Neuroepidemiology 2006;27:169–176

Decision Rules Guiding the Clinical Diagnosis of Alzheimer’s Disease in Two Community-Based Cohort Studies Compared to Standard Practice in a Clinic-Based Cohort Study

Bennett D.A.a, b · Schneider J.A.a-c · Aggarwal N.T.a, b · Arvanitakis Z.a, b · Shah R.C.a, e · Kelly J.F.a, f · Fox J.H.b · Cochran E.J.c · Arends D.a · Treinkman A.D.a · Wilson R.S.a, b, d
aRush Alzheimer’s Disease Center and Departments of bNeurological Sciences, cPathology, dBehavioral Sciences, eFamily Practice and fInternal Medicine, Rush University Medical Center, Chicago, Ill., USA
email Corresponding Author

 goto top of outline Key Words

  • Alzheimer’s disease
  • Alzheimer’s disease, diagnosis
  • Decision rules
  • Alzheimer’s disease, pathology

 goto top of outline Abstract

We developed prediction rules to guide the clinical diagnosis of Alzheimer’s disease (AD) in two community-based cohort studies (the Religious Orders Study and the Rush Memory and Aging Project). The rules were implemented without informant interviews, neuroimaging, blood work or routine case conferencing. Autopsies were performed at death and the pathologic diagnosis of AD made with a modified version of the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) criteria. We compared the positive predictive value of the clinical diagnosis in the two community-based studies to the positive predictive value of the clinical diagnosis of AD made by standard clinical practice in a clinic-based cohort study using AD pathology as the gold standard. Of 306 clinic cases with probable AD, 286 (93.5%) met CERAD neuropathologic criteria for AD; the results were comparable for those with possible AD (51 of 54, 94.4%). Of 141 study subjects with probable AD, 130 (92.2%) met CERAD neuropathologic criteria for AD; the results were lower but acceptable for those with possible AD (26 of 37, 70.3%). The results were similar in secondary analyses using alternate neuropathologic criteria for AD. The clinical diagnosis of AD can be made in community-based studies without the use of informant interviews, neuroimaging, blood work or routine case conferencing. This approach holds promise for reducing the operational costs of epidemiologic studies of aging and AD.

Copyright © 2006 S. Karger AG, Basel

 goto top of outline References
  1. Bennett DA, Schneider JA, Arvanitakis Z, et al: Neuropathology of older persons without cognitive impairment from two community-based studies. Neurology 2006;66:1837–1844.
  2. Bennett DA, Schneider JA, Buchman AS, Mendes de Leon CF, Bienias JL, Wilson RS: The Rush Memory and Aging Project: Study design and baseline characteristics of the study cohort. Neuroepidemiology 2005;25:163–175.
  3. Katzman R, Terry R, DeTeresa R, et al: Clinical, pathological, and neurochemical changes in dementia: a subgroup with preserved mental status and numerous neocortical plaques. Ann Neurol 1988;23:138–144.
  4. Hulette CM, Welsh-Bohmer KA, Murray MG, Saunders AM, Mash DC, McIntyre LM: Neuropathological and neuropsychological changes in ‘normal’ aging: evidence for preclinical Alzheimer disease in cognitively normal individuals. J Neuropathol Exp Neurol 1998;57:1168–1174.
  5. Knopman DS, Parisi JE, Salviati A, et al: Neuropathology of cognitively normal elderly. J Neuropathol Exp Neurol 2003;62:1087–1095.
  6. Schmitt FA, Davis DG, Wekstein DR, Smith CD, Ashford JW, Markesbery WR: ‘Preclinical’ AD revisited: neuropathology of cognitively normal older adults. Neurology 2000;55:370–376.
  7. Galvin JE, Powlishta KK, Wilkins K, et al: Predictors of preclinical Alzheimer disease and dementia: a clinicopathologic study. Arch Neurol 2005;62:758–765.
  8. Wilson RS, Gilley DW, Bennett DA, Hebert LE, Beckett LA, Evans DA: Person-specific paths of cognitive decline in Alzheimer’s disease and their relation to age. Psychol Aging 2000;15:18–28.
  9. Hui JS, Wilson RS, Bennett DA, Bienias JL, Gilley DW, Evans DA: Rate of cognitive decline and mortality in Alzheimer’s disease. Neurology 2003;61:1356–1361.
  10. Barnes LL, Wilson RS, Li Y, Gilley DW, Bennett DA, Evans DA: Change in cognitive function in Alzheimer’s disease in African-American and white persons. Neuroepidemiology 2005;25:16–22.
  11. Morris JC, Heyman A, Mohs RC, et al: The consortium to establish a registry for Alzheimer’s disease (CERAD). I. Clinical and neuropsychological assessment of Alzheimer’s disease. Neurology 1989;39:1159–1165.
  12. Knopman DS, DeKosky ST, Cummings JL, et al: Practice parameter: diagnosis of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2001;56:1143–1153.
  13. McKhann G, Drachmann D, Folstein M, Katzman R, Price D, Stadlan E: 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 1984;34:939.
  14. Roman GC, Tatemichi TK, Erkinjuntti T, et al: Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology 1993;43:250–260.
  15. Langston JW, Widner H, Goetz CGT, et al: Core Assessment Program for Intracerebral Transplantations (CAPIT). Mov Disord 1992;7:2–13.
  16. Hamilton, M: A rating scale for depression. J Neurol Neurosurg Psychiatry 1960;23:56–62.
  17. Robins LN, Helzer JE, Ratcliff KS, Seyfried W: Validity of the Diagnostic Interview Schedule. II. DSM-III diagnoses. Psychol Med 1982;12:855–870.
  18. Bennett DA, Shannon KM, Beckett LA, Goetz CG, Wilson RS: Metric properties of nurses’ ratings of parkinsonian signs with a modified Unified Parkinson’s Disease Rating Scale. Neurology 1997;49:1580–1587.
  19. Wilson RS, Beckett LA, Barnes LL, et al: Individual differences in rates of change in cognitive abilities of older persons. Psychol Aging 2002;17:179–193.
  20. Wilson RS, Bennett DA: Assessment of cognitive decline in old age with brief tests amenable to telephone administration. Neuroepidemiology 2005;25:19–25.
  21. Wasson JH, Sox HC, Neff RK, Goldman L: Clinical prediction rules: applications and methodological standards. N Engl J Med 1985;313:793–799.
  22. Laupacis A, Sekar N, Stiell IG: Clinical prediction rules: a review and suggested modifications of methodological standards. JAMA 1997;277:488–494.
  23. Reilly BM, Evans AT: Translating clinical research into clinical practice: impact of using prediction rules to make decisions. Ann Intern Med 2006;144:201–209.
  24. Bennett DA, Wilson RS, Schneider JA, et al: Natural history of mild cognitive impairment in older persons. Neurology 2002;59:198–205.
  25. Boyle PA, Wilson RS, Aggarwal NT, Tang Y, Bennett DA: Mild cognitive impairment: risk of Alzheimer disease and rate of cognitive decline. Neurology 2006;67:441–445.
  26. Petersen RC, Parisi JE, Dickson DW, et al: Neuropathologic features of amnestic mild cognitive impairment. Arch Neurol 2006;63:665–672.
  27. Barnes LL, Schneider JA, Boyle PA, Bienias JL, Bennett DA: Memory complaints are related to Alzheimer disease pathology in older persons. Neurology, in press.
  28. Petersen RC: Mild cognitive impairment: where are we? Alzheimer Dis Assoc Disord 2005;19:166–169.
  29. Bennett DA, Schneider JA, Bienias JL, Evans DA, Wilson RS: Mild cognitive impairment is related to Alzheimer disease pathology and cerebral infarctions. Neurology 2005;64:834–842.
  30. Mirra SS, Heyman A, McKeel D, et al: The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). II. Standardization of the neuropathologic assessment of Alzheimer’s disease. Neurology 1991;41:479–486.
  31. Braak H, Braak E: Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol (Berl) 1991;82:239–259.
  32. Consensus recommendations for the postmortem diagnosis of Alzheimer’s disease. The National Institute on Aging and Reagan Institute Working Group on Diagnostic Criteria for the Neuropathological Assessment of Alzheimer’s Disease. Neurobiol Aging 1997;18(suppl 4):S1–S2.
  33. Schneider JA, Bienias JL, Wilson RS, Berry-Kravis E, Evans DA, Bennett DA: Relation of the apolipoprotein E ε4 allele to cerebral infarction in older persons. Stroke 2005;36:954–959.
  34. Schneider JA, Bienias J, Gilley DW, Kvarnberg D, Mufson EJ, Bennett DA: Improved detection of neurofibrillary pathology in Alzheimer’s disease. J Histochem Cytochem 2002;50:99–106.
  35. McKeith IG, Galasko D, Kosaka K, et al: Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology 1996;47:1113–1124.
  36. Folstein MF, Folstein SE, McHugh PR: ‘Mini-Mental State’: a practical method for grading the mental state of patients for the clinician. J Psychiatr Res 1975;12:189–198.
  37. Kukull WA, Larson EB, Reifler BV, Lampe TH, Yerby MS, Hughes JP: The validity of 3 clinical diagnostic criteria for Alzheimer’s disease. Neurology 1990;40:1364–1369.
  38. Galasko D, Hansen LA, Katzman R, et al: Clinical-neuropathological correlations in Alzheimer’s disease and related dementias. Arch Neurol 1994;51:888–895.
  39. Victoroff J, Mack WJ, Lyness SA, Chui HC: Multicenter clinicopathological correlation in dementia. Am J Psychiatry 1995;152:1476–1484.
  40. Gearing M, Mirra SS, Hedreen JC, Sumi SM, Hansen LA, Heyman A: The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). X. Neuropathology confirmation of the clinical diagnosis of Alzheimer’s disease. Neurology 1995;45:461–466.
  41. Morris JC, McKeel DW Jr, Fulling K, Torack RM, Berg L: Validation of clinical diagnostic criteria for Alzheimer’s disease. Ann Neurol 1988;24:17–22.
  42. Neuropathology Group of the Medical Research Council Cognitive Function and Aging Study (MRC CFAS): Pathologic correlates of late-onset dementia in a multicentre, community-based population in England and Wales. Lancet 2001;357:169–175.
  43. Plassman BL, Khachaturian AS, Townsend JJ, et al: Comparison of clinical and neuropathologic diagnoses of Alzheimer’s disease in 3 epidemiologic samples. Alzheimer Dement 2006;2:2–11.
  44. Lim A, Tsuang D, Kukull W, et al: Clinico-neuropathological correlation of Alzheimer’s disease in a community-based case series. J Am Geriatr Soc 1999;47:564–569.
  45. Massoud F, Devi G, Stern Y, et al: A clinicopathological comparison of community-based and clinic-based cohorts of patients with dementia. Arch Neurol 1999;56:1368–1373.
  46. Petrovitch H, White LR, Ross GW, et al: Accuracy of clinical criteria for AD in the Honolulu-Asia Aging Study, a population-based study. Neurology 2001;57:226–234.
  47. Cacchione PZ, Powlishta KK, Grant EA, Buckles VD, Morris JC: Accuracy of collateral source reports in very mild to mild dementia of the Alzheimer type. J Am Geriatr Soc 2003;51:819–823.
  48. Ross GW, Abbott RD, Petrovitch H, et al: Frequency and characteristics of silent dementia among elderly Japanese-American men: the Honolulu-Asia Aging Study. JAMA 1997;277:800–805.
  49. Ganguli M, Rodriguez E, Mulsant B, et al: Detection and management of cognitive impairment in primary care: the Steel Valley Seniors Survey. J Am Geriatr Soc 2004;52:1668–1675.
  50. Lopez OL, Kuller LH, Becker JT, et al: Classification of vascular dementia in the Cardiovascular Health Study Cognition Study. Neurology 2005;64:1539–1547.
  51. Knopman DS, Parisi JE, Boeve BF, et al: Vascular dementia in a population-based autopsy study. Arch Neurol 2003;60:569–575.
  52. Pantoni L, Sarti C, Alafuzoff I, et al: Postmortem examination of vascular lesions in cognitive impairment: a survey among neuropathological services. Stroke 2006;37:1005–1009.
  53. Vinters HV, Ellis WG, Zarow C, et al: Neuropathologic substrates of ischemic vascular dementia. J Neuropathol Exp Neurol 2000;59:931–945.
  54. Schneider JA, Wilson RS, Bienias JL, Evans DA, Bennett DA: Cerebral infarctions and the likelihood of dementia from Alzheimer’s disease pathology. Neurology 2004;62:1148–1152.
  55. Snowdon DA, Greiner LH, Mortimer JA, Riley KP, Greiner PA, Markesbery WR: Brain infarction and the clinical expression of Alzheimer disease: the Nun Study. JAMA 1997;277:813–817.
  56. Petrovitch H, Ross GW, Steinhorn SC, et al: AD lesions and infarcts in demented and non-demented Japanese-American men. Ann Neurol 2005;57:98–103.

 goto top of outline Author Contacts

David A. Bennett, MD
Rush Alzheimer’s Disease Center
600 South Paulina, Suite 1028
Chicago, IL 60612 (USA)
Tel. +1 312 942 2362, E-Mail

 goto top of outline Article Information

Published online: October 10, 2006
Number of Print Pages : 8
Number of Figures : 1, Number of Tables : 3, Number of References : 56

 goto top of outline Publication Details


Vol. 27, No. 3, Year 2006 (Cover Date: October 2006)

Journal Editor: Román, G.C. (San Antonio, Tex.)
ISSN: 0251–5350 (print), 1423–0208 (Online)

For additional information:

Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.