Abstract
The leading current hypothesis of age-related dementia (Alzheimer’s disease) considers this a consequence of the beta-amyloid peptide or of the intracellular skeletal protein tau, causing breakdown of the cerebral capillary bed. External trauma to the head in boxing and football is known to induce similar dementia ( dementia pugilistica, chronic traumatic encephalopathy), usually showing onset years after the individual’s retirement from active sport. At autopsy in dementia pugilistica, haemorrhage from cerebral vessels is prominent. This presentation reviews evidence that age-related dementia (ARD) is caused by internal trauma to vascular bed of the brain, by the pulse itself. Between the ages of 50 and 80 years, the heart beats ~109 times and, because of the low impedance of the cerebral circulation, each pulse penetrates to the cerebral veins. Further, the stiffness of the walls of the aorta and great arteries increases with age; and the amplitude of the pressure pulse in cerebral vessels (a measure of the cerebral pulse intensity) increases several fold. This pounding of cerebral vessels by the pulse induces (we argue) haemorrhages from cerebral vessels. When the vessel that haemorrhages is large, the patient may display symptoms of stroke and any resulting dementia is designated ‘vascular’. When the vessels that haemorrhage are small (capillaries), the patient may experience no acute symptoms; but the cumulative effect of many such haemorrhages becomes evident as loss of memory and of cognition. The pathologies which Alzheimer described in the demented brain (senile plaques, neurofibrillary tangles and inflammation) occur, we argue, as a result of haemorrhage. The age at which dementia becomes evident is determined by the fragility of cerebral vessels, which may vary between individuals with genetic and lifestyle factors. The hypothesis accounts better than previous proposals for the greatest risk factor for dementia – age.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Alzeheimer A. Uber eine eigenartige Erkrankung der Himrinde. Allgemeine Zeitschrift Psychiatrie Psychisch-Gerichtliche Medizin. 1907;64:146–8.
Alzheimer A. Uber eigenartige Krankheitsfalle des spateren Alters. Zbl ges Neurol Psychiat. 1911;4:356–85.
Osler W. The principles and practice of medicine. 6th ed. New York: Appleton; 1906. p. 848–52.
Nichols WW, O’Rourke MF, Vlachopoulos C. McDonald’s blood flow in arteries. 6th ed. London: Arnold Hodder; 2011. p. 411–6, 499–6.
Kraepelin E. Senile and pre-senile dementias. In: Psychiatrie: ein Lehrbuch fur Studierende und Arzte. Leipzig: Johann Ambrosius Barth; 1910. p. 553–632.
Iadecola C. The pathobiology of vascular dementia. Neuron. 2013;80:844–66.
Bowler JV. Modern concept of vascular or cognitive dementia. Br Med Bull. 2007;83:291–305.
Kang J, Lemaire HG, Unterbeck A, et al. The precursor of Alzheimer’s disease amyloid A4 protein resembles a cell surface receptor. Nature. 1987;325:733–6.
Glenner GG, Wong CW. Alzheimer’s Disease: medical report on the purification and characterisation of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun. 1984;120:885–90.
Ropper M. Two centuries of neurology and psychiatry. N Engl J Med. 2012;367:58–65.
Gorelick PB, Scuteri A, Black SE, et al. Vascular contributions to cognitive impairment and dementia: a statement for health care professionals from the American Heart Association/American Stroke Association. Stroke. 2011;42:2671–713.
Fischer LCM. Lacunar strokes and infarcts: a review. Neurology. 1982;32:871–6.
Pickering G. High blood pressure. London: Churchill; 1968.
Russell RW. How does blood pressure cause stroke? Lancet. 1975;2:1283–5.
Greenberg SM. Small Vessels, big problems. N Engl J Med. 2006;354:1451–3.
Byrom F. The hypertensive vascular crisis – an experimental study. London: Heineman; 1969.
Verooij M, Ikram MA, Tanghe HL, et al. Incidental findings on brain MRI in the general population. N Engl J Med. 2007;357:1281–8.
O’Rourke MF, Safar ME. Hemodynamic basis for the relationship between aortic stiffening and microvascular disease in brain and kidney: implications for treatment. Hypertension. 2005;46:200–4.
Henry-Feugeas MC, de Marco G, Peretti II, et al. Age-related cerebral white matter changes and pulse wave encephalopathy: observations with three dimensional MRI. Magn Reson Imaging. 2005;23:929–37.
Bateman GA, Levi CR, Schofield P, et al. Quantitative measurement of cerebral hemodynamics in early vascular dementia and Alzheimer’s disease. J Clin Neurosci. 2006;13:563–8.
Henry-Feugeas MC, Koskas P. Cerebral vascular aging: extending the concept of pulse wave encephalopathy through capillaries to the cerebral veins. Curr Aging Sci. 2012;5:157–67.
Fry D. Acute vascular endothelial changes associated with increased blood velocity gradients. Circ Res. 1968;22:165–97.
Fry D. Certain histological and chemical response of the vascular interface to acutely induced mechanical stress in the aorta of the dog. Circ Res. 1969;24:93–108.
Cullen KM, Kocsi Z, Stone J. Microvascular pathology in the aging human brain: evidence that senile plaques are sites of microhaemorrhages. Neurobiol Aging. 2006;27:1786–96.
Cullen KM, Kocsi Z, Stone J. Pericapillary haem-rich deposits: evidence for microhaemorrhages in aging human cerebral cortex. J Cereb Blood Flow Metab. 2005;25:1656–67.
Stone J. What initiates the formation of senile plaques? The origin of Alzheimer-like dementias in capillary haemorrhages. Med Hypotheses. 2008;71:347–59.
Stone J, O’Rourke MF. ASMR 2013 abstract. The mechanical cause of age-related dementia: the brain is destroyed by the pulse.
Herbert LE, Scherr PA, Bienias JL, Bennett DA, Evans DA. Alzheimer’s disease in the US population. Arch Neurol. 2003;60:1119–22.
Osler W. “The fixed period”. In: Hinohara S, Niki H, editors. Osler’s way of life. Durham: Duke University Press; 2001. p. 287–304.
Thompson PH, Hobbs MST, Martin CA. The rise and fall of ischemic heart disease in Australia. Aust N Z J Med. 1988;18:327–37.
Levy D, Thom T. Death rates from coronary disease – progress and a puzzling paradox (editorial). N Engl J Med. 1998;339:915–6.
Levy D, Brink S. A change in heart. New York: Vintage; 2005.
Levy D, Kenchaiah S, Larson MG, et al. Long-term trends in the incidence and survival with heart failure. N Engl J Med. 2002;347:1397–402.
Levy D, Larson MG, Vasan RS, et al. The progression from hypertension to congestive heart failure. JAMA. 1996;275:1557–62.
Redfield MM. Heart failure – an epidemic of uncertain proportions. N Engl J Med. 2002;347:1442–4.
Redfield MM, Jacobsen SJ, Burnett JC, et al. Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA. 2003;289:194–202.
Systolic Hypertension in Elderly Program Cooperative Research Group (SHEP). 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). JAMA. 1991;265:3255–64.
Katz AM. Cardiomyopathy of overload. N Engl J Med. 1990;322:100–10.
Mackenzie J. The study of the pulse: arterial, venous and hepatic, and of the movement of the heart. Edinburgh: Young J Pentland; 1902.
Larson EB, Yaffe K, Langa K, et al. New insights into the dementia epidemic. N Engl J Med. 2013;369:2275–8.
Scuteri A, Lakatta E. Bringing prevention in geriatrics evidence from cardiovascular medicine supporting the new challenge. Exp Gerontol. 2013;48:64–8.
O’Rourke MF, Hashimoto J. Mechanical factors in arterial aging: a clinical perspective. J Am Coll Cardiol. 2007;50:1–13.
Taylor MG. The elastic properties of arteries in relation to the physiological functioning of the arterial system. Gastroenterology. 1967;52:358–63.
Milnor WR. Hemodynamics. 2nd ed. Baltimore: Williams & Wilkins; 1989.
O’Rourke MF. Commentary on: aortic wavelength as a determinant of the relationship between heart rate and body size in mammals. Am J Physiol. 1981;240:R393–5.
Redheuil A, Yu W-C, Wu CO, et al. Reduced ascending aortic strain and distensilibity: earlier manifestations of vascular aging in humans. Hypertension. 2010;55:319–26.
Scuteri A, Nilsson PM, Tzourio C, Redon J, Laurent S. Microvascular brain damage with aging and hypertension: pathophysiological consideration and clinical implications. J Hypertens. 2011;29:1469–77.
Hirata K, Yaginuma T, O’Rourke MF, Kawakami M. Age-related change in the carotid artery flow and pressure pulses implications to cerebral microvascular disease. Stroke. 2006;37:2552–6.
Hirata K, O’Rourke MF. Effect of nitrate on the carotid late systolic flow augmentation – a new strategy against stroke. J Hypertens. 2007;25 Suppl 2:S336–7.
Hirata K, O’Rourke M, Momomura S. Flow augmentation index as a risk factor for silent lacunar infarction. J Am Coll Cardiol. 2008;51(Suppl A):A303.
Xu TY, Staessen JA, Wei FF, et al. Blood flow pattern in the middle cerebral artery in relation to indices of arterial stiffness in the systemic circulation. Am J Hypertens. 2012;25:319–24.
Boutouyrie P, Laurent S, Benetos A, et al. Opposing effects of aging on distal and proximal larger arteries in hypertensives. J Hypertens. 1992;10 Suppl 6:S87–91.
Kim MO, Li Y, Wei F, Wang J, O’Rourke M, Avolio A. Influence of wave reflection and lower body arterial properties on cerebral perfusion in apparently normal humans. J Hypertens. 2013;31(e-Suppl A):e23.
Salloway S, Sperwing R, Fox N, et al. Two phase 3 trials of Bapineuzumab in mild-to-moderate Alzheimer’s disease. N Engl J Med. 2014;370:322–33.
Doody RS, Thomas RG, Farlow M, et al. Phase 3 trials of Solanezumab for mild-to-moderate Alzheimer’s disease. N Engl J Med. 2014;370:311–21.
Hashimoto J, Ito S. Central pulse pressure and aortic stiffness determine renal hemodynamics: Pathophysiological implication of micro albuminuria in hypertension. Hypertension. 2011;58:839–46.
Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Böhm M, et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013;31:1281–357.
Nilsson PM, Boutouyrie P, Cunha P, Kotsis V, Narkiewicz K, Parati G, Rietzschel E, Scuteri A, Laurent S. Early vascular aging in translation: from laboratory investigations to clinical applications in cardiovascular prevention. J Hypertens. 2013;31:1517–26.
Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, Pannier B, Vlachopoulos C, Wilkinson I. Struijker-Boudier H; European Network for Non-invasive Investigation of Large Arteries. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J. 2006;27:2588–605.
Esiri MM, Wilcock GK, Morris JH. Neuropathological assessment of the lesions of significance in vascular dementia. J Neurol Neurosurg Psychiatry. 1997;63:749–53.
Garrett KD, Browndyke JN, Whelihan W, Paul RH, DiCarlo M, Moser DJ, Cohen RA, Ott BR. The neuropsychological profile of vascular cognitive impairment–no dementia: Comparisons to patients at risk for cerebrovascular disease and vascular dementia. Arch Clin Neuropsychol. 2004;19:745–57.
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;18:41–9.
Troyer AK, Moscovitch M, Winocur G, Alexander MP, Stuss D. Clustering and switching on verbal fluency: the effects of focal frontal- and temporal-lobe lesions. Neuropsychologia. 1998;36:499–504.
Hachinski V, Iadecola C, Petersen RC, Breteler MM, Nyenhuis DL, Black SE, Powers WJ, DeCarli C, Merino JG, Kalaria RN, Vinters HV, Holtzman DM, Rosenberg GA, Wallin A, Dichgans M, Marler JR, Leblanc GG. National Institute of Neurological Disorders and Stroke-Canadian Stroke Network vascular cognitive impairment harmonization standards. Stroke. 2006;37:2220–41.
Carew TG, Lamar M, Cloud BS, Grossman M, Libon DJ. Impairment in category fluency in ischemic vascular dementia. Neuropsychology. 1997;11:400–12.
Lamar MPC, Davis KL, Kaplan E, Libon DJ. Capacity to maintain mental set in dementia. Neuropsychologia. 2002;40:435–45.
Wechsler D. WAIS-III administration and scoring manual. New York: The Psychological Corporation; 1997.
Kaplan E, Fein D, Morris R, Delis D. The WAIS-Rr as a neuropsychological instrument. San Antonio: Psychological Corporation; 1991.
Dufouil C, Chalmers J, Coskun O, et al. Effects of blood pressure lowering on cerebral white matter intensitities in patients with stroke. The PROGRESS Magnetic Resonance Imaging Substudy. Circulation. 2005;112:1644–50.
Lee TH. Eugene Braunwald and the rise of modern medicine. Cambridge: Harvard; 2013.
Cheng HM, Chuang SY, Sung SH, Yu WC, Pearson A, Lakatta EG, Pan WH, Chen CH. Derivation and validation of diagnostic thresholds for central blood pressure measurements based on long-term cardiovascular risks. J Am Coll Cardiol. 2013;62:1780–7.
Scuteri A, Tesauro M, Guglini L, Lauro D, Fini M, de Daniele N. Aortic stiffness and hypotension episodes are associated with impaired cognitive function in older subjects with subjective complements of memory loss. Int J Cardiol. 2013;169:371–7.
James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, et al. Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;18:2013. doi:10.1001/jama.2013.284427.
Bauchner H, Fontanarosa PB, Golub RM. Updated guidelines for management of high blood pressure: recommendations, review, and responsibility. JAMA. 2013. doi:10.1001/jama.2013.284432.
O’Rourke MF, Safar ME, Dzau V. The cardiovascular continuum extended: aging effects on the aorta and microvasculature. Vasc Med. 2010;15:461–8.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Additional information
Funding
JS was supported by the Sir Zelman Cowen Universities Fund
Declaration
JS is Director of CSCM Pty Ltd
Rights and permissions
Copyright information
© 2014 Springer-Verlag London
About this chapter
Cite this chapter
Scuteri, A., Stone, J., O’Rourke, M.F. (2014). The Relationship Between Aortic Stiffness, Microvascular Disease in the Brain and Cognitive Decline: Insights into the Emerging Epidemic of Alzheimer’s Disease. In: Safar, M., O'Rourke, M., Frohlich, E. (eds) Blood Pressure and Arterial Wall Mechanics in Cardiovascular Diseases. Springer, London. https://doi.org/10.1007/978-1-4471-5198-2_25
Download citation
DOI: https://doi.org/10.1007/978-1-4471-5198-2_25
Published:
Publisher Name: Springer, London
Print ISBN: 978-1-4471-5197-5
Online ISBN: 978-1-4471-5198-2
eBook Packages: MedicineMedicine (R0)