Skip to main content

Advertisement

SpringerLink
Log in

Cognitive and social lifestyle: links with neuropathology and cognition in late life

  • Review
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Abstract

Many studies report an association of cognitive and social experiential factors and related traits with dementia risk. Further, many clinical-pathologic studies find a poor correspondence between levels of neuropathology and the presence of dementia and level of cognitive impairment. The poor correspondence suggests that other factors contribute to the maintenance or loss of cognitive function, with factors associated with the maintenance of function referred to as neural or cognitive reserve. This has led investigators to examine the associations of cognitive and social experiential factors with neuropathology as a first step in disentangling the complex associations between these experiential risk factors, neuropathology, and cognitive impairment. Despite the consistent associations of a range of cognitive and social lifestyle factors with cognitive decline and dementia risk, the extant clinical-pathologic data find only a single factor from one cohort, linguistic ability, related to AD pathology. Other factors, including education, harm avoidance, and emotional neglect, are associated with cerebrovascular disease. Overall, the associations are weak. Some factors, such as education, social networks, and purpose in life, modify the relation of neuropathology to cognition. Finally, some factors such as cognitive activity appear to bypass known pathologies altogether suggesting a more direct association with biologic indices that promote person-specific differences in reserve and resilience. Future work will first need to replicate findings across more studies to ensure the veracity of the existing data. Second, effort is needed to identify the molecular substrates of neural reserve as potential mediators of the association of lifestyle factors with cognition.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Altman J, Das GD (1964) Autoradiographic examination of the effects of enriched environment on the rate of glial multiplication in the adult rat brain. Nature 204:1161–1163

    CAS  PubMed  Google Scholar 

  2. Arendash GW, Garcia MF, Costa DA, Cracchiolo JR, Wefes IM, Potter H (2004) Environmental enrichment improves cognition in aged Alzheimer’s transgenic mice despite stable beta-amyloid deposition. Neuroreport 6:1751–1754

    Google Scholar 

  3. Arnold SE, Louneva N, Cao K, Wang L-S, Han L-Y, Wolk DA, Negash S, Leurgans SE, Schneider JA, Buchman AS, Wilson RS, Bennett DA (2013) Cellular, synaptic, and biochemical features of resilient cognition in Alzheimer’s disease. Neurobiol Aging 34:157–168

    CAS  PubMed Central  PubMed  Google Scholar 

  4. Barrett JK, Siannis F, Farewell VT (2011) A semi-competing risks model for data with interval-censoring and informative observation: an application to the MRC cognitive function and ageing study. Stat Med 30:1–10

    PubMed Central  PubMed  Google Scholar 

  5. Beard CM, Kokmen E, Offord KP, Kurland LT (1992) Lack of association between Alzheimer’s disease and education, occupation, marital status, or living arrangement. Neurology 42:2063–2068

    CAS  PubMed  Google Scholar 

  6. Beekly DL, Ramos EM, Lee WW, Deitrich WD, Jacka ME, Wu J, Hubbard JL, Koepsell TD, Morris JC, Kukull WA, NIA Alzheimer’s Disease Centers (2007) The National Alzheimer’s Coordinating Center (NACC) database: the uniform data set. Alzheimer Dis Assoc Disord 21:249–258

    PubMed  Google Scholar 

  7. Beeri MS, Haroutunian V, Schmeidler J, Sano M, Fam P, Kavanaugh A, Barr AM, Honer WG, Katsel P (2012) Synaptic protein deficits are associated with dementia irrespective of extreme old age. Neurobiol Aging 33:1125.e1–1125.e8

    Google Scholar 

  8. Bennett DA, De Jager PL, Leurgans SE, Schneider JA (2009) Neuropathologic intermediate phenotypes enhance association to Alzheimer susceptibility alleles. Neurology 72:1495–1503

    PubMed  Google Scholar 

  9. Bennett DA, Schneider JA, Arnold SE, Tang Y, Wilson RS (2006) The effect of social networks on the relation between Alzheimer’s disease pathology and level of cognitive function in old people: a longitudinal cohort study. Lancet Neurol 5:406–412

    PubMed  Google Scholar 

  10. Bennett DA, Schneider JA, Arvanitakis Z, Wilson RS (2012) Overview and findings from the religious orders study. Curr Alzheimer Res 9:628–645

    CAS  PubMed Central  PubMed  Google Scholar 

  11. Bennett DA, Schneider JA, Buchman AS, Barnes LL, Boyle PA, Wilson RS (2012) Overview and findings from the rush memory and aging project. Curr Alzheimer Res 9:646–663

    CAS  PubMed Central  PubMed  Google Scholar 

  12. Bennett DA, Schneider JA, Wilson RS, Bienias JL, Arnold SE (2005) Education modifies the association of amyloid, but not tangles, with cognitive function. Neurology 65:953–955

    CAS  PubMed  Google Scholar 

  13. Bennett DA, Wilson RS, Boyle PA, Buchman AS, Schneider JA (2012) Relation of neuropathology to cognition in persons without cognitive impairment. Ann Neurol 72:599–609

    PubMed Central  PubMed  Google Scholar 

  14. Bennett DA, Wilson RS, Schneider JA, Evans DA, Mendes de Leon CF, Arnold SE, Barnes LL, Bienias JL (2003) Education modifies the relation of AD pathology to cognitive function in older persons. Neurology 60:1909–1915

    CAS  PubMed  Google Scholar 

  15. Bonaiuto S, Rocca WA, Lippi A, Giannandrea E, Mele M, Cavarzeran F, Amaducci L (1995) Education and occupation as risk factors for dementia: a population-based case-control study. Neuroepidemiology 14:101–109

    CAS  PubMed  Google Scholar 

  16. Borenstein GA, Mortimer JA, Bowen JD, McCormick WC, McCurry SM, Schellenberg GD, Larson EB (2001) Head circumference and incident Alzheimer’s disease: modification by apolipoprotein E. Neurology 57:1453–1460

    Google Scholar 

  17. Boyle PA, Barnes LL, Buchman AS, Bennett DA (2009) Purpose in life is associated with mortality among community-dwelling older persons. Psychosom Med 71:574–579

    PubMed Central  PubMed  Google Scholar 

  18. Boyle PA, Buchman AS, Barnes LL, Bennett DA (2010) Purpose in life is associated with a reduced risk of incident Alzheimer’s disease among community-dwelling older persons. Arch Gen Psychiatry 67:304–310

    PubMed Central  PubMed  Google Scholar 

  19. Boyle PA, Buchman AS, Wilson RS, Yu L, Schneider JA, Bennett DA (2012) Effect of purpose in life on the relation between Alzheimer disease pathologic changes on cognitive function in advanced age. Arch Gen Psychiatry 69:499–504

    PubMed Central  PubMed  Google Scholar 

  20. Brayne C, Gao L, Dewey M, Matthews FE, Medical Research Council Cognitive Function and Ageing Study Investigators (2006) Dementia before death in ageing societies—the promise of prevention and the reality. PLoS Med 3:e397

    PubMed Central  PubMed  Google Scholar 

  21. Brayne C, McCracken C, Matthews FE (2006) Cohort profile: the medical research council cognitive function and ageing study (CFAS). Int J Epidemiol 35:140–1145

    Google Scholar 

  22. Brayne C, Richardson K, Matthews FE, Fleming J, Hunter S, Xuereb JH, Paykel E, Mukaetova-Ladinska EB, Huppert FA, O’Sullivan A, Dening T, Cambridge City Over-75 s Cohort Cc75c Study Neuropathology Collaboration (2009) Neuropathological correlates of dementia in over-80-year-old brain donors from the population-based Cambridge city over-75 s cohort (CC75C) study. J Alzheimers Dis 18:645–658

    PubMed  Google Scholar 

  23. Briones TL, Klintsova AY, Greenough WT (2004) Stability of synaptic plasticity in the adult rat visual cortex induced by complex environment exposure”. Brain Res 1018:130–135

    CAS  PubMed  Google Scholar 

  24. Cacioppo JT, Norris CJ, Decety J, Monteleone G, Nusbaum H (2009) In the eye of the beholder: individual differences in perceived social isolation predict regional brain activation to social stimuli. J Cogn Neurosci 21:83–92

    PubMed Central  PubMed  Google Scholar 

  25. Callahan CM, Hall KS, Hui SL, Musick BS, Unverzagt FW, Hendrie HC (1996) Relationship of age, education, and occupation with dementia among a community-based sample of African Americans. Arch Neurol 53:134–140

    CAS  PubMed  Google Scholar 

  26. Cobb JL, Wolf PA, Au R, White R, D’Agostino RB (1995) The effect of education on the incidence of dementia and Alzheimer’s disease in the Framingham study. Neurology 45:1707–1712

    CAS  PubMed  Google Scholar 

  27. Costa DA, Cracchiolo JR, Bachstetter AD, Hughes TF, Bales KR, Paul SM, Mervis RF, Arendash GW, Potter H (2007) Enrichment improves cognition in AD mice by amyloid-related and unrelated mechanisms. Neurobiol Aging 28:831–844

    CAS  PubMed  Google Scholar 

  28. Cracchiolo JR, Mori T, Nazian SJ, Tan J, Potter H, Arendash GW (2007) Enhanced cognitive activity—over and above social or physical activity—is required to protect Alzheimer’s mice against cognitive impairment, reduce Abeta deposition, and increase synaptic immunoreactivity. Neurobiol Learn Mem 88:277–294

    CAS  PubMed Central  PubMed  Google Scholar 

  29. Crimmins EM, Beltrán-Sánchez H (2011) Mortality and morbidity trends: is there compression of morbidity? J Gerontol B Psychol Sci Soc Sci 66:75–86

    PubMed  Google Scholar 

  30. Crystal H, Dickson D, Fuld P, Masur D, Scott R, Mehler M, Masdeu J, Kawas C, Aronson M, Wolfson L (1988) Clinico-pathologic studies in dementia: nondemented subjects with pathologically confirmed Alzheimer’s disease. Neurology 38:1682–1687

    CAS  PubMed  Google Scholar 

  31. De Jager PL, Bennett DA (2013) An Inflection point in gene discovery efforts for neurodegenerative diseases: from syndromic diagnoses toward endophenotypes and the epigenome. JAMA Neurol 70:719–726

    PubMed  Google Scholar 

  32. Del Ser T, Hachinski V, Merskey H, Munoz DG (1999) An autopsy-verified study of the effect of education on degenerative dementia. Brain 122:2309–2319

    PubMed  Google Scholar 

  33. DeYoung CG, Hirsh JB, Shane MS, Papademetris X, Rajeevan N, Gray JR (2010) Testing predictions from personality neuroscience. Brain structure and the big five. Psychol Sci 1:820–828

    Google Scholar 

  34. Diamond MC, Krech D, Rosenzweig MR (1964) The effects of an enriched environment on the histology of the rat cerebral cortex. J Comp Neurol 123:111–120

    CAS  PubMed  Google Scholar 

  35. Dickson DW, Crystal HA, Bevona C, Honer W, Vincent I, Davies P (1995) Correlations of synaptic and pathological markers with cognition of the elderly. Neurobiol Aging 16:285–304

    CAS  PubMed  Google Scholar 

  36. Di Garbo A, Mainardi M, Chillemi S, Maffei L, Caleo M (2011) Environmental enrichment modulates cortico-cortical interactions in the mouse. PLoS One 6:e25285

    PubMed Central  PubMed  Google Scholar 

  37. Dong H, Csernansky JG (2009) Effects of stress and stress hormones on amyloid-beta protein and plaque deposition. J Alzheimers Dis 18:459–469

    CAS  PubMed Central  PubMed  Google Scholar 

  38. Dong H, Goico B, Martin M, Csernansky CA, Bertchume A, Csernansky JG (2004) Modulation of hippocampal cell proliferation, memory, and amyloid plaque deposition in APPsw (Tg2576) mutant mice by isolation stress. Neuroscience 127:601–609

    CAS  PubMed  Google Scholar 

  39. Driscoll I, Resnick SM, Troncoso JC, An Y, O’Brien R, Zonderman AB (2006) Impact of Alzheimer’s pathology on cognitive trajectories in nondemented elderly. Ann Neurol 60:688–695

    PubMed  Google Scholar 

  40. Duffy SN, Craddock KJ, Abel T, Nguyen PV (2001) Environmental enrichment modifies the PKA-dependence of hippocampal LTP and improves hippocampus-dependent memory. Learn Mem 8:26–34

    CAS  PubMed  Google Scholar 

  41. EClipSE Collaborative Members (2009) Cohort profile: epidemiological clinicopathological studies in Europe (EClipSE). J Alzheimers Dis 18:659–663

    Google Scholar 

  42. Brayne C, Ince PG, Keage HA, McKeith IG, Matthews FE, Polvikoski T, Sulkava R, EClipSE Collaborative Members (2010) Education, the brain and dementia: neuroprotection or compensation? Brain 133:2210–2216

    PubMed  Google Scholar 

  43. Esiri MM, Chance SA (2012) Cognitive reserve, cortical plasticity and resistance to Alzheimer’s disease. Alzheimers Res Ther 4:7

    PubMed Central  PubMed  Google Scholar 

  44. Evans DA, Hebert LE, Beckett LA, Scherr PA, Albert MS, Chown MJ, Pilgrim DM, Taylor JO (1997) Education and other measures of socioeconomic status and risk of incident Alzheimer disease in a defined population of older persons. Arch Neurol 54:1399–1405

    CAS  PubMed  Google Scholar 

  45. Fabrigoule C, Letenneur L, Dartigues JF, Zarrouk M, Commenges D, Barberger-Gateau P (1995) Social and leisure activities and risk of dementia: a prospective longitudinal study. J Am Geriatr Soc 43:485–490

    CAS  PubMed  Google Scholar 

  46. Farfel JM, Nitrini R, Suemoto CK, Grinberg LT, Ferretti FEL, Leite REP, Menezes PR, Fegni F, Bennett DA, Pasqualucci CA, Jacob-Filho W, Brazilian Aging Brain Study Group (2013) Elementary education protects against dementia: a clinicopathological study. Neurology 81:650–657

    PubMed  Google Scholar 

  47. Fleming J, Zhao E, O’Connor DW, Pollitt PA, Brayne C (2007) Cohort profile: the Cambridge City over-75 s Cohort (CC75C). Int J Epidemiol 36:40–46

    PubMed  Google Scholar 

  48. Fratiglioni L, Wang HX, Ericsson K, Maytan M, Winblad B (2000) Influence of social network on occurrence of dementia: a community-based longitudinal study. Lancet 355:1315–1319

    CAS  PubMed  Google Scholar 

  49. Freret T, Billard JM, Schumann-Bard P, Dutar P, Dauphin F, Boulouard M, Bouet V (2012) Rescue of cognitive aging by long-lasting environmental enrichment exposure initiated before median lifespan. Neurobiol Aging 33:1005.e1–1005.e10

    CAS  Google Scholar 

  50. Fries JF, Bruce B, Chakravarty E (2011) Compression of morbidity 1980-2011: a focused review of paradigms and progress. J Aging Res :261702

  51. Graves AB, Mortimer JA, Larson EB, Wenzlow A, Bowen JD, McCormick WC (1996) Head circumference as a measure of cognitive reserve. Association with severity of impairment in Alzheimer’s disease. Br J Psychiatry 169:86–92

    CAS  PubMed  Google Scholar 

  52. Greenough WT, Volkmar FR (1973) Pattern of dendritic branching in occipital cortex of rats reared in complex environments. Exp Neurol 40:491–504

    CAS  PubMed  Google Scholar 

  53. Grinberg LT, Ferretti RE, Farfel JM, Leite R, Pasqualucci CA, Rosemberg S, Nitrini R, Saldiva PH, Filho WJ, Brazilian Aging Brain Study Group (2007) Brain bank of the Brazilian aging brain study group—a milestone reached and more than 1,600 collected brains. Cell Tissue Bank 8:151–162

    PubMed  Google Scholar 

  54. Hall CB, Lipton RB, Sliwinski M, Katz MJ, Derby CA, Verghese J (2009) Cognitive activities delay onset of memory decline in persons who develop dementia. Neurology 73:356–361

    CAS  PubMed  Google Scholar 

  55. Head E, Corrada MM, Kahle-Wrobleski K, Kim RC, Sarsoza F, Goodus M, Kawas CH (2009) Synaptic proteins, neuropathology and cognitive status in the oldest-old. Neurobiol Aging 30:1125–1134

    CAS  PubMed  Google Scholar 

  56. Hebert LE, Bienias JL, Aggarwal NT, Wilson RS, Bennett DA, Shah RC, Evans DA (2010) Change in risk of Alzheimer disease over time. Neurology 75:786–791

    PubMed  Google Scholar 

  57. Helmes E, Merskey H, Fox H, Fry RN, Bowler JV, Hachinski VC (1995) Patterns of deterioration in senile dementia of the Alzheimer type. Arch Neurol 52:306–310

    CAS  PubMed  Google Scholar 

  58. Holwerda TJ, Deeg DJ, Beekman AT, van Tilburg TG, Stek ML, Jonker C, Schoevers RA (2012) Feelings of loneliness, but not social isolation, predict dementia onset: results from the Amsterdam Study of the Elderly (AMSTEL). J Neurol Neurosurg Psychiatry. doi:10.1136/jnnp-2012-302755

  59. Honer WG, Barr AM, Sawada K, Thornton AE, Morris MC, Leurgans SE, Schneider JA, Bennett DA (2012) Cognitive reserve, presynaptic proteins and dementia in the elderly. Transl Psychiatry 2:2114

    Google Scholar 

  60. Huang FL, Huang KP, Wu J, Boucheron C (2006) Environmental enrichment enhances neurogranin expression and hippocampal learning and memory but fails to rescue the impairments of neurogranin null mutant mice. J Neurosci 26:6230–6237

    CAS  PubMed  Google Scholar 

  61. Iacono D, Markesbery WR, Gross M, Pletnikova O, Rudow G, Zandi P, Troncoso JC (2009) The Nun study: clinically silent AD, neuronal hypertrophy, and linguistic skills in early life. Neurology 73:665–673

    CAS  PubMed  Google Scholar 

  62. Iacono D, O’Brien R, Resnick SM, Zonderman AB, Pletnikova O, Rudow G, An Y, West MJ, Crain B, Troncoso JC (2008) Neuronal hypertrophy in asymptomatic Alzheimer disease. J Neuropathol Exp Neurol 67:578–589

    PubMed Central  PubMed  Google Scholar 

  63. Ickes BR, Pham TM, Sanders LA, Albeck DS, Mohammed AH, Granholm AC (2000) Long-term environmental enrichment leads to regional increases in neurotrophin levels in rat brain. Exp Neurol 164:45–52

    CAS  PubMed  Google Scholar 

  64. Irvine GI, Abraham WC (2005) Enriched environment exposure alters the input-output dynamics of synaptic transmission in area CA1 of freely moving rats. Neurosci Lett 391:32–37

    CAS  PubMed  Google Scholar 

  65. Jacobs B, Schall M, Scheibel A (1993) A quantitative dendritic analysis of Wernicke’s area in humans and environmental factors. J Comp Neurol 327:97–111

    CAS  PubMed  Google Scholar 

  66. Kanai R, Bahrami B, Duchaine B, Janik A, Banissy MJ, Rees G (2012) Brain structure links loneliness to social perception. Curr Biol 22:1975–1979

    CAS  PubMed Central  PubMed  Google Scholar 

  67. Katzman R, Terry R, DeTeresa R, Brown T, Davies P, Fuld P, Renbing X, Peck A (1998) Clinical, pathological, and neurochemical changes in dementia: a subgroup with preserved mental status and numerous neocortical plaques. Ann Neurol 23:138–144

    Google Scholar 

  68. Knopman DS, Parisi JE, Salviati A, Floriach-Robert M, Boeve BF, Ivnik RJ, Smith GE, Dickson DW, Johnson KA, Petersen LE, McDonald WC, Braak H, Petersen RC (2003) Neuropathology of cognitively normal elderly. J Neuropathol Exp Neurol 62:1087–1095

    CAS  PubMed  Google Scholar 

  69. Koepsell TD, Kurland BF, Harel O, Johnson EA, Zhou XH, Kukull WA (2008) Education, cognitive function, and severity of neuropathology in Alzheimer disease. Neurology 70:1732–1739

    CAS  PubMed  Google Scholar 

  70. Krech D, Rosenzweig MR, Bennett EL (1960) Effects of environmental complexity and training on brain chemistry. J Comp Physiol Psychol 53:509–519

    CAS  PubMed  Google Scholar 

  71. Labonté B, Suderman M, Maussion G, Navaro L, Yerko V, Mahar I, Bureau A, Mechawar N, Szyf M, Meaney MJ, Turecki G (2012) Genome-wide epigenetic regulation by early-life trauma. Arch Gen Psychiatry 69:722–731

    PubMed  Google Scholar 

  72. Langa KM, Larson EB, Karlawish JH et al (2008) Trends in the prevalence and mortality of cognitive impairment in the United States: is there evidence of a compression of cognitive morbidity? Alzheimers Dement 4:134–144

    PubMed Central  PubMed  Google Scholar 

  73. Lobo A, Saz P, Marcos G, ZARADEMP Workgroup et al (2007) Prevalence of dementia in a southern European population in two diff erent time periods: the ZARADEMP project. Acta Psychiatr Scand 116:299–307

    CAS  PubMed  Google Scholar 

  74. Manton KC, Gu XL, Ukraintseva SV (2005) Declining prevalence of dementia in the U.S. elderly population. Adv Gerontol 16:30–37

    CAS  PubMed  Google Scholar 

  75. Marioni RE, Valenzuela MJ, van den Hout A, Brayne C, Matthews FE, MRC Cognitive Function and Ageing Study (2012) Active cognitive lifestyle is associated with positive cognitive health transitions and compression of morbidity from age sixty-five. PLoS One 7:e50940

    CAS  PubMed Central  PubMed  Google Scholar 

  76. Marioni RE, van den Hout A, Valenzuela MJ, Brayne C, Matthews FE, MRC Cognitive Function and Ageing Study (2012) Active cognitive lifestyle associates with cognitive recovery and a reduced risk of cognitive decline. J Alzheimers Dis 28:223–230

    PubMed  Google Scholar 

  77. Markett S, Weber B, Voigt G, Montag C, Felten A, Elger C, Reuter M (2013) Intrinsic connectivity networks and personality: the temperament dimension harm avoidance moderates functional connectivity in the resting brain. Neuroscience 240:98–105

    CAS  PubMed  Google Scholar 

  78. Marquine MJ, Segawa E, Wilson RS, Bennett DA, Barnes LL (2012) The association between cognitive activity and cognitive function in older Hispanics. J Int Neuropsychol Soc 18:1041–1051

    PubMed Central  PubMed  Google Scholar 

  79. Mathuranath PS, Cherian PJ, Mathew R, Kumar S, George A, Alexander A, Ranjith N, Sarma PS (2010) Dementia in Kerala, South India: prevalence and influence of age, education and gender. Int J Geriatr Psychiatry 25:290–297

    CAS  PubMed  Google Scholar 

  80. Matthews FE, Arthur A, Barnes LE, Bond J, Jagger C, Robinson L, Brayne C; on behalf of the Medical Research Council Cognitive Function and Ageing Collaboration (2013) A two-decade comparison of prevalence of dementia in individuals aged 65 years and older from three geographical areas of England: results of the Cognitive Function and Ageing Study I and II. Lancet 382:1405–1412

    Google Scholar 

  81. McGowan PO, Sasaki A, D’Alessio AC, Dymov S, Labonté B, Szyf M, Turecki G, Meaney MJ (2009) Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci 12:342–348

    CAS  PubMed Central  PubMed  Google Scholar 

  82. McGowan PO, Sasaki A, Huang TC, Unterberger A, Suderman M, Ernst C, Meaney MJ, Turecki G, Szyf M (2008) Promoter-wide hypermethylation of the ribosomal RNA gene promoter in the suicide brain. PLoS One 3:e2085

    PubMed Central  PubMed  Google Scholar 

  83. McNair K, Broad J, Riedel G, Davies CH, Cobb SR (2007) Global changes in the hippocampal proteome following exposure to an enriched environment. Neuroscience 145:413–422

    CAS  PubMed  Google Scholar 

  84. Mortimer JA, Borenstein AR, Gosche KM, Snowdon DA (2005) Very early detection of Alzheimer neuropathology and the role of brain reserve in modifying its clinical expression. J Geriatr Psychiatry Neurol 18:218–223

    PubMed Central  PubMed  Google Scholar 

  85. Mortimer JA, Snowdon DA, Markesbery WR (2003) Head circumference, education and risk of dementia: findings from the Nun study. J Clin Exp Neuropsychol 25:671–679

    PubMed  Google Scholar 

  86. Muniz-Terrera G, Matthews FE, Stephan B, Brayne C, CC75C Collaboration Group (2011) Are terminal decline and its potential indicators detectable in population studies of the oldest old? Int J Geriatr Psychiatry 26:584–592

    PubMed  Google Scholar 

  87. Muniz-Terrera G, van den Hout A, Piccinin AM, Matthews FE, Hofer SM (2013) Investigating terminal decline: results from a UK population-based study of aging. Psychol Aging 28:377–385

    PubMed Central  PubMed  Google Scholar 

  88. Murphy TE, Han L, Allore HG, Peduzzi PN, Gill TM, Lin H (2011) Treatment of death in the analysis of longitudinal studies of gerontological outcomes. J Gerontol A Biol Sci Med Sci 66:109–114

    CAS  PubMed  Google Scholar 

  89. Næss O, Hoff DA, Lawlor D, Mortensen LH (2012) Education and adult cause-specific mortality—examining the impact of family factors shared by 871 367 Norwegian siblings. Int J Epidemiol 41:1683–1691

    PubMed  Google Scholar 

  90. Naka F, Narita N, Okado N, Narita M (2005) Modification of AMPA receptor properties following environmental enrichment. Brain Dev 27:275–278

    PubMed  Google Scholar 

  91. Ott A, van Rossum CT, van Harskamp F, van de Mheen H, Hofman A, Breteler MM (1999) Education and the incidence of dementia in a large population-based study: the Rotterdam study. Neurology 52:663–666

    CAS  PubMed  Google Scholar 

  92. Polvikoski T, Sulkava R, Haltia M, Kainulainen K, Vuorio A, Verkkoniemi A, Niinisto L, Halonen P, Kontula K (1995) Apolipoprotein E, dementia, and cortical deposition of betaamyloid protein. N Engl J Med 333:242–1247

    Google Scholar 

  93. Prencipe M, Casini AR, Ferretti C, Lattanzio MT, Fiorelli M, Culasso F (1996) Prevalence of dementia in an elderly rural population: effects of age, sex, and education. J Neurol Neurosurg Psychiatry 60:628–633

    CAS  PubMed  Google Scholar 

  94. Price JL, McKeel DW, Buckles VD, Roe CM, Xiong C, Grundman M, Hansen LA, Petersen RC, Parisi JE, Dickson DW, Smith CD, Davis DG, Schmitt FA, Markesbery WR, Kaye J, Kurlan R, Hulette C, Kurland BF, Higdon R, Kukull W, Morris JC (2009) Neuropathology of nondemented aging: presumptive evidence for preclinical Alzheimer disease. Neurobiol Aging 30:1026–1036

    PubMed Central  PubMed  Google Scholar 

  95. Qiu C, Bäckman L, Winblad B, Agüero-Torres H, Fratiglioni L (2001) The influence of education on clinically diagnosed dementia incidence and mortality data from the Kungsholmen Project. Arch Neurol 58:2034–2039

    CAS  PubMed  Google Scholar 

  96. Qiu C, von Strauss E, Backman L, Winblad B, Fratiglioni L (2013) Twenty-year changes in dementia occurrence suggest decreasing incidence in central Stockholm, Sweden. Neurology 80:1888–1894

    PubMed  Google Scholar 

  97. Rampon C, Jiang CH, Dong H, Tang YP, Lockhart DJ, Schultz PG, Tsien JZ, Hu Y (2000) Effects of environmental enrichment on gene expression in the brain. Proc Natl Acad Sci USA 97:12880–12884

    CAS  PubMed  Google Scholar 

  98. Reed BR, Dowling M, Tomaszewski Farias S, Sonnen J, Strauss M, Schneider JA, Bennett DA, Mungas D (2011) Cognitive activities during adulthood are more important than education in building reserve. J Int Neuropsychol Soc 17:615–624

    PubMed Central  PubMed  Google Scholar 

  99. Riley KP, Snowdon DA, Desrosiers MF, Markesbery WR (2005) Early life linguistic ability, late life cognitive function, and neuropathology: findings from the Nun study. Neurobiol Aging 26:341–347

    PubMed  Google Scholar 

  100. Riudavets MA, Iacono D, Resnick SM, O’Brien R, Zonderman AB, Martin LJ, Rudow G, Pletnikova O, Troncoso JC (2007) Resistance to Alzheimer’s pathology is associated with nuclear hypertrophy in neurons. Neurobiol Aging 28:1484–1492

    CAS  PubMed Central  PubMed  Google Scholar 

  101. Rocca WA, Petersen RC, Knopman DS et al (2011) Trends in the incidence and prevalence of Alzheimer’s disease, dementia, and cognitive impairment in the United States. Alzheimers Dement 7:80–93

    PubMed Central  PubMed  Google Scholar 

  102. Roe CM, Xiong C, Miller JP, Cairns NJ, Morris JC (2008) Interaction of neuritic plaques and education predicts dementia. Alzheimer Dis Assoc Disord 22:188–193

    PubMed Central  PubMed  Google Scholar 

  103. Roe CM, Xiong C, Miller JP, Morris JC (2007) Education and Alzheimer disease without dementia: support for the cognitive reserve hypothesis. Neurology 68:223–228

    PubMed  Google Scholar 

  104. Rossi C, Angelucci A, Costantin L, Braschi C, Mazzantini M, Babbini F et al (2006) Brain-derived neurotrophic factor (BDNF) is required for the enhancement of hippocampal neurogenesis following environmental enrichment. Eur J Neurosci 24:1850–1856

    PubMed  Google Scholar 

  105. Saczynski JS, Pfeifer LA, Masaki K, Korf ES, Laurin D, White L, Launer LJ (2006) The effect of social engagement on incident dementia: the Honolulu-Asia aging study. Am J Epidemiol 63:433–440

    Google Scholar 

  106. Sato Y, Bernier F, Suzuki I, Nakagawa M, Oda Y (2013) Comparative lipidomics of mouse brain exposed to enriched environment. J Lipid Res 54:2687–2696

    CAS  PubMed  Google Scholar 

  107. Satz P, Morgenstern H, Miller EN, Selnes OA, McArthur JC, Cohen BA, Wesch J, Becker JT, Jacobson L, D’Elia LF et al (1993) Low education as a possible risk factor for cognitive abnormalities in HIV-1: findings from the multicenter AIDS Cohort study (MACS). J Acquir Immune Defic Syndr 6:503–511

    CAS  PubMed  Google Scholar 

  108. Carmeas N, Albert SM, Manly JJ, Stern Y (2006) Education and rates of cognitive decline in incident Alzheimer’s disease. J Neurol Neurosurg Psychiatry 77:308–316

    Google Scholar 

  109. Scarmeas N, Levy G, Tang MX, Manly J, Stern Y (2001) Influence of leisure activity on the incidence of Alzheimer’s disease. Neurology 57:2236–2242

    CAS  PubMed Central  PubMed  Google Scholar 

  110. Scarmeas N, Zarahn E, Anderson KE, Habeck CG, Hilton J, Flynn J, Marder KS, Bell KL, Sackeim HA, Van Heertum RL, Moeller JR, Stern Y (2003) Association of life activities with cerebral blood flow in Alzheimer disease: implications for the cognitive reserve hypothesis. Arch Neurol 60:359–365

    PubMed Central  PubMed  Google Scholar 

  111. Scheibel A, Paul A, Fried I, Forsythe A, Tomiyasu U, Wechsler A (1990) A quantitative study of dendrite complexity in selected areas of the human cortex. Brain Cogn 12:85–101

    CAS  PubMed  Google Scholar 

  112. Schmitt FA, Davis DG, Wekstein DR, Smith CD, Ashford JW, Markesbery WR (2000) “Preclinical” AD revisited: neuropathology of cognitively normal older adults. Neurology 55:370–376

    CAS  PubMed  Google Scholar 

  113. Schneider JA, Aggarwal NT, Barnes LL, Boyle PA, Bennett DA (2009) The neuropathology of older persons with and without dementia from community vs. clinic cohorts. J Alzheimer’s Dis 18:691–701

    Google Scholar 

  114. Schofield PW, Logroscino G, Andrews HF, Albert S, Stern Y (1997) An association between head circumference and Alzheimer’s disease in a population-based study of aging and dementia. Neurology 49:30–37

    CAS  PubMed  Google Scholar 

  115. Schofield P, Mosesson R, Stern Y, Mayeux R (1995) The age at onset of Alzheimer’s disease and an intracranial area measurement: a relationship. Arch Neurol 52:95–98

    CAS  PubMed  Google Scholar 

  116. Schrijvers EM, Verhaaren BF, Koudstaal PJ, Hofman A, Ikram MA, Breteler MM (2012) Is dementia incidence declining? Trends in dementia incidence since 1990 in the Rotterdam study. Neurology 78:1456–1463

    CAS  PubMed  Google Scholar 

  117. Schweizer TA, Ware J, Fischer CE, Craik FI, Bialystok E (2012) Bilingualism as a contributor to cognitive reserve: evidence from brain atrophy in Alzheimer’s disease. Cortex 48:991–996

    PubMed  Google Scholar 

  118. Shulman JM, Chen K, Keenan BT, Chibnik LB, Fleisher A, Thiyyagura P, McCabe C, Roontiva A, Patsopoulos NA, Corneveaux J, Yu L, Huentelman MJ, Evans DA, Schneider JA, Reiman E, De Jager PL, Bennett DA (2013) Genetic susceptibility for Alzheimer’s disease neuritic plaque pathology. JAMA Neurol 70:1150–1157

    PubMed  Google Scholar 

  119. Snowdon DA, Nun Study (2003) Healthy aging and dementia: findings from the Nun study. Ann Intern Med 139:450–454

    PubMed  Google Scholar 

  120. Snowdon DA, Kemper SJ, Mortimer JA, Greiner LH, Wekstein DR, Markesbery WR (1996) Linguistic ability in early life and cognitive function and Alzheimer’s disease in late life. Findings from the Nun study. JAMA 275:528–532

    CAS  PubMed  Google Scholar 

  121. Soetanto A, Wilson RS, Talbot K, Un A, Schneider JA, Sobiesk M, Kelly JF, Leurgans SE, Bennett DA, Arnold SE (2010) Association of anxiety and depression with microtubule-associated protein 2- and synaptopodin-immunolabeled dendrite and spine densities in hippocampal CA3 of older humans. Arch Gen Psychiatry 67:448–457

    PubMed Central  PubMed  Google Scholar 

  122. Soffie M, Hahn K, Terao E, Eclancher F (1999) Behavioural and glial changes in old rats following environmental enrichment. Behav Brain Res 101:37–49

    CAS  PubMed  Google Scholar 

  123. Sonnen JA, Larson EB, Crane PK, Haneuse S, Li G, Schellenberg GD, Craft S, Leverenz JB, Montine TJ (2007) Pathological correlates of dementia in a longitudinal, population-based sample of aging. Ann Neurol 62:406–413

    PubMed  Google Scholar 

  124. Sonnen JA, Santa Cruz K, Hemmy LS et al (2011) Ecology of the aging human brain. Arch Neurol 68:1049–1056

    PubMed Central  PubMed  Google Scholar 

  125. Stern Y (2012) Cognitive reserve in ageing and Alzheimer’s disease. Lancet Neurol 11:1006–1012

    PubMed Central  PubMed  Google Scholar 

  126. Stern Y, Gurland B, Tatemichi TK, Tang MX, Wilder D, Mayeux R (1994) Influence of education and occupation on the incidence of Alzheimer’s disease. JAMA 271:1004–1010

    CAS  PubMed  Google Scholar 

  127. Stern Y, Tang MX, Denaro J, Mayeux R (1995) Increased risk of mortality in Alzheimer’s disease patients with more advanced educational and occupational attainment. Ann Neurol 37:590–595

    CAS  PubMed  Google Scholar 

  128. Talbot K, Wang HY, Kazi H, Han LY, Bakshi KP, Stucky A, Fuino RL, Kawaguchi KR, Samoyedny AJ, Wilson RS, Arvanitakis Z, Schneider JA, Wolf BA, Bennett DA, Trojanowski JQ, Arnold SE (2013) Brain insulin resistance demonstrated in Alzheimer’s disease without diabetes is associated with dysregulated IRS-1, IFG-1, and cognitive decline. J Clin Investig 122:1316–1338

    Google Scholar 

  129. Thorvaldsson V, Hofer SM, Berg S, Skoog I, Sacuiu S, Johansson B (2008) Onset of terminal decline in cognitive abilities in individuals without dementia. Neurology 71:882–887

    CAS  PubMed  Google Scholar 

  130. Tomlinson BE, Blessed G, Roth M (1968) Observations on the brains of non-demented old people. J Neurol Sci 7:331–356

    CAS  PubMed  Google Scholar 

  131. Tomlinson BE, Blessed G, Roth M (1970) Observations on the brains of demented old people. J Neurol Sci 11:205–242

    CAS  PubMed  Google Scholar 

  132. Troncoso JC, Martin LJ, Dal Forno G, Kawas CH (1996) Neuropathology in controls and demented subjects from the Baltimore longitudinal study of aging. Neurobiol Aging 17:365–371

    CAS  PubMed  Google Scholar 

  133. Valenzuela MJ (2008) Brain reserve and the prevention of dementia. Curr Opin Psychiatry 21:296–302

    PubMed  Google Scholar 

  134. Valenzuela M, Brayne C, Sachdev P, Wilcock G, Matthews F, Medical Research Council Cognitive Function and Ageing Study (2011) Cognitive lifestyle and long-term risk of dementia and survival after diagnosis in a multicenter population-based cohort. Am J Epidemiol 173:1004–1012

    PubMed  Google Scholar 

  135. Valenzuela MJ, Breakspear M, Sachdev P (2007) Complex mental activity and the aging brain: molecular, cellular and cortical network mechanisms. Brain Res Rev 56:198–213

    CAS  PubMed  Google Scholar 

  136. Valero J, España J, Parra-Damas A, Martín E, Rodríguez-Álvarez J, Saura CA (2011) Short-term environmental enrichment rescues adult neurogenesis and memory deficits in APP(Sw, Ind) transgenic mice. PLoS One 9:e16832

    Google Scholar 

  137. Van Praag H, Kempermann G, Gage FH (2000) Neural consequences of environmental enrichment. Nat Rev Neurosci 1:191–198

    PubMed  Google Scholar 

  138. Verghese J, Lipton RB, Katz MJ, Hall CB, Derby CA, Kuslansky G, Ambrose AF, Sliwinski M, Buschke H (2003) Leisure activities and the risk of dementia in the elderly. N Engl J Med 48:2508–2516

    Google Scholar 

  139. Wang HX, Karp A, Winblad B, Fratiglioni L (2002) Late-life engagement in social and leisure activities is associated with a decreased risk of dementia: a longitudinal study from the Kungsholmen project. Am J Epidemiol 155:1081–1087

    PubMed  Google Scholar 

  140. Wang HY, Stucky A, Hahn CG, Weilson RS, Bennett DA, Arnold SE (2011) BDNF-TrkB signaling in late life cognitive decline and Alzheimer’s disease. Transl Neurosci 2:91–100

    CAS  Google Scholar 

  141. Weaver IC, Cervoni N, Champagne FA, D’Alessio AC, Sharma S, Seckl JR, Dymov S, Szyf M, Meaney MJ (2004) Epigenetic programming by maternal behavior. Nat Neurosci 7:847–854

    CAS  PubMed  Google Scholar 

  142. Weaver IC, Meaney MJ, Szyf M (2006) Maternal care effects on the hippocampal transcriptome and anxiety-mediated behaviors in the offspring that are reversible in adulthood. Proc Natl Acad Sci USA 103:3480–3485

    CAS  PubMed  Google Scholar 

  143. White L, Katzman R, Losonczy K, Salive M, Wallace R, Berkman L, Taylor J, Fillenbaum G, Havlik R (1994) Association of education with incidence of cognitive impairment in three established populations for epidemiologic studies of the elderly. J Clin Epidemiol 47:363–374

    CAS  PubMed  Google Scholar 

  144. Wilson RS, Beck TL, Bienias JL, Bennett DA (2007) Terminal cognitive decline: accelerated loss of cognition in the last years of life. Psychosom Med 69:131–137

    PubMed  Google Scholar 

  145. Wilson RS, Bennett DA, Beckett LA, Morris MC, Gilley DW, Bienias J, Scherr PA, Evans DA (1999) Cognitive activity in older persons from a geographically defined population. J Gerontol: Psychol Sci 54:P155–P160

    CAS  Google Scholar 

  146. Wilson RS, Boyle PA, Buchman AS, Arnold SE, Bennett DA (2011) Harm avoidance and risk of Alzheimer’s disease. Psychosom Med 73:690–696

    CAS  PubMed Central  PubMed  Google Scholar 

  147. Wilson RS, Boyle PA, Levine SR, Yu L, Anagnos SE, Buchman AS, Schneider JA, Bennett DA (2012) Emotional neglect in childhood and cerebral infarction in old age. Neurology 79:1534–1539

    PubMed  Google Scholar 

  148. Wilson RS, Boyle PA, Levine SR, Yu L, Hoganson GM, Buchman AS, Schneider JA, Bennett DA (in press). Harm avoidance and cerebral infarcts. Neuropsychology

  149. Wilson RS, Boyle PA, Yu L, Barnes LL, Schneider JA, Bennett DA (2013) Life span cognitive activity, neuropathologic burden, and cognitive aging. Neurology 81:314–321

    PubMed  Google Scholar 

  150. Wilson RS, Krueger KR, Arnold SE, Schneider JA, Kelly JF, Barnes LL, Tang Y, Bennett DA (2007) Loneliness and risk of Alzheimer’s disease. Arch Gen Psychiatry 64:234–240

    PubMed  Google Scholar 

  151. Wilson RS, Nag S, Boyle PA, Hizel LP, Yu L, Buchman AS, Schneider JA, Bennett DA (2013) Neural reserve, neuronal density in the locus coeruleous and cognitive decline. Neurology 80:1202–1208

    PubMed  Google Scholar 

  152. Wilson RS, Scherr PA, Schneider JA, Tang Y, Bennett DA (2007) The relation of cognitive activity to risk of developing Alzheimer’s disease. Neurology 69:1911–1920

    CAS  PubMed  Google Scholar 

  153. Wilson RS, Schneider JA, Arnold SE, Bienias JL, Bennett DA (2007) Conscientiousness and the incidence of Alzheimer’s disease and mild cognitive impairment. Arch Gen Psychiatry 64:1204–1212

    PubMed  Google Scholar 

  154. Wilson RS, Segawa E, Boyle PA, Bennett DA (2012) Influence of late life cognitive activity on cognitive health. Neurology 78:1123–1129

    PubMed  Google Scholar 

  155. Wilson RS, Yu L, Trojanowski JQT, Chen EY, Bennett DA, Schneider JA (2013) TDP-43 pathology, cognitive decline, and dementia in old age. JAMA Neurol 70:1418–1424

    Google Scholar 

  156. Yip AG, Brayne C, Matthews FE, MRC Cognitive Function and Ageing Study (2006) Risk factors for incident dementia in England and Wales: the medical research council cognitive function and ageing study. A population-based nested case-control study. Age Ageing 35:154–160

    PubMed  Google Scholar 

  157. Yu L, Boyle PA, Wilson RS, Segawa E, Leurgans SE, De Jager PL, Bennett DA (2012) A random change point model for cognitive decline in Alzheimer’s disease and mild cognitive impairment. Neuroepidemiology 39:73–83

    CAS  PubMed Central  PubMed  Google Scholar 

  158. Yuede CM, Zimmerman SD, Dong H, Kling MJ, Bero AW, Holtzman DM, Timson BF, Csernansky JG (2009) Effects of voluntary and forced exercise on plaque deposition, hippocampal volume, and behavior in the Tg2576 mouse model of Alzheimer’s disease. Neurobiol Dis 35:426–432

    CAS  PubMed Central  PubMed  Google Scholar 

  159. Zhang MY, Katzman R, Salmon D, Jin H, Cai GJ, Wang ZY, Qu GY, Grant I, Yu E, Levy P et al (1990) The prevalence of dementia and Alzheimer’s disease in Shanghai, China: impact of age, gender, and education. Ann Neurol 27:428–437

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by NIH grants P30AG10161, R01AG15819, R01AG17917, R01AG39478, MV is supported by a National Health and Medical Research Council of Australia Clinical Career Development Fellowship (#1004156).

Author information

Authors and Affiliations

  1. Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL, USA

    David A. Bennett & Julie A. Schneider

  2. University of Pennsylvania School of Medicine, Philadelphia, PA, USA

    Steven E. Arnold

  3. Regenerative Neuroscience Group, Brain and Mind Research Institute, University of Sydney, Sydney, NSW, Australia

    Michael J. Valenzuela

  4. Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Robinson Way, Cambridge, UK

    Carol Brayne

Authors
  1. David A. Bennett
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Steven E. Arnold
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael J. Valenzuela
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Carol Brayne
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Julie A. Schneider
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David A. Bennett.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bennett, D.A., Arnold, S.E., Valenzuela, M.J. et al. Cognitive and social lifestyle: links with neuropathology and cognition in late life. Acta Neuropathol 127, 137–150 (2014). https://doi.org/10.1007/s00401-013-1226-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00401-013-1226-2

Keywords

Search

Navigation