title: Resilient brain aging: characterization of discordance between Alzheimer's disease pathology and cognition.
abstract: BACKGROUND
  Although it is now evident that normal cognition can occur despite significant AD pathology, few studies have attempted to characterize this discordance, or examine factors that may contribute to resilient brain aging in the setting of AD pathology.
  
  
  METHODS
  More than 2,000 older persons underwent annual evaluation as part of participation in the Religious Orders Study or Rush Memory Aging Project. A total of 966 subjects who had brain autopsy and comprehensive cognitive testing proximate to death were analyzed. Resilience was quantified as a continuous measure using linear regression modeling, where global cognition was entered as a dependent variable and global pathology was an independent variable. Studentized residuals generated from the model represented the discordance between cognition and pathology, and served as measure of resilience. The relation of resilience index to known risk factors for AD and related variables was examined.
  
  
  RESULTS
  Multivariate regression models that adjusted for demographic variables revealed significant associations for early life socioeconomic status, reading ability, APOE-ε4 status, and past cognitive activity. A stepwise regression model retained reading level (estimate = 0.10, SE = 0.02; p< 0.0001) and past cognitive activity (estimate = 0.27, SE = 0.09; p = 0.002), suggesting the potential mediating role of these variables for resilience.
  
  
  CONCLUSIONS
  The construct of resilient brain aging can provide a framework for quantifying the discordance between cognition and pathology, and help identify factors that may mediate this relationship.
authors.affiliation: Penn Memory Center, 3615 Chestnut Street, University of Pennsylvania, Philadelphia, PA 19104, USA. Steven.Arnold@uphs.upenn.edu.
authors.forename: Selam
authors.initials: S
authors.lastname: Negash
authors.forename: Robert S
authors.initials: RS
authors.lastname: Wilson
authors.forename: Sue E
authors.initials: SE
authors.lastname: Leurgans
authors.forename: David A
authors.initials: DA
authors.lastname: Wolk
authors.forename: Julie A
authors.initials: JA
authors.lastname: Schneider
authors.forename: Aron S
authors.initials: AS
authors.lastname: Buchman
authors.forename: David A
authors.initials: DA
authors.lastname: Bennett
authors.forename: Steven E
authors.initials: SE
authors.lastname: Arnold
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology* / Q000523:psychology*; D000544:Alzheimer Disease / Q000473:pathology* / Q000523:psychology*; D001921:Brain / Q000473:pathology*; D003071:Cognition; D003072:Cognition Disorders / Q000473:pathology / Q000523:psychology; D005260:Female; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests
references.citation: Neurology. 1991 Apr;41(4):479-86
references.pmid: 2011243
references.citation: J Alzheimers Dis. 2009;18(3):713-25
references.pmid: 19661625
references.citation: Neurobiol Aging. 1997 Jul-Aug;18(4 Suppl):S1-2
references.pmid: 9330978
references.citation: Neurobiol Aging. 2007 Oct;28(10):1484-92
references.pmid: 17599696
references.citation: J Neuropathol Exp Neurol. 1997 Aug;56(8):933-44
references.pmid: 9258263
references.citation: Int J Evid Based Healthc. 2010 Mar;8(1):2-17
references.pmid: 20923507
references.citation: Neurology. 2009 Sep 1;73(9):665-73
references.pmid: 19587326
references.citation: Exp Brain Res. 2009 Jan;192(3):307-19
references.pmid: 19002678
references.citation: Neurology. 2004 Apr 13;62(7):1148-55
references.pmid: 15079015
references.citation: Exp Aging Res. 2005 Oct-Dec;31(4):393-407
references.pmid: 16147459
references.citation: Neuropharmacology. 2008 Sep;55(3):353-62
references.pmid: 18359495
references.citation: Arch Neurol. 2008 Sep;65(9):1211-7
references.pmid: 18779425
references.citation: Acta Neuropathol. 2010 Jan;119(1):7-35
references.pmid: 20012068
references.citation: Curr Alzheimer Res. 2011 Jun;8(4):336-40
references.pmid: 21222592
references.citation: J Neuropathol Exp Neurol. 2008 Jun;67(6):578-89
references.pmid: 18520776
references.citation: Ann Neurol. 1988 Feb;23(2):138-44
references.pmid: 2897823
references.citation: Physiol Rev. 2009 Oct;89(4):1079-103
references.pmid: 19789377
references.citation: Neurobiol Aging. 2009 Jul;30(7):1125-34
references.pmid: 18006193
references.citation: Alzheimer Dis Assoc Disord. 2006 Jul-Sep;20(3 Suppl 2):S63-8
references.pmid: 16917198
references.citation: Neurobiol Aging. 1995 May-Jun;16(3):271-8; discussion 278-84
references.pmid: 7566337
references.citation: Neurology. 2007 Nov 13;69(20):1911-20
references.pmid: 17596582
references.citation: J Psychiatr Res. 2008 Dec;43(2):148-54
references.pmid: 18455190
references.citation: Neuroepidemiology. 2005;25(4):163-75
references.pmid: 16103727
references.citation: N Engl J Med. 2009 May 28;360(22):2357-9
references.pmid: 19474435
references.citation: Neurology. 1996 Nov;47(5):1113-24
references.pmid: 8909416
references.citation: Neurology. 1984 Jul;34(7):939-44
references.pmid: 6610841
references.citation: Neurology. 2006 Jun 27;66(12):1837-44
references.pmid: 16801647
references.citation: J Am Geriatr Soc. 2011 Aug;59(8):1403-11
references.pmid: 21797830
references.citation: Neurobiol Aging. 2004 Oct;25(9):1205-12
references.pmid: 15312966
references.citation: Pain. 2006 Jul;123(1-2):90-7
references.pmid: 16563626
references.citation: Psychol Methods. 2002 Mar;7(1):19-40
references.pmid: 11928888
references.citation: Alzheimers Dement. 2013 May;9(3):e89-95
references.pmid: 23127468
references.citation: J Alzheimers Dis. 2009;18(3):665-75
references.pmid: 19661626
references.citation: N Engl J Med. 2009 May 28;360(22):2302-9
references.pmid: 19474427
references.citation: N Engl J Med. 2003 Jun 19;348(25):2508-16
references.pmid: 12815136
references.citation: Neurology. 2003 Jan 28;60(2):246-52
references.pmid: 12552039
references.citation: J Neurol Sci. 1968 Sep-Oct;7(2):331-56
references.pmid: 5707082