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Current Gerontology and Geriatrics Research
Volume 2010, Article ID 358531, 10 pages
http://dx.doi.org/10.1155/2010/358531
Review Article

Brain Aging in the Oldest-Old

1Service Universitaire de Psychiatrie de l'Age Avancé (SUPAA), Department of Psychiatry of CHUV, University of Lausanne, Route du Mont, 1008 Prilly, Switzerland
2Department of Psychiatry, HUG, Belle-Idée, University of Geneva School of Medicine, 1225 Geneva, Switzerland
3Unité de Psychopathologie Morphologique, Department of Psychiatry of HUG, 1225 Genève, Switzerland

Received 9 March 2010; Accepted 14 June 2010

Academic Editor: Bradley Willcox

Copyright © 2010 A. von Gunten et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. J.-M. Robine and F. Paccaud, “Nonagenarians and centenarians in Switzerland, 1860–2001: a demographic analysis,” Journal of Epidemiology and Community Health, vol. 59, no. 1, pp. 31–37, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  2. J. Ankri and M. Poupard, “Prevalence and incidence of dementia among the very old. Review of the literature,” Revue d'Epidemiologie et de Sante Publique, vol. 51, no. 3, pp. 349–360, 2003. View at Google Scholar · View at Scopus
  3. J.-M. Robine, Y. Saito, and C. Jagger, “The emergence of extremely old people: the case of Japan,” Experimental Gerontology, vol. 38, no. 7, pp. 735–739, 2003. View at Publisher · View at Google Scholar · View at Scopus
  4. T. J. Wilkinson and R. Sainsbury, “The association between mortality, morbidity and age in New Zealand's oldest old,” International Journal of Aging and Human Development, vol. 46, no. 4, pp. 333–343, 1998. View at Google Scholar · View at Scopus
  5. T. P. Miles and M. A. Bernard, “Morbidity, disability, and health status of black American elderly: a new look at the oldest-old,” Journal of the American Geriatrics Society, vol. 40, no. 10, pp. 1047–1054, 1992. View at Google Scholar · View at Scopus
  6. P. Gueresi, L. Troiano, and L. Troiano, “The MALVA (MAntova LongeVA) study: an investigation on people 98 years of age and over in a province of Northern Italy,” Experimental Gerontology, vol. 38, no. 10, pp. 1189–1197, 2003. View at Publisher · View at Google Scholar · View at Scopus
  7. H. Nybo, H. C. Petersen, and H. C. Petersen, “Predictors of mortality in 2,249 nonagenarians—the Danish 1905-Cohort Survey,” Journal of the American Geriatrics Society, vol. 51, no. 10, pp. 1365–1373, 2003. View at Publisher · View at Google Scholar · View at Scopus
  8. M. H. Silver, K. Newell, C. Brady, E. T. Hedley-White, and T. T. Perls, “Distinguishing between neurodegenerative disease and disease-free aging: correlating neuropsychological evaluations and neuropathological studies in centenarians,” Psychosomatic Medicine, vol. 64, no. 3, pp. 493–501, 2002. View at Google Scholar · View at Scopus
  9. M. L. Stek, J. Gussekloo, A. T. F. Beekman, W. Van Tilburg, and R. G. J. Westendorp, “Prevalence, correlates and recognition of depression in the oldest old: the Leiden 85-plus study,” Journal of Affective Disorders, vol. 78, no. 3, pp. 193–200, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  10. P. von Heideken Wågert, B. Rönnmark, and B. Rönnmark, “Morale in the oldest old: the Umeå 85+ study,” Age and Ageing, vol. 34, no. 3, pp. 249–255, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  11. E. Von Strauss, L. Fratiglioni, M. Viitanen, Y. Forsell, and B. Winblad, “Morbidity and comorbidity in relation to functional status: a community-based study of the oldest old (90+ years),” Journal of the American Geriatrics Society, vol. 48, no. 11, pp. 1462–1469, 2000. View at Google Scholar · View at Scopus
  12. H. R. Andersen, B. Jeune, H. Nybo, J. B. Nielsen, K. Andersen-Ranberg, and P. Grandjean, “Low activity of superoxide dismutase and high activity of glutathione reductase in erythrocytes from centenarians,” Age and Ageing, vol. 27, no. 5, pp. 643–648, 1998. View at Publisher · View at Google Scholar · View at Scopus
  13. F. Moroni, M. L. Di Paolo, and M. L. Di Paolo, “Interrelationship among neutrophil efficiency, inflammation, antioxidant activity and zinc pool in very old age,” Biogerontology, vol. 6, no. 4, pp. 271–281, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  14. R. Hitt, Y. Young-Xu, M. Silver, and T. Perls, “Centenarians: the older you get, the healthier you have been,” Lancet, vol. 354, no. 9179, p. 652, 1999. View at Publisher · View at Google Scholar · View at Scopus
  15. M. D. Buono, O. Urciuoli, and D. De Leo, “Quality of life and longevity: a study of centenarians,” Age and Ageing, vol. 27, no. 2, pp. 207–216, 1998. View at Publisher · View at Google Scholar · View at Scopus
  16. P. K. Hillerås, A. F. Jorm, A. Herlitz, and B. Winblad, “Activity patterns in very old people: a survey of cognitively intact subjects aged 90 years or older,” Age and Ageing, vol. 28, no. 2, pp. 147–152, 1999. View at Publisher · View at Google Scholar · View at Scopus
  17. M. Kliegel, C. Moor, and C. Rott, “Cognitive status and development in the oldest old: a longitudinal analysis from the Heidelberg Centenarian Study,” Archives of Gerontology and Geriatrics, vol. 39, no. 2, pp. 143–156, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  18. T. Perls, “Dementia-free centenarians,” Experimental Gerontology, vol. 39, no. 11-12, pp. 1587–1593, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  19. B. A. Blansjaar, R. Thomassen, and H. W. van Schaick, “Prevalence of dementia in centenarians,” International Journal of Geriatric Psychiatry, vol. 15, no. 3, pp. 219–225, 2000. View at Publisher · View at Google Scholar · View at Scopus
  20. E. L. Schneider, “Aging in the third millennium,” Science, vol. 283, no. 5403, pp. 796–797, 1999. View at Publisher · View at Google Scholar · View at Scopus
  21. R. Thomassen, H. W. van Schaick, and B. A. Blansjaar, “Prevalence of dementia over age 100,” Neurology, vol. 50, no. 1, pp. 283–286, 1998. View at Google Scholar · View at Scopus
  22. M. M. Fichter, I. Meller, H. Schroppel, and R. Steinkirchner, “Dementia and cognitive impairment in the oldest old in the community. Prevalence and comorbidity,” British Journal of Psychiatry, vol. 166, pp. 621–629, 1995. View at Google Scholar · View at Scopus
  23. D. B. Hoiuieson, A. Dame, R. Camicioli, G. Sexton, H. Payami, and J. A. Kaye, “Cognitive markers preceding Alzheimer's dementia in the healthy oldest old,” Journal of the American Geriatrics Society, vol. 45, no. 5, pp. 584–589, 1997. View at Google Scholar · View at Scopus
  24. N. T. Lautenschlager, L. A. Cupples, and L. A. Cupples, “Risk of dementia among relatives of Alzheimer's disease patients in the MIRAGE study: what is in store for the oldest old?” Neurology, vol. 46, no. 3, pp. 641–650, 1996. View at Google Scholar · View at Scopus
  25. U. Lucca, M. Garri, A. Nobili et al., “Risk of dementia continues to rise in the oldest old: the Monzino 80-plus study,” Alzheimer's & Dementia, vol. 5, no. 4, supplement, p. 381, 2009. View at Google Scholar
  26. M. M. Corrada, R. Brookmeyer, D. Berlau, A. Paganini-Hill, and C. H. Kawas, “Prevalence of dementia after age 90: results from the 90+ study,” Neurology, vol. 71, no. 5, pp. 337–343, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  27. K. Hestad, B. Kveberg, and K. Engedal, “Low blood pressure is a better predictor of cognitive deficits than the apolipoprotein e4 allele in the oldest old,” Acta Neurologica Scandinavica, vol. 111, no. 5, pp. 323–328, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  28. K. Juva, A. Verkkoniemi, P. Viramo, T. Polvikoski, K. Kainulainen, K. Kontula, and R. Sulkava, “APOE ε4 does not predict mortality, cognitive decline, or dementia in the oldest old,” Neurology, vol. 54, no. 2, pp. 412–415, 2000. View at Google Scholar · View at Scopus
  29. A. Salo, R. Ylikoski, and R. Ylikoski, “Does apolipoprotein E influence learning and memory in the nondemented oldest old?” International Psychogeriatrics, vol. 13, no. 4, pp. 451–459, 2001. View at Publisher · View at Google Scholar · View at Scopus
  30. D. C. Spencer, T. Zitzelberger, D. Spielman, and J. Kaye, “MRS in relation to hippocampal volume in the oldest old,” Neurology, vol. 60, no. 7, pp. 1194–1196, 2003. View at Google Scholar · View at Scopus
  31. P. Giannakopoulos, P. R. Hof, M. Surini, J. P. Michel, and C. Bouras, “Quantitative immunohistochemical analysis of the distribution of neurofibrillary tangles and senile plaques in the cerebral cortex of nonagenarians and centenarians,” Acta Neuropathologica, vol. 85, no. 6, pp. 602–610, 1993. View at Google Scholar · View at Scopus
  32. M. S. Green, J. A. Kaye, and M. J. Ball, “The Oregon Brain Aging Study: neuropathology accompanying healthy aging in the oldest old,” Neurology, vol. 54, no. 1, pp. 105–113, 2000. View at Google Scholar · View at Scopus
  33. T. Mizutani and H. Shimada, “Neuropathological background of twenty-seven centenarian brains,” Journal of the Neurological Sciences, vol. 108, no. 2, pp. 168–177, 1992. View at Publisher · View at Google Scholar · View at Scopus
  34. M. Ball, H. Braak, and H. Braak, “Consensus recommendations for the postmortem diagnosis of Alzheimer's disease,” Neurobiology of Aging, vol. 18, no. 4, supplement 1, pp. S1–S2, 1997. View at Publisher · View at Google Scholar · View at Scopus
  35. Z. S. Khachaturian, “Diagnosis of Alzheimer's disease,” Archives of Neurology, vol. 42, no. 11, pp. 1097–1105, 1985. View at Google Scholar · View at Scopus
  36. S. S. Mirra, A. Heyman, and A. Heyman, “The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease,” Neurology, vol. 41, no. 4, pp. 479–486, 1991. View at Google Scholar · View at Scopus
  37. P. Giannakopoulos, P. R. Hof, J.-P. Michel, J. Guimon, and C. Bouras, “Cerebral cortex pathology in aging and Alzheimer's disease: a quantitative survey of large hospital-based geriatric and psychiatric cohorts,” Brain Research Reviews, vol. 25, no. 2, pp. 217–245, 1997. View at Publisher · View at Google Scholar · View at Scopus
  38. J. H. Morrison and P. R. Hof, “Life and death of neurons in the aging brain,” Science, vol. 278, no. 5337, pp. 412–419, 1997. View at Publisher · View at Google Scholar · View at Scopus
  39. P. G. Ince, “Pathological correlates of late-onset dementia in a multicentre, community-based population in England and Wales,” Lancet, vol. 357, no. 9251, pp. 169–175, 2001. View at Publisher · View at Google Scholar · View at Scopus
  40. J. L. Price, D. W. McKeel Jr., and D. W. McKeel, “Neuropathology of nondemented aging: presumptive evidence for preclinical Alzheimer disease,” Neurobiology of Aging, vol. 30, no. 7, pp. 1026–1036, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  41. J. L. Price, P. B. Davis, J. C. Morris, and D. L. White, “The distribution of tangles, plaques and related immunohistochemical markers in healthy aging and Alzheimer's disease,” Neurobiology of Aging, vol. 12, no. 4, pp. 295–312, 1991. View at Publisher · View at Google Scholar · View at Scopus
  42. M. J. West, “Regionally specific loss of neurons in the aging human hippocampus,” Neurobiology of Aging, vol. 14, no. 4, pp. 287–293, 1993. View at Publisher · View at Google Scholar · View at Scopus
  43. M. J. West, P. D. Coleman, D. G. Flood, and J. C. Troncoso, “Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer's disease,” Lancet, vol. 344, no. 8925, pp. 769–772, 1994. View at Publisher · View at Google Scholar · View at Scopus
  44. P. Giannakopoulos, P. R. Hof, E. Kövari, P. G. Vallet, F. R. Herrmann, and C. Bouras, “Distinct patterns of neuronal loss and Alzheimer's disease lesion distribution in elderly individuals older than 90 years,” Journal of Neuropathology and Experimental Neurology, vol. 55, no. 12, pp. 1210–1220, 1996. View at Google Scholar · View at Scopus
  45. T. Gómez-Isla, J. L. Price, D. W. McKeel Jr., J. C. Morris, J. H. Growdon, and B. T. Hyman, “Profound loss of layer II entorhinal cortex neurons occurs in very mild Alzheimer's disease,” Journal of Neuroscience, vol. 16, no. 14, pp. 4491–4500, 1996. View at Google Scholar · View at Scopus
  46. G. McKhann, D. Drachman, and M. Folstein, “Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA work group under the auspices of Department of Health and Human Services Task Force on Alzheimer's disease,” Neurology, vol. 34, no. 7, pp. 939–944, 1984. View at Google Scholar · View at Scopus
  47. R. C. Petersen, “Clinical subtypes of Alzheimer's disease,” Dementia and Geriatric Cognitive Disorders, vol. 9, supplement 3, pp. 16–24, 1998. View at Publisher · View at Google Scholar · View at Scopus
  48. B. Reisberg, S. H. Ferris, M. J. de Leon, and T. Crook, “The global deterioration scale for assessment of primary degenerative dementia,” American Journal of Psychiatry, vol. 139, no. 9, pp. 1136–1139, 1982. View at Google Scholar · View at Scopus
  49. A. von Gunten, C. Bouras, E. Kövari, P. Giannakopoulos, and P. R. Hof, “Neural substrates of cognitive and behavioral deficits in atypical Alzheimer's disease,” Brain Research Reviews, vol. 51, no. 2, pp. 176–211, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  50. J. C. Morris, M. Storandt, D. W. McKeel Jr., E. H. Rubin, J. L. Price, E. A. Grant, and L. Berg, “Cerebral amyloid deposition and diffuse plaques in “normal” aging: evidence for presymptomatic and very mild Alzheimer's disease,” Neurology, vol. 46, no. 3, pp. 707–719, 1996. View at Google Scholar · View at Scopus
  51. D. W. Dickson, H. A. Crystal, and H. A. Crystal, “Identification of normal and pathological aging in prospectively studied nondemented elderly humans,” Neurobiology of Aging, vol. 13, no. 1, pp. 179–189, 1992. View at Publisher · View at Google Scholar · View at Scopus
  52. P. Delaere, C. Duyckaerts, C. Masters, K. Beyreuther, F. Piette, and J.-J. Hauw, “Large amounts of neocortical βA4 deposits without neuritic plaques nor tangles in a psychometrically assessed, non-demented person,” Neuroscience Letters, vol. 116, no. 1-2, pp. 87–93, 1990. View at Publisher · View at Google Scholar · View at Scopus
  53. H. Braak and E. Braak, “Neuropathological stageing of Alzheimer-related changes,” Acta Neuropathologica, vol. 82, no. 4, pp. 239–259, 1991. View at Google Scholar · View at Scopus
  54. D. L. Price, “Aging of the brain and dementia of the Alzheimer type,” in Principles of Neural Science, E. R. Kandel, J. H. Schwartz, and T. M. Jessell, Eds., pp. 1149–1168, McGraw-Hill, New York, NY, USA, 4th edition, 2000. View at Google Scholar
  55. L. R. Squire, “Mechanisms of memory,” Science, vol. 232, no. 4758, pp. 1612–1619, 1986. View at Google Scholar · View at Scopus
  56. L. R. Squire, “Memory systems of the brain: a brief history and current perspective,” Neurobiology of Learning and Memory, vol. 82, no. 3, pp. 171–177, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  57. L. R. Squire, C. E. L. Stark, and R. E. Clark, “The medial temporal lobe,” Annual Review of Neuroscience, vol. 27, pp. 279–306, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  58. J. L. Price, A. I. Ko, M. J. Wade, S. K. Tsou, D. W. McKeel, and J. C. Morris, “Neuron number in the entorhinal cortex and CA1 in preclinical alzheimer disease,” Archives of Neurology, vol. 58, no. 9, pp. 1395–1402, 2001. View at Google Scholar · View at Scopus
  59. L. M. Levy, R. I. Henkin, A. Hutter, C. S. Lin, D. Martins, and D. Schellinger, “Functional MRI of human olfaction,” Journal of Computer Assisted Tomography, vol. 21, no. 6, pp. 849–856, 1997. View at Publisher · View at Google Scholar · View at Scopus
  60. R. I. Mesholam, P. J. Moberg, R. N. Mahr, and R. L. Doty, “Olfaction in neurodegenerative disease: a meta-analysis of olfactory functioning in Ahlzheimer's and Parkinson's diseases,” Archives of Neurology, vol. 55, no. 1, pp. 84–90, 1998. View at Publisher · View at Google Scholar · View at Scopus
  61. D. P. Devanand, K. S. Michaels-Marston, and K. S. Michaels-Marston, “Olfactory deficits in patients with mild cognitive impairment predict Alzheimer's disease at follow-up,” American Journal of Psychiatry, vol. 157, no. 9, pp. 1399–1405, 2000. View at Publisher · View at Google Scholar · View at Scopus
  62. K. A. Nielson, B. J. Cummings, and C. W. Cotman, “Constructional apraxia in Alzheimer's disease correlates with neuritic neuropathology in occipital cortex,” Brain Research, vol. 741, no. 1-2, pp. 284–293, 1996. View at Publisher · View at Google Scholar · View at Scopus
  63. P. Giannakopoulos, G. Gold, M. Duc, J.-P. Michel, P. R. Hof, and C. Bouras, “Neuroanatomic correlates of visual agnosia in Alzheimer's disease: a clinicopathologic study,” Neurology, vol. 52, no. 1, pp. 71–77, 1999. View at Google Scholar · View at Scopus
  64. P. Giannakopoulos, G. Gold, M. Duc, J.-P. Michel, P.-R. Hof, and C. Bouras, “Impaired processing of famous faces in Alzheimer's disease is related to neurofibrillary tangle densities in the prefrontal and anterior cingulate cortex,” Dementia and Geriatric Cognitive Disorders, vol. 11, no. 6, pp. 336–341, 2000. View at Google Scholar · View at Scopus
  65. P. Giannakopoulos, G. Gold, M. Duc, J.-P. Michel, P. R. Hof, and C. Bouras, “Neural substrates of spatial and temporal disorientation in Alzheimer's disease,” Acta Neuropathologica, vol. 100, no. 2, pp. 189–195, 2000. View at Google Scholar · View at Scopus
  66. G. M. Savva, S. B. Wharton, P. G. Ince, G. Forster, F. E. Matthews, and C. Brayne, “Age, neuropathology, and dementia,” New England Journal of Medicine, vol. 360, no. 22, pp. 2302–2309, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  67. P. Delaere, Y. He, G. Fayet, C. Duyckaerts, and J.-J. Hau, “βA4 deposits are constant in the brain of the oldest old: an immunocytochemical study of 20 French centenarians,” Neurobiology of Aging, vol. 14, no. 2, pp. 191–194, 1993. View at Google Scholar · View at Scopus
  68. P. R. Hof, T. Bussière, and T. Bussière, “Stereologic evidence for persistence of viable neurons in layer II of the entorhinal cortex and the CA1 field in Alzheimer disease,” Journal of Neuropathology and Experimental Neurology, vol. 62, no. 1, pp. 55–67, 2003. View at Google Scholar · View at Scopus
  69. C. Bouras, P. R. Hof, and J. H. Morrison, “Neurofibrillary tangle densities in the hippocampal formation in a non-demented population define subgroups of patients with differential early pathologic changes,” Neuroscience Letters, vol. 153, no. 2, pp. 131–135, 1993. View at Publisher · View at Google Scholar · View at Scopus
  70. C. Bouras, P. R. Hof, P. Giannakopoulos, J.-P. Michel, and J. H. Morrison, “Regional distribution of neurofibrillary tangles and senile plaques in the cerebral cortex of elderly patients: a quantitative evaluation of a one-year autopsy population from a geriatric hospital,” Cerebral Cortex, vol. 4, no. 2, pp. 138–150, 1994. View at Google Scholar · View at Scopus
  71. P. R. Hof, L. M. Bierer, D. P. Perl, A. Delacourte, L. Buee, C. Bouras, and J. H. Morrison, “Evidence for early vulnerability of the medial and inferior aspects of the temporal lobe in an 82-year-old patient with preclinical signs of dementia: regional and laminar distribution of neurofibrillary tangles and senile plaques,” Archives of Neurology, vol. 49, no. 9, pp. 946–953, 1992. View at Google Scholar · View at Scopus
  72. J. H. Kordower, Y. Chu, G. T. Stebbins, S. T. Dekosky, E. J. Cochran, D. Bennett, and E. J. Mufson, “Loss and atrophy of layer II entorhinal cortex neurons in elderly people with mild cognitive impairment,” Annals of Neurology, vol. 49, no. 2, pp. 202–213, 2001. View at Publisher · View at Google Scholar · View at Scopus
  73. J. J. Kril, S. Patel, A. J. Harding, and G. M. Halliday, “Neuron loss from the hippocampus of Alzheimer's disease exceeds extracellular neurofibrillary tangle formation,” Acta Neuropathologica, vol. 103, no. 4, pp. 370–376, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  74. G. Šimić, I. Kostović, B. Winblad, and N. Bogdanović, “Volume and number of neurons of the human hippocampal formation in normal aging and Alzheimer's disease,” Journal of Comparative Neurology, vol. 379, no. 4, pp. 482–494, 1997. View at Publisher · View at Google Scholar · View at Scopus
  75. Y. Itoh, M. Yamada, N. Suematsu, M. Matsushita, and E. Otomo, “An immunohistochemical study of centenarian brains: a comparison,” Journal of the Neurological Sciences, vol. 157, no. 1, pp. 73–81, 1998. View at Publisher · View at Google Scholar · View at Scopus
  76. P. Giannakopoulos, P. R. Hof, A.-S. Giannakopoulos, V. Buee-Scherrer, M. Surini, A. Delacourte, and C. Bouras, “Dementia in the oldest-old: quantitative analysis of 12 cases from a psychiatric hospital,” Dementia, vol. 5, no. 6, pp. 348–356, 1994. View at Google Scholar · View at Scopus
  77. P. Giannakopoulos, P. R. Hof, A.-S. Giannakopoulos, F. R. Herrmann, J. P. Michel -, and C. Bouras, “Regional distribution of neurofibrillary tangles and senile plaques in the cerebral cortex of very old patients,” Archives of Neurology, vol. 52, no. 12, pp. 1150–1159, 1995. View at Google Scholar · View at Scopus
  78. A. von Gunten, E. Kövari, and E. Kövari, “Cognitive impact of neuronal pathology in the entorhinal cortex and CA1 field in Alzheimer's disease,” Neurobiology of Aging, vol. 27, no. 2, pp. 270–277, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  79. P. V. Arriagada, K. Marzloff, and B. T. Hyman, “Distribution of Alzheimer-type pathologic changes in nondemented elderly individuals matches the pattern in Alzheimer's disease,” Neurology, vol. 42, no. 9, pp. 1681–1688, 1992. View at Google Scholar · View at Scopus
  80. P. V. Arriagada, J. H. Growdon, E. T. Hedley-Whyte, and B. T. Hyman, “Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease,” Neurology, vol. 42, no. 3, pp. 631–639, 1992. View at Google Scholar · View at Scopus
  81. P. Giannakopoulos, F. R. Herrmann, and F. R. Herrmann, “Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer's disease,” Neurology, vol. 60, no. 9, pp. 1495–1500, 2003. View at Google Scholar · View at Scopus
  82. T. Bussière, P. D. Friend, and P. D. Friend, “Stereologic assessment of the total cortical volume occupied by amyloid deposits and its relationship with cognitive status in aging and Alzheimer's disease,” Neuroscience, vol. 112, no. 1, pp. 75–91, 2002. View at Publisher · View at Google Scholar · View at Scopus
  83. J.-J. Hauw, P. Vignolo, and C. Duyckaerts, “Etude neuropathologique de 12 centenaires: la fréquence de la démence sénile de type Alzheimer n'est pas particulièrement élevée danc ce groupe de personne très âgées,” Revue Neurologique, vol. 142, no. 2, pp. 107–115, 1986. View at Google Scholar
  84. F. García-Sierra, J. J. Hauw, C. Duyckaerts, C. M. Wischik, J. Luna-Muñoz, and R. Mena, “The extent of neurofibrillary pathology in perforant pathway neurons is the key determinant of dementia in the very old,” Acta Neuropathologica, vol. 100, no. 1, pp. 29–35, 2000. View at Publisher · View at Google Scholar · View at Scopus
  85. A. von Gunten, E. Kövari, C.-B. Rivara, C. Bouras, P. R. Hof, and P. Giannakopoulos, “Stereologic analysis of hippocampal Alzheimer's disease pathology in the oldest-old: evidence for sparing of the entorhinal cortex and CA1 field,” Experimental Neurology, vol. 193, no. 1, pp. 198–206, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  86. A. J. Harding, G. M. Halliday, and J. J. Kril, “Variation in hippocampal neuron number with age and brain volume,” Cerebral Cortex, vol. 8, no. 8, pp. 710–718, 1998. View at Google Scholar · View at Scopus
  87. D. W. Dickson, H. A. Crystal, C. Bevona, W. Honer, I. Vincent, and P. Davies, “Correlations of synaptic and pathological markers with cognition of the elderly,” Neurobiology of Aging, vol. 16, no. 3, pp. 285–298, 1995. View at Publisher · View at Google Scholar · View at Scopus
  88. T. W. Mitchell, J. Nissanov, and J. Nissanov, “Novel method to quantify neuropil threads in brains from elders with or without cognitive impairment,” Journal of Histochemistry and Cytochemistry, vol. 48, no. 12, pp. 1627–1637, 2000. View at Google Scholar · View at Scopus
  89. P. Giannakopoulos, A. von Gunten, E. Kövari, G. Gold, F. R. Herrmann, P. R. Hof, and C. Bouras, “Stereological analysis of neuropil threads in the hippocampal formation: relationships with Alzheimer's disease neuronal pathology and cognition,” Neuropathology and Applied Neurobiology, vol. 33, no. 3, pp. 334–343, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  90. G. Lace, G. M. Savva, and G. M. Savva, “Hippocampal tau pathology is related to neuroanatomical connections: an ageing population-based study,” Brain, vol. 132, no. 5, pp. 1324–1334, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  91. D. Iacono, W. R. Markesbery, M. Gross, O. Pletnikova, G. Rudow, P. Zandi, and J. C. Troncoso, “The Nun Study: clinically silent AD, neuronal hypertrophy, and linguistic skills in early life,” Neurology, vol. 73, no. 9, pp. 665–673, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  92. T. L. Bailey, C. B. Rivara, A. B. Rocher, and P. R. Hof, “The nature and effects of cortical microvascular pathology in aging and Alzheimer's disease,” Neurological Research, vol. 26, no. 5, pp. 573–578, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  93. L. Buee, P. R. Hof, C. Bouras, A. Delacourte, D. P. Perl, J. H. Morrison, and H. M. Fillit, “Pathological alterations of the cerebral microvasculature in Alzheimer's disease and related dementing disorders,” Acta Neuropathologica, vol. 87, no. 5, pp. 469–480, 1994. View at Publisher · View at Google Scholar · View at Scopus
  94. E. Farkas and P. G. M. Luiten, “Cerebral microvascular pathology in aging and Alzheimer's disease,” Progress in Neurobiology, vol. 64, no. 6, pp. 575–611, 2001. View at Publisher · View at Google Scholar · View at Scopus
  95. G. Gold, P. Giannakopoulos, and C. Bouras, “Reevaluating the role of vascular changes in the differential diagnosis of Alzheimer's disease and vascular dementia,” European Neurology, vol. 40, no. 3, pp. 121–129, 1998. View at Publisher · View at Google Scholar · View at Scopus
  96. W. Meier-Ruge, J. Ulrich, and S. Abdel-Al, “Stereologic findings in normal brain aging and Alzheimer's disease,” in Senile Dementia: Outlook for the Future, J. Werthemimer and M. Marios, Eds., pp. 125–135, Alan R. Liss, New York, NY, USA, 1984. View at Google Scholar
  97. W. B. Abernethy, M. A. Bell, M. Morris, and D. M. Moody, “Microvascular density of the human paraventricular nucleus decreases with aging but not hypertension,” Experimental Neurology, vol. 121, no. 2, pp. 270–274, 1993. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  98. F. Amenta, D. Cavallotti, M. Del Valle, M. Mancini, F. J. Naves, J. A. Vega, and Y.-C. Zeng, “Age-related changes in brain microanatomy: sensitivity to treatment with the dihydropyridine calcium channel blocker darodipine (PY 108-068),” Brain Research Bulletin, vol. 36, no. 5, pp. 453–460, 1995. View at Publisher · View at Google Scholar · View at Scopus
  99. F. Amenta, F. Ferrante, M. Mancini, M. Sabbatini, J. Vega, and D. Zaccheo, “Effect of long term treatment with the dihydropyridine-type calcium channel blocker darodipine (PY 108-068) on the cerebral capillary network in aged rats,” Mechanisms of Ageing and Development, vol. 78, no. 1, pp. 27–37, 1995. View at Publisher · View at Google Scholar · View at Scopus
  100. D. M. A. Mann, N. R. Eaves, B. Marcyniuk, and P. O. Yates, “Quantitative changes in cerebral cortical microvasculature in ageing and dementia,” Neurobiology of Aging, vol. 7, no. 5, pp. 321–330, 1986. View at Google Scholar · View at Scopus
  101. W. E. Sonntag, C. D. Lynch, P. T. Cooney, and P. M. Hutchins, “Decreases in cerebral microvasculature with age are associated with the decline in growth hormone and insulin-like growth factor 1,” Endocrinology, vol. 138, no. 8, pp. 3515–3520, 1997. View at Publisher · View at Google Scholar · View at Scopus
  102. M. A. Bell and M. J. Ball, “Morphometric comparison of hippocampal microvasculature in ageing and demented people: diameters and densities,” Acta Neuropathologica, vol. 53, no. 4, pp. 299–318, 1981. View at Google Scholar · View at Scopus
  103. O. Hunziker, S. Abdel'Al, and U. Schulz, “The aging human cerebral cortex: a serological characterization of changes in the capillary net,” Journals of Gerontology, vol. 34, no. 3, pp. 345–350, 1979. View at Google Scholar · View at Scopus
  104. G. D. Lee, J. H. Aruna, P. M. Barrett, D.-L. Lei, D. K. Ingram, and P. R. Mouton, “Stereological analysis of microvascular parameters in a double transgenic model of Alzheimer's disease,” Brain Research Bulletin, vol. 65, no. 4, pp. 317–322, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  105. A. Løkkegaard, J. R. Nyengaard, and M. J. West, “Stereological estimates of number and length of capillaries in subdivisions of the human hippocampal region,” Hippocampus, vol. 11, no. 6, pp. 726–740, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  106. C. Bouras, E. Kövari, and E. Kövari, “Stereologic analysis of microvascular morphology in the elderly: Alzheimer disease pathology and cognitive status,” Journal of Neuropathology and Experimental Neurology, vol. 65, no. 3, pp. 235–244, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  107. J. C. de la Torre and T. Mussivand, “Can disturbed brain microcirculation cause Alzheimer's disease?” Neurological Research, vol. 15, no. 3, pp. 146–153, 1993. View at Google Scholar · View at Scopus
  108. T. Kimura, T. Hashimura, and T. Miyakawa, “Observations of microvessels in the brain with Alzheimer's disease by the scanning electron microscopy,” Japanese Journal of Psychiatry and Neurology, vol. 45, no. 3, pp. 671–676, 1991. View at Google Scholar · View at Scopus
  109. G. I. De Jong, E. Farkas, C. M. Stienstra, J. R. M. Plass, J. N. Keijser, J. C. De La Torre, and P. G. M. Luiten, “Cerebral hypoperfusion yields capillary damage in the hippocampal CA1 area that correlates with spatial memory impairment,” Neuroscience, vol. 91, no. 1, pp. 203–210, 1999. View at Publisher · View at Google Scholar · View at Scopus
  110. W. Kuschinsky and O. B. Paulson, “Capillary circulation in the brain,” Cerebrovascular and Brain Metabolism Reviews, vol. 4, no. 3, pp. 261–286, 1992. View at Google Scholar · View at Scopus
  111. A. G. Hudetz, G. Fehér, and J. P. Kampine, “Heterogeneous autoregulation of cerebrocortical capillary flow: evidence for functional thoroughfare channels?” Microvascular Research, vol. 51, no. 1, pp. 131–136, 1996. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  112. T. Bär, “The vascular system of the cerebral cortex,” Advances in Anatomy, Embryology, and Cell Biology, vol. 59, pp. 1–62, 1980. View at Google Scholar · View at Scopus
  113. T. Perls, “Centenarians who avoid dementia,” Trends in Neurosciences, vol. 27, no. 10, pp. 633–636, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  114. J. J. Kril, “Alzheimer disease neuropathology in the oldest old,” Nature Reviews. Neurology, vol. 5, no. 8, pp. 411–412, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  115. R. G. Cutler, “Evolution of human longevity and the genetic complexity governing aging rate,” Proceedings of the National Academy of Sciences of the United States of America, vol. 72, no. 11, pp. 4664–4668, 1975. View at Google Scholar · View at Scopus
  116. F. Schächter, “Causes, effects, and constraints in the genetics of human longevity,” American Journal of Human Genetics, vol. 62, no. 5, pp. 1008–1014, 1998. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  117. J. A. Kaye, “Oldest-old healthy brain function: the genomic potentials,” Archives of Neurology, vol. 54, no. 10, pp. 1217–1221, 1997. View at Google Scholar · View at Scopus
  118. T. Perls, L. M. Kunkel, and A. A. Puca, “The genetics of exceptional human longevity,” Journal of the American Geriatrics Society, vol. 50, no. 2, pp. 359–368, 2002. View at Publisher · View at Google Scholar · View at Scopus
  119. A. A. Puca, M. J. Daly, and M. J. Daly, “A genome-wide scan for linkage to human exceptional longevity identifies a locus on chromosome 4,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 18, pp. 10505–10508, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  120. B. J. Geesaman, E. Benson, and E. Benson, “Haplotype-based identification of a microsomal transfer protein marker associated with the human lifespan,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 2, pp. 14115–14120, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  121. N. Barzilai, G. Atzmon, and G. Atzmon, “Unique lipoprotein phenotype and genotype associated with exceptional longevity,” Journal of the American Medical Association, vol. 290, no. 15, pp. 2030–2040, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus