title: Comparison of symptomatic and asymptomatic persons with Alzheimer disease neuropathology.
abstract: OBJECTIVE
  We sought to identify demographic and clinical features that were associated with expression of symptoms in the presence of Alzheimer disease (AD) neuropathologic changes.
  
  
  METHODS
  We studied 82 asymptomatic (Clinical Dementia Rating global score = 0) and 824 symptomatic subjects (Clinical Dementia Rating score >0) with low to high AD neuropathologic changes at autopsy who were assessed at 1 of 34 National Institute on Aging-funded Alzheimer's Disease Centers. All subjects underwent a clinical examination within 1 year of death. Logistic regression was used to evaluate factors associated with the odds of being asymptomatic vs symptomatic.
  
  
  RESULTS
  Asymptomatic subjects tended to have low neurofibrillary tangle scores but a wide range of neuritic plaque frequencies. There were, however, a few asymptomatic subjects with very high tangle and neuritic plaque burden, as well as symptomatic subjects with few changes. In the multivariable model, asymptomatic subjects were older (odds ratio [OR] = 1.04; 95% confidence interval [CI] = 1.01-1.07), had lower clinical Hachinski Ischemic Score (OR = 0.82; 95% CI = 0.69-0.97), were less likely to have an APOE ε4 allele (OR = 0.36; 95% CI = 0.16-0.83), and had lower neurofibrillary tangle score (OR = 0.28; 95% CI = 0.17-0.45) compared with symptomatic subjects.
  
  
  CONCLUSIONS
  Dissociating clinical symptoms from pathologic findings better allows for investigation of preclinical AD. Our results suggest that although the severity of the pathology, particularly neurofibrillary tangles, has a large role in determining the extent of symptoms, other factors, including age, APOE status, and comorbidities such as cerebrovascular disease also explain differences in clinical presentation.
authors: National Alzheimer's Coordinating Center, University of Washington, Seattle, WA, USA. smonsell@u.washington.edu
authors: Sarah E
authors: SE
authors: Monsell
authors: Charles
authors: C
authors: Mock
authors: Catherine M
authors: CM
authors: Roe
authors: Nupur
authors: N
authors: Ghoshal
authors: John C
authors: JC
authors: Morris
authors: Nigel J
authors: NJ
authors: Cairns
authors: Walter
authors: W
authors: Kukull
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000145:classification / Q000453:epidemiology / Q000235:genetics / Q000473:pathology*; D001057:Apolipoproteins E / Q000235:genetics; D002318:Cardiovascular Diseases / Q000453:epidemiology; D015897:Comorbidity; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D016874:Neurofibrillary Tangles / Q000473:pathology; D016017:Odds Ratio; D058225:Plaque, Amyloid / Q000473:pathology; D062706:Prodromal Symptoms; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index
chemical_list: D001057:Apolipoproteins E
references: Arch Gen Psychiatry. 2006 Feb;63(2):153-60
references: 16461857
references: Neuron. 2009 Aug 13;63(3):287-303
references: 19679070
references: Neurobiol Aging. 1997 Jul-Aug;18(4 Suppl):S1-2
references: 9330978
references: Ann Neurol. 2011 Feb;69(2):320-7
references: 21387377
references: J Geriatr Psychiatry Neurol. 2005 Dec;18(4):218-23
references: 16306243
references: Alzheimer Dis Assoc Disord. 2007 Jul-Sep;21(3):249-58
references: 17804958
references: Brain. 2012 Jul;135(Pt 7):2155-68
references: 22637583
references: Arch Gen Psychiatry. 2005 Jun;62(6):685-91
references: 15939846
references: Acta Neuropathol. 2006 Oct;112(4):389-404
references: 16906426
references: Neuropathol Appl Neurobiol. 2011 Feb;37(1):75-93
references: 20946241
references: Exp Neurol. 2002 Oct;177(2):475-93
references: 12429193
references: Neurology. 1992 Mar;42(3 Pt 1):631-9
references: 1549228
references: Neurology. 1992 Sep;42(9):1681-8
references: 1307688
references: Am J Epidemiol. 2001 Jan 15;153(2):132-6
references: 11159157
references: Neurology. 2002 Aug 13;59(3):364-70
references: 12177369
references: J Neuropathol Exp Neurol. 2012 May;71(5):362-81
references: 22487856
references: Neurobiol Aging. 2009 Jul;30(7):1026-36
references: 19376612
references: Neurology. 1991 Apr;41(4):479-86
references: 2011243
references: Arch Neurol. 2003 May;60(5):753-9
references: 12756140
references: Age Ageing. 2006 Mar;35(2):154-60
references: 16414964
references: Brain. 2011 Dec;134(Pt 12):3687-96
references: 22102649
references: Arch Gen Psychiatry. 2012 May;69(5):493-8
references: 22566581
references: J Neuropathol Exp Neurol. 2009 Jan;68(1):1-14
references: 19104448
references: Brain. 2009 Aug;132(Pt 8):2036-47
references: 19439419
references: Brain Imaging Behav. 2012 Dec;6(4):610-20
references: 22648764
references: J Neuropathol Exp Neurol. 2007 Dec;66(12):1136-46
references: 18090922
references: Neurology. 2007 Jan 16;68(3):223-8
references: 17224578
references: JAMA. 2012 May 2;307(17):1798-800
references: 22550192
references: Brain Pathol. 2010 Jan;20(1):66-79
references: 19021630
references: J Neuropathol Exp Neurol. 2006 Jul;65(7):685-97
references: 16825955
references: Ann Neurol. 1980 May;7(5):486-8
references: 7396427
references: Alzheimers Dement. 2012 Jan;8(1):1-13
references: 22265587
references: Acta Neuropathol. 2012 Jan;123(1):1-11
references: 22101365
references: Neurology. 2012 Jan 31;78(5):342-51
references: 22282647
references: Neurology. 1993 Nov;43(11):2412-4
references: 8232972
references: Am J Geriatr Psychiatry. 2008 Feb;16(2):168-74
references: 18239198
references: Neurology. 2002 Jun 25;58(12):1791-800
references: 12084879
references: Alzheimers Dement. 2011 May;7(3):280-92
references: 21514248