JR, Leblanc GG. National Institute of Neurological Disorders and Stroke-Canadian Stroke Network vascular cognitive impairment harmonization standards [published correction appears in Stroke. 2007;38:1118]. Stroke. 2006;37:2220-2241. doi: 10.1161/01.STR. 0000237236.88823.47.
102. Starr JM, Whalley LJ, Inch S, Shering PA. Blood pressure and cognitive function in healthy old people. J Am Geriatr Soc. 1993;41:753-756.
103. 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.
104. 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.
105. Obisesan TO, Obisesan OA, Martins S, Alamgir L, Bond V, Maxwell C, Gillum RF. High blood pressure, hypertension, and high pulse pressure are associated with poorer cognitive function in persons aged 60 and older: the Third National Health and Nutrition Examination Survey. J Am Geriatr Soc. 2008;56:501-509. doi: 10.1111/j.1532-5415.2007.01592.x.
106. 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.
107. Guo Z, Fratiglioni L, Winblad B, Viitanen M. Blood pressure and performance on the Mini-Mental State Examination in the very old: crosssectional and longitudinal data from the Kungsholmen Project. Am J Epidemiol. 1997;145:1106-1113.
108. 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. doi: 10.1161/01. HYP.0000156744.44218.74.
109. Farmer ME, White LR, Abbott RD, Kittner SJ, Kaplan E, Wolz MM, Brody JA, Wolf PA. Blood pressure and cognitive performance: the Framingham Study. Am J Epidemiol. 1987;126:1103-1114.
110. Richmond R, Law J, Kay-Lambkin F. Higher blood pressure associated with higher cognition and functionality among centenarians in Australia. Am J Hypertens. 2011;24:299-303. doi: 10.1038/ajh.2010.236.
111. Peltz CB, Corrada MM, Berlau DJ, Kawas CH. Cognitive impairment in nondemented oldest-old: prevalence and relationship to cardiovascular risk factors. Alzheimers Dement. 2012;8:87-94. doi: 10.1016/j. jalz.2011.02.008.
112. Lyngdoh T, Viswanathan B, Kobrosly R, van Wijngaarden E, Huber B, Davidson PW, Cory-Slechta DA, Strain JJ, Myers GJ, Bovet P. Blood pressure and cognitive function: a prospective analysis among adolescents in Seychelles [published correction appears in J Hypertens. 2013;31:2105]. J Hypertens. 2013;31:1175-1182. doi: 10.1097/ HJH.0b013e3283604176.
113. 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.
114. 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.
115. Elias PK, Elias MF, Robbins MA, Budge MM. Blood pressurerelated cognitive decline: does age make a difference? Hypertension. 2004;44:631-636. doi: 10.1161/01.HYP.0000145858.07252.99.
116. Chen KH, Henderson VW, Stolwyk RJ, Dennerstein L, Szoeke C. Prehypertension in midlife is associated with worse cognition a decade later in middle-aged and older women. Age Ageing. 2015;44:439-445. doi: 10.1093/ageing/afv026.
117. Taylor C, Tillin T, Chaturvedi N, Dewey M, Ferri CP, Hughes A, Prince M, Richards M, Shah A, Stewart R. Midlife hypertensive status and cognitive function 20 years later: the Southall and Brent revisited study. J Am Geriatr Soc. 2013;61:1489-1498. doi: 10.1111/jgs.12416.
118. Kesse-Guyot E, Julia C, Andreeva V, Fezeu L, Hercberg S, Galan P. Evidence of a cumulative effect of cardiometabolic disorders at midlife and subsequent cognitive function. Age Ageing. 2015;44:648-654. doi: 10.1093/ageing/afv053.
119. Hebert LE, Scherr PA, Bennett DA, Bienias JL, Wilson RS, Morris MC, Evans DA. Blood pressure and late-life cognitive function change: a biracial longitudinal population study. Neurology. 2004;62:2021-2024.
120. Solfrizzi V, Panza F, Colacicco AM, D'Introno A, Capurso C, Torres F, Grigoletto F, Maggi S, Del Parigi A, Reiman EM, Caselli RJ, Scafato E, Farchi G, Capurso A; Italian Longitudinal Study on Aging Working Group. Vascular risk factors, incidence of MCI, and rates of progression to dementia. Neurology. 2004;63:1882-1891.
121. Yaffe K, Haan M, Blackwell T, Cherkasova E, Whitmer RA, West N. Metabolic syndrome and cognitive decline in elderly Latinos: findings from the Sacramento Area Latino Study of Aging study. J Am Geriatr Soc. 2007;55:758-762. doi: 10.1111/j.1532-5415.2007.01139.x.
122. Johnson KC, Margolis KL, Espeland MA, Colenda CC, Fillit H, Manson JE, Masaki KH, Mouton CP, Prineas R, Robinson JG, Wassertheil-Smoller S; Women's Health Initiative Memory Study and Women's Health Initiative Investigators. A prospective study of the effect of hypertension and baseline blood pressure on cognitive decline and dementia in postmenopausal women: the Women's Health Initiative Memory Study. J Am Geriatr Soc. 2008;56:1449-1458. doi: 10.1111/j.1532-5415.2008.01806.x.
123. 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.
124. Dregan A, Stewart R, Gulliford MC. Cardiovascular risk factors and cognitive decline in adults aged 50 and over: a population-based cohort study. Age Ageing. 2013;42:338-345. doi: 10.1093/ageing/afs166.
125. Yasar S, Ko JY, Nothelle S, Mielke MM, Carlson MC. Evaluation of the effect of systolic blood pressure and pulse pressure on cognitive function: the Women's Health and Aging Study II. PLoS One. 2011;6:e27976. doi: 10.1371/journal.pone.0027976.
126. van Vliet P, Westendorp RG, van Heemst D, de Craen AJ, Oleksik AM. Cognitive decline precedes late-life longitudinal changes in vascular risk factors. J Neurol Neurosurg Psychiatry. 2010;81:1028-1032. doi: 10.1136/jnnp.2009.182519.
127. Euser SM, van Bemmel T, Schram MT, Gussekloo J, Hofman A, Westendorp RG, Breteler MM. The effect of age on the association between blood pressure and cognitive function later in life. J Am Geriatr Soc. 2009;57:1232-1237. doi: 10.1111/j.1532-5415.2009.02264.x.
128. Sabayan B, Oleksik AM, Maier AB, van Buchem MA, Poortvliet RK, de Ruijter W, Gussekloo J, de Craen AJ, Westendorp RG. High blood pressure and resilience to physical and cognitive decline in the oldest old: the Leiden 85-plus Study. J Am Geriatr Soc. 2012;60:2014-2019. doi: 10.1111/j.1532-5415.2012.04203.x.
129. Harrison SL, Stephan BC, Siervo M, Granic A, Davies K, Wesnes KA, Kirkwood TB, Robinson L, Jagger C. Is there an association between metabolic syndrome and cognitive function in very old adults? The Newcastle 85+ Study. J Am Geriatr Soc. 2015;63:667-675. doi: 10.1111/jgs.13358.
130. Suhr JA, Stewart JC, France CR. The relationship between blood pressure and cognitive performance in the Third National Health and Nutrition Examination Survey (NHANES III). Psychosom Med. 2004;66:291-297.
131. Elias MF, D'Agostino RB, Elias PK, Wolf PA. Neuropsychological test performance, cognitive functioning, blood pressure, and age: the Framingham Heart Study. Exp Aging Res. 1995;21:369-391. doi: 10.1080/03610739508253991.
132. Zilberman JM, Cerezo GH, Del Sueldo M, Fernandez-Pérez C, Martell-Claros N, Vicario A. Association between hypertension, menopause, and cognition in women. J Clin Hypertens (Greenwich). 2015;17:970-976. doi: 10.1111/jch.12643.
133. Wolf PA, D'Agostino RB, Belanger AJ, Kannel WB. Probability of stroke: a risk profile from the Framingham Study. Stroke. 1991;22:312-318.
134. Elias PK, Elias MF, D'Agostino RB, Cupples LA, Wilson PW, Silbershatz H, Wolf PA. NIDDM and blood pressure as risk factors for poor cognitive performance: the Framingham Study. Diabetes Care. 1997;20:1388-1395.
135. Wolf PA, Beiser A, Elias MF, Au R, Vasan RS, Seshadri S. Relation of obesity to cognitive function: importance of central obesity and synergistic influence of concomitant hypertension: the Framingham Heart Study. Curr Alzheimer Res. 2007;4:111-116.
136. Uiterwijk R, Huijts M, Staals J, Rouhl RP, De Leeuw PW, Kroon AA, Van Oostenbrugge RJ. Endothelial activation is associated with cognitive performance in patients with hypertension. Am J Hypertens. 2016;29:464-469. doi: 10.1093/ajh/hpv122.
137. Kovács KR, Bajkó Z, Szekeres CC, Csapó K, Oláh L, Magyar MT, Molnár S, Czuriga D, Kardos L, Burainé AB, Bereczki D, Soltész P, Csiba L. Elevated LDL-C combined with hypertension worsens subclinical vascular impairment and cognitive function. J Am Soc Hypertens. 2014;8:550-560. doi: 10.1016/j.jash.2014.04.007.
138. Bangen KJ, Beiser A, Delano-Wood L, Nation DA, Lamar M, Libon DJ, Bondi MW, Seshadri S, Wolf PA, Au R. APOE genotype modifies the relationship between midlife vascular risk factors and later cognitive decline. J Stroke Cerebrovasc Dis. 2013;22:1361-1369. doi: 10.1016/j. jstrokecerebrovasdis.2013.03.013.
139. 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.
140. Carmelli D, Swan GE, Reed T, Miller B, Wolf PA, Jarvik GP, Schellenberg GD. Midlife cardiovascular risk factors, ApoE, and cognitive decline in elderly male twins. Neurology. 1998;50:1580-1585.
141. Peila R, White LR, Petrovich H, Masaki K, Ross GW, Havlik RJ, Launer LJ. Joint effect of the APOE gene and midlife systolic blood pressure on late-life cognitive impairment: the Honolulu-Asia Aging Study. Stroke. 2001;32:2882-2889.
142. Andrews S, Das D, Anstey KJ, Easteal S. Interactive effect of APOE genotype and blood pressure on cognitive decline: the PATH through life study. J Alzheimers Dis. 2015;44:1087-1098. doi: 10.3233/JAD-140630.
143. de Frias CM, Schaie KW, Willis SL. Hypertension moderates the effect of APOE on 21-year cognitive trajectories. Psychol Aging. 2014;29:431-439. doi: 10.1037/a0036828.
144. Wersching H, Guske K, Hasenkamp S, Hagedorn C, Schiwek S, Jansen S, Witte V, Wellmann J, Lohmann H, Duning K, Kremerskothen J, Knecht S, Brand E, Floel A. Impact of common KIBRA allele on human cognitive functions. Neuropsychopharmacology. 2011;36:1296-1304. doi: 10.1038/npp.2011.16.
145. Østergaard SD, Mukherjee S, Sharp SJ, Proitsi P, Lotta LA, Day F, Perry JR, Boehme KL, Walter S, Kauwe JS, Gibbons LE, Alzheimer's Disease Genetics Consortium; GERAD1 Consortium; EPIC-InterAct Consortium; Larson EB, Powell JF, Langenberg C, Crane PK, Wareham NJ, Scott RA. Associations between potentially modifiable risk factors and Alzheimer disease: a mendelian randomization study. PLoS Med. 2015;12:e1001841. doi: 10.1371/journal.pmed.1001841.
146. Yoshitake T, Kiyohara Y, Kato I, Ohmura T, Iwamoto H, Nakayama K, Ohmori S, Nomiyama K, Kawano H, Ueda K, Sueishi K, Tsuneyoshi M, Fujishima M. Incidence and risk factors of vascular dementia and Alzheimer's disease in a defined elderly Japanese population: the Hisayama Study. Neurology. 1995;45:1161-1168.
147. Oveisgharan S, Hachinski V. Hypertension, executive dysfunction, and progression to dementia: the Canadian Study of Health and Aging. Arch Neurol. 2010;67:187-192. doi: 10.1001/archneurol.2009.312.
148. Posner HB, Tang MX, Luchsinger J, Lantigua R, Stern Y, Mayeux R. The relationship of hypertension in the elderly to AD, vascular dementia, and cognitive function. Neurology. 2002;58:1175-1181.
149. Qiu C, von Strauss E, Fastbom J, Winblad B, Fratiglioni L. Low blood pressure and risk of dementia in the Kungsholmen project: a 6-year follow-up study. Arch Neurol. 2003;60:223-228.
150. Skoog I, Lernfelt B, Landahl S, Palmertz B, Andreasson LA, Nilsson L, Persson G, Odén A, Svanborg A. 15-Year longitudinal study of blood pressure and dementia. Lancet. 1996;347:1141-1145.
151. Ruitenberg A, Skoog I, Ott A, Aevarsson O, Witteman JC, Lernfelt B, van Harskamp F, Hofman A, Breteler MM. Blood pressure and risk of dementia: results from the Rotterdam study and the Gothenburg H-70 Study. Dement Geriatr Cogn Disord. 2001;12:33-39. doi: 51233.
152. Qiu C, von Strauss E, Winblad B, Fratiglioni L. Decline in blood pressure over time and risk of dementia: a longitudinal study from the Kungsholmen project. Stroke. 2004;35:1810-1815. doi: 10.1161/01. STR.0000133128.42462.ef.
153. Kokmen E, Beard CM, Chandra V, Offord KP, Schoenberg BS, Ballard DJ. Clinical risk factors for Alzheimer's disease: a population-based case-control study. Neurology. 1991;41:1393-1397.
154. 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.
155. Kivipelto M, Helkala EL, Hänninen T, Laakso MP, Hallikainen M, Alhainen K, Soininen H, Tuomilehto J, Nissinen A. Midlife vascular risk factors and late-life mild cognitive impairment: a population-based study. Neurology. 2001;56:1683-1689.
156. Kivipelto M, Helkala EL, Laakso MP, Hänninen T, Hallikainen M, Alhainen K, Soininen H, Tuomilehto J, Nissinen A. Midlife vascular risk factors and Alzheimer's disease in later life: longitudinal, population based study. BMJ. 2001;322:1447-1451.
157. Whitmer RA, Sidney S, Selby J, Johnston SC, Yaffe K. Midlife cardiovascular risk factors and risk of dementia in late life. Neurology. 2005;64:277-281. doi: 10.1212/01.WNL.0000149519.47454.F2.
158. Launer LJ, Ross GW, Petrovitch H, Masaki K, Foley D, White LR, Havlik RJ. Midlife blood pressure and dementia: the Honolulu-Asia Aging Study. Neurobiol Aging. 2000;21:49-55.
159. Ivan CS, Seshadri S, Beiser A, Au R, Kase CS, Kelly-Hayes M, Wolf PA. Dementia after stroke: the Framingham Study. Stroke. 2004;35:1264-1268. doi: 10.1161/01.STR.0000127810.92616.78.
160. Waldstein SR, Rice SC, Thayer JF, Najjar SS, Scuteri A, Zonderman AB. Pulse pressure and pulse wave velocity are related to cognitive decline in the Baltimore Longitudinal Study of Aging. Hypertension. 2008;51:99-104. doi: 10.1161/HYPERTENSIONAHA.107.093674.
161. Stewart R, Xue QL, Masaki K, Petrovitch H, Ross GW, White LR, Launer LJ. Change in blood pressure and incident dementia: a 32-year prospective study. Hypertension. 2009;54:233-240. doi: 10.1161/ HYPERTENSIONAHA.109.128744.
162. Ishii M, Iadecola C. Metabolic and non-cognitive manifestations of Alzheimer's disease: the hypothalamus as both culprit and target of pathology. Cell Metab. 2015;22:761-776. doi: 10.1016/j.cmet.2015.08.016.
163. Iadecola C, Davisson RL. Hypertension and cerebrovascular dysfunction. Cell Metab. 2008;7:476-484. doi: 10.1016/j.cmet.2008.03.010.
164. Li JQ, Tan L, Wang HF, Tan MS, Tan L, Xu W, Zhao QF, Wang J, Jiang T, Yu JT. Risk factors for predicting progression from mild cognitive impairment to Alzheimer's disease: a systematic review and meta-analysis of cohort studies. J Neurol Neurosurg Psychiatry. 2016;87:476-484. doi: 10.1136/jnnp-2014-310095.
165. Xu W, Tan L, Wang HF, Jiang T, Tan MS, Tan L, Zhao QF, Li JQ, Wang J, Yu JT. Meta-analysis of modifiable risk factors for Alzheimer's disease. J Neurol Neurosurg Psychiatry. 2015;86:1299-1306. doi: 10.1136/ jnnp-2015-310548.
166. 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;22:646-659. doi: 10.1097/EDE.0b013e31822708b5.
167. Peila R, White LR, Masaki K, Petrovitch H, Launer LJ. Reducing the risk of dementia: efficacy of long-term treatment of hypertension. Stroke. 2006;37:1165-1170. doi: 10.1161/01.STR.0000217653.01615.93.
168. Khachaturian AS, Zandi PP, Lyketsos CG, Hayden KM, Skoog I, Norton MC, Tschanz JT, Mayer LS, Welsh-Bohmer KA, Breitner JC. Antihypertensive medication use and incident Alzheimer disease: the Cache County Study. Arch Neurol. 2006;63:686-692. doi: 10.1001/ archneur.63.5.noc60013.
169. Seshadri S. Delaying dementia: can antihypertensives prevent Alzheimer dementia? Neurology. 2013;81:860-862. doi: 10.1212/WNL. 0b013e3182a35296.
170. 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: Honolulu-Asia Aging Study. Neurobiol Aging. 2000;21:57-62.
171. Hoffman LB, Schmeidler J, Lesser GT, Beeri MS, Purohit DP, Grossman HT, Haroutunian V. Less Alzheimer disease neuropathology in medicated hypertensive than nonhypertensive persons. Neurology. 2009;72:1720-1726. doi: 10.1212/01.wnl.0000345881.82856.d5.
172. Bangen KJ, Nation DA, Delano-Wood L, Weissberger GH, Hansen LA, Galasko DR, Salmon DP, Bondi MW. Aggregate effects of vascular risk factors on cerebrovascular changes in autopsy-confirmed Alzheimer's disease. Alzheimers Dement. 2015;11:394-403.e1. doi: 10.1016/j. jalz.2013.12.025.
173. Nation DA, Delano-Wood L, Bangen KJ, Wierenga CE, Jak AJ, Hansen LA, Galasko DR, Salmon DP, Bondi MW. Antemortem pulse pressure elevation predicts cerebrovascular disease in autopsy-confirmed Alzheimer's disease. J Alzheimers Dis. 2012;30:595-603. doi: 10.3233/ JAD-2012-111697.
174. Wang LY, Larson EB, Sonnen JA, Shofer JB, McCormick W, Bowen JD, Montine TJ, Li G. Blood pressure and brain injury in older adults: findings from a community-based autopsy study. J Am Geriatr Soc. 2009;57:1975-1981. doi: 10.1111/j.1532-5415.2009.02493.x.
175. Young VG, Halliday GM, Kril JJ. Neuropathologic correlates of white matter hyperintensities. Neurology. 2008;71:804-811. doi: 10.1212/01. wnl.0000319691.50117.54.
176. Fernando MS, Simpson JE, Matthews F, Brayne C, Lewis CE, Barber R, Kalaria RN, Forster G, Esteves F, Wharton SB, Shaw PJ, O'Brien JT, Ince PG; MRC Cognitive Function and Ageing Neuropathology Study Group. White matter lesions in an unselected cohort of the elderly: molecular pathology suggests origin from chronic hypoperfusion injury. Stroke. 2006;37:1391-1398. doi: 10.1161/01.STR.0000221308. 94473.14.
177. Erten-Lyons D, Woltjer R, Kaye J, Mattek N, Dodge HH, Green S, Tran H, Howieson DB, Wild K, Silbert LC. Neuropathologic basis of white matter hyperintensity accumulation with advanced age. Neurology. 2013;81:977-983. doi: 10.1212/WNL.0b013e3182a43e45.
178. He J, Wong VS, Fletcher E, Maillard P, Lee DY, Iosif AM, Singh B, Martinez O, Roach AE, Lockhart SN, Beckett L, Mungas D, Farias ST, Carmichael O, DeCarli C. The contributions of MRI-based measures of gray matter, white matter hyperintensity, and white matter integrity to late-life cognition. AJNR Am J Neuroradiol. 2012;33:1797-1803. doi: 10.3174/ajnr.A3048.
179. Gouw AA, Seewann A, van der Flier WM, Barkhof F, Rozemuller AM, Scheltens P, Geurts JJ. Heterogeneity of small vessel disease: a systematic review of MRI and histopathology correlations. J Neurol Neurosurg Psychiatry. 2011;82:126-135. doi: 10.1136/jnnp.2009.204685.
180. van Dijk EJ, Prins ND, Vrooman HA, Hofman A, Koudstaal PJ, Breteler MM. Progression of cerebral small vessel disease in relation to risk factors and cognitive consequences: Rotterdam Scan study. Stroke. 2008;39:2712-2719. doi: 10.1161/STROKEAHA.107.513176.
181. Gouw AA, van der Flier WM, Fazekas F, van Straaten EC, Pantoni L, Poggesi A, Inzitari D, Erkinjuntti T, Wahlund LO, Waldemar G, Schmidt R, Scheltens P, Barkhof F; LADIS Study Group. Progression of white matter hyperintensities and incidence of new lacunes over a 3-year period: the Leukoaraiosis and Disability Study. Stroke. 2008;39:1414-1420. doi: 10.1161/STROKEAHA.107.498535.
182. Muller M, Sigurdsson S, Kjartansson O, Aspelund T, Lopez OL, Jonnson PV, Harris TB, van Buchem M, Gudnason V, Launer LJ; Age, Gene/ Environment Susceptibility-Reykjavik Study Investigators. Joint effect of mid-and late-life blood pressure on the brain: the AGES-Reykjavik study [published correction appears in Neurology. 2014;83:867]. Neurology. 2014;82:2187-2195. doi: 10.1212/WNL.0000000000000517.
183. Dufouil C, de Kersaint-Gilly A, Besançon V, Levy C, Auffray E, Brunnereau L, Alpérovitch A, Tzourio C. Longitudinal study of blood pressure and white matter hyperintensities: the EVA MRI Cohort. Neurology. 2001;56:921-926.
184. Henskens LH, Kroon AA, van Oostenbrugge RJ, Gronenschild EH, Hofman PA, Lodder J, de Leeuw PW. Associations of ambulatory blood pressure levels with white matter hyperintensity volumes in hypertensive patients. J Hypertens. 2009;27:1446-1452. doi: 10.1097/ HJH.0b013e32832b5204.
185. Liao D, Cooper L, Cai J, Toole J, Bryan N, Burke G, Shahar E, Nieto J, Mosley T, Heiss G. The prevalence and severity of white matter lesions, their relationship with age, ethnicity, gender, and cardiovascular disease risk factors: the ARIC Study. Neuroepidemiology. 1997;16:149-162.
186. de Leeuw FE, de Groot JC, Oudkerk M, Witteman JC, Hofman A, van Gijn J, Breteler MM. A follow-up study of blood pressure and cerebral white matter lesions. Ann Neurol. 1999;46:827-833.
187. Gottesman RF, Coresh J, Catellier DJ, Sharrett AR, Rose KM, Coker LH, Shibata DK, Knopman DS, Jack CR, Mosley TH Jr. Blood pressure and white-matter disease progression in a biethnic cohort: Atherosclerosis Risk in Communities (ARIC) study. Stroke. 2010;41:3-8. doi: 10.1161/ STROKEAHA.109.566992.
188. Swan GE, DeCarli C, Miller BL, Reed T, Wolf PA, Jack LM, Carmelli D. Association of midlife blood pressure to late-life cognitive decline and brain morphology. Neurology. 1998;51:986-993.
189. van Dijk EJ, Breteler MM, Schmidt R, Berger K, Nilsson LG, Oudkerk M, Pajak A, Sans S, de Ridder M, Dufouil C, Fuhrer R, Giampaoli S, Launer LJ, Hofman A; CASCADE Consortium. The association between blood pressure, hypertension, and cerebral white matter lesions: Cardiovascular Determinants of Dementia Study. Hypertension. 2004;44:625-630. doi: 10.1161/01.HYP.0000145857.98904.20.
190. Havlik RJ, Foley DJ, Sayer B, Masaki K, White L, Launer LJ. Variability in midlife systolic blood pressure is related to late-life brain white matter lesions: the Honolulu-Asia Aging Study. Stroke. 2002;33:26-30.
191. Longstreth WT Jr, Arnold AM, Beauchamp NJ Jr, Manolio TA, Lefkowitz D, Jungreis C, Hirsch CH, O'Leary DH, Furberg CD. Incidence, manifestations, and predictors of worsening white matter on serial cranial magnetic resonance imaging in the elderly: the Cardiovascular Health Study. Stroke. 2005;36:56-61. doi: 10.1161/01.STR.0000149625.99732.69.
192. Marcus J, Gardener H, Rundek T, Elkind MS, Sacco RL, Decarli C, Wright CB. Baseline and longitudinal increases in diastolic blood pressure are associated with greater white matter hyperintensity volume: the Northern Manhattan Study. Stroke. 2011;42:2639-2641. doi: 10.1161/ STROKEAHA.111.617571.
193. Veldink JH, Scheltens P, Jonker C, Launer LJ. Progression of cerebral white matter hyperintensities on MRI is related to diastolic blood pressure. Neurology. 1998;51:319-320.
194. den Heijer T, Launer LJ, Prins ND, van Dijk EJ, Vermeer SE, Hofman A, Koudstaal PJ, Breteler MM. Association between blood pressure, white matter lesions, and atrophy of the medial temporal lobe. Neurology. 2005;64:263-267. doi: 10.1212/01.WNL.0000149641.55751.2E.
195. Allan CL, Zsoldos E, Filippini N, Sexton CE, Topiwala A, Valkanova V, Singh-Manoux A, Tabák AG, Shipley MJ, Mackay C, Ebmeier KP, Kivimäki M. Lifetime hypertension as a predictor of brain structure in older adults: cohort study with a 28-year follow-up. Br J Psychiatry. 2015;206:308-315. doi: 10.1192/bjp.bp.114.153536.
196. Tsao CW, Seshadri S, Beiser AS, Westwood AJ, Decarli C, Au R, Himali JJ, Hamburg NM, Vita JA, Levy D, Larson MG, Benjamin EJ, Wolf PA, Vasan RS, Mitchell GF. Relations of arterial stiffness and endothelial function to brain aging in the community. Neurology. 2013;81:984-991. doi: 10.1212/WNL.0b013e3182a43e1c.
197. Poels MM, Ikram MA, van der Lugt A, Hofman A, Niessen WJ, Krestin GP, Breteler MM, Vernooij MW. Cerebral microbleeds are associated with worse cognitive function: the Rotterdam Scan Study. Neurology. 2012;78:326-333. doi: 10.1212/WNL.0b013e3182452928.
198. Jochemsen HM, Muller M, Bots ML, Scheltens P, Vincken KL, Mali WP, van der Graaf Y, Geerlings MI; SMART Study Group. Arterial stiffness and progression of structural brain changes: the SMART-MR study. Neurology. 2015;84:448-455. doi: 10.1212/ WNL.0000000000001201.
199. Dufouil C, Chalmers J, Coskun O, Besançon V, Bousser MG, Guillon P, MacMahon S, Mazoyer B, Neal B, Woodward M, Tzourio-Mazoyer N, Tzourio C; PROGRESS MRI Substudy Investigators. 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. doi: 10.1161/CIRCULATIONAHA.104.501163.
200. Firbank MJ, Wiseman RM, Burton EJ, Saxby BK, O'Brien JT, Ford GA. Brain atrophy and white matter hyperintensity change in older adults and relationship to blood pressure: brain atrophy, WMH change and blood pressure. J Neurol. 2007;254:713-721. doi: 10.1007/s00415-006-0238-4.
201. Wang R, Fratiglioni L, Laukka EJ, Lövdén M, Kalpouzos G, Keller L, Graff C, Salami A, Bäckman L, Qiu C. Effects of vascular risk factors and APOE ϵ4 on white matter integrity and cognitive decline. Neurology. 2015;84:1128-1135. doi: 10.1212/WNL.0000000000001379.
202. Gons RA, de Laat KF, van Norden AG, van Oudheusden LJ, van Uden IW, Norris DG, Zwiers MP, de Leeuw FE. Hypertension and cerebral diffusion tensor imaging in small vessel disease. Stroke. 2010;41:2801-2806. doi: 10.1161/STROKEAHA.110.597237.
203. Kennedy KM, Raz N. Pattern of normal age-related regional differences in white matter microstructure is modified by vascular risk. Brain Res. 2009;1297:41-56. doi: 10.1016/j.brainres.2009.08.058.
204. Leritz EC, Salat DH, Milberg WP, Williams VJ, Chapman CE, Grande LJ, Rudolph JL, Schnyer DM, Barber CE, Lipsitz LA, McGlinchey RE. Variation in blood pressure is associated with white matter microstructure but not cognition in African Americans. Neuropsychology. 2010;24:199-208. doi: 10.1037/a0018108.
205. Maclullich AM, Ferguson KJ, Reid LM, Deary IJ, Starr JM, Seckl JR, Bastin ME, Wardlaw JM. Higher systolic blood pressure is associated with increased water diffusivity in normal-appearing white matter. Stroke. 2009;40:3869-3871. doi: 10.1161/STROKEAHA.109.547877.
206. Maillard P, Seshadri S, Beiser A, Himali JJ, Au R, Fletcher E, Carmichael O, Wolf PA, DeCarli C. Effects of systolic blood pressure on white-matter integrity in young adults in the Framingham Heart Study: a crosssectional study. Lancet Neurol. 2012;11:1039-1047. doi: 10.1016/ S1474-4422(12)70241-7.
207. Maillard P, Carmichael OT, Reed B, Mungas D, DeCarli C. Cooccurrence of vascular risk factors and late-life white-matter integrity changes. Neurobiol Aging. 2015;36:1670-1677. doi: 10.1016/j. neurobiolaging.2015.01.007.
208. Godin O, Maillard P, Crivello F, Alpérovitch A, Mazoyer B, Tzourio C, Dufouil C. Association of white-matter lesions with brain atrophy markers: the three-city Dijon MRI study. Cerebrovasc Dis. 2009;28:177-184. doi: 10.1159/000226117.
209. Schilling S, DeStefano AL, Sachdev PS, Choi SH, Mather KA, DeCarli CD, Wen W, Høgh P, Raz N, Au R, Beiser A, Wolf PA, Romero JR, Zhu YC, Lunetta KL, Farrer L, Dufouil C, Kuller LH, Mazoyer B, Seshadri S, Tzourio C, Debette S. APOE genotype and MRI markers of cerebrovascular disease: systematic review and meta-analysis. Neurology. 2013;81:292-300. doi: 10.1212/WNL.0b013e31829bfda4.
210. Grimmer T, Faust M, Auer F, Alexopoulos P, Förstl H, Henriksen G, Perneczky R, Sorg C, Yousefi BH, Drzezga A, Kurz A. White matter hyperintensities predict amyloid increase in Alzheimer's disease. Neurobiol Aging. 2012;33:2766-2773. doi: 10.1016/j.neurobiolaging.2012.01.016.
211. de Leeuw FE, Richard F, de Groot JC, van Duijn CM, Hofman A, Van Gijn J, Breteler MM. Interaction between hypertension, apoE, and cerebral white matter lesions. Stroke. 2004;35:1057-1060. doi: 10.1161/01. STR.0000125859.71051.83.
212. Høgh P, Garde E, Mortensen EL, Jørgensen OS, Krabbe K, Waldemar G. The apolipoprotein E epsilon4-allele and antihypertensive treatment are associated with increased risk of cerebral MRI white matter hyperintensities. Acta Neurol Scand. 2007;115:248-253. doi: 10.1111/j.1600-0404.2006.00779.x.
213. Schneider JA, Boyle PA, Arvanitakis Z, Bienias JL, Bennett DA. Subcortical infarcts, Alzheimer's disease pathology, and memory function in older persons. Ann Neurol. 2007;62:59-66. doi: 10.1002/ ana.21142.
214. Arvanitakis Z, Leurgans SE, Barnes LL, Bennett DA, Schneider JA. Microinfarct pathology, dementia, and cognitive systems. Stroke. 2011;42:722-727. doi: 10.1161/STROKEAHA.110.595082.
215. White L. Brain lesions at autopsy in older Japanese-American men as related to cognitive impairment and dementia in the final years of life: a summary report from the Honolulu-Asia Aging Study. J Alzheimers Dis. 2009;18:713-725. doi: 10.3233/JAD-2009-1178.
216. Sonnen JA, Santa Cruz K, Hemmy LS, Woltjer R, Leverenz JB, Montine KS, Jack CR, Kaye J, Lim K, Larson EB, White L, Montine TJ. Ecology of the aging human brain. Arch Neurol. 2011;68:1049-1056. doi: 10.1001/archneurol.2011.157.
217. De Reuck JL. Histopathological stainings and definitions of vascular disruptions in the elderly brain. Exp Gerontol. 2012;47:834-837. doi: 10.1016/j.exger.2012.03.012.
218. Gao Z, Wang W, Wang Z, Zhao X, Shang Y, Guo Y, Gong M, Yang L, Shi X, Xu X, An N, Wu W. Cerebral microbleeds are associated with deep white matter hyperintensities, but only in hypertensive patients. PLoS One. 2014;9:e91637. doi: 10.1371/journal.pone.0091637.
219. Henskens LH, van Oostenbrugge RJ, Kroon AA, de Leeuw PW, Lodder J. Brain microbleeds are associated with ambulatory blood pressure levels in a hypertensive population. Hypertension. 2008;51:62-68. doi: 10.1161/HYPERTENSIONAHA.107.100610.
220. Goos JD, Henneman WJ, Sluimer JD, Vrenken H, Sluimer IC, Barkhof F, Blankenstein MA, Scheltens PH, van der Flier WM. Incidence of cerebral microbleeds: a longitudinal study in a memory clinic population. Neurology. 2010;74:1954-1960. doi: 10.1212/ WNL.0b013e3181e396ea.
221. Hara M, Yakushiji Y, Nannri H, Sasaki S, Noguchi T, Nishiyama M, Hirotsu T, Nakajima J, Hara H. Joint effect of hypertension and lifestylerelated risk factors on the risk of brain microbleeds in healthy individuals. Hypertens Res. 2013;36:789-794. doi: 10.1038/hr.2013.26.
222. Poels MM, Vernooij MW, Ikram MA, Hofman A, Krestin GP, van der Lugt A, Breteler MM. Prevalence and risk factors of cerebral microbleeds: an update of the Rotterdam scan study. Stroke. 2010;41(suppl):S103-S106. doi: 10.1161/STROKEAHA.110.595181.
223. Romero JR, Preis SR, Beiser A, DeCarli C, Viswanathan A, Martinez-Ramirez S, Kase CS, Wolf PA, Seshadri S. Risk factors, stroke prevention treatments, and prevalence of cerebral microbleeds in the Framingham Heart Study. Stroke. 2014;45:1492-1494. doi: 10.1161/ STROKEAHA.114.004130.
224. Park JH, Seo SW, Kim C, Kim GH, Noh HJ, Kim ST, Kwak KC, Yoon U, Lee JM, Lee JW, Shin JS, Kim CH, Noh Y, Cho H, Kim HJ, Yoon CW, Oh SJ, Kim JS, Choe YS, Lee KH, Lee JH, Ewers M, Weiner MW, Werring DJ, Na DL. Pathogenesis of cerebral microbleeds: in vivo imaging of amyloid and subcortical ischemic small vessel disease in 226 individuals with cognitive impairment. Ann Neurol. 2013;73:584-593. doi: 10.1002/ana.23845.
225. Shams S, Martola J, Granberg T, Li X, Shams M, Fereshtehnejad SM, Cavallin L, Aspelin P, Kristoffersen-Wiberg M, Wahlund LO. Cerebral microbleeds: different prevalence, topography, and risk factors depending on dementia diagnosis: the Karolinska Imaging Dementia Study. AJNR Am J Neuroradiol. 2015;36:661-666. doi: 10.3174/ajnr.A4176.
226. Qiu C, Cotch MF, Sigurdsson S, Jonsson PV, Jonsdottir MK, Sveinbjrnsdottir S, Eiriksdottir G, Klein R, Harris TB, van Buchem MA, Gudnason V, Launer LJ. Cerebral microbleeds, retinopathy, and dementia: the AGES-Reykjavik Study. Neurology. 2010;75:2221-2228. doi: 10.1212/WNL.0b013e3182020349.
227. van der Vlies AE, Goos JD, Barkhof F, Scheltens P, van der Flier WM. Microbleeds do not affect rate of cognitive decline in Alzheimer disease. Neurology. 2012;79:763-769. doi: 10.1212/WNL.0b013e3182661f91.
228. de Jong LW, Forsberg LE, Vidal JS, Sigurdsson S, Zijdenbos AP, Garcia M, Eiriksdottir G, Gudnason V, van Buchem MA, Launer LJ. Different susceptibility of medial temporal lobe and basal ganglia atrophy rates to vascular risk factors. Neurobiol Aging. 2014;35:72-78. doi: 10.1016/j. neurobiolaging.2013.07.009.
229. Jennings JR, Mendelson DN, Muldoon MF, Ryan CM, Gianaros PJ, Raz N, Aizenstein H. Regional grey matter shrinks in hypertensive individuals despite successful lowering of blood pressure. J Hum Hypertens. 2012;26:295-305. doi: 10.1038/jhh.2011.31.
230. Knopman DS, Penman AD, Catellier DJ, Coker LH, Shibata DK, Sharrett AR, Mosley TH Jr. Vascular risk factors and longitudinal changes on brain MRI: the ARIC Study. Neurology. 2011;76:1879-1885. doi: 10.1212/WNL.0b013e31821d753f.
231. Vlek AL, Visseren FL, Kappelle LJ, Geerlings MI, Vincken KL, Mali WP, van der Graaf Y; SMART Study Group. Blood pressure and progression of cerebral atrophy in patients with vascular disease. Am J Hypertens. 2009;22:1183-1189. doi: 10.1038/ajh.2009.166.
232. Beauchet O, Celle S, Roche F, Bartha R, Montero-Odasso M, Allali G, Annweiler C. Blood pressure levels and brain volume reduction: a systematic review and meta-analysis [published correction appears in J Hypertens. 2013;31:2106]. J Hypertens. 2013;31:1502-1516. doi: 10.1097/HJH.0b013e32836184b5.
233. 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. doi: 10.1161/01.HYP. 0000132475.32317.bb.
234. Korf ES, Scheltens P, Barkhof F, de Leeuw FE. Blood pressure, white matter lesions and medial temporal lobe atrophy: closing the gap between vascular pathology and Alzheimer's disease? Dement Geriatr Cogn Disord. 2005;20:331-337. doi: 10.1159/000088464.
235. Guzman VA, Carmichael OT, Schwarz C, Tosto G, Zimmerman ME, Brickman AM; Alzheimer's Disease Neuroimaging Initiative. White matter hyperintensities and amyloid are independently associated with entorhinal cortex volume among individuals with mild cognitive impairment. Alzheimers Dement. 2013;9(suppl):S124-S131. doi: 10.1016/j. jalz.2012.11.009.
236. de Leeuw FE, Barkhof F, Scheltens P. White matter lesions and hippocampal atrophy in Alzheimer's disease. Neurology. 2004;62:310-312.
237. Raji CA, Lopez OL, Kuller LH, Carmichael OT, Longstreth WT Jr, Gach HM, Boardman J, Bernick CB, Thompson PM, Becker JT. White matter lesions and brain gray matter volume in cognitively normal elders. Neurobiol Aging. 2012;33:834.e7-847.e16
238. Nitkunan A, Lanfranconi S, Charlton RA, Barrick TR, Markus HS. Brain atrophy and cerebral small vessel disease: a prospective followup study. Stroke. 2011;42:133-138. doi: 10.1161/STROKEAHA. 110.594267.
239. Tuladhar AM, Reid AT, Shumskaya E, de Laat KF, van Norden AG, van Dijk EJ, Norris DG, de Leeuw FE. Relationship between white matter hyperintensities, cortical thickness, and cognition. Stroke. 2015;46:425-432. doi: 10.1161/STROKEAHA.114.007146.
240. Kloppenborg RP, Nederkoorn PJ, Grool AM, Vincken KL, Mali WP, Vermeulen M, van der Graaf Y, Geerlings MI; SMART Study Group. Cerebral small-vessel disease and progression of brain atrophy: the SMART-MR study. Neurology. 2012;79:2029-2036. doi: 10.1212/ WNL.0b013e3182749f02.
241. Iliff JJ, Wang M, Liao Y, Plogg BA, Peng W, Gundersen GA, Benveniste H, Vates GE, Deane R, Goldman SA, Nagelhus EA, Nedergaard M. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Sci Transl Med. 2012;4:147ra111. doi: 10.1126/scitranslmed.3003748.
242. Jochemsen HM, Muller M, Visseren FL, Scheltens P, Vincken KL, Mali WP, van der Graaf Y, Geerlings MI; SMART Study Group. Blood pressure and progression of brain atrophy: the SMART-MR Study. JAMA Neurol. 2013;70:1046-1053. doi: 10.1001/jamaneurol.2013.217.
243. Hughes TM, Kuller LH, Barinas-Mitchell EJ, Mackey RH, McDade EM, Klunk WE, Aizenstein HJ, Cohen AD, Snitz BE, Mathis CA, Dekosky ST, Lopez OL. Pulse wave velocity is associated with β-amyloid deposition in the brains of very elderly adults. Neurology. 2013;81:1711-1718. doi: 10.1212/01.wnl.0000435301.64776.37.
244. Langbaum JB, Chen K, Launer LJ, Fleisher AS, Lee W, Liu X, Protas HD, Reeder SA, Bandy D, Yu M, Caselli RJ, Reiman EM. Blood pressure is associated with higher brain amyloid burden and lower glucose metabolism in healthy late middle-age persons. Neurobiol Aging. 2012;33:827.e11-827.e19. doi: 10.1016/j.neurobiolaging.2011.06.020.
245. Toledo JB, Toledo E, Weiner MW, Jack CR Jr, Jagust W, Lee VM, Shaw LM, Trojanowski JQ; Alzheimer's Disease Neuroimaging Initiative. Cardiovascular risk factors, cortisol, and amyloid-β deposition in Alzheimer's Disease Neuroimaging Initiative. Alzheimers Dement. 2012;8:483-489. doi: 10.1016/j.jalz.2011.08.008.
246. Rodrigue KM, Rieck JR, Kennedy KM, Devous MD Sr, Diaz-Arrastia R, Park DC. Risk factors for β-amyloid deposition in healthy aging: vascular and genetic effects. JAMA Neurol. 2013;70:600-606. doi: 10.1001/ jamaneurol.2013.1342.
247. Nation DA, Edland SD, Bondi MW, Salmon DP, Delano-Wood L, Peskind ER, Quinn JF, Galasko DR. Pulse pressure is associated with Alzheimer biomarkers in cognitively normal older adults. Neurology. 2013;81:2024-2027. doi: 10.1212/01.wnl.0000436935.47657.78.
248. Nation DA, Edmonds EC, Bangen KJ, Delano-Wood L, Scanlon BK, Han SD, Edland SD, Salmon DP, Galasko DR, Bondi MW; Alzheimer's Disease Neuroimaging Initiative Investigators. Pulse pressure in relation to tau-mediated neurodegeneration, cerebral amyloidosis, and progression to dementia in very old adults. JAMA Neurol. 2015;72:546-553. doi: 10.1001/jamaneurol.2014.4477.
249. 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;20:1083-1090. doi: 10.3233/JAD-2010-091198.
250. Peters R, Beckett N, Forette F, Tuomilehto J, Clarke R, Ritchie C, Waldman A, Walton I, Poulter R, Ma S, Comsa M, Burch L, Fletcher A, Bulpitt C; HYVET Investigators. 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;7:683-689. doi: 10.1016/S1474-4422(08)70143-1.
251. Forette F, Seux ML, Staessen JA, Thijs L, Birkenhäger WH, Babarskiene MR, Babeanu S, Bossini A, Gil-Extremera B, Girerd X, Laks T, Lilov E, Moisseyev V, Tuomilehto J, Vanhanen H, Webster J, Yodfat Y, Fagard R. Prevention of dementia in randomised double-blind placebocontrolled Systolic Hypertension in Europe (Syst-Eur) trial. Lancet. 1998;352:1347-1351.
252. Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, Savovic J, Schulz KF, Weeks L, Sterne JA; Cochrane Bias Methods Group; Cochrane Statistical Methods Group. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928.
253. Williamson JD, Launer LJ, Bryan RN, Coker LH, Lazar RM, Gerstein HC, Murray AM, Sullivan MD, Horowitz KR, Ding J, Marcovina S, Lovato L, Lovato J, Margolis KL, Davatzikos C, Barzilay J, Ginsberg HN, Linz PE, Miller ME; Action to Control Cardiovascular Risk in Diabetes Memory in Diabetes Investigators. Cognitive function and brain structure in persons with type 2 diabetes mellitus after intensive lowering of blood pressure and lipid levels: a randomized clinical trial. JAMA Intern Med. 2014;174:324-333. doi: 10.1001/jamainternmed.2013.13656.
254. Anderson C, Teo K, Gao P, Arima H, Dans A, Unger T, Commerford P, Dyal L, Schumacher H, Pogue J, Paolasso E, Holwerda N, Chazova I, Binbrek A, Young J, Yusuf S; ONTARGET and TRANSCEND Investigators. Renin-angiotensin system blockade and cognitive function in patients at high risk of cardiovascular disease: analysis of data from the ONTARGET and TRANSCEND studies. Lancet Neurol. 2011;10:43-53. doi: 10.1016/S1474-4422(10)70250-7.
255. SPS3 Investigators, Benavente OR, Hart RG, McClure LA, Szychowski JM, Coffey CS, Pearce LA. Effects of clopidogrel added to aspirin in patients with recent lacunar stroke. N Engl J Med. 2012;367:817-825. doi: 10.1056/NEJMoa1204133.
256. Lithell H, Hansson L, Skoog I, Elmfeldt D, Hofman A, Olofsson B, Trenkwalder P, Zanchetti A; SCOPE Study Group. 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. doi: 10.1097/01.hjh.0000059028.82022.89.
257. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension: final results of the Systolic Hypertension in the Elderly Program (SHEP): SHEP Cooperative Research Group. JAMA. 1991;265:3255-3264. doi:10.1001/jama.1991. 03460240051027
258. Diener HC, Sacco RL, Yusuf S, Cotton D, Ounpuu S, Lawton WA, Palesch Y, Martin RH, Albers GW, Bath P, Bornstein N, Chan BP, Chen ST, Cunha L, Dahlöf B, De Keyser J, Donnan GA, Estol C, Gorelick P, Gu V, Hermansson K, Hilbrich L, Kaste M, Lu C, Machnig T, Pais P, Roberts R, Skvortsova V, Teal P, Toni D, VanderMaelen C, Voigt T, Weber M, Yoon BW; Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) Study Group. Effects of aspirin plus extended-release dipyridamole versus clopidogrel and telmisartan on disability and cognitive function after recurrent stroke in patients with ischaemic stroke in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial: a double-blind, active and placebo-controlled study [published correction appears in Lancet Neurol. 2008;7:985]. Lancet Neurol. 2008;7:875-884. doi: 10.1016/S1474-4422(08)70198-4.
259. Pearce LA, McClure LA, Anderson DC, Jacova C, Sharma M, Hart RG, Benavente OR; SPS3 Investigators. Effects of long-term blood pressure lowering and dual antiplatelet treatment on cognitive function in patients with recent lacunar stroke: a secondary analysis from the SPS3 randomised trial. Lancet Neurol. 2014;13:1177-1185. doi: 10.1016/ S1474-4422(14)70224-8.
260. Tzourio C, Anderson C, Chapman N, Woodward M, Neal B, MacMahon S, Chalmers J; PROGRESS Collaborative Group. Effects of blood pressure lowering with perindopril and indapamide therapy on dementia and cognitive decline in patients with cerebrovascular disease. Arch Intern Med. 2003;163:1069-1075. doi: 10.1001/archinte.163.9.1069.
261. Hornslien AG, Sandset EC, Bath PM, Wyller TB, Berge E; Scandinavian Candesartan Acute Stroke Trial Study Group. Effects of candesartan in acute stroke on cognitive function and quality of life: results from the Scandinavian Candesartan Acute Stroke Trial. Stroke. 2013;44:2022-2024. doi: 10.1161/STROKEAHA.113.001022.
262. Applegate WB, Pressel S, Wittes J, Luhr J, Shekelle RB, Camel GH, Greenlick MR, Hadley E, Moye L, Perry HM Jr, Schron E, Wegener V. Impact of the treatment of isolated systolic hypertension on behavioral variables: results from the Systolic Hypertension in the Elderly Program. Arch Intern Med. 1994;154:2154-2160.
263. Hachinski VC, Iliff LD, Zilhka E, Du Boulay GH, McAllister VL, Marshall J, Russell RW, Symon L. Cerebral blood flow in dementia. Arch Neurol. 1975;32:632-637.
264. Weber R, Weimar C, Blatchford J, Hermansson K, Wanke I, Möller-Hartmann C, Gizewski ER, Forsting M, Demchuk AM, Sacco RL, Saver JL, Warach S, Diener HC, Diehl A; PRoFESS Imaging Substudy Group. Telmisartan on top of antihypertensive treatment does not prevent progression of cerebral white matter lesions in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) MRI substudy. Stroke. 2012;43:2336-2342. doi: 10.1161/STROKEAHA.111.648576.
265. Saxby BK, Harrington F, Wesnes KA, McKeith IG, Ford GA. Candesartan and cognitive decline in older patients with hypertension: a substudy of the SCOPE trial. Neurology. 2008;70(pt 2):1858-1866. doi: 10.1212/01. wnl.0000311447.85948.78.
266. Forette F, Seux ML, Staessen JA, Thijs L, Babarskiene MR, Babeanu S, Bossini A, Fagard R, Gil-Extremera B, Laks T, Kobalava Z, Sarti C, Tuomilehto J, Vanhanen H, Webster J, Yodfat Y, Birkenhäger WH; Systolic Hypertension in Europe Investigators. The prevention of dementia with antihypertensive treatment: new evidence from the Systolic Hypertension in Europe (Syst-Eur) study [published correction appears in Arch Intern Med. 2003;163:241]. Arch Intern Med. 2002;162:2046-2052.
267. Staessen JA, Thijs L, Richart T, Odili AN, Birkenhäger WH. Placebocontrolled trials of blood pressure-lowering therapies for primary prevention of dementia. Hypertension. 2011;57:e6-e7. doi: 10.1161/ HYPERTENSIONAHA.110.165142.
268. Skoog I, Lithell H, Hansson L, Elmfeldt D, Hofman A, Olofsson B, Trenkwalder P, Zanchetti A; SCOPE Study Group. Effect of baseline cognitive function and antihypertensive treatment on cognitive and cardiovascular outcomes: Study on COgnition and Prognosis in the Elderly (SCOPE). Am J Hypertens. 2005;18:1052-1059. doi: 10.1016/j. amjhyper.2005.02.013.
269. Di Bari M, Pahor M, Franse LV, Shorr RI, Wan JY, Ferrucci L, Somes GW, Applegate WB. Dementia and disability outcomes in large hypertension trials: lessons learned from the Systolic Hypertension in the Elderly Program (SHEP) trial. Am J Epidemiol. 2001;153:72-78.
270. Ambrosius WT, Sink KM, Foy CG, Berlowitz DR, Cheung AK, Cushman WC, Fine LJ, Goff DC Jr, Johnson KC, Killeen AA, Lewis CE, Oparil S, Reboussin DM, Rocco MV, Snyder JK, Williamson JD, Wright JT Jr, Whelton PK; SPRINT Study Research Group. The design and rationale of a multicenter clinical trial comparing two strategies for control of systolic blood pressure: the Systolic Blood Pressure Intervention Trial (SPRINT). Clin Trials. 2014;11:532-546. doi: 10.1177/1740774514537404.
271. SPRINT Research Group, Wright JT Jr, Williamson JD, Whelton PK, Snyder JK, Sink KM, Rocco MV, Reboussin DM, Rahman M, Oparil S, Lewis CE, Kimmel PL, Johnson KC, Goff DC Jr, Fine LJ, Cutler JA, Cushman WC, Cheung AK, Ambrosius WT. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373:2103-2116. doi: 10.1056/NEJMoa1511939.
272. Din-Dzietham R, Liu Y, Bielo MV, Shamsa F. High blood pressure trends in children and adolescents in national surveys, 1963 to 2002. Circulation. 2007;116:1488-1496. doi: 10.1161/CIRCULATIONAHA.106.683243.
273. Riley M, Bluhm B. High blood pressure in children and adolescents. Am Fam Physician. 2012;85:693-700.
274. Flynn JT, Daniels SR, Hayman LL, Maahs DM, McCrindle BW, Mitsnefes M, Zachariah JP, Urbina EM; on behalf of the American Heart Association Atherosclerosis, Hypertension and Obesity in Youth Committee of the Council on Cardiovascular Disease in the Young. Update: ambulatory blood pressure monitoring in children and adolescents: a scientific statement from the American Heart Association. Hypertension. 2014;63:1116-1135. doi: 10.1161/HYP.0000000000000007.
275. Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM. Prevalence of overweight and obesity in the United States, 1999-2004. JAMA. 2006;295:1549-1555. doi: 10.1001/jama.295.13.1549.
276. Chen W, Bao W, Begum S, Elkasabany A, Srinivasan SR, Berenson GS. Age-related patterns of the clustering of cardiovascular risk variables of syndrome X from childhood to young adulthood in a population made up of black and white subjects: the Bogalusa Heart Study. Diabetes. 2000;49:1042-1048.
277. Shear CL, Burke GL, Freedman DS, Berenson GS. Value of childhood blood pressure measurements and family history in predicting future blood pressure status: results from 8 years of follow-up in the Bogalusa Heart Study. Pediatrics. 1986;77:862-869.
278. Klumbiene J, Sileikiene L, Milasauskiene Z, Zaborskis A, Shatchkute A. The relationship of childhood to adult blood pressure: longitudinal study of juvenile hypertension in Lithuania. J Hypertens. 2000;18:531-538.
279. Strong JP, Malcom GT, McMahan CA, Tracy RE, Newman WP 3rd, Herderick EE, Cornhill JF. Prevalence and extent of atherosclerosis in adolescents and young adults: implications for prevention from the Pathobiological Determinants of Atherosclerosis in Youth Study. JAMA. 1999;281:727-735.
280. Berenson GS, Srinivasan SR, Bao W, Newman WP 3rd, Tracy RE, Wattigney WA. Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults: the Bogalusa Heart Study. N Engl J Med. 1998;338:1650-1656. doi: 10.1056/ NEJM199806043382302.
281. Kollias A, Dafni M, Poulidakis E, Ntineri A, Stergiou GS. Out-of-office blood pressure and target organ damage in children and adolescents: a systematic review and meta-analysis. J Hypertens. 2014;32:2315-2331. doi: 10.1097/HJH.0000000000000384.
282. Morrison JA, Friedman LA, Gray-McGuire C. Metabolic syndrome in childhood predicts adult cardiovascular disease 25 years later: the Princeton Lipid Research Clinics Follow-up Study. Pediatrics. 2007;120:340-345. doi: 10.1542/peds.2006-1699.
283. Lande MB, Kaczorowski JM, Auinger P, Schwartz GJ, Weitzman M. Elevated blood pressure and decreased cognitive function among school-age children and adolescents in the United States. J Pediatr. 2003;143:720-724. doi: 10.1067/S0022-3476(03)00412-8.
284. Adams HR, Szilagyi PG, Gebhardt L, Lande MB. Learning and attention problems among children with pediatric primary hypertension. Pediatrics. 2010;126:e1425-e1429. doi: 10.1542/peds.2010-1899.
285. Krause I, Cleper R, Kovalski Y, Sinai L, Davidovits M. Changes in behavior as an early symptom of renovascular hypertension in children. Pediatr Nephrol. 2009;24:2271-2274. doi: 10.1007/s00467-009-1205-y.
286. Chaturvedi S, Lipszyc DH, Licht C, Craig JC, Parekh R. Pharmacological interventions for hypertension in children. Cochrane Database Syst Rev. 2014:CD008117
287. Franklin SS, Jacobs MJ, Wong ND, L'Italien GJ, Lapuerta P. Predominance of isolated systolic hypertension among middle-aged and elderly US hypertensives: analysis based on National Health and Nutrition Examination Survey (NHANES) III. Hypertension. 2001;37:869-874.
288. Franklin SS, Pio JR, Wong ND, Larson MG, Leip EP, Vasan RS, Levy D. Predictors of new-onset diastolic and systolic hypertension: the Framingham Heart Study. Circulation. 2005;111:1121-1127. doi: 10.1161/01.CIR.0000157159.39889.EC.
289. 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 [published correction appears in Lancet. 2003;361:1060]. Lancet. 2002;360:1903-1913.
290. Blood Pressure Lowering Treatment Trialists' Collaboration, Turnbull F, Neal B, Ninomiya T, Algert C, Arima H, Barzi F, Bulpitt C, Chalmers J, Fagard R, Gleason A, Heritier S, Li N, Perkovic V, Woodward M, MacMahon S. Effects of different regimens to lower blood pressure on major cardiovascular events in older and younger adults: meta-analysis of randomised trials. BMJ. 2008;336:1121-1123
291. Appel LJ, Champagne CM, Harsha DW, Cooper LS, Obarzanek E, Elmer PJ, Stevens VJ, Vollmer WM, Lin PH, Svetkey LP, Stedman SW, Young DR; Writing Group of the PREMIER Collaborative Research Group. Effects of comprehensive lifestyle modification on blood pressure control: main results of the PREMIER clinical trial. JAMA. 2003;289:2083-2093. doi: 10.1001/jama.289.16.2083.
292. Musini VM, Tejani AM, Bassett K, Wright JM. Pharmacotherapy for hypertension in the elderly. Cochrane Database Syst Rev. 2009:CD000028
293. Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. BMJ. 2009;338:b1665.
294. Webb AJ, Fischer U, Mehta Z, Rothwell PM. Effects of antihypertensive-drug class on interindividual variation in blood pressure and risk of stroke: a systematic review and meta-analysis. Lancet. 2010;375:906-915. doi: 10.1016/S0140-6736(10)60235-8.
295. Sundström J, Arima H, Jackson R, Turnbull F, Rahimi K, Chalmers J, Woodward M, Neal B; Blood Pressure Lowering Treatment Trialists' Collaboration. Effects of blood pressure reduction in mild hypertension: a systematic review and meta-analysis. Ann Intern Med. 2015;162:184-191. doi: 10.7326/M14-0773.
296. 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. doi: 10.1097/01. hjh.0000244934.81180.16.
297. Feigin V, Ratnasabapathy Y, Anderson C. Does blood pressure lowering treatment prevents dementia or cognitive decline in patients with cardiovascular and cerebrovascular disease? J Neurol Sci. 2005;229-230:151-155. doi: 10.1016/j.jns.2004.11.020.
298. McGuinness B, Todd S, Passmore AP, Bullock R. Systematic review: blood pressure lowering in patients without prior cerebrovascular disease for prevention of cognitive impairment and dementia. J Neurol Neurosurg Psychiatry. 2008;79:4-5. doi: 10.1136/jnnp.2007.118505.
299. McGuinness B, Todd S, Passmore P, Bullock R. Blood pressure lowering in patients without prior cerebrovascular disease for prevention of cognitive impairment and dementia. Cochrane Database Syst Rev. 2009:CD004034
300. Gifford KA, Badaracco M, Liu D, Tripodis Y, Gentile A, Lu Z, Palmisano J, Jefferson AL. Blood pressure and cognition among older adults: a meta-analysis. Arch Clin Neuropsychol. 2013;28:649-664. doi: 10.1093/ arclin/act046.
301. Ngandu T, Lehtisalo J, Solomon A, Levälahti E, Ahtiluoto S, Antikainen R, Bäckman L, Hänninen T, Jula A, Laatikainen T, Lindström J, Mangialasche F, Paajanen T, Pajala S, Peltonen M, Rauramaa R, Stigsdotter-Neely A, Strandberg T, Tuomilehto J, Soininen H, Kivipelto M. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet. 2015;385:2255-2263. doi: 10.1016/S0140-6736(15)60461-5.
302. Makin SD, Turpin S, Dennis MS, Wardlaw JM. Cognitive impairment after lacunar stroke: systematic review and meta-analysis of incidence, prevalence and comparison with other stroke subtypes. J Neurol Neurosurg Psychiatry. 2013;84:893-900. doi: 10.1136/jnnp-2012-303645.
303. Vermeer SE, Prins ND, den Heijer T, Hofman A, Koudstaal PJ, Breteler MM. Silent brain infarcts and the risk of dementia and cognitive decline. N Engl J Med. 2003;348:1215-1222. doi: 10.1056/NEJMoa022066.
304. Christensen K, Thinggaard M, Oksuzyan A, Steenstrup T, Andersen-Ranberg K, Jeune B, McGue M, Vaupel JW. Physical and cognitive functioning of people older than 90 years: a comparison of two Danish cohorts born 10 years apart. Lancet. 2013;382:1507-1513. doi: 10.1016/ S0140-6736(13)60777-1.
305. Manton KC, Gu XL, Ukraintseva SV. Declining prevalence of dementia in the U.S. elderly population. Adv Gerontol. 2005;16:30-37.
306. Langa KM, Larson EB, Karlawish JH, Cutler DM, Kabeto MU, Kim SY, Rosen AB. Trends in the prevalence and mortality of cognitive impairment in the United States: is there evidence of a compression of cognitive morbidity? Alzheimers Dement. 2008;4:134-144. doi: 10.1016/j. jalz.2008.01.001.
307. Qiu C, von Strauss E, Bäckman L, Winblad B, Fratiglioni L. Twenty-year changes in dementia occurrence suggest decreasing incidence in central Stockholm, Sweden. Neurology. 2013;80:1888-1894. doi: 10.1212/ WNL.0b013e318292a2f9.
308. Matthews FE, Arthur A, Barnes LE, Bond J, Jagger C, Robinson L, Brayne C; Medical Research Council Cognitive Function and Ageing Collaboration. A two-decade comparison of prevalence of dementia in individuals aged 65 years and older from three geographical areas of England: results of the Cognitive Function and Ageing Study I and II. Lancet. 2013;382:1405-1412. doi: 10.1016/S0140-6736(13)61570-6.
309. Qiu C, Winblad B, Fratiglioni L. Low diastolic pressure and risk of dementia in very old people: a longitudinal study. Dement Geriatr Cogn Disord. 2009;28:213-219. doi: 10.1159/000236913.
310. 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.
311. Morris MC, Scherr PA, Hebert LE, Glynn RJ, Bennett DA, Evans DA. Association of incident Alzheimer disease and blood pressure measured from 13 years before to 2 years after diagnosis in a large community study. Arch Neurol. 2001;58:1640-1646.
312. Luukinen H, Koski K, Laippala P, Kivelä SL. Prognosis of diastolic and systolic orthostatic hypotension in older persons. Arch Intern Med. 1999;159:273-280.
313. Mitchell GF, Parise H, Benjamin EJ, Larson MG, Keyes MJ, Vita JA, Vasan RS, Levy D. Changes in arterial stiffness and wave reflection with advancing age in healthy men and women: the Framingham Heart Study. Hypertension. 2004;43:1239-1245. doi: 10.1161/01. HYP.0000128420.01881.aa.
314. Avolio AP, Deng FQ, Li WQ, Luo YF, Huang ZD, Xing LF, O'Rourke MF. Effects of aging on arterial distensibility in populations with high and low prevalence of hypertension: comparison between urban and rural communities in China. Circulation. 1985;71:202-210.
315. Fontana L, Meyer TE, Klein S, Holloszy JO. Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans. Proc Natl Acad Sci U S A. 2004;101:6659-6663. doi: 10.1073/ pnas.0308291101.
316. Meyer TE, Kovács SJ, Ehsani AA, Klein S, Holloszy JO, Fontana L. Long-term caloric restriction ameliorates the decline in diastolic function in humans. J Am Coll Cardiol. 2006;47:398-402. doi: 10.1016/j. jacc.2005.08.069.
317. García-Ortiz L, Recio-Rodríguez JI, Schmidt-Trucksäss A, Puigdomenech-Puig E, Martínez-Vizcaíno V, Fernández-Alonso C, Rubio-Galan J, Agudo-Conde C, Patino-Alonso MC, Rodríguez-Sánchez E, Gómez-Marcos MA; EVIDENT Group. Relationship between objectively measured physical activity and cardiovascular aging in the general population: the EVIDENT trial. Atherosclerosis. 2014;233:434-440. doi: 10.1016/j. atherosclerosis.2014.01.021.
318. Seals DR, Tanaka H, Clevenger CM, Monahan KD, Reiling MJ, Hiatt WR, Davy KP, DeSouza CA. Blood pressure reductions with exercise and sodium restriction in postmenopausal women with elevated systolic pressure: role of arterial stiffness. J Am Coll Cardiol. 2001;38:506-513.
319. Beason-Held LL, Moghekar A, Zonderman AB, Kraut MA, Resnick SM. Longitudinal changes in cerebral blood flow in the older hypertensive brain. Stroke. 2007;38:1766-1773. doi: 10.1161/ STROKEAHA.106.477109.
320. Willette AA, Xu G, Johnson SC, Birdsill AC, Jonaitis EM, Sager MA, Hermann BP, La Rue A, Asthana S, Bendlin BB. Insulin resistance, brain atrophy, and cognitive performance in late middle-aged adults. Diabetes Care. 2013;36:443-449. doi: 10.2337/dc12-0922.
321. Jack CR Jr, Knopman DS, Jagust WJ, Petersen RC, Weiner MW, Aisen PS, Shaw LM, Vemuri P, Wiste HJ, Weigand SD, Lesnick TG, Pankratz VS, Donohue MC, Trojanowski JQ. Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol. 2013;12:207-216. doi: 10.1016/ S1474-4422(12)70291-0.
322. Anderson G. Chronic Care: Making the Case for Ongoing Care. Princeton, NJ: Robert Woods Johnson Foundation; 2010.
323. Bauer L, Pozehl B, Hertzog M, Johnson J, Zimmerman L, Filipi M. A brief neuropsychological battery for use in the chronic heart failure population. Eur J Cardiovasc Nurs. 2012;11:223-230. doi: 10.1016/j. ejcnurse.2011.03.007.
324. Tarasoff-Conway JM, Carare RO, Osorio RS, Glodzik L, Butler T, Fieremans E, Axel L, Rusinek H, Nicholson C, Zlokovic BV, Frangione B, Blennow K, Ménard J, Zetterberg H, Wisniewski T, de Leon MJ. Clearance systems in the brain-implications for Alzheimer disease [published correction appears in Nat Rev Neurol. 2016;12:248]. Nat Rev Neurol. 2015;11:457-470. doi: 10.1038/nrneurol.2015.119.
325. Roberts KF, Elbert DL, Kasten TP, Patterson BW, Sigurdson WC, Connors RE, Ovod V, Munsell LY, Mawuenyega KG, Miller-Thomas MM, Moran CJ, Cross DT 3rd, Derdeyn CP, Bateman RJ. Amyloid-β efflux from the central nervous system into the plasma. Ann Neurol. 2014;76:837-844. doi: 10.1002/ana.24270.
326. Louveau A, Smirnov I, Keyes TJ, Eccles JD, Rouhani SJ, Peske JD, Derecki NC, Castle D, Mandell JW, Lee KS, Harris TH, Kipnis J. Structural and functional features of central nervous system lymphatic vessels [published correction appears in Nature. 2016;533:278]. Nature. 2015;523:337-341. doi: 10.1038/nature14432.