Skip to main content

Advertisement

SpringerLink
Log in

Criteria for the neuropathological diagnosis of dementing disorders: routes out of the swamp?

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

Abstract

There are several consensus criteria for both the clinical and neuropathological diagnosis of different types of dementias. The clinical diagnostic accuracy using revised research criteria and newly developed biomarkers (MRI, PET, CSF analysis, genetic markers) ranges from 65 to 96% (for Alzheimer disease) with a specificity of diagnostic criteria versus other dementias of 23–88%. Neuropathological assessment of dementing disorders using immunohistochemistry, molecular biologic and genetic methods can achieve a diagnosis/classification, based on the homogeneous definitions, harmonized inter-laboratory methods and standards for the assessment of nervous system lesions, in about 99%, without, however, being able to clarify the causes/etiology of most of these disorders. Further prospective and concerted clinicopathological studies using revised methodological and validated protocols and uniform techniques are required to establish the nature, distribution pattern and grades of lesions and; thus, to overcome the limitations of the current diagnostic framework. By data fusion this my allow their more uniform application and correlation with the clinical data in order to approach a diagnostic “gold standard”, and to create generally accepted criteria for differentiating cognitive disorders from healthy brain aging. The detection of disease-specific pathologies will be indispensable to determinate the efficacy of new therapy options.

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

Similar content being viewed by others

References

  1. Aho L, Parkkinen L, Pirttila T, Alafuzoff I (2008) Systematic appraisal using immunohistochemistry of brain pathology in aged and demented subjects. Dement Geriatr Cogn Disord 25:423–432

    PubMed  CAS  Google Scholar 

  2. Aizenstein HJ, Nebes RD, Saxton JA, Price JC, Mathis CA, Tsopelas ND, Ziolko SK, James JA, Snitz BE, Houck PR, Bi W, Cohen AD, Lopresti BJ, DeKosky ST, Halligan EM, Klunk WE (2008) Frequent amyloid deposition without significant cognitive impairment among the elderly. Arch Neurol 65:1509–1517

    PubMed  Google Scholar 

  3. Alafuzoff I, Pikkarainen M, Al-Sarraj S, Arzberger T, Bell J, Bodi I, Bogdanovic N, Budka H, Bugiani O, Ferrer I, Gelpi E, Giaccone G, Graeber MB, Hauw JJ, Kamphorst W, King A, Kopp N, Korkolopoulou P, Kovacs GG, Meyronet D, Parchi P, Patsouris E, Preusser M, Ravid R, Roggendorf W, Seilhean D, Streichenberger N, Thal DR, Kretzschmar H (2006) Interlaboratory comparison of assessments of Alzheimer disease-related lesions: a study of the BrainNet Europe consortium. J Neuropathol Exp Neurol 65:740–757

    PubMed  CAS  Google Scholar 

  4. Alafuzoff I, Arzberger T, Al-Sarraj S, Bodi I, Bogdanovic N, Braak H, Bugiani O, Del-Tredici K, Ferrer I, Gelpi E, Giaccone G, Graeber MB, Ince P, Kamphorst W, King A, Korkolopoulou P, Kovacs GG, Larionov S, Meyronet D, Monoranu C, Parchi P, Patsouris E, Roggendorf W, Seilhean D, Tagliavini F, Stadelmann C, Streichenberger N, Thal DR, Wharton SB, Kretzschmar H (2008) Staging of neurofibrillary pathology in Alzheimer’s disease: a study of the BrainNet Europe Consortium. Brain Pathol 18:484–496

    PubMed  Google Scholar 

  5. Alafuzoff I, Parkkinen L, Al-Sarraj S, Arzberger T, Bell J, Bodi I, Bogdanovic N, Budka H, Ferrer I, Gelpi E, Gentleman S, Giaccone G, Kamphorst W, King A, Korkolopoulou P, Kovacs GG, Larionov S, Meyronet D, Monoranu C, Morris J, Parchi P, Patsouris E, Roggendorf W, Seilhean D, Streichenberger N, Thal DR, Kretzschmar H (2008) Assessment of alpha-synuclein pathology: a study of the BrainNet Europe consortium. J Neuropathol Exp Neurol 67:125–143

    PubMed  Google Scholar 

  6. Alafuzoff I, Pikkarainen M, Arzberger T, Thal DR, Al-Sarraj S, Bell J, Bodi I, Budka H, Capetillo-Zarate E, Ferrer I, Gelpi E, Gentleman S, Giaccone G, Kavantzas N, King A, Korkolopoulou P, Kovacs GG, Meyronet D, Monoranu C, Parchi P, Patsouris E, Roggendorf W, Stadelmann C, Streichenberger N, Tagliavini F, Kretzschmar H (2008) Inter-laboratory comparison of neuropathological assessments of beta-amyloid protein: a study of the BrainNet Europe consortium. Acta Neuropathol 115:533–546

    PubMed  CAS  Google Scholar 

  7. Alafuzoff I, Pikkarainen M, Arzberger T, Thal DR, Al-Sarraj S, Bell J, Bodi I, Budka H, Capetillo-Zarate E, Ferrer I, Gelpi E, Gentleman S, Giaccone G, Kavantzas N, King A, Korkolopoulou P, Kovács GG, Meyronet D, Monoranu C, Parchi P, Patsouris E, Roggendorf W, Stadelmann C, Streichenberger N, Tagliavini F, Kretzschmar H, BrainNet E (2009) Inter-laboratory comparison of neuropathological assessments of beta amyloid protein: a study of the BrainNet Europe consortium. Acta Neuropathol (in press)

  8. American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders. Text Revision, 4th edn. American Psychiatric Association, Washington DC

    Google Scholar 

  9. Andin U, Gustafson L, Passant U, Brun A (2005) A clinico-pathological study of heart and brain lesions in vascular dementia. Dement Geriatr Cogn Disord 19:222–228

    PubMed  Google Scholar 

  10. Arriagada PV, Marzloff K, Hyman BT (1992) Distribution of Alzheimer-type pathologic changes in nondemented elderly individuals matches the pattern in Alzheimer’s disease. Neurology 42:1681–1688

    PubMed  CAS  Google Scholar 

  11. Ballard C, Ziabreva I, Perry R, Larsen JP, O’Brien J, McKeith I, Perry E, Aarsland D (2006) Differences in neuropathologic characteristics across the Lewy body dementia spectrum. Neurology 67:1931–1934

    PubMed  CAS  Google Scholar 

  12. Bancher C, Jellinger K, Lassmann H, Fischer P, Leblhuber F (1996) Correlations between mental state and quantitative neuropathology in the Vienna longitudinal study on dementia. Eur Arch Psychiatry Clin Neurosci 246:137–146

    PubMed  CAS  Google Scholar 

  13. Bancher C, Paulus W, Paukner K, Jellinger K (1997) Neuropathologic diagnosis of Alzheimer disease: consensus between practicing neuropathologists? Alzheimer Dis Assoc Disord 11:207–219

    PubMed  CAS  Google Scholar 

  14. Bartzokis G, Sultzer D, Lu PH, Nuechterlein KH, Mintz J, Cummings JL (2004) Heterogeneous age-related breakdown of white matter structural integrity: implications for cortical “disconnection” in aging and Alzheimer’s disease. Neurobiol Aging 25:843–851

    PubMed  CAS  Google Scholar 

  15. Bennett DA, Schneider JA, Wilson RS, Bienias JL, Arnold SE (2004) Neurofibrillary tangles mediate the association of amyloid load with clinical Alzheimer disease and level of cognitive function. Arch Neurol 61:378–384

    PubMed  Google Scholar 

  16. Bennett DA, Schneider JA, Bienias JL, Evans DA, Wilson RS (2005) Mild cognitive impairment is related to Alzheimer disease pathology and cerebral infarctions. Neurology 64:834–841

    PubMed  CAS  Google Scholar 

  17. Bennett DA, Schneider JA, Arvanitakis Z, Kelly JF, Aggarwal NT, Shah RC, Wilson RS (2006) Neuropathology of older persons without cognitive impairment from two community-based studies. Neurology 66:1837–1844

    PubMed  CAS  Google Scholar 

  18. 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 (1998) 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 55:326–335

    PubMed  CAS  Google Scholar 

  19. Bierer LM, Hof PR, Purohit DP, Carlin L, Schmeidler J, Davis KL, Perl DP (1995) Neocortical neurofibrillary tangles correlate with dementia severity in Alzheimer’s disease. Arch Neurol 52:81–88

    PubMed  CAS  Google Scholar 

  20. Bowler JV, Munoz DG, Merskey H, Hachinski V (1998) Fallacies in the pathological confirmation of the diagnosis of Alzheimer’s disease. J Neurol Neurosurg Psychiatry 64:18–24

    PubMed  CAS  Google Scholar 

  21. Braak H, Braak E (1991) Neuropathological staging of Alzheimer-related changes. Acta Neuropathol (Berl) 82:239–259

    CAS  Google Scholar 

  22. Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 24:197–211

    PubMed  Google Scholar 

  23. Braak H, Alafuzoff I, Arzberger T, Kretzschmar H, Del Tredici K (2006) Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol (Berl) 112:389–404

    Google Scholar 

  24. Braak H, Bohl JR, Muller CM, Rub U, de Vos RA, Del Tredici K (2006) Stanley Fahn Lecture 2005: the staging procedure for the inclusion body pathology associated with sporadic Parkinson’s disease reconsidered. Mov Disord 21:2042–2051

    PubMed  Google Scholar 

  25. Cairns NJ, Bigio EH, Mackenzie IR, Neumann M, Lee VM, Hatanpaa KJ, White CLIII, 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 (2007) Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the consortium for frontotemporal lobar degeneration. Acta Neuropathol (Berl) 114:5–22

    Google Scholar 

  26. Chui HC, Victoroff JI, Margolin D, Jagust W, Shankle R, Katzman R (1992) Criteria for the diagnosis of ischemic vascular dementia proposed by the State of California Alzheimer’s disease diagnostic and treatment centers. Neurology 42:473–480

    PubMed  CAS  Google Scholar 

  27. Chui HC (2006) Vascular cognitive impairment: today and tomorrow. Alzheimers Demen 2:185–194

    Google Scholar 

  28. Chui HC, Zarow C, Mack WJ, Ellis WG, Zheng L, Jagust WJ, Mungas D, Reed BR, Kramer JH, Decarli CC, Weiner MW, Vinters HV (2006) Cognitive impact of subcortical vascular and Alzheimer’s disease pathology. Ann Neurol 60:677–687

    PubMed  Google Scholar 

  29. Claassen DO, Parisi JE, Giannini C, Boeve BF, Dickson DW, Josephs KA (2008) Frontotemporal dementia mimicking dementia with Lewy bodies. Cogn Behav Neurol 21:157–163

    PubMed  Google Scholar 

  30. Clark CM, Davatzikos C, Borthakur A, Newberg A, Leight S, Lee VM, Trojanowski JQ (2008) Biomarkers for early detection of Alzheimer pathology. Neurosignals 16:11–18

    PubMed  CAS  Google Scholar 

  31. Cochran EJ, Schneider JA, Bennett DA et al (1998) Application of NIA/Reagan Institute Working Group Criteria for diagnosis of Alzheimer’s disease to members of the religious orders study (abstr.). J Neuropathol Exp Neurol 57:508

    Google Scholar 

  32. 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

    PubMed  CAS  Google Scholar 

  33. Crystal HA, Dickson D, Davies P, Masur D, Grober E, Lipton RB (2000) The relative frequency of “dementia of unknown etiology” increases with age and is nearly 50% in nonagenarians. Arch Neurol 57:713–719

    PubMed  CAS  Google Scholar 

  34. Davis DG, Schmitt FA, Wekstein DR, Markesbery WR (1999) Alzheimer neuropathologic alterations in aged cognitively normal subjects. J Neuropathol Exp Neurol 58:376–388

    PubMed  CAS  Google Scholar 

  35. Delatour B, Blanchard V, Pradier L, Duyckaerts C (2004) Alzheimer pathology disorganizes cortico-cortical circuitry: direct evidence from a transgenic animal model. Neurobiol Dis 16:41–47

    PubMed  CAS  Google Scholar 

  36. Dubois B, Burn D, Goetz C, Aarsland D, Brown RG, Broe GA, Dickson D, Duyckaerts C, Cummings J, Gauthier S, Korczyn A, Lees A, Levy R, Litvan I, Mizuno Y, McKeith IG, Olanow CW, Poewe W, Sampaio C, Tolosa E, Emre M (2007) Diagnostic procedures for Parkinson’s disease dementia: recommendations from the movement disorder society task force. Mov Disord 22:2314–2324

    PubMed  Google Scholar 

  37. Dubois B, Feldman HH, Jacova C, Dekosky ST, Barberger-Gateau P, Cummings J, Delacourte A, Galasko D, Gauthier S, Jicha G, Meguro K, O’Brien J, Pasquier F, Robert P, Rossor M, Salloway S, Stern Y, Visser PJ, Scheltens P (2007) Research criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS-ADRDA criteria. Lancet Neurol 6:734–746

    PubMed  Google Scholar 

  38. Duyckaerts C, Delaère P, Hauw JJ, Abbamondi-Pinto AL, Sorbi S, Allen I, Brion JP, Flament-Durand J, Duchen L, Kauss J, Schlote W, Lowe J, Probst A, Ravid R, Swaab DF, Renkawek K, Tomlinson B (1990) Rating of the lesions in senile dementia of the Alzheimer type: concordance between laboratories. A European multicenter study under the auspices of EURAGE. J Neurol Sci 97:295–323

    PubMed  CAS  Google Scholar 

  39. Duyckaerts C (2008) Neuropathologic classification of dementias: introduction. In: Duyckaerts C, Litvan I (eds) Handbook of clinical neurology, vol 89 (3rd series). Elsevier, Edinburgh, pp 147–159

  40. Duyckaerts C, Litvan I (2008) Handbook of clinical neurology, vol 89 (3rd series). Edinburgh, Elsevier

  41. Edison P, Rowe CC, Rinne JO, Ng S, Ahmed I, Kemppainen N, Villemagne VL, O’Keefe G, Nagren K, Chaudhuri R, Masters CL, Brooks DJ (2008) Amyloid load in Parkinson’s disease dementia and Lewy Body dementia measured with [11C]PIB-PET. J Neurol Neurosurg Psychiatry (in press). doi:10.1136/jnnp.2007.127878

  42. Emre M, Aarsland D, Brown R, Burn DJ, Duyckaerts C, Mizuno Y, Broe GA, Cummings J, Dickson DW, Gauthier S, Goldman J, Goetz C, Korczyn A, Lees A, Levy R, Litvan I, McKeith I, Olanow W, Poewe W, Quinn N, Sampaio C, Tolosa E, Dubois B (2007) Clinical diagnostic criteria for dementia associated with Parkinson’s disease. Mov Disord 22:1689–1707

    PubMed  Google Scholar 

  43. Fein JA, Sokolow S, Miller CA, Vinters HV, Yang F, Cole GM, Gylys KH (2008) Co-localization of amyloid beta and tau pathology in Alzheimer’s disease synaptosomes. Am J Pathol 172:1683–1692

    PubMed  CAS  Google Scholar 

  44. Fernando MS, Ince PG (2004) Vascular pathologies and cognition in a population-based cohort of elderly people. J Neurol Sci 226:13–17

    PubMed  Google Scholar 

  45. Forman MS, Trojanowski JQ, Lee VM (2007) TDP-43: a novel neurodegenerative proteinopathy. Curr Opin Neurobiol 17:548–555

    PubMed  CAS  Google Scholar 

  46. Fujishiro H, Ferman TJ, Boeve BF, Smith GE, Graff-Radford NR, Uitti RJ, Wszolek ZK, Knopman DS, Petersen RC, Parisi JE, Dickson DW (2008) Validation of the neuropathologic criteria of the third consortium for dementia with Lewy bodies for prospectively diagnosed cases. J Neuropathol Exp Neurol 67:649–656

    Article  PubMed  Google Scholar 

  47. Geschwind MD, Shu H, Haman A, Sejvar JJ, Miller BL (2008) Rapidly progressive dementia. Ann Neurol 64:97–108

    PubMed  Google Scholar 

  48. Geula C, Nagykery N, Nicholas A, Wu CK (2008) Cholinergic neuronal and axonal abnormalities are present early in aging and in Alzheimer disease. J Neuropathol Exp Neurol 67:309–318

    PubMed  Google Scholar 

  49. Giannakopoulos P, Hof PR, Giannakopoulos AS, Herrmann FR, Michel JP, Bouras C (1995) Regional distribution of neurofibrillary tangles and senile plaques in the cerebral cortex of very old patients. Arch Neurol 52:1150–1159

    PubMed  CAS  Google Scholar 

  50. Giannakopoulos P, Hof PR, Kovari E, Vallet PG, Herrmann FR, Bouras C (1996) Distinct patterns of neuronal loss and Alzheimer’s disease lesion distribution in elderly individuals older than 90 years. J Neuropathol Exp Neurol 55:1210–1220

    PubMed  CAS  Google Scholar 

  51. Giannakopoulos P, Gold G, Kovari E, von Gunten A, Imhof A, Bouras C, Hof PR (2007) Assessing the cognitive impact of Alzheimer disease pathology and vascular burden in the aging brain: the Geneva experience. Acta Neuropathol 113:1–12

    PubMed  Google Scholar 

  52. Gold G, Bouras C, Kovari E, Canuto A, Glaria BG, Malky A, Hof PR, Michel JP, Giannakopoulos P (2000) Clinical validity of Braak neuropathological staging in the oldest-old. Acta Neuropathol (Berl) 99:579–582

    CAS  Google Scholar 

  53. Gold G, Giannakopoulos P, Herrmann FR, Bouras C, Kovari E (2007) Identification of Alzheimer and vascular lesion thresholds for mixed dementia. Brain 130:2830–2836

    PubMed  Google Scholar 

  54. Gomperts SN, Rentz DM, Moran E, Becker JA, Locascio JJ, Klunk WE, Mathis CA, Elmaleh DR, Shoup T, Fischman AJ, Hyman BT, Growdon JH, Johnson KA (2008) Imaging amyloid deposition in Lewy body diseases. Neurology 71:903–910

    PubMed  CAS  Google Scholar 

  55. Gross RG, Siderowf A, Hurtig HI (2008) Cognitive impairment in Parkinson’s disease and dementia with Lewy bodies: a spectrum of disease. Neurosignals 16:24–34

    Google Scholar 

  56. Halliday G, Ng T, Rodriguez M, Harding A, Blumbergs P, Evans W, Fabian V, Fryer J, Gonzales M, Harper C, Kalnins R, Masters CL, McLean C, Milder DG, Pamphlett R, Scott G, Tannenberg A, Kril J (2002) Consensus neuropathological diagnosis of common dementia syndromes: testing and standardising the use of multiple diagnostic criteria. Acta Neuropathol (Berl) 104:72–78

    CAS  Google Scholar 

  57. Hansen L, Salmon D, Galasko D, Masliah E, Katzman R, DeTeresa R, Thal L, Pay MM, Hofstetter R, Klauber M et al (1990) The Lewy body variant of Alzheimer’s disease: a clinical and pathologic entity. Neurology 40:1–8

    PubMed  CAS  Google Scholar 

  58. Harding AJ, Kril JJ, Halliday GM (2000) Practical measures to simplify the Braak tangle staging method for routine pathological screening. Acta Neuropathol 99:199–208

    PubMed  CAS  Google Scholar 

  59. Haroutunian V, Schnaider-Beeri M, Schmeidler J, Wysocki M, Purohit DP, Perl DP, Libow LS, Lesser GT, Maroukian M, Grossman HT (2008) Role of the neuropathology of Alzheimer disease in dementia in the oldest-old. Arch Neurol 65:1211–1217

    PubMed  Google Scholar 

  60. Hu NW, Smith IM, Walsh DM, Rowan MJ (2008) Soluble amyloid-beta peptides potently disrupt hippocampal synaptic plasticity in the absence of cerebrovascular dysfunction in vivo. Brain 131:2414–2424

    PubMed  Google Scholar 

  61. Hulette CM, Welsh-Bohmer KA, Murray MG, Saunders AM, Mash DC, McIntyre LM (1998) Neuropathological and neuropsychological changes in “normal” aging: evidence for preclinical Alzheimer disease in cognitively normal individuals. J Neuropathol Exp Neurol 57:1168–1174

    PubMed  CAS  Google Scholar 

  62. 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

    PubMed  CAS  Google Scholar 

  63. ICDNS, Duyckaerts C (2003) Alzheimer disease diagnosis. http://www.icdns.org/forums/index.php?showtopic=27

  64. Imhof A, Kovari E, von Gunten A, Gold G, Rivara CB, Herrmann FR, Hof PR, Bouras C, Giannakopoulos P (2007) Morphological substrates of cognitive decline in nonagenarians and centenarians: a new paradigm? J Neurol Sci 257:72–79

    PubMed  Google Scholar 

  65. Jellinger KA (2001) Frequency of “dementia of unknown origin” increases with age (Letter). Arch Neurol 58:1498–1499

    PubMed  CAS  Google Scholar 

  66. Jellinger KA (2003) Plaque-predominant and tangle-predominant variants of Alzheimer’s disease. In: Dickson DW (ed) Neurodegeneration: the molecular pathology of dementia and movement disorders. ISN Neuropath Press, Basel, pp 66–68

  67. Jellinger KA, Attems J (2005) Prevalence and pathogenic role of cerebrovascular lesions in Alzheimer’s disease. J Neurol Sci 229–230:37–41

    PubMed  Google Scholar 

  68. Jellinger KA (2006) A view on early diagnosis of dementias from neuropathology. In: Herholz K, Morris C, Perani D (eds) The dementias: early diagnosis and evaluation. Taylor & Francis, New York, pp 311–428

    Google Scholar 

  69. Jellinger KA, Attems J (2006) Does striatal pathology distinguish Parkinson disease with dementia and dementia with Lewy bodies? Acta Neuropathol 112:253–260

    PubMed  Google Scholar 

  70. Jellinger KA (2007) Lewy body disorders. In: Youdim MBH, Riederer P, Mandel SA, Battistin L, Lajtha A (eds) Degenerative diseases of the nervous system. Springer, New York, pp 267–343

    Google Scholar 

  71. Jellinger KA (2007) The enigma of mixed dementia. Alzheimer Demen 3:40–53

    Google Scholar 

  72. Jellinger KA (2007) The enigma of vascular cognitive disorder and vascular dementia. Acta Neuropathol (Berl) 113:349–388

    Google Scholar 

  73. Jellinger KA, Attems J (2007) Neuropathological evaluation of mixed dementia. J Neurol Sci 257:80–87

    PubMed  CAS  Google Scholar 

  74. Jellinger KA, Attems J (2007) Neurofibrillary tangle-predominant dementia: comparison with classical Alzheimer disease. Acta Neuropathol 113:107–117

    PubMed  CAS  Google Scholar 

  75. Jellinger KA (2008) A critical reappraisal of current staging of Lewy-related pathology in human brain. Acta Neuropathol 116:1–16

    PubMed  CAS  Google Scholar 

  76. Jellinger KA (2009) Significance of brain lesions in Parkinson’s disease dementia and Lewy body dementia. In: Giannakopoulos P, Hof P (eds) Front Neurol Neurosci: Dementia in Clinical Practice. Karger, Basel, pp 1–12 (in press)

  77. Josephs KA (2008) Frontotemporal dementia and related disorders: deciphering the enigma. Ann Neurol 64:4–14

    PubMed  CAS  Google Scholar 

  78. Kalaria RN, Kenny RA, Ballard CG, Perry R, Ince P, Polvikoski T (2004) Towards defining the neuropathological substrates of vascular dementia. J Neurol Sci 226:75–80

    PubMed  Google Scholar 

  79. Khachaturian ZS (1985) Diagnosis of Alzheimer’s disease. Arch Neurol 42:1097–1105

    PubMed  CAS  Google Scholar 

  80. Klatka LA, Schiffer RB, Powers JM, Kazee AM (1996) Incorrect diagnosis of Alzheimer’s disease. A clinicopathologic study. Arch Neurol 53:35–42

    PubMed  CAS  Google Scholar 

  81. 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

    PubMed  CAS  Google Scholar 

  82. Kovacs GG, Alafuzoff I, Al-Sarraj S, Arzberger T, Bogdanovic N, Capellari S, Ferrer I, Gelpi E, Kovari V, Kretzschmar H, Nagy Z, Parchi P, Seilhean D, Soininen H, Troakes C, Budka H (2008) Mixed brain pathologies in dementia: the BrainNet Europe consortium experience. Dement Geriatr Cogn Disord 26:343–350

    PubMed  Google Scholar 

  83. Kramer ML, Schultz-Schaeffer WJ (2007) Presynaptic alpha-synuclein aggregates, not Lewy bodies, cause neurodegeneration in dementia with Lewy bodies. J Neurosci 27:1405–1410

    PubMed  CAS  Google Scholar 

  84. Launer LJ, Petrovitch H, Ross GW, Markesbery W, White LR (2008) AD brain pathology: vascular origins? Results from the HAAS autopsy study. Neurobiol Aging 29:1587–1590

    PubMed  CAS  Google Scholar 

  85. Lee JH, Olichney JM, Hansen LA, Hofstetter CR, Thal LJ (2000) Small concomitant vascular lesions do not influence rates of cognitive decline in patients with Alzheimer disease. Arch Neurol 57:1474–1479

    PubMed  CAS  Google Scholar 

  86. Leverenz JB, Hamilton R, Tsuang DW, Schantz A, Vavrek D, Larson EB, Kukull WA, Lopez O, Galasko D, Masliah E, Kaye J, Woltjer R, Clark C, Trojanowski JQ, Montine TJ (2008) Empiric refinement of the pathologic assessment of Lewy-related pathology in the dementia patient. Brain Pathol 18:220–224

    PubMed  Google Scholar 

  87. Liang T, Noorigian J, Duda JE (2006) Does striatal pathology distinguish DLB from PDD? (abstr). Mov Disord 21(suppl 13):S69–S70

    Google Scholar 

  88. Lim A, Tsuang D, Kukull W, Nochlin D, Leverenz J, McCormick W, Bowen J, Teri L, Thompson J, Peskind ER, Raskind M, Larson EB (1999) Clinico-neuropathological correlation of Alzheimer’s disease in a community-based case series. J Am Geriatr Soc 47:564–569

    PubMed  CAS  Google Scholar 

  89. Lowe J (2008) Neuropathology of dementia with Lewy bodies. In: Duyckaerts C, Litvan I (eds) Handbook of clinical neurology, vol 89 (3rd series). Elsevier, Edinburgh, pp 321–330

  90. Mackenzie IR, Neumann M, Bigio EH, Cairns NJ, Alafuzoff I, Kril J, Kovacs GG, Ghetti B, Halliday G, Holm IE, Ince PG, Kamphorst W, Revesz T, Rozemuller AJ, Kumar-Singh S, Akiyama H, Baborie A, Spina S, Dickson DW, Trojanowski JQ, Mann DM (2009) Nomenclature for neuropathologic subtypes of frontotemporal lobar degeneration: consensus recommendations. Acta Neuropathol 117:15–18

    PubMed  Google Scholar 

  91. Mann DM (1996) Pyramidal nerve cell loss in Alzheimer’s disease. Neurodegeneration 5:423–427

    PubMed  CAS  Google Scholar 

  92. Markesbery WR, Schmitt FA, Kryscio RJ, Davis DG, Smith CD, Wekstein DR (2006) Neuropathologic substrate of mild cognitive impairment. Arch Neurol 63:38–46

    PubMed  Google Scholar 

  93. McKee AC, Kowall NW, Au R (2002) Topography of neurofibrillary tangles distinguishes aging from Alzheimer disease (abstr.). J Neuropathol Exp Neurol 61:488

    Google Scholar 

  94. McKee AC, Au R, Cabral HJ, Kowall NW, Seshadri S, Kubilus CA, Drake J, Wolf PA (2006) Visual association pathology in preclinical Alzheimer disease. J Neuropathol Exp Neurol 65:621–630

    PubMed  Google Scholar 

  95. McKeel DW Jr, Ball MJ, Price JL, Smith DS, Miller JP, Berg L, Morris JC (1993) Interlaboratory histopathologic assessment of Alzheimer neuropathology: different methodologies yield comparable diagnostic results. Alzheimer Dis Assoc Disord 7:136–151

    PubMed  Google Scholar 

  96. McKeel DW Jr, Price JL, Miller JP, Grant EA, Xiong C, Berg L, Morris JC (2004) Neuropathologic criteria for diagnosing Alzheimer disease in persons with pure dementia of Alzheimer type. J Neuropathol Exp Neurol 63:1028–1037

    PubMed  Google Scholar 

  97. 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 (2005) Diagnosis and management of dementia with Lewy bodies: third report of the DLB consortium. Neurology 65:1863–1872

    PubMed  CAS  Google Scholar 

  98. 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

    PubMed  CAS  Google Scholar 

  99. Metsaars WP, Hauw JJ, van Welsem ME, Duyckaerts C (2003) A grading system of Alzheimer disease lesions in neocortical areas. Neurobiol Aging 24:563–572

    PubMed  Google Scholar 

  100. Mintun MA, Larossa GN, Sheline YI, Dence CS, Lee SY, Mach RH, Klunk WE, Mathis CA, DeKosky ST, Morris JC (2006) [11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease. Neurology 67:446–452

    PubMed  CAS  Google Scholar 

  101. Mirra SS, Heyman A, McKeel D, Sumi SM, Crain BJ, Brownlee LM, Vogel FS, Hughes JP, van Belle G, Berg L (1991) The consortium to establish a registry for Alzheimer’s disease (CERAD). Part II. standardization of the neuropathologic assessment of Alzheimer’s disease. Neurology 41:479–486

    PubMed  CAS  Google Scholar 

  102. Mirra SS, Gearing M, McKeel DW Jr, Crain BJ, Hughes JP, van Belle G, Heyman A (1994) Interlaboratory comparison of neuropathology assessments in Alzheimer’s disease: a study of the consortium to establish a registry for Alzheimer’s disease (CERAD). J Neuropathol Exp Neurol 53:303–315

    PubMed  CAS  Google Scholar 

  103. Morris JC (2005) Dementia update 2005. Alzheimer Dis Assoc Disord 19:100–117

    PubMed  Google Scholar 

  104. Morrison JH, Hof PR (2007) Life and death of neurons in the aging cerebral cortex. Int Rev Neurobiol 81:41–57

    PubMed  CAS  Google Scholar 

  105. Munoz DG, Dickson DW, Bergeron C, Mackenzie IR, Delacourte A, Zhukareva V (2003) The neuropathology and biochemistry of frontotemporal dementia. Ann Neurol 54(Suppl 5):S24–S28

    PubMed  Google Scholar 

  106. Murray ME, Knopman DS, Dickson DW (2007) Vascular dementia: clinical, neuroradiologic and neuropathologic aspects. Panminerva Med 49:197–207

    PubMed  CAS  Google Scholar 

  107. Nagy Z, Esiri MM, Jobst KA, Morris JH, King E-F, McDonald B, Joachim C, Litchfield S, Barnetson L, Smith AD (1997) The effects of additional pathology on the cognitive deficit in Alzheimer disease. J Neuropathol Exp Neurol 56:165–170

    PubMed  CAS  Google Scholar 

  108. Nagy Z, Vatter-Bittner B, Braak H, Braak E, Yilmazer DM, Schultz C, Hanke J (1997) Staging of Alzheimer-type pathology: an interrater-intrarater study. Dement Geriatr Cogn Disord 8:248–251

    PubMed  CAS  Google Scholar 

  109. Neary D, Snowden JS, Gustafson L, Passant U, Stuss D, Black S, Freedman M, Kertesz A, Robert PH, Albert M, Boone K, Miller BL, Cummings J, Benson DF (1998) Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 51:1546–1554

    PubMed  CAS  Google Scholar 

  110. Nelson PT, Jicha GA, Schmitt FA, Liu H, Davis DG, Mendiondo MS, Abner EL, Markesbery WR (2007) Clinicopathologic correlations in a large Alzheimer disease center autopsy cohort: neuritic plaques and neurofibrillary tangles “do count” when staging disease severity. J Neuropathol Exp Neurol 66:1136–1146

    PubMed  Google Scholar 

  111. Nelson PT, Abner EL, Schmitt FA, Kryscio RJ, Jicha GA, Smith CD, Davis DG, Poduska JW, Patel E, Mendiondo MS, Markesbery WR (2008) Modeling the association between 43 different clinical and pathological variables and the severity of cognitive impairment in a large autopsy cohort of elderly persons. Brain Pathol [Epub ahead of print]

  112. Newell KL, Hyman BT, Growdon JH, Hedley-Whyte ET (1999) Application of the National Institute on Aging (NIA)-Reagan Institute criteria for the neuropathological diagnosis of Alzheimer disease. J Neuropathol Exp Neurol 58:1147–1155

    PubMed  CAS  Google Scholar 

  113. Nolan KA, Lino MM, Seligmann AW, Blass JP (1998) Absence of vascular dementia in an autopsy series from a dementia clinic. J Am Geriatr Soc 46:597–604

    PubMed  CAS  Google Scholar 

  114. O’Sullivan M, Jones DK, Summers PE, Morris RG, Williams SC, Markus HS (2001) Evidence for cortical “disconnection” as a mechanism of age-related cognitive decline. Neurology 57:632–638

    PubMed  CAS  Google Scholar 

  115. Pantoni L, Sarti C, Alafuzoff I, Jellinger K, Munoz DG, Ogata J, Palumbo V (2006) Postmortem examination of vascular lesions in cognitive impairment: a survey among neuropathological services. Stroke 37:1005–1009

    PubMed  Google Scholar 

  116. Parkkinen L, Pirttila T, Alafuzoff I (2008) Applicability of current staging/categorization of alpha-synuclein pathology and their clinical relevance. Acta Neuropathol 115:399–407

    PubMed  Google Scholar 

  117. Peng FC (2003) Is dementia a disease? Gerontology 49:384–391

    PubMed  Google Scholar 

  118. Petrovitch H, Ross GW, Steinhorn SC, Abbott RD, Markesberry W, Davis DG, Nelson J, Hardman J, Masaki KH, Vogt MR, Launer LJ, White LR (2005) AD lesions and infarcts in demented and no-demented Japanese-American men. Ann Neurol 57:98–103

    PubMed  Google Scholar 

  119. Polvikoski T, Sulkava R, Myllykangas L, Notkola IL, Niinisto L, Verkkoniemi A, Kainulainen K, Kontula K, Perez-Tur J, Hardy J, Haltia M (2001) Prevalence of Alzheimer’s disease in very elderly people: a prospective neuropathological study. Neurology 56:1690–1696

    PubMed  CAS  Google Scholar 

  120. Price JL, Morris JC (1999) Tangles and plaques in nondemented aging and “preclinical” Alzheimer’s disease. Ann Neurol 45:358–368

    PubMed  CAS  Google Scholar 

  121. Prohovnik I, Perl DP, Davis KL, Libow L, Lesser G, Haroutunian V (2006) Dissociation of neuropathology from severity of dementia in late-onset Alzheimer disease. Neurology 66:49–55

    PubMed  CAS  Google Scholar 

  122. Ranginwala NA, Hynan LS, Weiner MF, White CL 3rd (2008) Clinical criteria for the diagnosis of Alzheimer disease: still good after all these years. Am J Geriatr Psychiatry 16:384–388

    PubMed  Google Scholar 

  123. Reddy PH, Mani G, Park BS, Jacques J, Murdoch G, Whetsell W Jr, Kaye J, Manczak M (2005) Differential loss of synaptic proteins in Alzheimer’s disease: implications for synaptic dysfunction. J Alzheimers Dis 7:103–117 discussion 173–180

    PubMed  CAS  Google Scholar 

  124. Riley KP, Snowdon DA, Markesbery WR (2002) Alzheimer’s neurofibrillary pathology and the spectrum of cognitive function: findings from the nun study. Ann Neurol 51:567–577

    PubMed  Google Scholar 

  125. Román GC, Tatemichi TK, Erkinjuntti T, Cummings JL, Masdeu JC, Garcia JH, Amaducci L, Orgogozo JM, Brun A, Hofman A et al (1993) Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology 43:250–260

    PubMed  Google Scholar 

  126. Román GC, Sachdev P, Royall DR, Bullock RA, Orgogozo JM, Lopez-Pousa S, Arizaga R, Wallin A (2004) Vascular cognitive disorder: a new diagnostic category updating vascular cognitive impairment and vascular dementia. J Neurol Sci 226:81–87

    PubMed  Google Scholar 

  127. Rowe CC, Ng S, Ackermann U, Gong SJ, Pike K, Savage G, Cowie TF, Dickinson KL, Maruff P, Darby D, Smith C, Woodward M, Merory J, Tochon-Danguy H, O’Keefe G, Klunk WE, Mathis CA, Price JC, Masters CL, Villemagne VL (2007) Imaging betaamyloid burden in aging and dementia. Neurology 68:1718–1725

    PubMed  CAS  Google Scholar 

  128. Scheff SW, Price DA (2003) Synaptic pathology in Alzheimer’s disease: a review of ultrastructural studies. Neurobiol Aging 24:1029–1046

    PubMed  CAS  Google Scholar 

  129. Scheff SW, Price DA (2006) Alzheimer’s disease-related alterations in synaptic density: neocortex and hippocampus. J Alzheimers Dis 9:101–115

    PubMed  Google Scholar 

  130. 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

    PubMed  CAS  Google Scholar 

  131. Schnaider Beeri M, Silverman JM, Schmeidler J, Wysocki M, Grossman HZ, Purohit DP, Perl DP, Haroutunian V (2008) Clinical dementia rating performed several years prior to death predicts regional Alzheimer’s neuropathology. Dement Geriatr Cogn Disord 25:392–398

    PubMed  Google Scholar 

  132. Schneider JA, Wilson RS, Bienias JL, Evans DA, Bennett DA (2004) Cerebral infarctions and the likelihood of dementia from Alzheimer disease pathology. Neurology 62:1148–1155

    PubMed  CAS  Google Scholar 

  133. Schneider JA, Arvanitakis Z, Bang W, Bennett DA (2007) Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology 69:2197–2204

    PubMed  Google Scholar 

  134. Schneider JA, Boyle PA, Arvanitakis Z, Bienias JL, Bennett DA (2007) Subcortical infarcts, Alzheimer’s disease pathology, and memory function in older persons. Ann Neurol 62:59–66

    PubMed  Google Scholar 

  135. Shin J, Lee SY, Kim SH, Kim YB, Cho SJ (2008) Multitracer PET imaging of amyloid plaques and neurofibrillary tangles in Alzheimer’s disease. Neuroimage 43:236–244

    PubMed  Google Scholar 

  136. Silver MH, Newell K, Brady C, Hedley-White ET, Perls TT (2002) Distinguishing between neurodegenerative disease and disease-free aging: correlating neuropsychological evaluations and neuropathological studies in centenarians. Psychosom Med 64:493–501

    PubMed  Google Scholar 

  137. Snowdon DA (1997) Aging and Alzheimer’s disease: lessons from the nun study. Gerontologist 37:150–156

    PubMed  CAS  Google Scholar 

  138. 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 

  139. Terry RD, Hansen LA, DeTeresa R, Davies P, Tobias H, Katzman R (1987) Senile dementia of the Alzheimer type without neocortical neurofibrillary tangles. J Neuropathol Exp Neurol 46:262–268

    PubMed  CAS  Google Scholar 

  140. Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R, Hansen LA, Katzman R (1991) Physical basis of cognitive alterations in Alzheimer’s disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol 30:572–580

    PubMed  CAS  Google Scholar 

  141. Terry RD (2000) Cell death or synaptic loss in Alzheimer disease. J Neuropathol Exp Neurol 59:1118–1119

    PubMed  CAS  Google Scholar 

  142. Thal DR, Rub U, Orantes M, Braak H (2002) Phases of A beta-deposition in the human brain and its relevance for the development of AD. Neurology 58:1791–1800

    PubMed  Google Scholar 

  143. Thal DR, Griffin WST, Braak H (2008) Parenchymal and vascular Abeta-deposition and its effects on the degeneration of neurons and cognition in Alzheimer’s disease. J Cell Mol Med 12:1–15

    Google Scholar 

  144. Tiraboschi P, Hansen LA, Thal LJ, Corey-Bloom J (2004) The importance of neuritic plaques and tangles to the development and evolution of AD. Neurology 62:1984–1989

    PubMed  CAS  Google Scholar 

  145. Tiraboschi P, Sabbagh MN, Hansen LA, Salmon DP, Merdes A, Gamst A, Masliah E, Alford M, Thal LJ, Corey-Bloom J (2004) Alzheimer disease without neocortical neurofibrillary tangles: “a second look”. Neurology 62:1141–1147

    PubMed  CAS  Google Scholar 

  146. Troncoso JC, Zonderman AB, Resnick SM, Crain B, Pletnikova O, O’Brien RJ (2008) Effect of infarcts on dementia in the Baltimore longitudinal study of aging. Ann Neurol 64:168–176

    PubMed  Google Scholar 

  147. Uchikado H, Lin WL, DeLucia MW, Dickson DW (2006) Alzheimer disease with amygdala Lewy bodies: a distinct form of alpha-synucleinopathy. J Neuropathol Exp Neurol 65:685–697

    PubMed  CAS  Google Scholar 

  148. Uitti RJ, Calne DB, Dickson DW, Wszolek ZK (2004) Is the neuropathological ‘gold standard’ diagnosis dead? Implications of clinicopathological findings in an autosomal dominant neurodegenerative disorder. Parkinsonism Relat Disord 10:461–463

    PubMed  Google Scholar 

  149. van der Zee J, Sleegers K, Van Broeckhoven C (2008) Invited article: the Alzheimer disease-frontotemporal lobar degeneration spectrum. Neurology 71:1191–1197

    PubMed  Google Scholar 

  150. von Gunten A, Kovari E, Rivara CB, Bouras C, Hof PR, Giannakopoulos P (2005) Stereologic analysis of hippocampal Alzheimer’s disease pathology in the oldest-old: evidence for sparing of the entorhinal cortex and CA1 field. Exp Neurol 193:198–206

    Google Scholar 

  151. von Gunten A, Bouras C, Kovari E, Giannakopoulos P, Hof PR (2006) Neural substrates of cognitive and behavioral deficits in atypical Alzheimer’s disease. Brain Res Rev 51:176–211

    Google Scholar 

  152. Wang K, Liang M, Wang L, Tian L, Zhang X, Li K, Jiang T (2007) Altered functional connectivity in early Alzheimer’s disease: a resting-state fMRI study. Hum Brain Mapp 28:967–978

    PubMed  Google Scholar 

  153. Warren JD, Schott JM, Fox NC, Thom M, Revesz T, Holton JL, Scaravilli F, Thomas DG, Plant GT, Rudge P, Rossor MN (2005) Brain biopsy in dementia. Brain 128:2016–2025

    PubMed  CAS  Google Scholar 

  154. Whitwell JL, Josephs KA, Murray ME, Kantarci K, Przybelski SA, Weigand SD, Vemuri P, Senjem ML, Parisi JE, Knopman DS, Boeve BF, Petersen RC, Dickson DW, Jack CR Jr (2008) MRI correlates of neurofibrillary tangle pathology at autopsy: a voxel-based morphometry study. Neurology 71:743–749

    PubMed  CAS  Google Scholar 

  155. Williamson JB, Nyenhuis DL, Pedelty L, Byrd S, Jhaveri M, Wang C, deToledo-Morrell L, Sripathirathan K, Gorelick P (2008) Baseline differences between vascular cognitive impairment no dementia reverters and non-reverters. J Neurol Neurosurg Psychiatry 79:1208–1214

    PubMed  CAS  Google Scholar 

  156. Wisniewski HM, Robe A, Zigman W, Silverman W (1989) Neuropathological diagnosis of Alzheimer disease. J Neuropathol Exp Neurol 48:606–609

    PubMed  CAS  Google Scholar 

  157. Woodhouse A, Shepherd CE, Sokolova A, Carroll VL, King AE, Halliday GM, Dickson TC, Vickers JC (2009) Cytoskeletal alterations differentiate presenilin-1 and sporadic Alzheimer’s disease. Acta Neuropathol 117:19–29

    PubMed  CAS  Google Scholar 

  158. Xuereb JH, Brayne C, Dufouil C, Gertz H, Wischik C, Harrington C, Mukaetova-Ladinska E, McGee MA, O’Sullivan A, O’Connor D, Paykel ES, Huppert FA (2000) Neuropathological findings in the very old. Results from the first 101 brains of a population-based longitudinal study of dementing disorders. Ann N Y Acad Sci 903:490–496

    PubMed  CAS  Google Scholar 

  159. Zaccai J, Brayne C, McKeith I, Matthews F, Ince PG (2008) Patterns and stages of alpha-synucleinopathy: relevance in a population-based cohort. Neurology 70:1042–1048

    PubMed  CAS  Google Scholar 

  160. Zekry D, Duyckaerts C, Belmin J, Geoffre C, Herrmann F, Moulias R, Hauw JJ (2003) The vascular lesions in vascular and mixed dementia: the weight of functional neuroanatomy. Neurobiol Aging 24:213–219

    PubMed  Google Scholar 

Download references

Acknowledgments

The study was supported in part by the Society for the Support of Research in Experimental Neurology, Vienna, Austria. The author thanks Mrs. V. Rappelsberger for excellent laboratory work and Mr. E. Mitter-Ferstl, PhD, for secretarial and computer work.

Author information

Authors and Affiliations

  1. Institute of Clinical Neurobiology, Kenyongasse 18, 1070, Vienna, Austria

    Kurt A. Jellinger

Authors
  1. Kurt A. Jellinger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kurt A. Jellinger.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jellinger, K.A. Criteria for the neuropathological diagnosis of dementing disorders: routes out of the swamp?. Acta Neuropathol 117, 101–110 (2009). https://doi.org/10.1007/s00401-008-0466-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00401-008-0466-z

Keywords

Search

Navigation