The mechanical cause of age-related dementia (Alzheimer's Disease): The brain is destroyed by the pulse

Journal of Alzheimer's Disease

Volumn 44, Issue 2, 2015, Pages 355-373

  Stone, Jonathan ^a,b   Johnstone, Daniel M ^a,b   Mitrofanis, John ^a,b   O'Rourke, Michael ^c  

^a Bosch Institute   (Australia)

^b UNIVERSITY OF SYDNEY   (Australia)

^c VICTOR CHANG CARDIAC RESEARCH INSTITUTE   (Australia)

Author keywords

Alzheimer's disease; causes of death; dementia; pulse; vascular aging

Indexed keywords

AGED; AGING; ALZHEIMER DISEASE; ALZHEIMER DISEASE ASSESSMENT SCALE; ARTERIAL STIFFNESS; ARTERY; BRAIN BLOOD VESSEL; BRAIN DISEASE; BRAIN HEMORRHAGE; CARDIOVASCULAR DISEASE; CAUSE OF DEATH; CEREBROVASCULAR ACCIDENT; CONDITIONING; DEMENTIA; DOWN SYNDROME; ENDOTHELIAL PROGENITOR CELL; GENETIC RISK; HUMAN; INFLAMMATION; KIDNEY FAILURE; LONGEVITY; MECHANICAL STRESS; MULTIINFARCT DEMENTIA; MUTATION; NERVOUS SYSTEM INFLAMMATION; NEUROPATHOLOGY; NEUROPIL; PENETRANCE; PRIORITY JOURNAL; PULSE RATE; REVIEW; SHORT STATURE; SIGNAL TRANSDUCTION; VASCULAR DISEASE; VASCULAR REMODELING; VASCULARIZATION; ANIMAL; BLOOD PRESSURE; BRAIN; CEREBROVASCULAR DISORDERS; GENETICS; PATHOPHYSIOLOGY; PHYSIOLOGY;

AGING; ALZHEIMER DISEASE; ANIMALS; BLOOD PRESSURE; BRAIN; CEREBROVASCULAR DISORDERS; HUMANS; PULSE;

EID: 84921454500     PISSN: 13872877     EISSN: 18758908     Source Type: Journal    
DOI: 10.3233/JAD-141884     Document Type: Review

References (173)

1. Dufouil C, Chalmers J, Coskun O, Besancon V, Bousser MG, Guillon P, MacMahon S, Mazoyer B, Neal B, Woodward M, Tzourio-Mazoyer N, Tzourio C (2005) 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 112, 1644-1650.
2. Alzheimer A (1911) Über eigenartige Krankheitsfälle des späteren Alters. Zbl ges Neurol Psychiatrie 4, 356-385.
3. Alzheimer A (1907) Über eine eigenartige Erkrankung der Hirnrinde. Allgemeine Zeitschrift Psychiatrie Psychisch-Gerichtliche Medizin, 146-148.
4. Consensus (1998) Consensus report of the Working Group on: "Molecular and Biochemical Markers of Alzheimer's Disease". The Ronald and Nancy Reagan Research Institute of the Alzheimer's Association and the National Institute on Aging Working Group. Neurobiol Aging 19, 109-116.
5. Kraepelin E (1910) Senile and pre-senile dementias. In Psychiatrie: Ein Lehrbuch für Studierende und Ärzte. Johann Ambrosius Barth, Leipzig, pp. 553-632.
6. Bick K, Amaducci L, Pepeu G (1986) The Early Story of Alzheimer's Disease, Raven Press, New York.
7. Boland B (1997) Cerbrovascular Pathology in Alzheimer's Disease, The New York Academy of Sciences, New York.
8. Goldman B (2002) Alzheimer's Disease: Vascular Etiology and Pathology, The New York Academy of Sciences, New York.
9. de la Torre J (2000) Preface. Neurobiol Aging 21, III-IV.
10. Korczyn AD (2002) The complex nosological concept of vascular dementia. J Neurol Sci 203-204, 3-6.
11. Iadecola C (2013) The pathobiology of vascular dementia. Neuron 80, 844-866.
12. Bowler J, Eliasziw M, Steenhuis R, Munoz D, Fry R, Merskey H, Hachinski V (1997) Comparative evolution of Alzheimer disease, vascular dementia, and mixed dementia. Arch Neurol 54, 697-703.
13. de la Torre JC (2004) Alzheimer's disease is a vasocognopathy: A new term to describe its nature. Neurol Res 26, 517-524.
14. de la Torre JC (2002) Vascular basis of Alzheimer's pathogenesis. Ann N Y Acad Sci 977, 196-215.
15. Cullen KM, Kocsi Z, Stone J (2006) Microvascular pathology in the aging human brain: Evidence that senile plaques are sites of microhaemorrhages. Neurobiol Aging 27, 1786-1796.
16. Cullen K, Kocsi Z, Stone J (2005) Pericapillary haem-rich deposits: Evidence for microhaemorrhages in aging human cerebral cortex. J Cereb Blood Flow Metab 25, 1656-1667.
17. Kumar-Singh S, Pirici D, McGowan E, Serneels S, Ceuterick C, Hardy J, Duff K, Dickson D, Van Broeckhoven C (2005) Dense-core plaques in Tg2576 and PSAPP mouse models of Alzheimer's disease are centered on vessel walls. Am J Pathol 167, 527-543.
18. Stone J (2008) What initiates the formation of senile plaques? The origin of Alzheimer-like dementias in capillary haemorrhages. Med Hypotheses 71, 347-359.
19. Obrenovich ME, Morales LA, Cobb CJ, Shenk JC, Mendez GM, Fischbach K, Smith MA, Qasimov EK, Perry G, Aliev G (2009) Insights into cerebrovascular complications and Alzheimer disease through the selective loss of GRK2 regulation. J Cell Mol Med 13, 853-865.
20. Breteler MM, Bots ML, Ott A, Hofman A (1998) Risk factors for vascular disease and dementia. Haemostasis 28, 167-173.
21. Breteler MM (2000) Vascular risk factors for Alzheimer's disease: An epidemiologic perspective. Neurobiol Aging 21, 153-160.
22. Decarli C (2004)Vascular factors in dementia: An overview. J Neurol Sci 226, 19-23.
23. Launer LJ (2005) The epidemiologic study of dementia: A life-long quest? Neurobiol Aging 26, 335-340.
24. Sacco RL (1997) Risk factors, outcomes, and stroke subtypes for ischemic stroke. Neurology 49, S39-S44.
25. O'Donnell MJ, Xavier D, Liu L, Zhang H, Chin SL, Rao-Melacini P, Rangarajan S, Islam S, Pais P, McQueen MJ, Mondo C, Damasceno A, Lopez-Jaramillo P, Hankey GJ, Dans AL, Yusoff K, Truelsen T, Diener HC, Sacco RL, Ryglewicz D, Czlonkowska A,Weimar C,Wang X, Yusuf S (2010) Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries (the INTERSTROKE study): A case-control study. Lancet 376, 112-123.
26. Daviglus ML, Bell CC, Berrettini W, Bowen PE, Connolly ES, Jr., Cox NJ, Dunbar-Jacob JM, Granieri EC, Hunt G, McGarry K, Patel D, Potosky AL, Sanders-Bush E, Silberberg D, Trevisan M (2010) NIH state-of-the-science conference statement: Preventing Alzheimer's disease and cognitive decline. NIH Consens State Sci Statements 27, 1-30.
27. Elwood P, Galante J, Pickering J, Palmer S, Bayer A, Ben-Shlomo Y, Longley M, Gallacher J (2013) Healthy lifestyles reduce the incidence of chronic diseases and dementia: Evidence from the caerphilly cohort study. PLoS One 8, e81877.
28. Muller U,Winter P, Graeber MB(2013)Apresenilin 1 mutation in the first case of Alzheimer's disease. Lancet Neurol 12, 129-130.
29. Wakutani Y, Kowa H, Kusumi M, Yamagata K, Wada-Isoe K, AdachiY, Takeshima T, Urakami K, Nakashima K(2002) Genetic analysis of vascular factors in Alzheimer's disease. Ann N Y Acad Sci 977, 232-238.
30. Levy E, Carman MD, Fernandez-Madrid IJ, Power MD, Lieberburg I, van Duinen SG, Bots GT, Luyendijk W, FrangioneB( 1990) Mutation of the Alzheimer's disease amyloid gene in hereditary cerebral hemorrhage, Dutch type. Science 248, 1124-1126.
31. Kumar-Singh S, Cras P, Wang R, Kros JM, van Swieten J, Lubke U, Ceuterick C, Serneels S, Vennekens K, Timmermans JP, Van Marck E, Martin JJ, van Duijn CM, Van Broeckhoven C (2002) Dense-core senile plaques in the Flemish variant of Alzheimer's disease are vasocentric. Am J Pathol 161, 507-520.
32. Grabowski TJ, Cho HS, Vonsattel JP, Rebeck GW, Greenberg SM (2001) Novel amyloid precursor protein mutation in an Iowa family with dementia and severe cerebral amyloid angiopathy. Ann Neurol 49, 697-705.
33. Hendriks L, van Duijn CM, Cras P, Cruts M, Van Hul W, van Harskamp F, Warren A, McInnis MG, Antonarakis SE, Martin JJ, et al. (1992) Presenile dementia and cerebral haemorrhage linked to a mutation at codon 692 of the beta-amyloid precursor protein gene. Nat Genet 1, 218-221.
34. Yamada M, Naiki H (2012) Cerebral amyloid angiopathy. Prog Mol Biol Transl Sci 107, 41-78.
35. Carter DA, Desmarais E, Bellis M, Campion D, Clerget-Darpoux F, Brice A, Agid Y, Jaillard-Serradt A, Mallet J (1992) More missense in amyloid gene. Nat Genet 2, 255-256.
36. Cras P, van Harskamp F, Hendriks L, Ceuterick C, van Duijn CM, Stefanko SZ, Hofman A, Kros JM, Van Broeckhoven C, Martin JJ (1998) Presenile Alzheimer dementia characterized by amyloid angiopathy and large amyloid core type senile plaques in the APP 692Ala->Gly mutation. Acta Neuropathol 96, 253-260.
37. Kamino K, Orr HT, Payami H, Wijsman EM, Alonso ME, Pulst SM, Anderson L, O'Dahl S, Nemens E, White JA, et al. (1992) Linkage and mutational analysis of familial Alzheimer disease kindreds for the APP gene region. Am J Hum Genet 51, 998-1014.
38. Nilsberth C,Westlind-Danielsson A, Eckman CB, Condron MM, Axelman K, Forsell C, Stenh C, Luthman J, Teplow DB, Younkin SG, Naslund J, Lannfelt L (2001) The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced Abeta protofibril formation. Nat Neurosci 4, 887-893.
39. Rossi G, Giaccone G, Maletta R, Morbin M, Capobianco R, Mangieri M, Giovagnoli AR, Bizzi A, Tomaino C, Perri M, Di Natale M, Tagliavini F, Bugiani O, Bruni AC (2004) A family with Alzheimer disease and strokes associated with A713T mutation of the APP gene. Neurology 63, 910-912.
40. Dermaut B, Kumar-Singh S, De Jonghe C, Cruts M, Lofgren A, Lubke U, Cras P, Dom R, De Deyn PP, Martin JJ, Van Broeckhoven C (2001) Cerebral amyloid angiopathy is a pathogenic lesion in Alzheimer's disease due to a novel presenilin 1 mutation. Brain 124, 2383-2392.
41. Mann DM, Pickering-Brown SM, Takeuchi A, Iwatsubo T (2001) Amyloid angiopathy and variability in amyloid beta deposition is determined by mutation position in presenilin-1-linked Alzheimer's disease. Am J Pathol 158, 2165-2175.
42. Nochlin D, Bird TD, Nemens EJ, Ball MJ, Sumi SM (1998) Amyloid angiopathy in a Volga German family with Alzheimer's disease and a presenilin-2 mutation (N141I). Ann Neurol 43, 131-135.
43. Sanchez-Valle R, Llado A, Ezquerra M, Rey MJ, Rami L, Molinuevo JL (2007) A novel mutation in the PSEN1 gene (L286P) associated with familial early-onset dementia of Alzheimer type and lobar haematomas. Eur J Neurol 14, 1409-1412.
44. Shen J, Bronson RT, Chen DF, XiaW, Selkoe DJ, Tonegawa S (1997) Skeletal and CNS defects in Presenilin-1-deficient mice. Cell 89, 629-639.
45. Tanzi RE (2012) The genetics of Alzheimer disease. Cold Spring Harb Perspect Med 2, pii: a006296.
46. Folin M, Baiguera S, Conconi MT, Di Liddo R, De Carlo E, Parnigotto PP, Nussdorfer GG (2004) Apolipoprotein E as vascular risk factor in neurodegenerative dementia. Int J Mol Med 14, 609-613.
47. Finch CE (2005) Developmental origins of aging in brain and blood vessels: An overview. Neurobiol Aging 26, 281-291.
48. Jordan BD, Relkin NR, Ravdin LD, Jacobs AR, Bennett A, Gandy S (1997) Apolipoprotein E epsilon4 associated with chronic traumatic brain injury in boxing. JAMA 278, 136-140.
49. Scuteri A, Bos AJ, Zonderman AB, Brant LJ, Lakatta EG, Fleg JL (2001) Is the apoE4 allele an independent predictor of coronary events? Am J Med 110, 28-32.
50. Smith JD (2000) Apolipoprotein E4: An allele associated with many diseases. Ann Med 32, 118-127.
51. Fryer JD, Taylor JW, DeMattos RB, Bales KR, Paul SM, Parsadanian M, Holtzman DM (2003) Apolipoprotein E markedly facilitates age-dependent cerebral amyloid angiopathy and spontaneous hemorrhage in amyloid precursor protein transgenic mice. J Neurosci 23, 7889-7896.
52. Bell RD, Winkler EA, Singh I, Sagare AP, Deane R, Wu Z, Holtzman DM, Betsholtz C, Armulik A, Sallstrom J, Berk BC, Zlokovic BV (2012) Apolipoprotein E controls cerebrovascular integrity via cyclophilin A. Nature 485, 512-516.
53. Zlokovic BV (2005) Neurovascular mechanisms of Alzheimer's neurodegeneration. Trends Neurosci 28, 202-208.
54. Zlokovic BV (2013) Cerebrovascular effects of apolipoprotein E: Implications for Alzheimer disease. JAMA Neurol 70, 440-444.
55. AlzGene, Alzheimer Research Forum, http://www.alzgene. org/TopResults.asp.
56. Schellenberg GD, Montine TJ (2012) The genetics and neuropathology of Alzheimer's disease. Acta Neuropathol 124, 305-323.
57. Garrett MC, Otten ML, Starke RM, Komotar RJ, Magotti P, Lambris JD, Rynkowski MA, Connolly ES (2009) Synergistic neuroprotective effects of C3a and C5a receptor blockade following intracerebral hemorrhage. Brain Res 1298, 171-177.
58. Rynkowski MA, Kim GH, Garrett MC, Zacharia BE, Otten ML, Sosunov SA, Komotar RJ, Hassid BG, Ducruet AF, Lambris JD, Connolly ES (2009) C3a receptor antagonist attenuates brain injury after intracerebral hemorrhage. J Cereb Blood Flow Metab 29, 98-107.
59. Liu G, Yao L, Liu J, Jiang Y, Ma G, Chen Z, Zhao B, Li K (2014) Cardiovascular disease contributes to Alzheimer's disease: Evidence from large-scale genome-wide association studies. Neurobiol Aging 35, 786-792.
60. Vis JC, Duffels MG, Winter MM, Weijerman ME, Cobben JM, Huisman SA, Mulder BJ (2009) Down syndrome: A cardiovascular perspective. J Intellect Disabil Res 53, 419-425.
61. Nagasaka T, Shiozawa Z, Kobayashi M, Shindo K, Tsunoda S, Amino A (1996) Autopsy findings in Down's syndrome with cerebrovascular disorder. Clin Neuropathol 15, 145-149.
62. Golewale N, Paltiel HJ, Fishman SJ, Alomari AI (2010) Portal vascular anomalies in Down syndrome: Spectrum of clinical presentation and management approach. J Pediatr Surg 45, 1676-1681.
63. Parsa CF, Almer Z (2008) Supranumerary optic disc vessels may indicate reduced systemic angiogenesis in Down syndrome. Br J Ophthalmol 92, 432-433.
64. CostaV, Sommese L, Casamassimi A, Colicchio R, Angelini C, MarchesanoV, Milone L, Farzati B, Giovane A, Fiorito C, Rienzo M, Picardi M, Avallone B, Marco Corsi M, Sarubbi B, Calabro R, Salvatore P, Ciccodicola A, Napoli C (2010) Impairment of circulating endothelial progenitors in Down syndrome. BMC Med Genomics 3, 40.
65. Miyakawa T, Kimura T, Hirata S, Fujise N, Ono T, Ishizuka K, Nakabayashi J (2000) Role of blood vessels in producing pathological changes in the brain with Alzheimer's disease. Ann N Y Acad Sci 903, 46-54.
66. Purushothuman S, Marotte L, Stowe S, Johnstone D, Stone J (2013) The response of cerebral cortex to haemorrhagic damage: Experimental evidence from a penetrating injury model. PLoS One 8, e59740.
67. Wu CW, Liao PC, Yu L, Wang ST, Chen ST, Wu CM, Kuo YM (2004) Hemoglobin promotes Abeta oligomer formation and localizes in neurons and amyloid deposits. Neurobiol Dis 17, 367-377.
68. Chuang JY, Lee CW, Shih YH, Yang T, Yu L, Kuo YM (2012) Interactions between amyloid-beta and hemoglobin: Implications for amyloid plaque formation in Alzheimer's disease. PLoS One 7, e33120.
69. Obrenovich ME, Joseph JA, Atwood CS, Perry G, Smith MA (2002) Amyloid-beta: A (life) preserver for the brain. Neurobiol Aging 23, 1097-1099.
70. McKee AC, Cantu RC, Nowinski CJ, Hedley-Whyte ET, Gavett BE, Budson AE, Santini VE, Lee HS, Kubilus CA, Stern RA (2009) Chronic traumatic encephalopathy in athletes: Progressive tauopathy after repetitive head injury. J Neuropathol Exp Neurol 68, 709-735.
71. Gavett BE, Stern RA, McKee AC (2011) Chronic traumatic encephalopathy: A potential late effect of sport-related concussive and subconcussive head trauma. Clin Sports Med 30, 179-188, xi.
72. Stone J, de la Torre J (2013) Commentary: Where angels fear to tread: The microvascular basis of dementia. Evid Based Mental Health 16, 88.
73. McGeer PL (1992) Anti-inflammatory agents as a therapeutic approach to Alzheimer's disease. Neurology 42, 447-449.
74. Rogers J, Kirby LC, Hempelman SR, Berry DL, McGeer PL, Kaszniak AW, Zalinski J, Cofield M, Mansukhani L, Willson P, Kogan F (1993) Clinical trial of indomethacin in Alzheimer's disease. Neurology 43, 1609-1611.
75. Rogers J, Webster S, Lih-Fen L, Brachova L, Civin W, Emmerling M, Shivers B, Walker D, McGeer P (1996) Inflammation and Alzheimer's disease pathogenesis. Neurobiol Aging 17, 681-686.
76. Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM, Cooper NR, Eikelenboom P, Emmerling M, Fiebich BL, Finch CE, Frautschy S, Griffin WS, Hampel H, Hull M, Landreth G, Lue L, Mrak R, Mackenzie IR, McGeer PL, O'Banion MK, Pachter J, Pasinetti G, Plata-Salaman C, Rogers J, Rydel R, Shen Y, Streit W, Strohmeyer R, Tooyoma I, Van Muiswinkel FL, Veerhuis R, Walker D, Webster S, Wegrzyniak B, Wenk G, Wyss-Coray T (2000) Inflammation and Alzheimer's disease. Neurobiol Aging 21, 383-421.
77. Jenkinson ML, Bliss MR, Brain AT, Scott Dl (1989) Rheumatoid arthritis and senile dementia of the Alzheimer's type. Brit J Rheumat 28, 86-88.
78. McGeer P, McGeer E, Rogers J, Sibley J (1991) Antiinflammatory drugs and Alzheimer's disease. Lancet 335, 1037.
79. de Jong D, Jansen R, Hoefnagels W, Jellesma-Eggenkamp M, Verbeek M, Borm G, Kremer B (2008) No effect of oneyear treatment with indomethacin on Alzheimer's disease progression: A randomized controlled trial. PLoS One 3, e1475.
80. Jaturapatporn D, Isaac MG, McCleery J, Tabet N (2012) Aspirin, steroidal and non-steroidal anti-inflammatory drugs for the treatment of Alzheimer's disease. Cochrane Database Syst Rev 2, CD006378.
81. Wagner K, Sharp FR, Ardizzone TD, Lu A, JFC (2003) Heme and iron metabolism: Role in cerebral hemorrhage. J Cereb Blood Flow Metab 23, 629-652.
82. Leary MC, Saver JL (2003) Annual incidence of first silent stroke in the United States: A preliminary estimate. Cerebrovasc Dis 16, 280-285.
83. Poels MM, Vernooij MW, Ikram MA, Hofman A, Krestin GP, van der Lugt A, Breteler MM(2010) Prevalence and risk factors of cerebral microbleeds: An update of the Rotterdam scan study. Stroke 41, S103-S106.
84. Cordonnier C, van der Flier WM, Sluimer JD, Leys D, Barkhof F, Scheltens P (2006) Prevalence and severity of microbleeds in a memory clinic setting. Neurology 66, 1356-1360.
85. Kovari E, Gold G, Herrmann FR, Canuto A, Hof PR, Bouras C, Giannakopoulos P (2007) Cortical microinfarcts and demyelination affect cognition in cases at high risk for dementia. Neurology 68, 927-931.
86. Yates PA, Sirisriro R, Villemagne VL, Farquharson S, Masters CL, Rowe CC (2011) Cerebral microhemorrhage and brain beta-amyloid in aging and Alzheimer disease. Neurology 77, 48-54.
87. Henry-Feugeas MC (2008) Alzheimer's disease in late-life dementia: A minor toxic consequence of devastating cerebrovascular dysfunction. Med Hypotheses 70, 866-875.
88. Bateman GA (2004) Pulse wave encephalopathy: A spectrum hypothesis incorporating Alzheimer's disease, vascular dementia and normal pressure hydrocephalus. Med Hypotheses 62, 182-187.
89. Henry-Feugeas MC, Onen F, Claeys ES (2008) Classifying late-onset dementia with MRI: Is arteriosclerotic brain degeneration the most common cause of Alzheimer's syndrome? Clin Interv Aging 3, 187-199.
90. Byrom FB (1954) The pathogenesis of hypertensive encephalopathy and its relation to the malignant phase of hypertension; experimental evidence from the hypertensive rat. Lancet 267, 201-211.
91. Wagshul ME, Eide PK, Madsen JR (2011) The pulsating brain: A review of experimental and clinical studies of intracranial pulsatility. Fluids Barriers CNS 8, 5.
92. Zhang W, Ito Y, Berlin E, Roberts R, Berkowitz BA (2003) Role of hypoxia during normal retinal vessel development and in experimental retinopathy of prematurity. Invest Ophthalmol Vis Sci 44, 3119-3123.
93. Plassman BL, Havlik RJ, Steffens DC, Helms MJ, Newman TN, Drosdick D, Phillips C, Gau BA, Welsh-Bohmer KA, Burke JR, Guralnik JM, Breitner JC (2000) Documented head injury in early adulthood and risk of Alzheimer's disease and other dementias. Neurology 55, 1158-1166.
94. Mayeux R, Ottman R, Maestre G, Ngai C, Tang MX, Ginsberg H, Chun M, Tycko B, Shelanski M (1995) Synergistic effects of traumatic head injury and apolipoprotein-epsilon 4 in patients with Alzheimer's disease. Neurology 45, 555-557.
95. McKenzie JE, Roberts GW, Royston MC (1996) Comparative investigation of neurofibrillary damage in the temporal lobe in Alzheimer's disease, Down's syndrome and dementia pugilistica. Neurodegeneration 5, 259-264.
96. Jordan BD (2000) Chronic traumatic brain injury associated with boxing. Semin Neurol 20, 179-185.
97. Dale GE, Leigh PN, Luthert P, Anderton BH, Roberts GW (1991) Neurofibrillary tangles in dementia pugilistica are ubiquitinated. J Neurol Neurosurg Psychiatry 54, 116-118.
98. Tokuda T, Ikeda S, Yanagisawa N, Ihara Y, Glenner GG (1991) Re-examination of ex-boxers' brains using immunohistochemistry with antibodies to amyloid beta-protein and tau protein. Acta Neuropathol (Berl) 82, 280-285.
99. Perry EK (1990) Nerve growth factor and the basal forebrain cholinergic system: A link in the etiopathology of neurodegenerative dementias? Alzheimer Dis Assoc Disord 4, 1-13.
100. Martland H (1928) Punch drunk. J Amer Med Ass 91, 1103-1107.
101. Maxwell WL, Irvine A, Adams JH, Graham DI, Gennarelli TA (1988) Response of cerebral microvasculature to brain injury. J Pathol 155, 327-335.
102. Manley GT, Rosenthal G, Lam M, Morabito D,Yan D, Derugin N, Bollen A, Knudson MM,Panter SS (2006) Controlled cortical impact in swine: Pathophysiology and biomechanics. J Neurotrauma 23, 128-139.
103. Gentleman SM, Nash MJ, Sweeting CJ, Graham DI, Roberts GW (1993) Beta-amyloid precursor protein (beta APP) as a marker for axonal injury after head injury. Neurosci Lett 160, 139-144.
104. Roberts GW, Gentleman SM, Lynch A, Murray L, Landon M, Graham DI (1994) Beta amyloid protein deposition in the brain after severe head injury: Implications for the pathogenesis of Alzheimer's disease. J Neurol Neurosurg Psychiatry 57, 419-425.
105. Ikonomovic MD, Uryu K, Abrahamson EE, Ciallella JR, Trojanowski JQ, Lee VM, Clark RS, Marion DW, Wisniewski SR, DeKosky ST (2004) Alzheimer's pathology in human temporal cortex surgically excised after severe brain injury. Exp Neurol 190, 192-203.
106. Jordan BD (2013) The clinical spectrum of sport-related traumatic brain injury. Nat Rev Neurol 9, 222-230.
107. DeKosky ST, Blennow K, Ikonomovic MD, Gandy S (2013) Acute and chronic traumatic encephalopathies: Pathogenesis and biomarkers. Nat Rev Neurol 9, 192-200.
108. Smith DH, Johnson VE, Stewart W (2013) Chronic neuropathologies of single and repetitive TBI: Substrates of dementia? Nat Rev Neurol 9, 211-221.
109. O'Rourke MF, Hashimoto J (2008) Arterial stiffness: A modifiable cardiovascular risk factor? J Cardiopulm Rehabil Prev 28, 225-237.
110. O'Rourke MF, Hashimoto J (2007) Mechanical factors in arterial aging: A clinical perspective. J Am Coll Cardiol 50, 1-13.
111. Kovacic JC, Moreno P, Hachinski V, Nabel EG, Fuster V (2011) Cellular senescence, vascular disease, and aging: Part 1 of a 2-part review. Circulation 123, 1650-1660.
112. Kovacic JC, Moreno P, Nabel EG, Hachinski V, Fuster V (2011) Cellular senescence, vascular disease, and aging: Part 2 of a 2-part review: Clinical vascular disease in the elderly. Circulation 123, 1900-1910.
113. Osler W (1906) The Principles and Practices of Medicine, 6th edition, Appleton, New York.
114. Bateman GA, Levi CR, Schofield P, Wang Y, Lovett EC (2008) The venous manifestations of pulse wave encephalopathy: Windkessel dysfunction in normal aging and senile dementia. Neuroradiology 50, 491-497.
115. Henry-Feugeas MC (2009) Intracranial MR dynamics in clinically diagnosed Alzheimer's disease: The emerging concept of "pulse wave encephalopathy". Curr Alzheimer Res 6, 488-502.
116. Lehoux S (2006) Redox signalling in vascular responses to shear and stretch. Cardiovasc Res 71, 269-279.
117. Galland RB (2007) Popliteal aneurysms: From John Hunter to the 21st century. Ann R Coll Surg Engl 89, 466-471.
118. Murley R (1984) John Hunter, velvet and vascular surgery. Ann R Coll Surg Engl 66, 214-218.
119. Moore W (2005) The Knife Man, Bantam Press, London.
120. Fujiwara Y, Chaves PH, Takahashi R, Amano H, Yoshida H, Kumagai S, Fujita K, Wang DG, Shinkai S (2005) Arterial pulse wave velocity as a marker of poor cognitive function in an elderly community-dwelling population. J Gerontol A Biol Sci Med Sci 60, 607-612.
121. Hanon O, Haulon S, Lenoir H, Seux ML, Rigaud AS, Safar M, Girerd X, Forette F (2005) Relationship between arterial stiffness and cognitive function in elderly subjects with complaints of memory loss. Stroke 36, 2193-2197.
122. Scuteri A, Brancati AM,Gianni W, Assisi A,Volpe M(2005) Arterial stiffness is an independent risk factor for cognitive impairment in the elderly: A pilot study. J Hypertens 23, 1211-1216.
123. Elias MF, Robbins MA, Budge MM, AbhayaratnaWP, Dore GA, Elias PK (2009) Arterial pulse wave velocity and cognition with advancing age. Hypertension 53, 668-673.
124. Singer J, Trollor JN, Crawford J, O'Rourke MF, Baune BT, Brodaty H, Samaras K, Kochan NA, Campbell L, Sachdev PS, Smith E (2013) The association between pulse wave velocity and cognitive function: The Sydney Memory and Ageing Study. PLoS One 8, e61855.
125. Jani B, Rajkumar C (2006) Ageing and vascular ageing. Postgrad Med J 82, 357-362.
126. Agabiti-Rosei E, Porteri E, Rizzoni D (2009) Arterial stiffness, hypertension, and rational use of nebivolol. Vasc Health Risk Manag 5, 353-360.
127. Shimizu M, Kario K (2008) Role of the augmentation index in hypertension. Ther Adv Cardiovasc Dis 2, 25-35.
128. Vlachopoulos C, Aznaouridis K, O'Rourke MF, Safar ME, Baou K, Stefanadis C (2010) Prediction of cardiovascular events and all-cause mortality with central haemodynamics: A systematic review and meta-analysis. Eur Heart J 31, 1865-1871.
129. Henry-Feugeas MC, Koskas P (2012) Cerebral vascular aging: Extending the concept of pulse wave encephalopathy through capillaries to the cerebral veins. Curr Aging Sci 5, 157-167.
130. Mogi M, Horiuchi M (2011) Clinical Interaction between Brain and Kidney in SmallVessel Disease. Cardiol Res Prac 2011, 306189.
131. Leonhardt KO, Landes RR (1963) Oxygen tension of the urine and renal structures. Preliminary report of clinical findings. N Engl J Med 269, 115-121.
132. O'Rourke MF, Safar ME(2005) Relationship between aortic stiffening and microvascular disease in brain and kidney: Cause and logic of therapy. Hypertension 46, 200-204.
133. Safar ME, London GM, Plante GE (2004) Arterial stiffness and kidney function. Hypertension 43, 163-168.
134. Ito S, Nagasawa T, Abe M, Mori T (2009) Strain vessel hypothesis: A viewpoint for linkage of albuminuria and cerebro-cardiovascular risk. Hypertens Res 32, 115-121.
135. Abdelhafiz AH, Brown SH, Bello A, El Nahas M (2010) Chronic kidney disease in older people: Physiology, pathology or both? Nephron Clin Pract 116, c19-c24.
136. Smulyan H, Marchais SJ, Pannier B, Guerin AP, Safar ME, London GM (1998) Influence of body height on pulsatile arterial hemodynamic data. J Am Coll Cardiol 31, 1103-1109.
137. Laitala VS, Hjelmborg J, Koskenvuo M, Raiha I, Rinne JO, Christensen K, Kaprio J, Silventoinen K (2011) Shorter adult stature increases the impact of risk factors for cognitive impairment: A comparison of two Nordic twin cohorts. Twin Res Hum Genet 14, 544-552.
138. Petot GJ, Vega U, Traore F, Fritsch T, Debanne SM, Friedland RP, Lerner AJ (2007) Height and Alzheimer's disease: Findings from a case-control study. J Alzheimers Dis 11, 337-341.
139. Abbott RD, White LR, Ross GW, Petrovitch H, Masaki KH, Snowdon DA, Curb JD (1998) Height as a marker of childhood development and late-life cognitive function: The Honolulu-Asia Aging Study. Pediatrics 102, 602-609.
140. Smulyan H, Asmar RG, Rudnicki A, London GM, Safar ME (2001) Comparative effects of aging in men and women on the properties of the arterial tree. J Am Coll Cardiol 37, 1374-1380.
141. London GM, Guerin AP, Pannier B, Marchais SJ, Stimpel M (1995) Influence of sex on arterial hemodynamics and blood pressure. Role of body height. Hypertension 26, 514-519.
142. Yaginuma T, Avolio A, O'Rourke M, Nichols W, Morgan JJ, Roy P, Baron D, Branson J, Feneley M (1986) Effect of glyceryl trinitrate on peripheral arteries alters left ventricular hydraulic load in man. Cardiovasc Res 20, 153-160.
143. Nichols W, O'Rourke M, Vlachopoulos C (2011) McDonald's Blood Flow in Arteries: Theoretical, Experimental and Clinical Principles, Arnold Hodder, London.
144. Eells JT, Henry MM, Summerfelt P, Wong-Riley MT, Buchmann EV, Kane M, Whelan NT, Whelan HT (2003) Therapeutic photobiomodulation for methanol-induced retinal toxicity. Proc Natl Acad Sci U S A 100, 3439-3444.
145. Johnstone D, Coleman K, Moro C, Torres N, Eells J, Baker GE, Ashkan K, Stone J, Benabid AL, Mitrofanis J (2014) The potential of light therapy in Parkinson's disease. Chronophysiol Ther, 4, 1-14.
146. Marco FD, Romeo S, Nandasena C, Purushothuman S, Adams C, Bisti S, Stone J (2013) The time course of action of two neuroprotectants, dietary saffron and photobiomodulation, assessed in the rat retina. Am J Neurodegener Dis 2, 208-220.
147. Otani A, Kojima H, Guo C, Oishi A, Yoshimura N (2012) Low-dose-rate, low-dose irradiation delays neurodegeneration in a model of retinitis pigmentosa. Am J Pathol 180, 328-336.
148. Mattson MP (2008) Dietary factors, hormesis and health. Ageing Res Rev 7, 43-48.
149. Mattson MP (2005) Energy intake, meal frequency, and health: A neurobiological perspective. Annu Rev Nutr 25, 237-260.
150. Jensen HA, Loukogeorgakis S,Yannopoulos F, Rimpilainen E, Petzold A, Tuominen H, Lepola P, Macallister RJ, Deanfield JE, Makela T, Alestalo K, Kiviluoma K, Anttila V, Tsang V, Juvonen T (2011) Remote ischemic preconditioning protects the brain against injury after hypothermic circulatory arrest. Circulation 123, 714-721.
151. Ding Y, Li J, Luan X, Ding YH, Lai Q, Rafols JA, Phillis JW, Clark JC, Diaz FG (2004) Exercise pre-conditioning reduces brain damage in ischemic rats that may be associated with regional angiogenesis and cellular overexpression of neurotrophin. Neuroscience 124, 583-591.
152. Maccarone R, Di Marco S, Bisti S (2008) Saffron supplement maintains morphology and function after exposure to damaging light in mammalian retina. Invest Ophthalmol Vis Sci 49, 1254-1261.
153. Purushothuman S, Nandasena C, Peoples C, El Masri N, Johnstone D, Mitrofanis J, Stone J (2013) Saffron pre-treatment offers neuroprotection to nigral and retinal dopaminergic cells of MPTP-treated mice. J Parkinsons Dis 3, 77-83.
154. Natoli R, Zhu Y, Valter K, Bisti S, Eells J, Stone J (2010) Gene and noncoding RNA regulation underlying photoreceptor protection: Microarray study of dietary antioxidant saffron and photobiomodulation in rat retina. Mol Vis 16, 1801-1822.
155. Marangoni D, Falsini B, Piccardi M, Ambrosio L, Minnella AM, Savastano MC, Bisti S, Maccarone R, Fadda A, Mello E, Concolino P, Capoluongo E (2013) Functional effect of Saffron supplementation and risk genotypes in early agerelated macular degeneration:Apreliminary report. J Transl Me 11, 228.
156. Piccardi M, Marangoni D, Minnella AM, Savastano MC, Valentini P, Ambrosio L, Capoluongo E, Maccarone R, Bisti S, FalsiniB(2012)Alongitudinal follow-up study of saffron supplementation in early age-related macular degeneration: Sustained benefits to central retinal function. Evid Based Complement Alternat Med 2012, 429124.
157. Falsini B, Piccardi M, Minnella A, Savastano C, Capoluongo E, Fadda A, Balestrazzi E, Maccarone R, Bisti S (2010) Influence of saffron supplementation on retinal flicker sensitivity in early age-related macular degeneration. Invest Ophthalmol Vis Sci 51, 6118-6124.
158. Lampl Y, Zivin JA, Fisher M, Lew R, Welin L, Dahlof B, Borenstein P, Andersson B, Perez J, Caparo C, Ilic S, Oron U (2007) Infrared laser therapy for ischemic stroke: A new treatment strategy: Results of the NeuroThera Effectiveness and Safety Trial-1 (NEST-1). Stroke 38, 1843-1849.
159. Ivandic BT, Ivandic T (2008) Low-level laser therapy improves vision in patients with age-related macular degeneration. Photomed Laser Surg 26, 241-245.
160. Merry G, Devenyi R, Dotson R, Markowitz S, Reyes S (2013) Treatment of dry age-related-macular degeneration with photobiomodulation. In Proceedings of the 9th WALT Congress, Laakso E-L, Young C, eds. Medimond, Bologna, pp. 81-84.
161. Yokobori S, Mazzeo AT, Hosein K, Gajavelli S, Dietrich WD, Bullock MR (2013) Preconditioning for traumatic brain injury. Transl Stroke Res 4, 25-39.
162. Dezfulian C, Garrett M, Gonzalez NR (2013) Clinical application of preconditioning and postconditioning to achieve neuroprotection. Transl Stroke Res 4, 19-24.
163. Grammas P (2011) Neurovascular dysfunction, inflammation and endothelial activation: Implications for the pathogenesis of Alzheimer's disease. J Neuroinflammation 8, 26.
164. Goldsmith HS (2011) A new approach to the treatment of Alzheimer's disease: The need for a controlled study. J Alzheimers Dis 25, 209-212.
165. Krizanac-Bengez L, Mayberg MR, Janigro D (2004) The cerebral vasculature as a therapeutic target for neurological disorders and the role of shear stress in vascular homeostatis and pathophysiology. Neurol Res 26, 846-853.
166. Lee ST, Chu K, Jung KH, Park HK, Kim DH, Bahn JJ, Kim JH, Oh MJ, Lee SK, Kim M, Roh JK (2009) Reduced circulating angiogenic cells in Alzheimer disease. Neurology 72, 1858-1863.
167. Jones DS, Podolsky SH, Greene JA (2012) The burden of disease and the changing task of medicine. N Engl J Med 366, 2333-2338.
168. Gwatkin DR, Brandel SK (1982) Life expectancy and population growth in the Third World. Sci Am 246, 57-65.
169. US Department of Commerce, Bureau of Statistics (2007) Historical Statistics of the United States, http://www. infoplease.com/ipa/A0005140.
170. Minino AM, Arias E, Kochanek KD, Murphy SL, Smith BL (2002) Deaths: Final data for 2000. Natl Vital Stat Rep 50, 1-119.
171. Heron M(2013) Deaths: Leading causes for 2010. Natl Vital Stat Rep 62, 1-97.
172. Center for Disease Control and Prevention National Center for Health Statistics, http://www.cdc.gov/nchs/products /nvsr.htm.
173. Australian Bureau of Statistics (2014) Causes of Death, Australia, 2012, http://www.abs.gov.au/ausstats/absnsf/Lookup/by Subject/3303.02012Main FeaturesLeading Causes of Death10001.