Centenarians as Models of Resistance and Resilience to Alzheimer’s Disease and Related Dementias-Advances in Geriatric Medicine and Research-CSCIED科技核心评价数据库-手机版

Centenarians as Models of Resistance and Resilience to Alzheimer’s Disease and Related Dementias

Centenarians as Models of Resistance and Resilience to Alzheimer’s Disease and Related Dementias

ES评分 0 浏览量：357 下载量：0

DOI	10.20900/agmr20200018
刊名	Advances in Geriatric Medicine and Research AGMR
年，卷(期)	2020, 2(3)
作者	Stacy L. Andersen*,
作者单位	Department of Medicine, Boston University School of Medicine, Boston, MA 02118 ;
Abstract	The majority of research to understand the pathogenesis of and contributors to Alzheimer’s disease (AD) pathology, dementia, and disease progression has focused on studying individuals who have the disease or are at increased risk of having the disease. Yet there may be much to learn from individuals who have a paradoxical decreased risk of AD suggesting underlying protective factors. Centenarians demonstrate exceptional longevity that for a subset of the cohort is associated with an increased health span characterized by the delay or escape of age-related diseases including dementia. Here, I give evidence of the association of exceptional longevity with resistance and resilience to AD and describe how cohorts of centenarians and their offspring may serve as models of neuroprotection from AD. Discoveries of novel genetic, environmental, and behavioral factors that are associated with a decreased risk of AD may inform the development of interventions to slow or prevent AD in the general population. Centenarian cohorts may also be instrumental in serving as controls to individuals with AD to identify additional risk factors.
KeyWord	centenarian; longevity; health span; dementia; resilience; resistance; neurodegenerative
基金项目
页码	-

参考文献
相关文献

1.Arenaza-Urquijo EM, Vemuri P. Resistance vs resilience to Alzheimer disease: Clarifying terminology for preclinical studies. Neurology. 2018;90(15):695-703. doi: 10.1212/WNL.0000000000005303

2.Andersen SL, Sebastiani P, Dworkis DA, Feldman L, Perls TT. Health span approximates life span among many supercentenarians: compression of morbidity at the approximate limit of life span. J Gerontol A Biol Sci Med Sci. 2012;67(4):395-405. doi: 10.1093/gerona/glr223

3.Niccoli T, Partridge L. Ageing as a risk factor for disease. Curr Biol. 2012;22(17):R741-52. doi: 10.1016/j.cub.2012.07.024

4.Crimmins EM, Beltran-Sanchez H. Mortality and morbidity trends: is there compression of morbidity? J Gerontol B Psychol Sci Soc Sci. 2011;66(1):75-86. doi: 10.1093/geronb/gbq088

5.DALYs GBD, Collaborators H. Global, regional, and national disability-adjusted life-years (DALYs) for 359 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392(10159):1859-922. doi: 10.1016/S0140-6736(18)32335-3

6.Ismail K, Nussbaum L, Sebastiani P, Andersen S, Perls T, Barzilai N, et al. Compression of Morbidity Is Observed Across Cohorts with Exceptional Longevity. J Am Geriatr Soc. 2016;64(8):1583-91. doi: 10.1111/jgs.14222

7.Ailshire JA, Beltran-Sanchez H, Crimmins EM. Becoming centenarians: disease and functioning trajectories of older US Adults as they survive to 100. J Gerontol A. 2015;70(2):193-201. doi: 10.1093/gerona/glu124

8.Engberg H, Oksuzyan A, Jeune B, Vaupel JW, Christensen K. Centenarians--a useful model for healthy aging? A 29-year follow-up of hospitalizations among 40,000 Danes born in 1905. Aging Cell. 2009;8(3):270-6. doi: 10.1111/j.1474-9726.2009.00474.x

9.Fries JF. Aging, natural death, and the compression of morbidity. N Engl J Med. 1980;303(3):130-5. doi: 10.1056/NEJM198007173030304

10.Arai Y, Inagaki H, Takayama M, Abe Y, Saito Y, Takebayashi T, et al. Physical independence and mortality at the extreme limit of life span: supercentenarians study in Japan. J Gerontol A. 2014;69(4):486-94. doi: 10.1093/gerona/glt146

11.Hebert LE, Weuve J, Scherr PA, Evans DA. Alzheimer disease in the United States (2010–2050) estimated using the 2010 census. Neurology. 2013;80(19):1778-83. doi: 10.1212/WNL.0b013e31828726f5

12.Andersen-Ranberg K, Vasegaard L, Jeune B. Dementia is not inevitable: a population-based study of Danish centenarians. J Gerontol B. 2001;56(3):P152-9. doi: 10.1093/geronb/56.3.P152

13.Neltner JH, Abner EL, Jicha GA, Schmitt FA, Patel E, Poon LW, et al. Brain pathologies in extreme old age. Neurobiol Aging. 2016;37:1-11. doi: 10.1016/j.neurobiolaging.2015.10.009

14.Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP. The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement. 2013;9(1):63-75.e2. doi: 10.1016/j.jalz.2012.11.007

15.Ritchie K, Kildea D. Is senile dementia “age-related” or “ageing-related”?--evidence from meta-analysis of dementia prevalence in the oldest old. Lancet. 1995;346(8980):931-4. doi: 10.1016/S0140-6736(95)91556-7

16.Calvert JF Jr, Hollander-Rodriguez J, Kaye J, Leahy M. Dementia-free survival among centenarians: an evidence-based review. J Gerontol A. 2006;61(9):951-6. doi: 10.1093/gerona/61.9.951

17.Silver MH, Jilinskaia E, Perls TT. Cognitive functional status of age-confirmed centenarians in a population-based study. J Gerontol B. 2001;56(3):P134-40. doi: 10.1093/geronb/56.3.P134

18.Kliegel M, Moor C, Rott C. Cognitive status and development in the oldest old: a longitudinal analysis from the Heidelberg Centenarian Study. Arch Gerontol Geriatr. 2004;39(2):143-56. doi: 10.1016/j.archger.2004.02.004

19.Motta M, Ferlito L, Magnolfi SU, Petruzzi E, Pinzani P, Malentacchi F, et al. Cognitive and functional status in the extreme longevity. Arch Gerontol Geriatr. 2008;46(2):245-52. doi: 10.1016/j.archger.2007.04.004

20.Engberg H, Christensen K, Andersen-Ranberg K, Jeune B. Cohort changes in cognitive function among Danish centenarians. A comparative study of 2 birth cohorts born in 1895 and 1905. Dement Geriatr Cogn Disord. 2008;26(2):153-60. doi: 10.1159/000149819

21.Poon LW, Woodard JL, Stephen Miller L, Green R, Gearing M, Davey A, et al. Understanding dementia prevalence among centenarians. J Gerontol A Biol Sci Med Sci. 2012;67(4):358-65. doi: 10.1093/gerona/glr250

22.Zeng Y, Feng Q, Gu D, Vaupel JW. Demographics, phenotypic health characteristics and genetic analysis of centenarians in China. Mech Ageing Dev. 2017;165(Pt B):86-97. doi: 10.1016/j.mad.2016.12.010

23.Sebastiani P, Solovieff N, Dewan AT, Walsh KM, Puca A, Hartley SW, et al. Genetic signatures of exceptional longevity in humans. PLoS One. 2012;7(1):e29848. doi: 10.1371/journal.pone.0029848

24.Garagnani P, Giuliani C, Pirazzini C, Olivieri F, Bacalini MG, Ostan R, et al. Centenarians as super-controls to assess the biological relevance of genetic risk factors for common age-related diseases: a proof of principle on type 2 diabetes. Aging. 2013;5(5):373-85. doi: 10.18632/aging.100562

25.Tesi N, van der Lee SJ, Hulsman M, Jansen IE, Stringa N, van Schoor N, et al. Centenarian controls increase variant effect sizes by an average twofold in an extreme case-extreme control analysis of Alzheimerʼs disease. Eur J Hum Genet. 2019;27(2):244-53. doi: 10.1038/s41431-018-0273-5

26.Freudenberg-Hua Y, Freudenberg J, Vacic V, Abhyankar A, Emde AK, Ben-Avraham D, et al. Disease variants in genomes of 44 centenarians. Mol Genet Genomic Med. 2014;2(5):438-50. doi: 10.1002/mgg3.86

27.Sebastiani P, Gurinovich A, Bae H, Andersen S, Malovini A, Atzmon G, et al. Four Genome-Wide Association Studies Identify New Extreme Longevity Variants. J Gerontol A. 2017;72(11):1453-64. doi: 10.1093/gerona/glx027

28.Zeng Y, Nie C, Min J, Liu X, Li M, Chen H, et al. Novel loci and pathways significantly associated with longevity. Sci Rep. 2016;6:21243. doi: 10.1038/srep21243

29.Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al. NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018;14(4):535-62. doi: 10.1016/j.jalz.2018.02.018

30.Braak H, Thal DR, Ghebremedhin E, Del Tredici K. Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years. J Neuropathol Exp Neurol. 2011;70(11):960-9. doi: 10.1097/NEN.0b013e318232a379

31.Ganz AB, Beker N, Hulsman M, Sikkes S, Netherlands Brain B, Scheltens P, et al. Neuropathology and cognitive performance in self-reported cognitively healthy centenarians. Acta Neuropathol Commun. 2018;6(1):64. doi: 10.1186/s40478-018-0558-5

32.Crary JF, Trojanowski JQ, Schneider JA, Abisambra JF, Abner EL, Alafuzoff I, et al. Primary age-related tauopathy (PART): a common pathology associated with human aging. Acta Neuropathol. 2014;128(6):755-66. doi: 10.1007/s00401-014-1349-0

33.Duyckaerts C, Braak H, Brion JP, Buee L, Del Tredici K, Goedert M, et al. PART is part of Alzheimer disease. Acta Neuropathol. 2015;129(5):749-56. doi: 10.1007/s00401-015-1390-7

34.Del Tredici K, Braak H. Neurofibrillary changes of the Alzheimer type in very elderly individuals: neither inevitable nor benign: Commentary on “No disease in the brain of a 115-year-old woman”. Neurobiol Aging. 2008;29(8):1133-6. doi: 10.1016/j.neurobiolaging.2008.04.016

35.Brookmeyer R, Gray S, Kawas C. Projections of Alzheimerʼs disease in the United States and the public health impact of delaying disease onset. Am J Public Health. 1998;88(9):1337-42. doi: 10.2105/ajph.88.9.1337

36.Alzgene. Meta-analysis of all published AD association studies (case-control only) APOE_E2/3/4. Available from: http://www.alzgene.org/meta.asp?geneID=83. Accessed 2020 Jun 30.

37.Yamazaki Y, Zhao N, Caulfield TR, Liu CC, Bu G. Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies. Nat Rev Neurol. 2019;15(9):501-18. doi: 10.1038/s41582-019-0228-7

38.Ryu S, Atzmon G, Barzilai N, Raghavachari N, Suh Y. Genetic landscape of APOE in human longevity revealed by high-throughput sequencing. Mech Ageing Dev. 2016;155:7-9. doi: 10.1016/j.mad.2016.02.010

39.Schachter F, Faure-Delanef L, Guenot F, Rouger H, Froguel P, Lesueur-Ginot L, et al. Genetic associations with human longevity at the APOE and ACE loci. Nat Genet. 1994;6(1):29-32. doi: 10.1038/ng0194-29

40.Sebastiani P, Gurinovich A, Nygaard M, Sasaki T, Sweigart B, Bae H, et al. APOE Alleles and Extreme Human Longevity. J Gerontol A. 2019;74(1):44-51. doi: 10.1093/gerona/gly174

41.Sebastiani P, Monti S, Morris M, Gurinovich A, Toshiko T, Andersen SL, et al. A serum protein signature of APOE genotypes in centenarians. Aging Cell. 2019;18(6):e13023. doi: 10.1111/acel.13023

42.Hadar A, Milanesi E, Walczak M, Puzianowska-Kuznicka M, Kuznicki J, Squassina A, et al. SIRT1, miR-132 and miR-212 link human longevity to Alzheimerʼs Disease. Sci Rep. 2018;8(1):8465. doi: 10.1038/s41598-018-26547-6

43.Spira AP, Gamaldo AA, An Y, Wu MN, Simonsick EM, Bilgel M, et al. Self-reported sleep and beta-amyloid deposition in community-dwelling older adults. JAMA Neurol. 2013;70(12):1537-43. doi: 10.1001/jamaneurol.2013.4258

44.Klein L, Gao T, Barzilai N, Milman S. Association between Sleep Patterns and Health in Families with Exceptional Longevity. Front Med. 2017;4:214. doi: 10.3389/fmed.2017.00214

45.Nyberg L, Lovden M, Riklund K, Lindenberger U, Backman L. Memory aging and brain maintenance. Trends Cogn Sci. 2012;16(5):292-305. doi: 10.1016/j.tics.2012.04.005

46.Windle G, Bennett KM, Noyes J. A methodological review of resilience measurement scales. Health Qual Life Outcomes. 2011;9:8. doi: 10.1186/1477-7525-9-8

47.Kapasi A, DeCarli C, Schneider JA. Impact of multiple pathologies on the threshold for clinically overt dementia. Acta Neuropathol. 2017;134(2):171-86. doi: 10.1007/s00401-017-1717-7

48.Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R, et al. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA. 1997;278(16):1349-56.

49.Jansen WJ, Ossenkoppele R, Knol DL, Tijms BM, Scheltens P, Verhey FR, et al. Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis. JAMA. 2015;313(19):1924-38. doi: 10.1001/jama.2015.4668

50.Mortimer JA, Snowdon DA, Markesbery WR. The effect of APOE-epsilon4 on dementia is mediated by Alzheimer neuropathology. Alzheimer Dis Assoc Disord. 2009;23(2):152-7. doi: 10.1097/wad.0b013e318190a855

51.Nicoll JA, Savva GM, Stewart J, Matthews FE, Brayne C, Ince P, et al. Association between APOE genotype, neuropathology and dementia in the older population of England and Wales. Neuropathol Appl Neurobiol. 2011;37(3):285-94. doi: 10.1111/j.1365-2990.2010.01130.x

52.Yu L, Boyle PA, Leurgans S, Schneider JA, Bennett DA. Disentangling the effects of age and APOE on neuropathology and late life cognitive decline. Neurobiol Aging. 2014;35(4):819-26. doi: 10.1016/j.neurobiolaging.2013.10.074

53.Savva GM, Wharton SB, Ince PG, Forster G, Matthews FE, Brayne C. Age, neuropathology, and dementia. N Engl J Med. 2009;360(22):2302-9. doi: 10.1056/NEJMoa0806142

54.Gold G, Bouras C, Kovari E, Canuto A, Glaria BG, Malky A, et al. Clinical validity of Braak neuropathological staging in the oldest-old. Acta Neuropathol. 2000;99(5):579-82; discussion 83-4. doi: 10.1007/s004010051163

55.Yang Z, Wen W, Jiang J, Crawford JD, Reppermund S, Levitan C, et al. Age-associated differences on structural brain MRI in nondemented individuals from 71 to 103 years. Neurobiol Aging. 2016;40:86-97. doi: 10.1016/j.neurobiolaging.2016.01.006

56.Jack CR Jr, Knopman DS, Jagust WJ, Shaw LM, Aisen PS, Weiner MW, et al. Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. Lancet Neurol. 2010;9(1):119-28. doi: 10.1016/S1474-4422(09)70299-6

57.Nelson PT, Abner EL, Schmitt FA, Kryscio RJ, Jicha GA, Smith CD, et al. Modeling the association between 43 different clinical and pathological variables and the severity of cognitive impairment in a large autopsy cohort of elderly persons. Brain Pathol. 2010;20(1):66-79. doi: 10.1111/j.1750-3639.2008.00244.x

58.Stern Y. Cognitive reserve in ageing and Alzheimer's disease. Lancet Neurology. 2012;11(11):1006-12. doi: 10.1016/S1474-4422(12)70191-6

59.Katzman R, Terry R, DeTeresa R, Brown T, Davies P, Fuld P, et al. Clinical, pathological, and neurochemical changes in dementia: a subgroup with preserved mental status and numerous neocortical plaques. Ann Neurol. 1988;23(2):138-44. doi: 10.1002/ana.410230206

60.Satz P. Brain reserve capacity on symptom onset after brain injury: A formulation and review of evidence for threshold theory. Neuropsychology. 1993;7(3):273-95. doi: 10.1037/0894-4105.7.3.273

61.Stern Y. Cognitive reserve. Neuropsychologia. 2009;47(10):2015-28. doi: 10.1016/j.neuropsychologia.2009.03.004

62.Cabeza R. Hemispheric asymmetry reduction in older adults: the HAROLD model. Psychol Aging. 2002;17(1):85-100. doi: 10.1037//0882-7974.17.1.85

63.Lam B, Masellis M, Freedman M, Stuss DT, Black SE. Clinical, imaging, and pathological heterogeneity of the Alzheimer's disease syndrome. Alzheimers Res Ther. 2013;5(1):1. doi: 10.1186/alzrt155

64.Nelson PT, Schmitt FA, Lin Y, Abner EL, Jicha GA, Patel E, et al. Hippocampal sclerosis in advanced age: clinical and pathological features. Brain. 2011;134(Pt 5):1506-18. doi: 10.1093/brain/awr053

65.Ding ZT, Wang Y, Jiang YP, Yoshida M, Mimuro M, Inagaki T, et al. Argyrophilic grain disease: frequency and neuropathology in centenarians. Acta Neuropathol. 2006;111(4):320-8. doi: 10.1007/s00401-006-0043-2

66.Ding ZT, Wang Y, Jiang YP, Hashizume Y, Yoshida M, Mimuro M, et al. Characteristics of alpha-synucleinopathy in centenarians. Acta Neuropathol. 2006;111(5):450-8. doi: 10.1007/s00401-005-0015-y

67.Rahimi J, Kovacs GG. Prevalence of mixed pathologies in the aging brain. Alzheimers Res Ther. 2014;6(9):82. doi: 10.1186/s13195-014-0082-1

68.Sebastiani P, Nussbaum L, Andersen SL, Black MJ, Perls TT. Increasing Sibling Relative Risk of Survival to Older and Older Ages and the Importance of Precise Definitions of “Aging”, “Life Span”, and “Longevity”. J Gerontol A. 2016;71(3):340-6. doi: 10.1093/gerona/glv020

69.Terry DF, Wilcox MA, McCormick MA, Pennington JY, Schoenhofen EA, Andersen SL, et al. Lower all-cause, cardiovascular, and cancer mortality in centenariansʼ offspring. J Am Geriatr Soc. 2004;52(12):2074-6. doi: 10.1111/j.1532-5415.2004.52561.x

70.Mitchell BD, Hsueh WC, King TM, Pollin TI, Sorkin J, Agarwala R, et al. Heritability of life span in the Old Order Amish. Am J Med Genet. 2001;102(4):346-52. doi: 10.1002/ajmg.1483

71.Ruby JG, Wright KM, Rand KA, Kermany A, Noto K, Curtis D, et al. Estimates of the Heritability of Human Longevity Are Substantially Inflated due to Assortative Mating. Genetics. 2018;210(3):1109-24. doi: 10.1534/genetics.118.301613

72.Sebastiani P, Perls TT. The genetics of extreme longevity: lessons from the New England Centenarian Study. Front Genet. 2012;3:277. doi: 10.3389/fgene.2012.00277

73.Sebastiani P, Sun FX, Andersen SL, Lee JH, Wojczynski MK, Sanders JL, et al. Families Enriched for Exceptional Longevity also have Increased Health-Span: Findings from the Long Life Family Study. Front Public Health. 2013;1:38. doi: 10.3389/fpubh.2013.00038

74.Ash AS, Kroll-Desrosiers AR, Hoaglin DC, Christensen K, Fang H, Perls TT. Are Members of Long-Lived Families Healthier Than Their Equally Long-Lived Peers? Evidence From the Long Life Family Study. J Gerontol A. 2015;70(8):971-6. doi: 10.1093/gerona/glv015

75.Terry DF, Wilcox MA, McCormick MA, Perls TT. Cardiovascular disease delay in centenarian offspring. J Gerontol A Biol Sci Med Sci. 2004;59(4):385-9. doi: 10.1093/gerona/59.4.M385

76.Barzilai N, Gabriely I, Gabriely M, Iankowitz N, Sorkin JD. Offspring of centenarians have a favorable lipid profile. J Am Geriatr Soc. 2001;49(1):76-9. doi: 10.1046/j.1532-5415.2001.49013.x

77.Arai Y, Martin-Ruiz CM, Takayama M, Abe Y, Takebayashi T, Koyasu S, et al. Inflammation, But Not Telomere Length, Predicts Successful Ageing at Extreme Old Age: A Longitudinal Study of Semi-supercentenarians. EBioMedicine. 2015;2(10):1549-58. doi: 10.1016/j.ebiom.2015.07.029

78.Bucci L, Ostan R, Cevenini E, Pini E, Scurti M, Vitale G, et al. Centenarians' offspring as a model of healthy aging: a reappraisal of the data on Italian subjects and a comprehensive overview. Aging. 2016;8(3):510-9. doi: 10.18632/aging.100912

79.Zeng Y, Chen H, Shi X, Yin Z, Yang Z, Gu J, et al. Health consequences of familial longevity influence among the Chinese elderly. J Gerontol A. 2013;68(4):473-82. doi: 10.1093/gerona/gls203

80.Andersen SL, Sweigart B, Sebastiani P, Drury J, Sidlowski S, Perls TT. Reduced Prevalence and Incidence of Cognitive Impairment Among Centenarian Offspring. J Gerontol A. 2019;74(1):108-13. doi: 10.1093/gerona/gly141

81.Marone S, Bloore K, Sebastiani P, Flynn C, Leonard B, Whitaker K, et al. Purpose in Life Among Centenarian Offspring. J Gerontol B. 2020;75(2):308-15. doi: 10.1093/geronb/gby023

82.Givens JL, Frederick M, Silverman L, Anderson S, Senville J, Silver M, et al. Personality traits of centenarians' offspring. J Am Geriatr Soc. 2009;57(4):683-5. doi: 10.1111/j.1532-5415.2009.02189.x

83.Kaufman LB, Setiono TK, Doros G, Andersen S, Silliman RA, Friedman PK, et al. An oral health study of centenarians and children of centenarians. J Am Geriatr Soc. 2014;62(6):1168-73. doi: 10.1111/jgs.12842

84.United Nations, Department of Economic and Social Affairs, Population Dynamics. World Population Prospects 2019. Available from: https://population.un.org/wpp/. Accessed 2020 Jun 30.

85.Sierra F. The Emergence of Geroscience as an Interdisciplinary Approach to the Enhancement of Health Span and Life Span. Cold Spring Harb Perspect Med. 2016;6(4):a025163. doi: 10.1101/cshperspect.a025163

86.Kahn A, Longevity C. The Longevity Consortium: Harnessing diverse approaches to understand the genetic basis of human longevity and healthy aging. An introduction to a series of articles. Ageing Res Rev. 2011;10(2):179-80. doi: 10.1016/j.arr.2010.04.008

引用本文

Stacy L. Andersen*. Centenarians as Models of Resistance and Resilience to Alzheimer’s Disease and Related Dementias, Advances in Geriatric Medicine and Research. 2020; 2; (3). https://doi.org/10.20900/agmr20200018.

文献评论

相关学者

相关机构