Neuropsychology Review

, Volume 24, Issue 3, pp 371–387 | Cite as

Preventing Vascular Effects on Brain Injury and Cognition Late in Life: Knowns and Unknowns

  • Owen Carmichael


For some researchers, the relationship between prevalent cardiovascular risk factors and late-life cognitive decline is not worthy of further study. It is already known that effective treatment of vascular risk factors lowers risk of such major outcomes as stroke and heart attack, the argument goes; thus, any new information about the relationship between vascular risk factors and another major outcome - late-life cognitive decline-- is unlikely to have an impact on clinical practice. The purpose of this review is to probe the logic of this argument by focusing on what is known, and what is not known, about the relationship between vascular risk factors and late-life cognitive decline. The unknowns are substantial: in particular, there is relatively little evidence that current vascular risk factor treatment protocols are adequate to prevent late-life cognitive decline or the clinically silent brain injury that precedes it. In addition, there is relatively little understanding of which factors lead to differential vulnerability or resilience to the effects of vascular risk factors on silent brain injury. Differential effects of different classes of treatments are similarly unclear. Finally, there is limited understanding of the impact of clinically-silent neurodegenerative disease processes on cerebrovascular processes. Further study of the relationships among vascular risk factors, brain injury, and late-life cognitive decline could have a major impact on development of new vascular therapies and on clinical management of vascular risk factors, and there are promising avenues for future research in this direction.


Brain MRI Vascular risk factors Silent brain injury Cognitive decline Clinical trials Aging 



This work was supported by NIH grants P30 AG010129 and K01 AG030514, as well as grants from the California State Department of Public Health and the Alzheimer’s Association.


  1. Adams, A., Uratsu, C., Dyer, W., et al. (2013). Health system factors and antihypertensive adherence in a racially and ethnically diverse cohort of new users. JAMA Internal Medicine, 173(1), 54–61.PubMedGoogle Scholar
  2. Alexander, C. M., Landsman, P. B., Teutsch, S. M., Haffner, S. M., Third National, H, Nutrition Examination, S, & National Cholesterol Education, P. (2003). NCEP-defined metabolic syndrome, diabetes, and prevalence of coronary heart disease among NHANES III participants age 50 years and older. Diabetes, 52(5), 1210–1214.PubMedGoogle Scholar
  3. Amarenco, P., Cohen, A., Tzourio, C., Bertrand, B., Hommel, M., Besson, G., & Bousser, M. G. (1994). Atherosclerotic disease of the aortic arch and the risk of ischemic stroke. The New England Journal of Medicine, 331(22), 1474–1479. doi: 10.1056/NEJM199412013312202.PubMedGoogle Scholar
  4. Appelman, A. P., van der Graaf, Y., Vincken, K. L., Tiehuis, A. M., Witkamp, T. D., Mali, W. P., & Geerlings, M. I. (2008). Total cerebral blood flow, white matter lesions and brain atrophy: the SMART-MR study. Journal of Cerebral Blood Flow and Metabolism, 28(3), 633–639.PubMedGoogle Scholar
  5. Au, R., Massaro, J. M., Wolf, P. A., Young, M. E., Beiser, A., Seshadri, S., & DeCarli, C. (2006). Association of white matter hyperintensity volume with decreased cognitive functioning: the Framingham Heart Study. Archives of Neurology, 63(2), 246–250.PubMedGoogle Scholar
  6. Barnes, D. E., & Yaffe, K. (2011). The projected effect of risk factor reduction on Alzheimer's disease prevalence. Lancet Neurology, 10(9), 819–828. doi: 10.1016/S1474-4422(11)70072-2.PubMedCentralGoogle Scholar
  7. Barnes, J., Carmichael, O. T., Leung, K. K., Schwarz, C., Ridgway, G. R., Bartlett, J. W., & Biessels, G. J. (2013). Vascular and Alzheimer’s disease markers independently predict brain atrophy rate in Alzheimer’s disease neuroimaging initiative controls. Neurobiology of Aging, 34(8), 1996–2002.PubMedPubMedCentralGoogle Scholar
  8. Berenson, G. S., Srinivasan, S. R., Bao, W., Newman, W. P., Tracy, R. E., & Wattigney, W. A. (1998). Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. New England Journal of Medicine, 338(23), 1650–1656.PubMedGoogle Scholar
  9. Birns, J., Morris, R., Donaldson, N., & Kalra, L. (2006). The effects of blood pressure reduction on cognitive function: a review of effects based on pooled data from clinical trials. Journal of Hypertension, 24(10), 1907–1914.PubMedGoogle Scholar
  10. Biswal, B. B., Mennes, M., Zuo, X. N., Gohel, S., Kelly, C., Smith, S. M., & Milham, M. P. (2010). Toward discovery science of human brain function. Proceedings of the National Academy of Sciences of the United States of America, 107(10), 4734–4739. doi: 10.1073/pnas.0911855107.PubMedPubMedCentralGoogle Scholar
  11. Bombois, S., Debette, S., Bruandet, A., Delbeuck, X., Delmaire, C., Leys, D., & Pasquier, F. (2008). Vascular subcortical hyperintensities predict conversion to vascular and mixed dementia in MCI patients. Stroke, 39(7), 2046–2051.PubMedGoogle Scholar
  12. Bots, M. L., Breteler, M. M. B., Hofman, A., Grobbee, D. E., van Swieten, J. C., van Gijn, J., & de Jong, P. T. V. M. (1993). Cerebral white matter lesions and atherosclerosis in the Rotterdam Study. The Lancet, 341(8855), 1232–1237.Google Scholar
  13. Brayne, C., Richardson, K., Matthews, F. E., Fleming, J., Hunter, S., Xuereb, J. H., & The Cambridge City over-75 s Cohort study neuropathology, c. (2009). Neuropathological correlates of dementia in over-80-year-Old brain donors from the population-based Cambridge city over-75 s cohort (CC75C) study. Journal of Alzheimer's Disease, 18(3), 645–658.PubMedGoogle Scholar
  14. Brundel, M., van den Heuvel, M., de Bresser, J., Kappelle, L. J., Biessels, G. J., & Utrecht Diabetic Encephalopathy Study, G. (2010). Cerebral cortical thickness in patients with type 2 diabetes. Journal of Neurological Sciences, 299(1–2), 126–130. doi: 10.1016/j.jns.2010.08.048.Google Scholar
  15. Cardenas, V. A., Reed, B., Chao, L. L., Chui, H., Sanossian, N., Decarli, C. C., & Weiner, M. W. (2012). Associations among vascular risk factors, carotid atherosclerosis, and cortical volume and thickness in older adults. Stroke. doi: 10.1161/STROKEAHA.112.659722.PubMedPubMedCentralGoogle Scholar
  16. Carlson, N. E., Moore, M. M., Dame, A., Howieson, D., Silbert, L. C., Quinn, J. F., & Kaye, J. A. (2008). Trajectories of brain loss in aging and the development of cognitive impairment. Neurology, 70(11), 828–833.PubMedGoogle Scholar
  17. Carmelli, D., Swan, G. E., Reed, T., Wolf, P. A., Miller, B. L., & DeCarli, C. (1999). Midlife cardiovascular risk factors and brain morphology in identical older male twins. Neurology, 52(6), 1119.PubMedGoogle Scholar
  18. Carmichael, O., & Lockhart, S. (2012). The role of diffusion tensor imaging in the study of cognitive aging. Current Topics in Behavioral Neurosciences, 11, 289–320. doi: 10.1007/7854_2011_176.PubMedGoogle Scholar
  19. Carmichael, O. T., Kuller, L. H., Lopez, O. L., Thompson, P. M., Dutton, R. A., Lu, A., & Becker, J. T. (2007). Ventricular volume and dementia progression in the cardiovascular health study. Neurobiology of Aging, 28(3), 389–397.PubMedPubMedCentralGoogle Scholar
  20. Chauveau, F., Boutin, H., Van Camp, N., Dollé, F., & Tavitian, B. (2008). Nuclear imaging of neuroinflammation: a comprehensive review of [11C] PK11195 challengers. European Journal of Nuclear Medicine and Molecular Imaging, 35(12), 2304–2319.PubMedGoogle Scholar
  21. Chen, Y., Gurol, M., Rosand, J., Viswanathan, A., Rakich, S., Groover, T., & Smith, E. (2006). Progression of white matter lesions and hemorrhages in cerebral amyloid angiopathy. Neurology, 67(1), 83–87.PubMedPubMedCentralGoogle Scholar
  22. Ching, A. S. C., Kuhnast, B., Damont, A., Roeda, D., Tavitian, B., & Dollé, F. (2012). Current paradigm of the 18-kDa translocator protein (TSPO) as a molecular target for PET imaging in neuroinflammation and neurodegenerative diseases. Insights into imaging, 3(1), 111–119.PubMedPubMedCentralGoogle Scholar
  23. Chobanian, A. V., Bakris, G. L., Black, H. R., Cushman, W. C., Green, L. A., Izzo, J. L., Jr., & Roccella, E. J. (2003). The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report. JAMA, 289(19), 2560–2572. doi: 10.1001/jama.289.19.2560.PubMedGoogle Scholar
  24. Chou, S.-Y., Shulman, J., Keenan, B., Secor, E., Buchman, A., Schneider, J., & De Jager, P. (2013). Genetic susceptibility for ischemic infarction and arteriolosclerosis based on neuropathologic evaluations. Cerebrovascular Diseases, 36(3), 181–188.PubMedGoogle Scholar
  25. Cordonnier, C., Al-Shahi Salman, R., & Wardlaw, J. (2007). Spontaneous brain microbleeds: systematic review, subgroup analyses and standards for study design and reporting. Brain, 130(8), 1988–2003.PubMedGoogle Scholar
  26. Crawford, A. G., Cote, C., Couto, J., Daskiran, M., Gunnarsson, C., Haas, K., & Schuette, R. (2010). Prevalence of obesity, type II diabetes mellitus, hyperlipidemia, and hypertension in the united states: findings from the GE centricity electronic medical record database. Population Health Management, 13(3), 151–161. doi: 10.1089/pop.2009.0039.PubMedGoogle Scholar
  27. D’Esposito, M., Zarahn, E., Aguirre, G. K., & Rypma, B. (1999). The effect of normal aging on the coupling of neural activity to the bold hemodynamic response. NeuroImage, 10(1), 6–14.PubMedGoogle Scholar
  28. Dai, W., Lopez, O. L., Carmichael, O. T., Becker, J. T., Kuller, L. H., & Gach, H. M. (2008). Abnormal regional cerebral blood flow in cognitively normal elderly subjects with hypertension. Stroke, 39(2), 349–354.PubMedPubMedCentralGoogle Scholar
  29. Das, R. R., Seshadri, S., Beiser, A. S., Kelly-Hayes, M., Au, R., Himali, J. J., & Wolf, P. A. (2008). Prevalence and correlates of silent cerebral infarcts in the Framingham offspring study. Stroke, 39(11), 2929–2935.PubMedPubMedCentralGoogle Scholar
  30. Debette, S., & Markus, H. S. (2010). The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis. BMJ, 341, c3666.PubMedPubMedCentralGoogle Scholar
  31. Debette, S., Bis, J. C., Fornage, M., Schmidt, H., Ikram, M. A., Sigurdsson, S., & van der Lugt, A. (2010). Genome-wide association studies of MRI-defined brain infarcts meta-analysis from the CHARGE consortium. Stroke, 41(2), 210–217.PubMedPubMedCentralGoogle Scholar
  32. Debette, S., Seshadri, S., Beiser, A., Au, R., Himali, J. J., Palumbo, C., & DeCarli, C. (2011). Midlife vascular risk factor exposure accelerates structural brain aging and cognitive decline. Neurology, 77(5), 461–468.PubMedPubMedCentralGoogle Scholar
  33. DeCarli, C., Murphy, D. G., Tranh, M., Grady, C. L., Haxby, J. V., Gillette, J. A., et al. (1995). The effect of white matter hyperintensity volume on brain structure, cognitive performance, and cerebral metabolism of glucose in 51 healthy adults. Neurology, 45(11), 2077–2084.PubMedGoogle Scholar
  34. DeCarli, C., Massaro, J., Harvey, D., Hald, J., Tullberg, M., Au, R., & Wolf, P. A. (2005). Measures of brain morphology and infarction in the Framingham heart study: establishing what is normal. Neurobiology of Aging, 26(4), 491–510.PubMedGoogle Scholar
  35. Dietschy, J. M., & Turley, S. D. (2001). Cholesterol metabolism in the brain. Current Opinion in Lipidology, 12(2), 105–112.PubMedGoogle Scholar
  36. Dinarello, C. (1996). Role of pro-and anti-inflammatory cytokines during inflammation: experimental and clinical findings. Journal of Biological Regulators and Homeostatic Agents, 11(3), 91–103.Google Scholar
  37. Dirnagl, U., Iadecola, C., & Moskowitz, M. A. (1999). Pathobiology of ischaemic stroke: an integrated view. Trends in Neurosciences, 22(9), 391–397.PubMedGoogle Scholar
  38. Dufouil, C., Chalmers, J., Coskun, O., Besancon, V., Bousser, M.-G., Guillon, P., & PROGRESS MRI Substudy Investigators. (2005). Effects of blood pressure lowering on cerebral white matter hyperintensities in patients with stroke. Circulation, 112(11), 1644–1650. doi: 10.1161/circulationaha.104.501163.PubMedGoogle Scholar
  39. Ebrahim, S., Papacosta, O., Whincup, P., Wannamethee, G., Walker, M., Nicolaides, A. N., & Rumley, A. (1999). Carotid plaque, intima media thickness, cardiovascular risk factors, and prevalent cardiovascular disease in men and women the British regional heart study. Stroke, 30(4), 841–850.PubMedGoogle Scholar
  40. Fazekas, F., Kleinert, R., Offenbacher, H., Schmidt, R., Kleinert, G., Payer, F., & Lechner, H. (1993). Pathologic correlates of incidental MRI white matter signal hyperintensities. Neurology, 43(9), 1683–1683.PubMedGoogle Scholar
  41. Fazekas, F., Schmidt, R., Kleinert, R., Kapeller, P., Roob, G., & Flooh, E. (1998). The spectrum of age-associated brain abnormalities: their measurement and histopathological correlates. Journal of Neural Transmission, Supplement, 53, 31–39.Google Scholar
  42. Flasque, N., Desvignes, M., Constans, J.-M., & Revenu, M. (2001). Acquisition, segmentation and tracking of the cerebral vascular tree on 3D magnetic resonance angiography images. Medical Image Analysis, 5(3), 173–183.PubMedGoogle Scholar
  43. Fornage, M., Chiang, Y. A., O’Meara, E. S., Psaty, B. M., Reiner, A. P., Siscovick, D. S., & Longstreth, W. T. (2008). Biomarkers of inflammation and MRI-defined small vessel disease of the brain: the cardiovascular health study. Stroke, 39(7), 1952–1959. doi: 10.1161/strokeaha.107.508135.PubMedPubMedCentralGoogle Scholar
  44. Gearing, A. J., & Newman, W. (1993). Circulating adhesion molecules in disease. Immunology Today, 14(10), 506–512.PubMedGoogle Scholar
  45. Gilbert, J., & Vinters, H. (1983). Cerebral amyloid angiopathy: incidence and complications in the aging brain. I. Cerebral hemorrhage. Stroke, 14(6), 915–923.PubMedGoogle Scholar
  46. Go, A. S., Mozaffarian, D., Roger, V. L., Benjamin, E. J., Berry, J. D., Borden, W. B., … Stroke Statistics, S. (2013). Heart disease and stroke statistics–2013 update: a report from the American heart association. Circulation, 127(1), e6–e245. doi: 10.1161/CIR.0b013e31828124ad.Google Scholar
  47. Godin, O., Tzourio, C., Maillard, P., Mazoyer, B., & Dufouil, C. (2011). Antihypertensive treatment and change in blood pressure Are associated with the progression of white matter lesion VolumesClinical perspective the three-city (3C)–Dijon magnetic resonance imaging study. Circulation, 123(3), 266–273.PubMedGoogle Scholar
  48. Goos, J. D., Henneman, W. J., Sluimer, J. D., Vrenken, H., Sluimer, I. C., Barkhof, F., & van der Flier, W. M. (2010). Incidence of cerebral microbleeds: a longitudinal study in a memory clinic population. Neurology, 74(24), 1954–1960. doi: 10.1212/WNL.0b013e3181e396ea.PubMedGoogle Scholar
  49. Gorelick, P. B., Scuteri, A., Black, S. E., Decarli, C., Greenberg, S. M., Iadecola, C., & Seshadri, S. (2011). Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American heart association/american stroke association. Stroke, 42(9), 2672–2713. doi: 10.1161/STR.0b013e3182299496.PubMedPubMedCentralGoogle Scholar
  50. Gouw, A. A., Seewann, A., van der Flier, W. M., Barkhof, F., Rozemuller, A. M., Scheltens, P., & Geurts, J. J. (2011). Heterogeneity of small vessel disease: a systematic review of MRI and histopathology correlations. Journal of Neurology, Neurosurgery & Psychiatry, 82(2), 126–135.Google Scholar
  51. Grimmer, T., Faust, M., Auer, F., Alexopoulos, P., Förstl, H., Henriksen, G., & Drzezga, A. (2012). White matter hyperintensities predict amyloid increase in Alzheimer’s disease. Neurobiology of Aging, 33(12), 2766–2773.PubMedGoogle Scholar
  52. Guo, X., Pantoni, L., Simoni, M., Bengtsson, C., Björkelund, C., Lissner, L., & Skoog, I. (2009). Blood pressure components and changes in relation to white matter lesions. Hypertension, 54(1), 57–62. doi: 10.1161/hypertensionaha.109.129700.PubMedGoogle Scholar
  53. Guzman, V. A., Carmichael, O. T., Schwarz, C., Tosto, G., Zimmerman, M. E., & Brickman, A. M. (2013). White matter hyperintensities and amyloid are independently associated with entorhinal cortex volume among individuals with mild cognitive impairment. Alzheimer’s & Dementia, 9(5), s124–s131.Google Scholar
  54. Haight, T., Carmichael, O., Landau, S., Schwarz, C., DeCarli, C., & Jagust, W. (2013). Dissociable effects of Alzheimer’s Disease and white matter hyperintensities on brain metabolism. Archives of neurology, In Press.Google Scholar
  55. Hajjar, I., Zhao, P., Alsop, D., & Novak, V. (2010). Hypertension and cerebral vasoreactivity a continuous arterial spin labeling magnetic resonance imaging study. Hypertension, 56(5), 859–864.PubMedPubMedCentralGoogle Scholar
  56. Hajjar, I., Brown, L., Mack, W. J., & Chui, H. (2012). Impact of angiotensin receptor blockers on Alzheimer disease neuropathology in a large brain autopsy SeriesARB impact on AD neuropathology. Archives of Neurology, 69(12), 1632–1638.PubMedPubMedCentralGoogle Scholar
  57. Hajjar, I., Hart, M., Chen, Y. L., Mack, W., Novak, V., Chui, H., & Lipsitz, L. (2013). Antihypertensive therapy and cerebral hemodynamics in executive mild cognitive impairment: results of a pilot randomized clinical trial. Journal of the American Geriatrics Society, 61(2), 194–201. doi: 10.1111/jgs.12100.PubMedGoogle Scholar
  58. Hansen, T. W., Staessen, J. A., Torp-Pedersen, C., Rasmussen, S., Thijs, L., Ibsen, H., & Jeppesen, J. (2006). Prognostic value of aortic pulse wave velocity as index of arterial stiffness in the general population. Circulation, 113(5), 664–670.Google Scholar
  59. Harvey, D., Laurel, B., & Mungas, D. (2003). Multivariate modeling of two associated cognitive outcomes in a longitudinal study. Journal of Alzheimer’s Disease, 5(5), 357–365.PubMedGoogle Scholar
  60. Havlik, R. J., Foley, D. J., Sayer, B., Masaki, K., White, L., & Launer, L. J. (2002). Variability in midlife systolic blood pressure is related to late-life brain white matter lesions. Stroke, 33(1), 26–30. doi: 10.1161/hs0102.101890.PubMedGoogle Scholar
  61. Hedden, T., Mormino, E. C., Amariglio, R. E., Younger, A. P., Schultz, A. P., Becker, J. A., & Rentz, D. M. (2012). Cognitive profile of amyloid burden and white matter hyperintensities in cognitively normal older adults. The Journal of Neuroscience, 32(46), 16233–16242.PubMedPubMedCentralGoogle Scholar
  62. Henskens, L. H., Kroon, A. A., van Oostenbrugge, R. J., Gronenschild, E. H., Fuss-Lejeune, M. M., Hofman, P. A., & de Leeuw, P. W. (2008). Increased aortic pulse wave velocity is associated with silent cerebral small-vessel disease in hypertensive patients. Hypertension, 52(6), 1120–1126.PubMedGoogle Scholar
  63. Höglund, K., Wiklund, O., Vanderstichele, H., Eikenberg, O., Vanmechelen, E., & Blennow, K. (2004). Plasma levels of β-amyloid (1–40), β-amyloid (1–42), and total β-amyloid remain unaffected in adult patients with hypercholesterolemia after treatment with statins. Archives of Neurology, 61(3), 333–337.PubMedGoogle Scholar
  64. Hoshi, T., Kitagawa, K., Yamagami, H., Furukado, S., Hougaku, H., & Hori, M. (2005). Relations of serum high-sensitivity C-reactive protein and interleukin-6 levels with silent brain infarction. Stroke, 36(4), 768–772.PubMedGoogle Scholar
  65. Hsu, J. L., Chen, Y. L., Leu, J. G., Jaw, F. S., Lee, C. H., Tsai, Y. F., & Leemans, A. (2012). Microstructural white matter abnormalities in type 2 diabetes mellitus: a diffusion tensor imaging study. NeuroImage, 59(2), 1098–1105. doi: 10.1016/j.neuroimage.2011.09.041.PubMedGoogle Scholar
  66. Iliff, J. J., Wang, M., Liao, Y., Plogg, B. A., Peng, W., Gundersen, G. A., & Goldman, S. A. (2012). A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Science Translational Medicine, 4(147), 147ra111–147ra111.PubMedPubMedCentralGoogle Scholar
  67. Imabayashi, E., Matsuda, H., Yoshimaru, K., Kuji, I., Seto, A., Shimano, Y., & Araki, N. (2011). Pilot data on telmisartan short-term effects on glucose metabolism in the olfactory tract in Alzheimer’s disease. Brain and behavior, 1(2), 63–69.PubMedPubMedCentralGoogle Scholar
  68. Ishikawa, J., Tamura, Y., Hoshide, S., Eguchi, K., Ishikawa, S., Shimada, K., & Kario, K. (2007). Low-grade inflammation is a risk factor for clinical stroke events in addition to silent cerebral infarcts in Japanese older hypertensives the Jichi Medical School ABPM Study, wave 1. Stroke, 38(3), 911–917.PubMedGoogle Scholar
  69. Jagust, W. J., Zheng, L., Harvey, D. J., Mack, W. J., Vinters, H. V., Weiner, M. W., & Chui, H. C. (2008). Neuropathological basis of magnetic resonance images in aging and dementia. Annals of Neurology, 63(1), 72–80. doi: 10.1002/ana.21296.PubMedPubMedCentralGoogle Scholar
  70. Jeerakathil, T., Wolf, P. A., Beiser, A., Massaro, J., Seshadri, S., D’Agostino, R. B., & DeCarli, C. (2004). Stroke risk profile predicts white matter hyperintensity volume: the Framingham Study. Stroke, 35(8), 1857–1861.PubMedGoogle Scholar
  71. Jefferson, A., Massaro, J., Wolf, P., Seshadri, S., Au, R., Vasan, R., & Lipinska, I. (2007). Inflammatory biomarkers are associated with total brain volume the Framingham heart study. Neurology, 68(13), 1032–1038.PubMedPubMedCentralGoogle Scholar
  72. Joas, E., Bäckman, K., Gustafson, D., Östling, S., Waern, M., Guo, X., & Skoog, I. (2012). Blood pressure trajectories from midlife to late life in relation to dementia in women followed for 37 years. Hypertension, 59(4), 796–801.PubMedGoogle Scholar
  73. Kannel, W. B., & Gordan, T. (1978). Evaluation of cardiovascular risk in the elderly: the Framingham study. Bulletin of the New York Academy of Medicine, 54(6), 573–591.PubMedPubMedCentralGoogle Scholar
  74. Kiechl, S., & Willeit, J. (1999). The natural course of atherosclerosis. Part II: vascular remodeling. Bruneck Study Group. Arterioscler Thrombosis Vascular Biology, 19(6), 1491–1498.Google Scholar
  75. Kimura, Y., Kitagawa, K., Oku, N., Kajimoto, K., Kato, H., Tanaka, M., & Hatazawa, J. (2010). Blood pressure lowering with valsartan is associated with maintenance of cerebral blood flow and cerebral perfusion reserve in hypertensive patients with cerebral small vessel disease. Journal of Stroke and Cerebrovascular Diseases, 19(2), 85–91.PubMedGoogle Scholar
  76. Kin, T., Yamano, S., Sakurai, R., Kajitani, M., Okahashi, Y., Nishiura, N., & Ueno, S. (2007). Carotid atherosclerosis is associated with brain atrophy in Japanese elders. Gerontology, 53(1), 1–6. doi: 10.1159/000095385.PubMedGoogle Scholar
  77. Kivipelto, M., Helkala, E. L., Laakso, M. P., Hanninen, T., Hallikainen, M., Alhainen, K., & Nissinen, A. (2001). Midlife vascular risk factors and Alzheimer’s disease in later life: longitudinal, population based study. BMJ, 322(7300), 1447–1451.PubMedPubMedCentralGoogle Scholar
  78. Knopman, D. S., & Roberts, R. (2010). Vascular risk factors: imaging and neuropathologic correlates. Journal of Alzheimer’s Disease, 20(3), 699–709. doi: 10.3233/JAD-2010-091555.PubMedPubMedCentralGoogle Scholar
  79. Knopman, Boland, L. L., Mosley, T., Howard, G., Liao, D., Szklo, M., & Atherosclerosis Risk in Communities Study, I. (2001). Cardiovascular risk factors and cognitive decline in middle-aged adults. Neurology, 56(1), 42–48.PubMedGoogle Scholar
  80. Knopman, D. S., Penman, A. D., Catellier, D. J., Coker, L. H., Shibata, D. K., Sharrett, A. R., & Mosley, T. H., Jr. (2011). Vascular risk factors and longitudinal changes on brain MRI: the ARIC study. Neurology, 76(22), 1879–1885.PubMedPubMedCentralGoogle Scholar
  81. Korf, E. S. C., White, L. R., Scheltens, P., & Launer, L. J. (2004). Midlife blood pressure and the risk of Hippocampal atrophy. Hypertension, 44(1), 29–34. doi: 10.1161/ Scholar
  82. Kuller, L. H., Lopez, O. L., Newman, A., Beauchamp, N. J., Burke, G., Dulberg, C., & Haan, M. N. (2003). Risk factors for dementia in the cardiovascular health cognition study. Neuroepidemiology, 22(1), 13–22. doi: 10.1159/000067109.PubMedGoogle Scholar
  83. Kuller, L. H., Margolis, K. L., Gaussoin, S. A., Bryan, N. R., Kerwin, D., Limacher, M., & Robinson, J. G. (2010). Relationship of hypertension, blood pressure, and blood pressure control with white matter abnormalities in the Women’s health initiative memory study (WHIMS)—MRI trial. The Journal of Clinical Hypertension, 12(3), 203–212.PubMedPubMedCentralGoogle Scholar
  84. Launer, L. J., Hughes, T., Yu, B., Masaki, K., Petrovitch, H., Ross, G. W., & White, L. R. (2010). Lowering midlife levels of systolic blood pressure as a public health strategy to reduce late-life dementia: perspective from the Honolulu heart program/Honolulu Asia aging study. Hypertension, 55(6), 1352–1359. doi: 10.1161/HYPERTENSIONAHA.109.147389.PubMedPubMedCentralGoogle Scholar
  85. Le Bihan, D. (2003). Looking into the functional architecture of the brain with diffusion MRI. Nature Review Neuroscience, 4(6), 469–480. doi: 10.1038/nrn1119.Google Scholar
  86. Lehmann, E., Parker, J., Hopkins, K., Taylor, M., & Gosling, R. (1993). Validation and reproducibility of pressure-corrected aortic distensibility measurements using pulse-wave-velocity Doppler ultrasound. Journal of Biomedical Engineering, 15(3), 221–228.PubMedGoogle Scholar
  87. Libby, P., Ridker, P. M., & Maseri, A. (2002). Inflammation and atherosclerosis. Circulation, 105(9), 1135–1143.PubMedGoogle Scholar
  88. Liu, Q., Zerbinatti, C. V., Zhang, J., Hoe, H.-S., Wang, B., Cole, S. L., & Bu, G. (2007). Amyloid precursor protein regulates brain apolipoprotein E and cholesterol metabolism through lipoprotein receptor LRP1. Neuron, 56(1), 66–78.PubMedPubMedCentralGoogle Scholar
  89. Loessner, A., Alavi, A., Lewandrowski, K. U., Mozley, D., Souder, E., & Gur, R. E. (1995). Regional cerebral function determined by FDG-PET in healthy volunteers: normal patterns and changes with age. Journal of Nuclear Medicine, 36(7), 1141–1149.PubMedGoogle Scholar
  90. Logothetis, N. K., & Pfeuffer, J. (2004). On the nature of the BOLD fMRI contrast mechanism. Magnetic Resonance Imaging, 22(10), 1517–1531. doi: 10.1016/j.mri.2004.10.018.PubMedGoogle Scholar
  91. Lopez, O. L., Jagust, W. J., Dulberg, C., Becker, J. T., DeKosky, S. T., Fitzpatrick, A., & Kuller, L. H. (2003). Risk factors for mild cognitive impairment in the cardiovascular health study cognition study: part 2. Archives of Neurology, 60(10), 1394–1399.PubMedGoogle Scholar
  92. Madamanchi, N. R., Vendrov, A., & Runge, M. S. (2005). Oxidative stress and vascular disease. Arteriosclerosis, Thrombosis, and Vascular Biology, 25(1), 29–38. doi: 10.1161/01.atv.0000150649.39934.13.PubMedGoogle Scholar
  93. Maillard, P., Seshadri, S., Beiser, A., Himali, J., Au, R., Fletcher, E., & DeCarli, C. (2012). Effects of systolic blood pressure on white matter integrity in young adults: from the Framingham heart study. The Lancet Neurology, 11(12), 1039–1047.PubMedPubMedCentralGoogle Scholar
  94. Manolio, T. A., Burke, G. L., O’Leary, D. H., Evans, G., Beauchamp, N., Knepper, L., & Ward, B. (1999). Relationships of cerebral MRI findings to ultrasonographic carotid atherosclerosis in older adults : the cardiovascular health study. CHS Collaborative Research Group. Arterioscler Thrombosis Vasculaer Biology, 19(2), 356–365.Google Scholar
  95. Marchant, N. L., Reed, B. R., DeCarli, C. S., Madison, C. M., Weiner, M. W., Chui, H. C., & Jagust, W. J. (2012). Cerebrovascular disease, beta-amyloid, and cognition in aging. Neurobiology of Aging, 33(5), 1006. e1025–1006. e1036.Google Scholar
  96. Matsumoto, S., Shimodozono, M., Miyata, R., & Kawahira, K. (2009). Effect of the angiotensin II type 1 receptor antagonist olmesartan on cerebral hemodynamics and rehabilitation outcomes in hypertensive post-stroke patients. Brain Injury, 23(13–14), 1065–1072.PubMedGoogle Scholar
  97. McGeer, P. L., & McGeer, E. G. (2001). Polymorphisms in inflammatory genes and the risk of Alzheimer disease. Archives of Neurology, 58(11), 1790–1792.PubMedGoogle Scholar
  98. McGuinness, B., Todd, S., Passmore, P., & Bullock, R. (2009). Blood pressure lowering in patients without prior cerebrovascular disease for prevention of cognitive impairment and dementia. Cochrane Database Syst Rev, (4), CD004034. doi: 10.1002/14651858.CD004034.pub3 [doi].Google Scholar
  99. Miranda, P. J., DeFronzo, R. A., Califf, R. M., & Guyton, J. R. (2005). Metabolic syndrome: definition, pathophysiology, and mechanisms. American Heart Journal, 149(1), 33–45. doi: 10.1016/j.ahj.2004.07.013.PubMedGoogle Scholar
  100. Mitchell, G. F., van Buchem, M. A., Sigurdsson, S., Gotal, J. D., Jonsdottir, M. K., Kjartansson, Ó., & Gudnason, V. (2011). Arterial stiffness, pressure and flow pulsatility and brain structure and function: the Age, Gene/Environment Susceptibility–Reykjavik Study. Brain, 134(11), 3398–3407.PubMedPubMedCentralGoogle Scholar
  101. Miwa, K., Tanaka, M., Okazaki, S., Furukado, S., Sakaguchi, M., & Kitagawa, K. (2011). Relations of blood inflammatory marker levels with cerebral microbleeds. Stroke, 42(11), 3202–3206.PubMedGoogle Scholar
  102. Moran, C., Phan, T. G., Chen, J., Blizzard, L., Beare, R., Venn, A., & Srikanth, V. (2013). Brain atrophy in type 2 diabetes: regional distribution and influence on cognition. Diabetes Care. doi: 10.2337/dc13-0143.Google Scholar
  103. Morris, J. C., & Price, A. L. (2001). Pathologic correlates of nondemented aging, mild cognitive impairment, and early-stage Alzheimer’s disease. Journal of Molecular Neuroscience, 17(2), 101–118.PubMedGoogle Scholar
  104. Muller, M., van der Graaf, Y., Algra, A., Hendrikse, J., Mali, W. P., & Geerlings, M. I. (2011). Carotid atherosclerosis and progression of brain atrophy: the SMART-MR study. Annals of Neurology, 70(2), 237–244. doi: 10.1002/ana.22392.PubMedGoogle Scholar
  105. Muller, M., van der Graaf, Y., Visseren, F. L., Mali, W. P., Geerlings, M. I., & for the, S. S. G. (2012). Hypertension and longitudinal changes in cerebral blood flow: the SMART-MR study. Annals of Neurology. doi: 10.1002/ana.23554.PubMedCentralGoogle Scholar
  106. Ninomiya, T., Ohara, T., Hirakawa, Y., Yoshida, D., Doi, Y., Hata, J., & Kiyohara, Y. (2011). Midlife and late-life blood pressure and dementia in Japanese elderly the hisayama study. Hypertension, 58(1), 22–28.PubMedGoogle Scholar
  107. Novak, V., & Hajjar, I. (2010). The relationship between blood pressure and cognitive function. Nature Reviews Cardiology, 7(12), 686–698. doi: 10.1038/nrcardio.2010.161.PubMedPubMedCentralGoogle Scholar
  108. O’Leary, D., Polak, J., Kronmal, R., Kittner, S., Bond, M., Wolfson, S., Jr., & Savage, P. (1992). Distribution and correlates of sonographically detected carotid artery disease in the cardiovascular health study. The CHS Collaborative Research Group. Stroke, 23(12), 1752–1760.PubMedGoogle Scholar
  109. O’Rourke, M. F., & Safar, M. E. (2005). Relationship between aortic stiffening and microvascular disease in brain and kidney cause and logic of therapy. Hypertension, 46(1), 200–204.PubMedGoogle Scholar
  110. O’Sullivan, M., Morris, R. G., Huckstep, B., Jones, D. K., Williams, S. C. R., & Markus, H. S. (2004). Diffusion tensor MRI correlates with executive dysfunction in patients with ischaemic leukoaraiosis. Journal Neurology Neurosurgery Psychiatry, 75(3), 441–447.Google Scholar
  111. Ohmine, T., Miwa, Y., Yao, H., Yuzuriha, T., Takashima, Y., Uchino, A., & Sasaguri, T. (2008). Association between arterial stiffness and cerebral white matter lesions in community-dwelling elderly subjects. Hypertension Research, 31(1), 75–81.PubMedGoogle Scholar
  112. Owen, D. R., Yeo, A. J., Gunn, R. N., Song, K., Wadsworth, G., Lewis, A., & Parker, C. A. (2012). An 18-kDa translocator protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28. Journal of Cerebral Blood Flow & Metabolism, 32(1), 1–5.Google Scholar
  113. Pantoni, L., & Garcia, J. H. (1997). Pathogenesis of leukoaraiosis : a review. Stroke, 28(3), 652–659. doi: 10.1161/01.str.28.3.652.PubMedGoogle Scholar
  114. Pappolla, M., Bryant-Thomas, T., Herbert, D., Pacheco, J., Garcia, M. F., Manjon, M., & Zambon, D. (2003). Mild hypercholesterolemia is an early risk factor for the development of Alzheimer amyloid pathology. Neurology, 61(2), 199–205.PubMedGoogle Scholar
  115. Parkes, L. M., Rashid, W., Chard, D. T., & Tofts, P. S. (2004). Normal cerebral perfusion measurements using arterial spin labeling: reproducibility, stability, and age and gender effects. Magnetic Resonance in Medicine, 51(4), 736–743. doi: 10.1002/mrm.20023.PubMedGoogle Scholar
  116. Petersen, E. T., Zimine, I., Ho, Y. C., & Golay, X. (2006). Non-invasive measurement of perfusion: a critical review of arterial spin labelling techniques. The British Journal of Radiology, 79(944), 688–701. doi: 10.1259/bjr/67705974.PubMedGoogle Scholar
  117. Pico, F., Dufouil, C., Levy, C., Besancon, V., de Kersaint-Gilly, A., Bonithon-Kopp, C., & Alperovitch, A. (2002). Longitudinal study of carotid atherosclerosis and white matter hyperintensities: the EVA-MRI cohort. Cerebrovasc Dis, 14(2), 109–115.PubMedGoogle Scholar
  118. Poels, M. M., Vernooij, M. W., Ikram, M. A., Hofman, A., Krestin, G. P., van der Lugt, A., & Breteler, M. M. (2010). Prevalence and risk factors of cerebral microbleeds: an update of the Rotterdam scan study. Stroke, 41(10 Suppl), S103–106.PubMedGoogle Scholar
  119. Prabhakaran, S., Wright, C. B., Yoshita, M., Delapaz, R., Brown, T., DeCarli, C., & Sacco, R. L. (2008). Prevalence and determinants of subclinical brain infarction: the northern Manhattan study. Neurology, 70(6), 425–430. doi: 10.1212/01.wnl.0000277521.66947.e5.PubMedPubMedCentralGoogle Scholar
  120. Preston, S. D., Steart, P. V., Wilkinson, A., Nicoll, J. A., & Weller, R. O. (2003). Capillary and arterial cerebral amyloid angiopathy in Alzheimer’s disease: defining the perivascular route for the elimination of amyloid beta from the human brain. Neuropathology and Applied Neurobiology, 29(2), 106–117.PubMedGoogle Scholar
  121. Provenzano, F. A., Muraskin, J., Tosto, G., Narkhede, A., Wasserman, B. T., Griffith, E. Y., & Brickman, A. M. (2013). White matter hyperintensities and cerebral amyloidosis: necessary and sufficient for clinical expression of Alzheimer disease? JAMA Neurology, 70(4), 455–461.PubMedPubMedCentralGoogle Scholar
  122. Raz, N., Lindenberger, U., Rodrigue, K. M., Kennedy, K. M., Head, D., Williamson, A., & Acker, J. D. (2005). Regional brain changes in aging healthy adults: general trends, individual differences and modifiers. Cerebral Cortex, 15(11), 1676–1689.PubMedGoogle Scholar
  123. Refolo, L. M., Pappolla, M. A., Malester, B., LaFrancois, J., Bryant-Thomas, T., Wang, R., & Duff, K. (2000). Hypercholesterolemia accelerates the Alzheimer’s amyloid pathology in a transgenic mouse model. Neurobiology of Disease, 7(4), 321–331.PubMedGoogle Scholar
  124. Roses, M., & Allen, D. (1996). Apolipoprotein E alleles as risk factors in Alzheimer’s disease. Annual Review of Medicine, 47(1), 387–400.PubMedGoogle Scholar
  125. Ruchoux, M.-M., & Maurage, C.-A. (1997). CADASIL: cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Journal of Neuropathology & Experimental Neurology, 56(9), 947–964.Google Scholar
  126. Salminen, A., Ojala, J., Kauppinen, A., Kaarniranta, K., & Suuronen, T. (2009). Inflammation in Alzheimer’s disease: amyloid-β oligomers trigger innate immunity defence via pattern recognition receptors. Progress in Neurobiology, 87(3), 181–194.PubMedGoogle Scholar
  127. Salonen, R., & Salonen, J. T. (1991). Determinants of carotid intima‐media thickness: a population‐based ultrasonography study in eastern Finnish men. Journal of Internal Medicine, 229(3), 225–231.PubMedGoogle Scholar
  128. Schnabel, R., Larson, M. G., Dupuis, J., Lunetta, K. L., Lipinska, I., Meigs, J. B., & Newton-Cheh, C. (2008). Relations of inflammatory biomarkers and common genetic variants with arterial stiffness and wave reflection. Hypertension, 51(6), 1651–1657.PubMedPubMedCentralGoogle Scholar
  129. Schneider, J. A., Arvanitakis, Z., Bang, W., & Bennett, D. A. (2007a). Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology, 69(24), 2197–2204.PubMedGoogle Scholar
  130. Schneider, J. A., Boyle, P. A., Arvanitakis, Z., Bienias, J. L., & Bennett, D. A. (2007b). Subcortical infarcts, Alzheimer’s disease pathology, and memory function in older persons. Annals of Neurology, 62(1), 59–66.PubMedGoogle Scholar
  131. Schroeder, E. B., Hanratty, R., Beaty, B. L., Bayliss, E. A., Havranek, E. P., & Steiner, J. F. (2012). Simultaneous control of diabetes mellitus, hypertension, and hyperlipidemia in 2 health systems. Circulation. Cardiovascular Quality and Outcomes, 5(5), 645–653. doi: 10.1161/CIRCOUTCOMES.111.963553.PubMedPubMedCentralGoogle Scholar
  132. Sega, R., Facchetti, R., Bombelli, M., Cesana, G., Corrao, G., Grassi, G., & Mancia, G. (2005). Prognostic value of ambulatory and home blood pressures compared with office blood pressure in the general population follow-up results from the pressioni arteriose monitorate e loro associazioni (PAMELA) study. Circulation, 111(14), 1777–1783.PubMedGoogle Scholar
  133. Seshadri, S., Wolf, P. A., Beiser, A., Elias, M. F., Au, R., Kase, C. S., & DeCarli, C. (2004). Stroke risk profile, brain volume, and cognitive function: the Framingham Offspring Study. Neurology, 63(9), 1591–1599.PubMedGoogle Scholar
  134. Siegel, D., Lopez, J., & Meier, J. (2007). Antihypertensive medication adherence in the department of veterans affairs. The American Journal of Medicine, 120(1), 26–32.PubMedGoogle Scholar
  135. Simons, M., Keller, P., De Strooper, B., Beyreuther, K., Dotti, C. G., & Simons, K. (1998). Cholesterol depletion inhibits the generation of β-amyloid in hippocampal neurons. Proceedings of the National Academy of Sciences, 95(11), 6460–6464.Google Scholar
  136. Stewart, R., Xue, Q. L., Masaki, K., Petrovitch, H., Ross, G. W., White, L. R., & Launer, L. J. (2009). Change in blood pressure and incident dementia: a 32-year prospective study. Hypertension, 54(2), 233–240. doi: 10.1161/HYPERTENSIONAHA.109.128744.PubMedPubMedCentralGoogle Scholar
  137. Swan, G. E., DeCarli, C., Miller, B. L., Reed, T., Wolf, P. A., Jack, L. M., & Carmelli, D. (1998). Association of midlife blood pressure to late-life cognitive decline and brain morphology. Neurology, 51(4), 986–993.PubMedGoogle Scholar
  138. Tan, Z. S., Beiser, A. S., Fox, C. S., Au, R., Himali, J. J., Debette, S., & Seshadri, S. (2011). Association of metabolic dysregulation with volumetric brain magnetic resonance imaging and cognitive markers of subclinical brain aging in middle-aged adults: the Framingham Offspring Study. Diabetes Care, 34(8), 1766–1770. doi: 10.2337/dc11-0308.PubMedPubMedCentralGoogle Scholar
  139. Tanaka, H., Munakata, M., Kawano, Y., Ohishi, M., Shoji, T., Sugawara, J., & Sawayama, T. (2009). Comparison between carotid-femoral and brachial-ankle pulse wave velocity as measures of arterial stiffness. Journal of Hypertension, 27(10), 2022–2027.PubMedGoogle Scholar
  140. Tell, G. S., Crouse, J. R., & Furberg, C. D. (1988). Relation between blood lipids, lipoproteins, and cerebrovascular atherosclerosis. A review. Stroke, 19(4), 423–430.PubMedGoogle Scholar
  141. Thöne-Reineke, C., Zimmermann, M., Neumann, C., Krikov, M., Li, J., Gerova, N., & Unger, T. (2004). Are angiotensin receptor blockers neuroprotective? Current Hypertension Reports, 6(4), 257–266.PubMedGoogle Scholar
  142. Touboul, P.-J., Hennerici, M., Meairs, S., Adams, H., Amarenco, P., Bornstein, N., & Fatar, M. (2006). Mannheim carotid intima-media thickness consensus (2004–2006). Cerebrovascular Diseases, 23(1), 75–80.PubMedGoogle Scholar
  143. Tsao, C. W., Seshadri, S., Beiser, A. S., Westwood, A. J., DeCarli, C., Au, R., & Mitchell, G. F. (2013). Relations of arterial stiffness and endothelial function to brain aging in the community. Neurology, 81(11), 984–91.PubMedGoogle Scholar
  144. Valeo, T. (2013). NEWS FROM THE AAN ANNUAL MEETING: autopsied brains show seniors on beta blockers Had fewer signs of dementia. Neurology Today, 13(5), 1–6.Google Scholar
  145. van den Heuvel, M. P., & Hulshoff Pol, H. E. (2010). Exploring the brain network: a review on resting-state fMRI functional connectivity. European Neuropsychopharmacology, 20(8), 519–534.PubMedGoogle Scholar
  146. van Dijk, E. J. (2005). C-Reactive Protein and Cerebral Small-Vessel Disease: The Rotterdam Scan Study. Circulation, 112(6), 900–905. doi: 10.1161/circulationaha.104.506337.PubMedGoogle Scholar
  147. van Es, A. C., van der Grond, J., ten Dam, V. H., de Craen, A. J., Blauw, G. J., Westendorp, R. G., & Group, P. S. (2010). Associations between total cerebral blood flow and age related changes of the brain. PloS One, 5(3), e9825. doi: 10.1371/journal.pone.0009825.PubMedPubMedCentralGoogle Scholar
  148. van Popele, N. M., Grobbee, D. E., Bots, M. L., Asmar, R., Topouchian, J., Reneman, R. S., & Witteman, J. C. (2001). Association between arterial stiffness and atherosclerosis: the Rotterdam Study. Stroke, 32(2), 454–460.PubMedGoogle Scholar
  149. Vasan, R. S., Larson, M. G., Leip, E. P., Evans, J. C., O’Donnell, C. J., Kannel, W. B., & Levy, D. (2001). Impact of high-normal blood pressure on the risk of cardiovascular disease. The New England Journal of Medicine, 345(18), 1291–1297. doi: 10.1056/NEJMoa003417.PubMedGoogle Scholar
  150. Verdecchia, P., Porcellati, C., Schillaci, G., Borgioni, C., Ciucci, A., Battistelli, M., & Santucci, A. (1994). Ambulatory blood pressure. An independent predictor of prognosis in essential hypertension. Hypertension, 24(6), 793–801.PubMedGoogle Scholar
  151. Vermeer, S. E., Longstreth, W. T., Jr., & Koudstaal, P. J. (2007). Silent brain infarcts: a systematic review. Lancet Neurology, 6(7), 611–619.Google Scholar
  152. Vinters, H., & Gilbert, J. (1983). Cerebral amyloid angiopathy: incidence and complications in the aging brain. II. The distribution of amyloid vascular changes. Stroke, 14(6), 924–928.PubMedGoogle Scholar
  153. White, J. A., Manelli, A. M., Holmberg, K. H., Van Eldik, L. J., & LaDu, M. J. (2005a). Differential effects of oligomeric and fibrillar amyloid-β1–42 on astrocyte-mediated inflammation. Neurobiology of Disease, 18(3), 459–465.PubMedGoogle Scholar
  154. White, L., Small, B. J., Petrovitch, H., Ross, G. W., Masaki, K., Abbott, R. D., & Markesbery, W. (2005b). Recent clinical-pathologic research on the causes of dementia in late life: update from the Honolulu-Asia aging study. Journal of Geriatric Psychiatry and Neurology, 18(4), 224–227. doi: 10.1177/0891988705281872.PubMedGoogle Scholar
  155. White, L., Gelber, R., Launer, L., Zarow, C., Sonnen, J., Uyehara-Lock, J., Petrovitch, H. (2013). Beta Blocker Treatment of Hypertensive Older Persons Ameliorates the Brain Lesions of Dementia Measured at Autopsy: The Honolulu-Asia Aging Study. Paper presented at the American Academy of Neurology Annual Meeting, San Diego.Google Scholar
  156. Whitmer, R. A., Sidney, S., Selby, J., Johnston, S. C., & Yaffe, K. (2005). Midlife cardiovascular risk factors and risk of dementia in late life. Neurology, 64(2), 277–281. doi: 10.1212/01.wnl.0000149519.47454.f2.PubMedGoogle Scholar
  157. Wills, A. K., Lawlor, D. A., Matthews, F. E., Sayer, A. A., Bakra, E., Ben-Shlomo, Y., & Kivimaki, M. (2011). Life course trajectories of systolic blood pressure using longitudinal data from eight UK cohorts. PLoS Medicine, 8(6), e1000440.PubMedPubMedCentralGoogle Scholar
  158. Wills, A. K., Lawlor, D. A., Muniz-Terrera, G., Matthews, F., Cooper, R., Ghosh, A. K., & Hardy, R. (2012). Population heterogeneity in trajectories of midlife blood pressure. Epidemiology (Cambridge, Mass), 23(2), 203–11.Google Scholar
  159. Wilms, H., Rosenstiel, P., Unger, T., Deuschl, G., & Lucius, R. (2005). Neuroprotection with angiotensin receptor antagonists. American Journal of Cardiovascular Drugs, 5(4), 245–253.PubMedGoogle Scholar
  160. Wolf, P. A., D’Agostino, R. B., Belanger, A. J., & Kannel, W. B. (1991). Probability of stroke: a risk profile from the Framingham Study. Stroke, 22(3), 312–318.PubMedGoogle Scholar
  161. Wright, C. B., Moon, Y., Paik, M. C., Brown, T. R., Rabbani, L., Yoshita, M., & Elkind, M. S. (2009). Inflammatory biomarkers of vascular risk as correlates of leukoariosis. Stroke, 40(11), 3466–3471.PubMedPubMedCentralGoogle Scholar
  162. Yamashina, A., Tomiyama, H., Takeda, K., Tsuda, H., Arai, T., Hirose, K., & Yamamoto, Y. (2002). Validity, reproducibility, and clinical significance of noninvasive brachial-ankle pulse wave velocity measurement. Hypertension Research, 25(3), 359–364.PubMedGoogle Scholar
  163. Yip, A., McKee, A., Green, R., Wells, J., Young, H., Cupples, L., & Farrer, L. (2005). APOE, vascular pathology, and the AD brain. Neurology, 65(2), 259–265.PubMedGoogle Scholar
  164. Yuan, C., & Kerwin, W. S. (2004). MRI of atherosclerosis. Journal of Magnetic Resonance Imaging, 19(6), 710–719. doi: 10.1002/jmri.20070.PubMedGoogle Scholar
  165. Zieman, S. J., Melenovsky, V., & Kass, D. A. (2005). Mechanisms, pathophysiology, and therapy of arterial stiffness. Arteriosclerosis, Thrombosis, and Vascular Biology, 25(5), 932–943.PubMedGoogle Scholar

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© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Pennington Biomedical Research CenterBaton RougeUSA

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