Microvascular brain damage with aging and hypertension: Pathophysiological consideration and clinical implications

Journal of Hypertension

Volumn 29, Issue 8, 2011, Pages 1469-1477

  Scuteri, Angelo ^a   Nilsson, Peter M ^b   Tzourio, Christopher ^c   Redon, Josep ^d   Laurent, Stephane ^e  

^a INRCA   (Italy)

^b LUND UNIVERSITY   (Sweden)

^c INSERM   (France)

^d UNIVERSITY OF VALENCIA   (Spain)

^e HÔPITAL EUROPÉEN GEORGES POMPIDOU   (France)

Author keywords

arterial aging; arterial stiffness; cognitive function; dementia; microvascular brain damage; prevention; white matter lesion

Indexed keywords

ANGIOTENSIN 1 RECEPTOR; ANGIOTENSIN II; INDAPAMIDE; PERINDOPRIL;

AGING; ANTIHYPERTENSIVE THERAPY; ARTERY COMPLIANCE; BLOOD PRESSURE; BRAIN ARTERY; BRAIN ATROPHY; BRAIN DAMAGE; BRAIN DISEASE; COGNITION; COGNITIVE DEFECT; COMPUTER ASSISTED TOMOGRAPHY; DEMENTIA; DISEASE ASSOCIATION; DISEASE COURSE; DRUG EFFICACY; HEART LEFT VENTRICLE HYPERTROPHY; HEART LEFT VENTRICLE MASS; HUMAN; HYPERTENSION; MICROVASCULATURE; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; PRIORITY JOURNAL; REVIEW; RISK FACTOR; RISK REDUCTION; STROKE; WHITE MATTER;

EID: 79960594573     PISSN: 02636352     EISSN: 14735598     Source Type: Journal    
DOI: 10.1097/HJH.0b013e328347cc17     Document Type: Review

References (134)

1. Lobo A, Launer LJ, Fratiglioni L, Andersen K, Di Carlo A, BretelerMM, et al. Prevalence of dementia and major subtypes in Europe: a collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group. Neurology 2000; 54 (11 Suppl 5):S4-S9. (Pubitemid 30390598)
2. Rocca WA, Hofman A, Brayne C, Breteler MM, Clarke M, Copeland JR, et al. The prevalence of vascular dementia in Europe: facts and fragments from 1980-1990 studies. EURODEM-Prevalence Research Group. Ann Neurol 1991; 30:817-824.
3. White L, Petrovitch H, Ross GW, Masaki KH, Abbott RD, Teng EL, et al. Prevalence of dementia in older Japanese-American men in Hawaii: the Honolulu-Asia Aging Study. JAMA 1996; 276:955-960. (Pubitemid 26318224)
4. Melzer D, Ely M, Brayne C. Cognitive impairment in elderly people: population based estimate of the future in England, Scotland, and Wales. BMJ 1997; 315:462. (Pubitemid 27348468)
5. Scuteri A, Najjar SS, Orru' M, Albai G, Strait J, Tarasov KV, et al. Age-and gender-specific awareness, treatment, and control of cardiovascular risk factors and subclinical vascular lesions in a founder population: the SardiNIA Study. Nutr Metab Cardiovasc Dis 2009; 19:532-541.
6. Izzo JL Jr, Levy D, Black HR. Clinical Advisory Statement. Importance of systolic blood pressure in older Americans. Hypertension 2000; 35:1021-1024. (Pubitemid 30327249)
7. Kannel WB, Gordon T, Schwartz MJ. Systolic versus diastolic blood pressure and risk of coronary heart disease. The Framingham study. Am J Cardiol 1971; 27:335-346.
8. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JLJr, et al.; National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA; 289:2560-2572.
9. 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. (Pubitemid 32221606)
10. Najjar SS, Scuteri A, Shetty V, Wright JG, Muller DC, Fleg JL, et al. Pulse wave velocity is an independent predictor of the longitudinal increase in systolic blood pressure and of incident hypertension in the Baltimore Longitudinal Study of Aging. J Am Coll Cardiol 2008; 51:1377-1383. (Pubitemid 351443076)
11. Najjar SS, Scuteri A, Lakatta EG. Arterial aging: is it an immutable cardiovascular risk factor? Hypertension 2005; 46:454-462. (Pubitemid 41376818)
12. Scuteri A. Slowing arterial aging: how far have we progressed? J Hypertens 2007; 25:509-510. (Pubitemid 46213785)
13. Nilsson PM, Boutouyrie P, Laurent S. Vascular aging: a tale of EVA and ADAM in cardiovascular risk assessment and prevention. Hypertension 2009; 54:3-10.
14. Laurent S, Boutouyrie P, Asmar R, Gautier I, Laloux B,Guize L, et al. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension 2001; 37:1236-1241. (Pubitemid 34163575)
15. Boutouyrie P, Tropeano AI, Asmar R, Gautier I, Benetos A, Lacolley P, Laurent S. Aortic stiffness is an independent predictor of primary coronary events in hypertensive patients: a longitudinal study. Hypertension 2002; 39:10-15. (Pubitemid 34098081)
16. Safar ME, Levy BI, Struijker-Boudier H. Current perspectives on arterial stiffness and pulse pressure in hypertension and cardiovascular diseases. Circulation 2003; 107:2864-2869. (Pubitemid 36705999)
17. Koller A. Signaling pathways of mechanotransduction in arteriolar endothelium and smooth muscle cells in hypertension. Microcirculation 2002; 9:277-294. (Pubitemid 135685863)
18. O'Rourke MF, Safar ME. Relationship between aortic stiffening and microvascular disease in brain and kidney: cause and logic of therapy. Hypertension 2005; 46:200-204. (Pubitemid 40946514)
19. Vyas M, Izzo JL Jr, Lacourciere Y, Arnold JM, Dunlap ME, Amato JL, et al. Augmentation index and central aortic stiffness in middle-aged to elderly individuals. Am J Hypertens 2007; 20:642-647. (Pubitemid 46777263)
20. Baumbach GL. Effects of increased pulse pressure on cerebral arterioles. Hypertension 1996; 27:159-167. (Pubitemid 26045912)
21. Baumbach GL, Siems JE, Heistad DD. Effects of local reduction in pressure on distensibility and composition of cerebral arterioles. Circ Res 1991; 68:338-351.
22. Christensen KL. Reducing pulse pressure in hypertension may normalize small artery structure. Hypertension 1991; 18:722-727.
23. James MA, Watt PA, Potter JF, Thurston H, Swales JD. Pulse pressure and resistance artery structure in the elderly. Hypertension 1996; 26:301-306.
24. Mitchell GF, Lacourciere Y, Ouellet JP, Izzo JL Jr, Neutel J, Kerwin LJ, et al. Determinants of elevated pulse pressure in middle-aged and older subjects with uncomplicated systolic hypertension: the role of proximal aortic diameter and the aortic pressure-flow relationship. Circulation 2003; 108:1592-1598. (Pubitemid 37187786)
25. Mitchell GF. Impedance progress: aortic diameter rears its head again? Hypertension 2007; 49:1207-1209. (Pubitemid 46809354)
26. Laurent S, Briet M, Boutouyrie P. Large and small artery cross-talk and recent morbidity-mortality trials in hypertension. Hypertension 2009; 54:388-392.
27. Kawaguchi M, Hay I, Fetics B, Kass DA. Combined ventricular systolic and arterial stiffening in patients with heart failure and preserved ejection fraction: implications for systolic and diastolic reserve limitations. Circulation 2003; 107:714-720. (Pubitemid 36222599)
28. Hanon O, Haulon S, Lenoir H, Seux ML, Rigaud AS, Safar M, et al. Relationship between arterial stiffness and cognitive function in elderly subjects with complaints of memory loss. Stroke 2005; 36:2193-2197. (Pubitemid 41429244)
29. Laurent S, Boutouyrie P. Recent advances in arterial stiffness and wave reflection in human hypertension. Hypertension 2007; 49:1202-1206. (Pubitemid 46809353)
30. Laurent S, Katsahian S, Fassot C, Tropeano AI, Gautier I, Laloux B, Boutouyrie P. Aortic stiffness is an independent predictor of fatal stroke in essential hypertension. Stroke 2003; 34:1203-1206. (Pubitemid 36547514)
31. Farasat SM, Morrell CH, Scuteri A, Ting CT, Yin FC, Spurgeon HA, et al. Pulse pressure is inversely related to aortic root diameter implications for the pathogenesis of systolic hypertension. Hypertension 2008; 51:196-202. (Pubitemid 351159928)
32. Loutzenhiser R, Bidani A, Chilton L. Renal myogenic response: kinetic attributes and physiological role. Circ Res 2002; 90:1316-1324. (Pubitemid 34787414)
33. Safar ME, Lacolley P. Disturbance of macro-and microcirculation: relations with pulse pressure and cardiac organ damage. Am J Physiol Heart Circ Physiol 2007; 293:H1-7. (Pubitemid 47105053)
34. Kalaria RN. Linking cerebrovascular defense mechanisms in brain ageing and Alzheimer's disease. Neurobiol Aging 2009; 30:1512-1514.
35. Jacobsen JC, Mulvany MJ, Holstein-Rathlou NH. A mechanism for arteriolar remodeling based on maintenance of smooth muscle cell activation. Am J Physiol Regul Integr Comp Physiol 2008; 294:R1379-R1389. (Pubitemid 351490660)
36. Selnes OA, Vinters HV. Vascular cognitive impairment. Nat Clin Pract 2006; 2:538-547. (Pubitemid 44445810)
37. Brown WR, Moody DM, Thore CR, Challa VR, Anstrom JA. Vascular dementia in leukoaraiosis may be a consequence of capillary loss not only in the lesions, but in normal-appearing white matter and cortex as well. J Neurol Sci 2007; 257:62-66. (Pubitemid 46856487)
38. Fernando MS, Simpson JE, Matthews F, Brayne C, Lewis CE, Barber R, et al. White matter lesions in an unselected cohort of the elderly: molecular pathology suggests origin from chronic hypoperfusion injury. Stroke 2006; 37:1391-1398. (Pubitemid 44305715)
39. Guo H, Chow N, Sallstrom J, Bell RD, Deane R, Brooks AI, et al. Role of the MEOX2 homeobox gene in neurovascular dysfunction in Alzheimer disease. Nat Med 2005; 11:959-965. (Pubitemid 41294441)
40. Suzuki N, Cheung TT, Cai XD, Odaka A, Otvos L Jr, Eckman C, et al. An increased percentage of long amyloid beta protein secreted by familial amyloid beta protein precursor (beta APP717) mutants. Science 1994; 264:1336-1340.
41. Thomas T, Thomas G, McLendon C, Sutton T, Mullan M. ß- Amyloidmediated vasoactivity and vascular endothelial damage. Nature 1996; 380:168-171.
42. Niwa K, Porter VA, Kazama K, Cornfield D, Carlson GA, Iadecola C. Abeta-peptides enhance vasoconstriction in cerebral circulation. Am J Physiol 2001; 281:H2417-H2424.
43. Iadecola C, Zhang F, Niwa K, Eckman C, Turner SK, Fischer E, et al. SOD1 rescues cerebral endothelial dysfunction in mice overexpressing amyloid precursor protein. Nat Neurosci 1999; 2:157-161; 76. (Pubitemid 30491316)
44. Niwa K, Younkin L, Ebeling C, Turner SK, Westaway D, Younkin S, et al. Abeta 1-40-related reduction in functional hyperemia in mouse neocortex during somatosensory activation. Proc Natl Acad Sci USA 2000; 97:9735-9740. (Pubitemid 30650845)
45. Han BH, Zhou ML, Abousaleh F, Brendza RP, Dietrich HH, Koenigsknecht-Talboo J, et al. Cerebrovascular dysfunction in amyloid precursor protein transgenic mice: contribution of soluble and insoluble amyloid-beta peptide, partial restoration via gamma-secretase inhibition. J Neurosci 2008; 28:13542-13550.
46. Weller RO, Boche D, Nicoll JA. Microvasculature changes and cerebral amyloid angiopathy in Alzheimer's disease and their potential impact on therapy. Acta Neuropathol 2009; 118:87-102.
47. Scuteri A, Brancati AM, Gianni W, Assisi A, Volpe M. Arterial stiffness is an independent risk factor for cognitive impairment in the elderly: a pilot study. J Hypertens 2005; 23:1211-1216. (Pubitemid 40862725)
48. Scuteri A, Tesauro M, Appolloni S, Preziosi F, Brancati AM, Volpe M. Arterial stiffness as an independent predictor of longitudinal changes in cognitive function in the older individual. J Hypertens 2007; 25:1035-1040. (Pubitemid 46573123)
49. 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. (Pubitemid 350307110)
50. Poels MM, van Oijen M, Mattace-Raso FU, Hofman A, Koudstaal PJ, Witteman JC, Breteler MM. Arterial stiffness, cognitive decline, and risk of dementia: the Rotterdam study. Stroke 2007; 38:888-892. (Pubitemid 46568448)
51. Hu K, Peng CK, Czosnyka M, Zhao P, Novak V. Nonlinear assessment of cerebral autoregulation from spontaneous blood pressure and cerebral blood flow fluctuations. Cardiovasc Eng 2008; 8:60-71.
52. Novak V, Yang AC, Lepicovsky L, Goldberger AL, Lipsitz LA, Peng CK. Multimodal pressure-flow method to assess dynamics of cerebral autoregulation in stroke and hypertension. Biomed Eng Online 2004; 3:39.
53. Hu K, Peng CK, Huang NE, Wu Z, Lipsitz LA, Cavallerano J, Novak V. Altered phase interactions between spontaneous blood pressure and flow fluctuations in type 2 diabetes mellitus: nonlinear assessment of cerebral autoregulation. Physica A 2008; 387:2279-2292.
54. Rizzoni D, Porteri E, Boari GE, De Ciuceis C, Sleiman I, Muiesan ML, et al. Prognostic significance of small-artery structure in hypertension. Circulation 2003; 108:2230-2235. (Pubitemid 37363040)
55. Cheung N, Sharrett AR, Klein R, Criqui MH, Islam FM, Macura KJ, et al. Aortic distensibility and retinal arteriolar narrowing: the multiethnic study of atherosclerosis. Hypertension 2007; 50:617-622. (Pubitemid 47442723)
56. Kwa VI, van der Sande JJ, Stam J, Tijmes N, Vrooland JL. Retinal arterial changes correlate with cerebral small-vessel disease. Neurology 2002; 59:1536-1540. (Pubitemid 35387058)
57. Lindley RI, Wang JJ, Wong MC, Mitchell P, Liew G, Hand P, et al. Retinal microvasculature in acute lacunar stroke: a cross-sectional study. Lancet Neurol 2009; 8:628-634.
58. Selvetella G, Notte A, Maffei A, Calistri V, Scamardella V, Frati G, et al. Left ventricular hypertrophy is associated with asymptomatic cerebral damage in hypertensive patients. Stroke 2003; 34:1766-1770. (Pubitemid 36842643)
59. Scuteri A, Coluccia R, Castello L, Nevola E, Brancati AM, Volpe M. Left ventricular mass increase is associated with cognitive decline and dementia in the elderly independently of blood pressure. Eur Heart J 2009; 30:1525-1529.
60. Brain damage with aging and hypertension Scuteri et al. 1475 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
61. Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, et al.; ESH-ESC Task Force on the Management of Arterial Hypertension. 2007. ESH-ESC Practice Guidelines for the Management of Arterial Hypertension: ESH-ESC Task Force on the Management of Arterial Hypertension. J Hypertens 2007; 25:1751-1762. (Pubitemid 47356612)
62. Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, et al. European Network for Noninvasive Investigation of Large Arteries. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J 2006; 27:2588-2605. (Pubitemid 44627304)
63. Esiri MM, Wilcock GK, Morris JH. Neuropathological assessment of the lesions of significance in vascular dementia. J Neurol Neurosurg Psychiatry 1997; 63:749-753. (Pubitemid 27520751)
64. Garrett KD, Browndyke JN, Whelihan W, Paul RH, DiCarlo M, Moser DJ, et al. The neuropsychological profile of vascular cognitive impairment-no dementia: comparisons to patients at risk for cerebrovascular disease and vascular dementia. Arch Clin Neuropsychol 2004; 19:745-757. (Pubitemid 39013340)
65. Nyenhuis DL, Gorelick PB, Geenen EJ, Smith CA, Gencheva E, Freels S, DeToledo-Morrell L. The pattern of neuropsychological deficits in vascular cognitive impairment-no dementia (vascular CIND). Clin Neuropsychol 2004; 18:41-49. (Pubitemid 39177529)
66. Troyer AK, Moscovitch M, Winocur G, Alexander MP, Stuss D. Clustering and switching on verbal fluency: the effects of focal frontal-and temporallobe lesions. Neuropsychologia 1998; 36:499-504. (Pubitemid 28342185)
67. Hachinski V, Iadecola C, Petersen RC, Breteler MM, Nyenhuis DL, Black SE, et al. National Institute of Neurological Disorders and Stroke-Canadian Stroke Network vascular cognitive impairment harmonization standards. Stroke 2006; 37:2220-2241. (Pubitemid 44337162)
68. Carew TG, Lamar M, Cloud BS, Grossman M, Libon DJ. Impairment in category fluency in ischemic vascular dementia. Neuropsychology 1997; 11:400-412. (Pubitemid 27294663)
69. Lamar MPC, Davis KL, Kaplan E, Libon DJ. Capacity to maintain mental set in dementia. Neuropsychologia 2002; 40:435-445. (Pubitemid 33000480)
70. Wechsler D. WAIS-III Administration and Scoring Manual. New York: The Psychological Corporation; 1997.
71. Kaplan E, Fein D, Morris R, Delis D. The WAIS-Rr as a neuropsychological instrument. San Antonio: Psychological Corporation; 1991.
72. Wahlund LO, Barkhof F, Fazekas F, Bronge L, Augustin M, Sjogren M, et al. A new rating scale for age-related white matter changes applicable to MRI and CT. Stroke 2001; 32:1318-1322. (Pubitemid 32530416)
73. Frisoni GB, Geroldi C, Beltramello A, Bianchetti A, Binetti G, Bordiga G, et al. Radial width of the temporal horn: a sensitive measure in Alzheimer disease. Am J Neuroradiol 2002; 23:35-47. (Pubitemid 34098259)
74. Awad IA, Johnson PC, Spetzler RF, Hodak JA. Incidental subcortical lesions identified on magnetic resonance imaging in the elderly. II. Postmortem pathological correlations. Stroke 1986; 17:1090-1097. (Pubitemid 17008935)
75. van Swieten JC, van den Hout JHW, Van Ketel BA, Hijdra A, Wokke JH, van Gijn J. Periventricular lesions in the white matter on magnetic resonance imaging in the elderly. A morphometric correlation with arteriolosclerosis and dilated perivascular spaces. Brain 1991; 114:761-774.
76. Fazekas F, Kleinert R, Offenbacher H, Schmidt R, Kleinert G, Payer F, et al. Pathologic correlates of incidental MRI white matter signal hyperintensities. Neurology 1993; 43:1683-1689. (Pubitemid 23307935)
77. Scheltens P, Erkinjuntti T, Leys D, Wahlund LO, Inzitari D, del Ser T, et al. White matter changes on CT and MRI: an overview of visual rating scales. Eur Neurol 1998; 39:80-89. (Pubitemid 28069798)
78. Kapeller P, Barber R, Vermeulen RJ, Ader H, Scheltens P, Freidl W, et al. Visual rating of age-related white matter changes on magnetic resonance imaging: scale comparison, interrater agreement, and correlations with quantitative measurements. Stroke 2003; 34:441-445. (Pubitemid 36210903)
79. Pantoni L, Simoni M, Pracucci G, Schmidt R, Barkhof F, Inzitari D. Visual rating scales for age-related white matter changes (leukoaraiosis): can the heterogeneity be reduced? Stroke 2002; 33:2827-2833. (Pubitemid 35462851)
80. Carmelli D, Swan GE, Reed T, Wolf PA, Miller BL, DeCarli C. Midlife cardiovascular risk factors and brain morphology in identical older male twins. Neurology 1999; 52:1119-1124. (Pubitemid 29177909)
81. de Leeuw FE, De Groot JC, Oudkerk M, Witteman JC, Hofman A, van Gijn J, Breteler MM. Hypertension and cerebral white matter lesions in a prospective cohort study. Brain 2002; 125:765-772. (Pubitemid 34279772)
82. 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. (Pubitemid 34052179)
83. Liao D, Cooper L, Cai J, Toole J, Bryan N, Burke G, et al. 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. (Pubitemid 27215864)
84. Longstreth WT Jr, Manolio TA, Arnold A, Burke GL, Bryan N, Jungreis CA, et al. Clinical correlates of white matter findings on cranial magnetic resonance imaging of 3301 elderly people: the Cardiovascular Health Study. Stroke 1996; 27:1274-1282. (Pubitemid 26286152)
85. Pantoni L, Garcia JH. Pathogenesis of leukoaraiosis: a review. Stroke 1997; 28:652-659. (Pubitemid 27118393)
86. Henskens LH, Kroon AA, van Oostenbrugge RJ, Gronenschild EH, Fuss-Lejeune MM, Hofman PA, et al. Increased aortic pulse wave velocity is associated with silent cerebral small-vessel disease in hypertensive patients. Hypertension 2008; 52:1120-1126.
87. Harazny JM, Ritt M, Baleanu D, Ott C, Heckmann J, Schlaich MP, et al. Increased wall:lumen ratio of retinal arterioles in male patients with a history of a cerebrovascular event. Hypertension 2007; 50:623-629. (Pubitemid 47442724)
88. Bakker SL, de Leeuw FE, De Groot JC, Hofman A, Koudstaal PJ, Breteler MM. Cerebral vasomotor reactivity and cerebral white matter lesions in the elderly. Neurology 1999; 52:578-583. (Pubitemid 29075607)
89. Marstrand JR, Garde E, Rostrup E, Ring P, Rosenbaum S, Mortensen EL, Larsson HB. Cerebral perfusion and cerebrovascular reactivity are reduced in white matter hyperintensities. Stroke 2002; 33:972-976. (Pubitemid 34293577)
90. Ballard C, O'Brien J, Barber B, Scheltens P, Shaw F, McKeith I, Kenny RA. Neurocardiovascular instability, hypotensive episodes, and MRI lesions in neurodegenerative dementia. Ann NY Acad Sci 2000; 903:442-445. (Pubitemid 30251586)
91. DeCarli C, Miller BL, Swan GE, Reed T, Wolf PA, Garner J, et al. Predictors of brain morphology for the men of the NHLBI twin study. Stroke 1999; 30:529-536. (Pubitemid 29115387)
92. McQuinn BA, O'Leary DH. White matter lucencies on computed tomography, subacute arteriosclerotic encephalopathy (Binswanger's disease), and blood pressure. Stroke 1987; 18:900-905. (Pubitemid 17126633)
93. Junqué C, Pujol J, Vendrell P, Bruna O, Jó dar M, Ribas JC, et al. Leukoaraiosis on magnetic resonance imaging and speed of mental processing. Arch Neurol 1990; 47:151-156. (Pubitemid 20058110)
94. Steingart A, Hachinski V, Lau C, Fox AJ, Diaz F, Cape R, et al. Cognitive and neurologic findings in subjects with diffuse white matter lucencies on computed tomographic scan (leuko-araiosis). Arch Neurol 1987; 44:32-35. (Pubitemid 17087609)
95. Liao DP, Cooper L, Cai JW, Toole JF, Bryan NR, Hutchinson RG, Tyroler HA. Presence and severity of cerebral white matter lesions and hypertension, its treatment, and its control: the ARIC study. Stroke 1996; 27:2262-2270. (Pubitemid 26427203)
96. Prins ND, Van Dijk EJ, den Heijer T, Vermeer SE, Koudstaal PJ, Oudkerk M, et al. Cerebral white matter lesions and the risk of dementia. Arch Neurol 2004; 61:1531-1534. (Pubitemid 39350263)
97. Kuller LH, Lopez OL, Newman A, Beauchamp NJ, Burke G, Dulberg C, et al. Risk factors for dementia in the cardiovascular health cognition study. Neuroepidemiology 2003; 22:13-22. (Pubitemid 36131969)
98. Vermeer SE, Prins ND, denHeijer 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. (Pubitemid 36359297)
99. Hatazawa J, Shimosegawa E, Osaki Y, Ibaraki M, Oku N, Hasegawa S, et al. Long-term angiotensin-converting enzyme inhibitor perindopril therapy improves cerebral perfusion reserve in patients with previous minor stroke. Stroke 2004; 35:2117-2122. (Pubitemid 39129571)
100. Kuller LH, Lopez OL, Jagust WJ, Becker JT, DeKosky ST, Lyketsos C, et al. Determinants of vascular dementia in the Cardiovascular Health Cognition Study. Neurology 2005; 64:1548-1552. (Pubitemid 40617690)
101. Dufouil C, Godin O, Chalmers J, Coskun O, MacMahon S, Tzourio-Mazoyer N, et al. Severe cerebral white matter hyperintensities predict severe cognitive decline in patients with cerebrovascular disease history. Stroke 2009; 40:2219-2221.
102. 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.
103. Longstreth WT Jr, Arnold AM, Beauchamp NJ Jr, Manolio TA, Lefkowitz D, Jungreis C, et al. 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. (Pubitemid 40054175)
104. Savva GM, Wharton SB, Ince PG, Forster G, Matthews FE, Brayne C, Medical Research Council Cognitive Function and Ageing Study. Age, neuropathology, and dementia. N Engl J Med 2009; 360:2302-2309.
105. Maillard P, Delcroix N, Crivello F, Dufouil C, Gicquel S, Joliot M, et al. An automated procedure for the assessment of white matter hyperintensities by multispectral (T1, T2, PD) MRI and an evaluation of its between-centre reproducibility based on two large community databases. Neuroradiology 2008; 50:31-42.
106. Maillard P, Crivello F, Dufouil C, Tzourio-Mazoyer N, Tzourio C, Mazoyer B. Longitudinal follow-up of individual white matter hyperintensities in a large cohort of elderly. Neuroradiology 2009; 51:209-220.
107. Godin O, Tzourio C, Maillard P, Mazoyer B, Dufouil C. Antihypertensive treatment and change in blood pressure are associated with the progression of white matter lesion volumes: the Three-City (3C)-Dijon Magnetic Resonance Imaging Study. Circulation 2011; 123:266-273.
108. London GM, Asmar RG, O'Rourke MF, Safar ME. REASON Project Investigators. Mechanism(s) of selective systolic blood pressure reduction after a low-dose combination of perindopril/indapamide in hypertensive subjects: comparison with atenolol. J Am Coll Cardiol 2004; 43:92-99. (Pubitemid 38045921)
109. The CAFÉ Investigators, for the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) Investigators. Differential impact of blood pressurelowering drugs on central aortic pressure and clinical outcomes. Principal results of the Conduit Artery Function Evaluation (CAFÉ ) Study. Circulation 2006; 113:1213-1225.
110. Tanaka H, Safar ME. Influence of lifestyle modification on arterial stiffness and wave reflections. Am J Hypertens 2005; 18: 137-144. (Pubitemid 40187360)
111. Safar ME, Thuilliez C, Richard V, Benetos A. Pressure-independent contribution of sodium to large artery structure and function in hypertension. Cardiovasc Res 2000; 46:269-276. (Pubitemid 30204599)
112. Madden KM, Lockhart C, Cuff D, Potter TF, Meneilly GS. Short-term aerobic exercise reduces arterial stiffness in older adults with type 2 diabetes, hypertension, and hyper-cholesterolemia. Diabetes Care 2009; 32:1531-1535.
113. He FJ, Marciniak M, Visagie E, Markandu ND, Anand V, Dalton RN, MacGregor GA. Effect of modest salt reduction on blood pressure, urinary albumin, and pulse wave velocity in white, black, and Asian mild hypertensives. Hypertension 2009; 54:482-488.
114. Riccioni G, Bazzano LA. Antioxidant plasma concentration and supplementation in carotid intima media thickness. Expert Rev Cardiovasc Ther 2008; 6:723-729.
115. Staessen JA, Fagard R, Thijs L, Celis H, Arabidze GG, Birkenhager WH, et al. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Lancet 1997; 350:757-764. (Pubitemid 27387202)
116. PROGRESS Collaborative Group. Randomised trial of a perindoprilbased blood-pressure-lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack. Lancet 2001; 358:1033-1041.
117. SHEP Cooperative Research Group. 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.
118. Diener HC, Sacco RL, Yusuf S, Cotton D, Ounpuu S, Lawton WA, et al. 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. Lancet Neurol 2008; 7:875-884.
119. Forette F, Seux ML, Staessen JA, Thijs L, Birkenhager WH, Babarskiene MR, et al. Prevention of dementia in randomised double-blind placebocontrolled Systolic Hypertension in Europe (Syst-Eur) trial. Lancet 1998; 352:1347-1351. (Pubitemid 28510916)
120. Lithell H, Hansson L, Skoog I, Elmfeldt D, Hofman A, Olofsson B, et al. The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double-blind intervention trial. J Hypertens 2003; 21:875-886. (Pubitemid 36677151)
121. Peters R, Beckett N, Forette F, Tuomilehto J, Clarke R, Ritchie C, et al. Incident dementia and blood pressure lowering in the Hypertension in the Very Elderly Trial cognitive function assessment (HYVET-COG): a double-blind, placebo controlled trial. Lancet Neurol 2008; 7:683-689.
122. Tzourio C, Anderson C, Chapman N, Woodward M, Neal B, MacMahon S, Chalmers J. 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. (Pubitemid 36548935)
123. Ryan SM, Waack BJ, Weno BL, Heistad DD. Increases in pulse pressure impair acetylcholine-induced vascular relaxation. Am J Physiol Heart Circ Physiol 1995; 268:H359-H363.
124. Ungvari Z, Csiszar A, Kaminski PM, Wolin MS, Koller A. Chronic high pressure-induced arterial oxidative stress: involvement of protein kinase C-dependent NAD(P)H oxidase and local renin-angiotensin system. Am J Pathol 2004; 165:219-226. (Pubitemid 38821829)
125. Wang M, Takagi G, Asai K, Resuello RG, Natividad FF, Vatner DE, et al. Aging increases aortic MMP-2 activity and angiotensin II in nonhuman primates. Hypertension 2003; 41:1308-1316. (Pubitemid 36706082)
126. Wang M, Zhang J, Jiang LQ, Spinetti G, Pintus G, Monticone R, et al. Proinflammatory profile within the grossly normal aged human aortic wall. Hypertension 2007; 50:219-227. (Pubitemid 46986044)
127. Basso N, Cini Pietrelli AR, Ferder L, Terragno NA, Inserra F. Protective effect of long-term angiotensin II inhibition. Am J Physiol Heart Circ Physiol 2007; 293:H1351-H1358. (Pubitemid 47367173)
128. Benigni A, Corna D, Zoja C, Sonzogni A, Latini R, Salio M, et al. Disruption of the Ang II type 1 receptor promotes longevity in mice. J Clin Invest 2009; 119:524-530.
129. Modrick ML, Didion SP, Sigmund CD, Faraci FM. Role of oxidative stress and AT1 receptors in cerebral vascular dysfunction with aging. Am J Physiol Heart Circ Physiol 2009; 296:H1914-H1919.
130. Whitman GT, Tang T, Lin A, Baloh RW. A prospective study of cerebral white matter abnormalities in older people with gait dysfunction. Neurology 2001; 57:990-994. (Pubitemid 32880191)
131. Schmidt R, Enzinger C, Ropele S, Schmidt H, Fazekas F. Progression of cerebral white matter lesions: 6-year results of the Austrian Stroke Prevention Study. Lancet 2003; 361:2046-2048. (Pubitemid 36695049)
132. Dufouil C, Chalmers J, Coskun O, Besançon V, Bousser M-G, Guillon P, et al. Effect 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. (Pubitemid 41324527)
133. Qiu CX, Winblad B, Fratiglioni L. The age-dependent relation of blood pressure to cognitive function and dementia. Lancet Neurol 2005; 4:487-499. (Pubitemid 40982459)
134. Viswanathan A, Rocca WA, Tzourio C. Vascular risk factors and dementia: how to move forward? Neurology 2009; 72:368-374.