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Clinicopathologic study of Alzheimer’s disease: Alzheimer mimics

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Shim, Yong S., Roe, Catherine M., Buckles, Virginia D., Morris, John C.·2013·Journal of Alzheimer’s Disease
DOI 10.3233/jad-121594PMC PMC3725959
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Abstract

A definite diagnosis of Alzheimer's disease (AD) can only be made at autopsy. Even at expert research centers, diagnostic accuracy is relatively low. We conducted this study to examine the accuracy of clinical diagnosis of AD and present a list of clinical and neuropsychological findings that could render the clinical diagnosis difficult. Using the National Alzheimer's Coordinating Center database, the records of 533 patients who had been diagnosed clinically with AD, and later underwent autopsy, were reviewed retrospectively. Since the pathologic results of 119 subjects did not meet the criteria for definite AD, we labeled them as Alzheimer “mimics”. The neuropathological diagnoses of Alzheimer mimics consisted of dementia with Lewy bodies (n = 35, 29%), insufficient AD (n = 22, 18%), vascular disease (n = 15, 13%), frontotemporal lobar degeneration (n = 14, 12%), and hippocampal sclerosis (n = 10, 8%). History of pacemaker insertion (10.92% versus 4.11%, p = 0.005), congestive heart failure (13.45% versus 6.04%, p = 0.007), hypertension (56.30% versus 47.83%, p = 0.037), and resting tremor (14.29% versus 10.87%, p = 0.170) was more prevalent in Alzheimer mimics. Clinical Dementia Rating score and frequency of Neuropsychiatric Inventory Questionnaire items reflecting delusions, agitation, depression, and motor disturbance were more severe in confirmed AD. In addition to Mini-Mental State Examination (16.97 ± 8.29 versus 12.74 ± 15.26, p < 0.001), Logical Memory, Animal Fluency, Boston Naming Test, and Digit Span scores showed more severe impairment in confirmed AD. Continuing systematic comparisons of the current criteria for the clinical and pathological dementia diagnoses are essential to clinical practice and research, and may also lead to further improvement of the diagnostic procedure.

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  • Shim et al found that AD-Mimics had more impairment on the UPDRS and exhibited more parkinsonian signs than Confirmed-AD participants, concluding that the presence of these signs should warn clinicians of the possibility of an alternate diagnosis.

    “Shim et al (1) found that AD-Mimics had more impairment on the Unified Parkinson's Disease Rating Scale (UPDRS) and exhibited more parkinsonian signs than Confirmed-AD participants, concluding that the presence of these signs should warn clinicians of the possibility of an alternate diagnosis.”

    From Concordance of Clinical Alzheimer Diagnosis and Neuropathological Features at Autopsy (2020) · cites this paper as [1]

    Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

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  • Previous studies have shown that LBD and cerebrovascular injury are the most common AD-dementia mimics.

    “Previous studies (1,15) have shown that LBD and cerebrovascular injury are the most common AD-dementia mimics.”

    From Concordance of Clinical Alzheimer Diagnosis and Neuropathological Features at Autopsy (2020) · cites this paper as [1]

    The Results (‘Neuropathological diagnoses’) identify dementia with Lewy bodies as the most common Alzheimer mimic (35 cases, 29%). Vascular disease was also a mimic (15 cases, 13%), but ranked third, behind insufficient AD (22 cases, 18%); the source therefore does not support calling both the most common mimics. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • AD-Mimics were more likely to have a history of pacemaker insertion, congestive heart failure, hypertension, and resting tremor than participants who had autopsy-confirmed AD.

    “AD-Mimics were more likely to have a history of pacemaker insertion, congestive heart failure, hypertension, and resting tremor than participants who had autopsy-confirmed AD.”

    From Concordance of Clinical Alzheimer Diagnosis and Neuropathological Features at Autopsy (2020) · cites this paper as [1]

  • Autopsy-confirmed AD participants showed more impairment on neuropsychological tests and clinically evaluated scales than AD-Mimics.

    “Autopsy-confirmed AD participants also showed more impairment on neuropsychological tests and clinically evaluated scales.”

    From Concordance of Clinical Alzheimer Diagnosis and Neuropathological Features at Autopsy (2020) · cites this paper as [1]

  • Shim et al compared 533 patients who were diagnosed with AD, referring to the 119 patients who did not meet neuropathological criteria for AD as AD-Mimics.

    “Using data from the National Alzheimer's Coordinating Center (NACC), Shim et al (1) compared 533 patients who were diagnosed with AD, referring to the 119 patients who did not meet neuropathological criteria for AD as AD-Mimics.”

    From Concordance of Clinical Alzheimer Diagnosis and Neuropathological Features at Autopsy (2020) · cites this paper as [1]

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Research works printed but not linked: 47

  1. [1]Klatka LA Schiffer RB Powers JM Kazee AM 1996 Incorrect diagnosis of Alzheimer’s disease. A clinicopathologic study Arch Neurol 53 35 42 8599556
  2. [2]Neary D Snowden JS Bowen DM Sims NR Mann DM Benton JS Northen B Yates PO Davison AN 1986 Neuropsychological syndromes in presenile dementia due to cerebral atrophy J Neurol Neurosurg Psychiatry 49 163 174 2419511 PMC1028682
  3. [3]Sulkava R Haltia M Paetau A Wikstrom J Palo J 1983 Accuracy of clinical diagnosis in primary degenerative dementia: correlation with neuropathological findings J Neurol Neurosurg Psychiatry 46 9 13 6842208 PMC1027256
  4. [4]Molsa PK Paljarvi L Rinne JO Rinne UK Sako E 1985 Validity of clinical diagnosis in dementia: a prospective clinicopathological study J Neurol Neurosurg Psychiatry 48 1085 1090 4078573 PMC1028565
  5. [5]Wade JP Mirsen TR Hachinski VC Fisman M Lau C Merskey H 1987 The clinical diagnosis of Alzheimer’s disease Arch Neurol 44 24 29 3800717
  6. [7]Joachim CL Morris JH Selkoe DJ 1988 Clinically diagnosed Alzheimer’s disease: autopsy results in 150 cases Ann Neurol 24 50 56 3415200
  7. [8]McKhann G Drachman D Folstein M Katzman R Price D Stadlan EM 1984 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 34 939 944 6610841
  8. [9]Khachaturian ZS 1985 Diagnosis of Alzheimer’s disease Arch Neurol 42 1097 1105 2864910
  9. [10]Risse SC Raskind MA Nochlin D Sumi SM Lampe TH Bird TD Cubberley L Peskind ER 1990 Neuropathological findings in patients with clinical diagnoses of probable Alzheimer’s disease Am J Psychiatry 147 168 172 2301654
  10. [11]Boller F Lopez OL Moossy J 1989 Diagnosis of dementia: clinicopathologic correlations Neurology 39 76 79 2642615
  11. [12]Gilleard CJ Kellett JM Coles JA Millard PH Honavar M Lantos PL 1992 The St. George’s dementia bed investigation study: a comparison of clinical and pathological diagnosis Acta Psychiatr Scand 85 264 269 1595359
  12. [13]Burns A Luthert P Levy R Jacoby R Lantos P 1990 Accuracy of clinical diagnosis of Alzheimer’s disease BMJ 301 1026 2249050 PMC1664030
  13. [14]Tierney MC Fisher RH Lewis AJ Zorzitto ML Snow WG Reid DW Nieuwstraten P 1988 The NINCDS-ADRDA Work Group criteria for the clinical diagnosis of probable Alzheimer’s disease: a clinicopathologic study of 57 cases Neurology 38 359 364 3347338
  14. [15]Morris JC McKeel DW Jr Fulling K Torack RM Berg L 1988 Validation of clinical diagnostic criteria for Alzheimer’s disease Ann Neurol 24 17 22 3415196
  15. [16]Berg L McKeel DW Jr Miller JP Storandt M Rubin EH Morris JC Baty J Coats M Norton J Goate AM Price JL Gearing M Mirra SS Saunders AM 1988 Clinicopathologic studies in cognitively healthy aging and Alzheimer’s disease: relation of histologic markers to dementia severity, age, sex, and apolipoprotein E genotype Arch Neurol 55 326 35 9520006
  16. [17]Beekly DL Ramos EM van Belle G Deitrich W Clark AD Jacka ME Kukull WA NIA-Alzheimer’s Disease Centers 2004 The National Alzheimer’s Coordinating Center (NACC) Database: an Alzheimer disease database Alzheimer Dis Assoc Disord 18 270 277 15592144
  17. [18]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 58 17804958
  18. [19]Morris JC Weintraub S Chui HC Cummings J Decarli C Ferris S Foster NL Galasko D Graff-Radford N Peskind ER Beekly D Ramos EM Kukull WA 2006 The Uniform Data Set (UDS): clinical and cognitive variables and descriptive data from Alzheimer Disease Centers Alzheimer Dis Assoc Disord 20 210 216 17132964
  19. [20]Hyman BT Trojanowski JQ 1997 Consensus recommendations for the postmortem diagnosis of Alzheimer disease from the National Institute on Aging and the Reagan Institute Working Group on diagnostic criteria for the neuropathological assessment of Alzheimer disease J Neuropathol Exp Neurol 56 1095 1097 9329452
  20. [21]Mirra SS Hart MN Terry RD 1993 Making the diagnosis of Alzheimer’s disease. A primer for practicing pathologists Arch Pathol Lab Med 117 132 144 8427562
  21. [22]Nagy Z Yilmazer-Hanke DM Braak H Braak E Schultz C Hanke J 1998 Assessment of the pathological stages of Alzheimer’s disease in thin paraffin sections: a comparative study Dement Geriatr Cogn Disord 9 140 144 9622001
  22. [24]McKeith IG Galasko D Kosaka K Perry EK Dickson DW Hansen LA Salmon DP Lowe J Mirra SS Byrne EJ Lennox G Quinn NP Edwardson JA Ince PG Bergeron C Burns A Miller BL Lovestone S Collerton D Jansen EN Ballard C de Vos RA Wilcock GK Jellinger KA Perry RH 1996 Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop Neurology 47 1113 1124 8909416
  23. [25]McKeith IG Dickson DW Lowe J Emre M O’Brien JT Feldman H Cummings J Duda JE Lippa C Perry EK Aarsland D Arai H Ballard CG Boeve B Burn DJ Costa D Del Ser T Dubois B Galasko D Gauthier S Goetz CG Gomez-Tortosa E Halliday G Hansen LA Hardy J Iwatsubo T Kalaria RN Kaufer D Kenny RA Korczyn A Kosaka K Lee VM Lees A Litvan I Londos E Lopez OL Minoshima S Mizuno Y Molina JA Mukaetova-Ladinska EB Pasquier F Perry RH Schulz JB Trojanowski JQ Yamada M Consortium on DLB 2005 Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium Neurology 65 1863 1872 16237129
  24. [26]Cairns NJ Bigio EH Mackenzie IR Neumann M Lee VM Hatanpaa KJ White CL 3rd Schneider JA Grinberg LT Halliday G Duyckaerts C Lowe JS Holm IE Tolnay M Okamoto K Yokoo H Murayama S Woulfe J Munoz DG Dickson DW Ince PG Trojanowski JQ Mann DM Consortium for Frontotemporal Lobar Degeneration 2007 Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration Acta Neuropathol 114 5 22 17579875 PMC2827877
  25. [27]Kaufer DI Cummings JL Ketchel P Smith V MacMillan A Shelley T Lopez OL DeKosky ST 2000 Validation of the NPI-Q, a brief clinical form of the Neuropsychiatric Inventory J Neuropsychiatry Clin Neurosci 12 233 239 11001602
  26. [29]Folstein MF Folstein SE McHugh PR 1975 “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician J Psychiatr Res 12 189 198 1202204
  27. [30]Morris JC 1993 The Clinical Dementia Rating (CDR): current version and scoring rules Neurology 43 2412 2414 8232972
  28. [32]Morris JC Heyman A Mohs RC Hughes JP van Belle G Fillenbaum G Mellits ED Clark C 1989 The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) Part I. Clinical and neuropsychological assessment of Alzheimer’s disease Neurology 39 1159 1165 2771064
  29. [36]Gay BE Taylor KI Hohl U Tolnay M Staehelin HB 2008 The validity of clinical diagnoses of dementia in a group of consecutively autopsied memory clinic patients J Nutr Health Aging 12 132 137 18264641
  30. [37]Rosen WG Terry RD Fuld PA Katzman R Peck A 1980 Pathological verification of ischemic score in differentiation of dementias Ann Neurol 7 486 488 7396427
  31. [38]Burns A Jacoby R Levy R 1991 Neurological signs in Alzheimer’s disease Age Ageing 20 45 51 2028851
  32. [39]Chen JY Stern Y Sano M Mayeux R 1991 Cumulative risks of developing extrapyramidal signs, psychosis, or myoclonus in the course of Alzheimer’s disease Arch Neurol 48 1141 1143 1953398
  33. [40]Corey-Bloom J Galasko D Hofstetter CR Jackson JE Thal LJ 1993 Clinical features distinguishing large cohorts with possible AD, probable AD, and mixed dementia J Am Geriatr Soc 41 31 37 8418119
  34. [41]Molsa PK Marttila RJ Rinne UK 1984 Extrapyramidal signs in Alzheimer’s disease Neurology 34 1114 1116 6540392
  35. [42]Stern Y Mayeux R Sano M Hauser WA Bush T 1987 Predictors of disease course in patients with probable Alzheimer’s disease Neurology 37 1649 1653 3658173
  36. [43]Mayeux R Stern Y Spanton S 1985 Heterogeneity in dementia of the Alzheimer type: evidence of subgroups Neurology 35 453 461 3982631
  37. [44]Ditter SM Mirra SS 1987 Neuropathologic and clinical features of Parkinson’s disease in Alzheimer’s disease patients Neurology 37 754 760 3033544
  38. [45]Galasko D Kwo-on-Yuen PF Klauber MR Thal LJ 1990 Neurological findings in Alzheimer’s disease and normal aging Arch Neurol 47 625 627 2346387
  39. [46]McDaniel LD Lukovits T McDaniel KD 1993 Alzheimer’s disease: the problem of incorrect clinical diagnosis J Geriatr Psychiatry Neurol 6 230 234 8251052
  40. [47]Lennox G Lowe J Morrell K Landon M Mayer RJ 1989 Anti-ubiquitin immunocytochemistry is more sensitive than conventional techniques in the detection of diffuse Lewy body disease J Neurol Neurosurg Psychiatry 52 67 71 2540286 PMC1032659
  41. [48]Spillantini MG Schmidt ML Lee VM Trojanowski JQ Jakes R Goedert M 1997 Alpha-synuclein in Lewy bodies Nature 388 839 840 9278044
  42. [49]Jellinger KA 2006 Clinicopathological analysis of dementia disorders in the elderly-an update J Alzheimers Dis 9 61 70 16914845
  43. [50]Knopman DS Parisi JE Boeve BF Cha RH Apaydin H Salviati A Edland SD Rocca WA 2003 Vascular dementia in a population-based autopsy study Arch Neurol 60 569 575 12707071
  44. [51]Brunnstrom H Englund E 2009 Clinicopathological concordance in dementia diagnostics Am J Geriatr Psychiatry 17 664 670 19634210
  45. [52]Josephs KA Petersen RC Knopman DS Boeve BF Whitwell JL Duffy JR Parisi JE Dickson DW 2006 Clinicopathologic analysis of frontotemporal and corticobasal degenerations and PSP Neurology 66 41 48 16401843
  46. [53]Cairns NJ Bigio EH Mackenzie IR Neumann M Lee VM Hatanpaa KJ White CL 3rd Schneider JA Grinberg LT Halliday G Duyckaerts C Lowe JS Holm IE Tolnay M Okamoto K Yokoo H Murayama S Woulfe J Munoz DG Dickson DW Ince PG Trojanowski JQ Mann DM Consortium for Frontotemporal Lobar Degeneration 2007 Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration Acta Neuropathol 114 5 22 17579875 PMC2827877
  47. [54]Snowden JS Thompson JC Stopford CL Richardson AMT Gerhard A Neary D Mann DMA 2011 The clinical diagnosis of early-onset dementias: diagnostic accuracy and clinicopathological relationships Brain 134 2478 2492 21840888

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Authors
Shim, Y. S., Roe, C. M., Buckles, V. D., & Morris, J. C.
Affiliations
  • The Catholic University of Korea Bucheon St. Mary's Hospital (KR)
  • Washington University in St. Louis (US)
ORCID
Venue
Journal of Alzheimer’s Disease
Publisher
SAGE Publications
Published
2013-05-21
Volume
35
Issue
4
Pages
799-811
ISSN
  • 1387-2877 (ISSN-L)
  • 1875-8908
DOI
10.3233/jad-121594
PMC
PMC3725959
OpenAlex
W1815544646
Cited by
49
References
2
Citations by year
2025: 4 · 2024: 4 · 2023: 3 · 2022: 4 · 2021: 3 · 2020: 3 · 2019: 4 · 2018: 2 · 2017: 4 · 2016: 1 · 2015: 8 · 2014: 5 · 2013: 4
FWCI
4.27
Type
journal article
Language
en
Open access
Licence
journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations
  • Journal of Alzheimer s Disease (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute on Aging (U01AG016976, P50AG005681, P01AG003991)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Social Sciences › Psychology › Clinical Psychology › Historical and Modern Theater Studies
Keywords
Alzheimer's disease
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Autopsy, Brain, Female, Follow-Up Studies, Humans, Immunohistochemistry, Male, Neuropsychological Tests, Psychomotor Performance, Reproducibility of Results, Databases, Factual, Lewy Body Disease

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