Background: While the prevalence of Alzheimer disease (AD) increases with age, little is known about the frequency of dementia with Lewy bodies (DLB) in the oldest old. A retrospective hospital-based study compared the relative prevalence of DLB among very old individuals. Methods: 1,100 consecutive autopsy cases of demented patients aged over 70 years (mean age: 83.9 ± 5.4 years) were examined using standardized neuropathological methods and current diagnostic consensus criteria. Results: Evaluation of three age groups (8th–10th decade) showed a significant increase in the relative prevalence of AD with cerebrovascular lesions including mixed dementia, while AD with Lewy body (LB) pathology showed a mild but insignificant age-related increase. Both ‘pure’ AD and vascular dementia showed a mild but insignificant decline, while DLB (without severe AD pathology) decreased progressively. While the severity of Lewy pathology in DLB slightly decreased with age, concomitant Alzheimer-like pathology increased progressively. Conclusion: Whether DLB in the oldest old represents a distinct group is a matter of discussion, but the relative prevalence of AD with LB in our sample remained fairly stable.

1.
Jellinger KA: Synucleinopathies; in Kompoliti K, Verhagen Metman L (eds): The Encyclopedia of Movement Disordorders. Oxford, Elsevier, 2010, vol 3, pp 203–207.
2.
Jellinger KA, Attems J: Prevalence and pathology of vascular dementia in the oldest-old. J Alzheimers Dis 2010;21:1283–1298.
3.
Jellinger KA, Attems J: Prevalence of dementia disorders in the oldest-old: an autopsy study. Acta Neuropathol 2010;119:421–433.
4.
Giannakopoulos P, Hof PR, Kövari E, Vallet PG, Herrmann FR, Bouras C: Distinct patterns of neuronal loss and Alzheimer’s disease lesion distribution in elderly individuals older than 90 years. J Neuropathol Exp Neurol 1996;55:1210–1220.
5.
Haroutunian V, Schnaider-Beeri M, Schmeidler J, Wysocki M, Purohit DP, Perl DP, Libow LS, Lesser GT, Maroukian M, Grossman HT: Role of the neuropathology of Alzheimer disease in dementia in the oldest-old. Arch Neurol 2008;65:1211–1217.
6.
Laukka EJ, Fratiglioni L, Bäckman L: The influence of vascular disease on cognitive performance in the preclinical and early phases of Alzheimer’s disease. Dement Geriatr Cogn Disord 2010;29:498–503.
7.
Jellinger KA, Attems J: Prevalence and pathogenic role of cerebrovascular lesions in Alzheimer disease. J Neurol Sci 2005;229–230:37–41.
8.
Jellinger KA: Prevalence and impact of cerebrovascular lesions in Alzheimer and Lewy body diseases. Neurodegener Dis 2010;7:112–115.
9.
Kawas CH, Corrada MM: Alzheimer’s and dementia in the oldest-old: a century of challenges. Curr Alzheimer Res 2006;3:411–419.
10.
Polvikoski T, Sulkava R, Myllykangas L, Notkola IL, Niinistö L, Verkkoniemi A, Kainulainen K, Kontula K, Pérez-Tur J, Hardy J, Haltia M: Prevalence of Alzheimer’s disease in very elderly people: a prospective neuropathological study. Neurology 2001;56:1690–1696.
11.
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: Neuropathological findings in the very old: results from the first 101 brains of a population-based longitudinal study of dementing disorders. Ann NY Acad Sci 2000;903:490–496.
12.
Zaccai J, Ince P, Brayne C: Population-based neuropathological studies of dementia: design, methods and areas of investigation – a systematic review. BMC Neurol 2006;6:2.
13.
Brayne C, Richardson K, Matthews FE, Fleming J, Hunter S, Xuereb JH, Paykel E, Mukaetova-Ladinska EB, Huppert FA, O’Sullivan A, Dening T, Cambridge City over-75s Cohort CC75C Study Neuropathology Collaboration: Neuropathological correlates of dementia in over-80-year-old brain donors from the population-based Cambridge City over-75s Cohort (CC75C) study. J Alzheimers Dis 2009;18:645–658.
14.
Riley KP, Snowdon DA, Markesbery WR: Alzheimer’s neurofibrillary pathology and the spectrum of cognitive function: findings from the Nun Study. Ann Neurol 2002;51:567–577.
15.
Petrovitch H, Ross GW, Steinhorn SC, Abbott RD, Markesberry W, Davis DG, Nelson J, Hardman J, Masaki KH, Vogt MR, Launer LJ, White LR: AD lesions and infarcts in demented and non-demented Japanese-American men. Ann Neurol 2005;57:98–103.
16.
Fernando MS, Ince PG: Vascular pathologies and cognition in a population-based cohort of elderly people. J Neurol Sci 2004;226:13–17.
17.
Sonnen JA, Larson EB, Crane PK, Haneuse S, Li G, Schellenberg GD, Craft S, Leverenz JB, Montine TJ: Pathological correlates of dementia in a longitudinal, population-based sample of aging. Ann Neurol 2007;62:406–413.
18.
Jellinger KA: The enigma of vascular cognitive disorder and vascular dementia. Acta Neuropathol 2007;113:349–388.
19.
Jellinger KA: The enigma of mixed dementia. Alzheimers Dement 2007;3:40–53.
20.
Kovacs GG, Alafuzoff I, Al-Sarraj S, Arzberger T, Bogdanovic N, Capellari S, Ferrer I, Gelpi E, Kövari V, Kretzschmar H, Nagy Z, Parchi P, Seilhean D, Soininen H, Troakes C, Budka H: Mixed brain pathologies in dementia: the BrainNet Europe consortium experience. Dement Geriatr Cogn Disord 2008;26:343–350.
21.
Schneider JA, Arvanitakis Z, Leurgans SE, Bennett DA: The neuropathology of probable Alzheimer disease and mild cognitive impairment. Ann Neurol 2009;66:200–208.
22.
Schneider JA, Aggarwal NT, Barnes L, Boyle P, Bennett DA: The neuropathology of older persons with and without dementia from community versus clinic cohorts. J Alzheimers Dis 2009;18:691–701.
23.
Schneider JA, Arvanitakis Z, Bang W, Bennett DA: Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology 2007;69:2197–2204.
24.
Schneider JA, Boyle PA, Arvanitakis Z, Bienias JL, Bennett DA: Subcortical infarcts, Alzheimer’s disease pathology, and memory function in older persons. Ann Neurol 2007;62:59–66.
25.
White L: Brain lesions at autopsy in older Japanese-American men as related to cognitive impairment and dementia in the final years of life: a summary report from the Honolulu-Asia Aging Study. J Alzheimers Dis 2009;18:713–725.
26.
Woodward M, Mackenzie IR, Feldman H: High prevalence of multiple brain pathologies in dementia. Alzheimers Dement 2006;2(suppl 1):426.
27.
Jicha GA, Parisi JE, Dickson DW, Johnson K, Cha R, Ivnik RJ, Tangalos EG, Boeve BF, Knopman DS, Braak H, Petersen RC: Neuropathologic outcome of mild cognitive impairment following progression to clinical dementia. Arch Neurol 2006;63:674–681.
28.
Rockwood K, Macknight C, Wentzel C, Black S, Bouchard R, Gauthier S, Feldman H, Hogan D, Kertesz A, Montgomery P: The diagnosis of ‘mixed’ dementia in the Consortium for the Investigation of Vascular Impairment of Cognition (CIVIC). Ann NY Acad Sci 2000;903:522–528.
29.
Mizutani T, Shimada H: Neuropathological background of twenty-seven centenarian brains. J Neurol Sci 1992;108:168–177.
30.
Seno H, Ishino H, Inagaki T, Iijima M, Kaku K, Inata T: A neuropathological study of dementia in nursing homes over a 17-year period, in Shimane Prefecture, Japan. Gerontology 1999;45:44–48.
31.
Akatsu H, Takahashi M, Matsukawa N, Ishikawa Y, Kondo N, Sato T, Nakazawa H, Yamada T, Okada H, Yamamoto T, Kosaka K: Subtype analysis of neuropathologically diagnosed patients in a Japanese geriatric hospital. J Neurol Sci 2002;196:63–69.
32.
Riekse RG, Leverenz JB, McCormick W, Bowen JD, Teri L, Nochlin D, Simpson K, Eugenio C, Larson EB, Tsuang D: Effect of vascular lesions on cognition in Alzheimer’s disease: a community-based study. J Am Geriatr Soc 2004;52:1442–1448.
33.
White L, Small BJ, Petrovitch H, Ross GW, Masaki K, Abbott RD, Hardman J, Davis D, Nelson J, Markesbery W: Recent clinical-pathologic research on the causes of dementia in late life: update from the Honolulu-Asia Aging Study. J Geriatr Psychiatry Neurol 2005;18:224–227.
34.
Bacchetta JP, Kövari E, Merlo M, Canuto A, Herrmann FR, Bouras C, Gold G, Hof PR, Giannakopoulos P: Validation of clinical criteria for possible vascular dementia in the oldest-old. Neurobiol Aging 2007;28:579–585.
35.
Grinberg LT, Ferretti RE, Leite REP, Farfel JM, Santos EB, Andrade MP, Alho ATL, do Carmo Lima M, Oliveira KC, Caetano A Jr, Santos ET, Polichiso L, Zoriki CS, Pasqualucci CAG, Jacob-Filho W, Nitrini R, Brazilian Aging Brain Study Group: Vascular dementia, an avoidable disease, may be much more common than presumed: a postmortem study in a large population-based series (abstract). Alzheimers Dement 2009;5(suppl 1):P164.
36.
Jellinger KA: The pathology of ‘vascular dementia’: a critical update. J Alzheimers Dis 2008;14:107–123.
37.
Jellinger KA: Criteria for the neuropathological diagnosis of dementing disorders: routes out of the swamp? Acta Neuropathol 2009;117:101–110.
38.
Nitrini R, Grinberg LT, Ferretti REL, Leite REP, Farfel JM, Santos EB, Andrade MP, Alho ATL, do Carmo Lima M, Oliveira KC, Santos EB, Polichiso L, Santos GAB, Suemoto CK, Ueda K, Pasqualucci CAG, Jacob- Filho W: High prevalence of vascular dementia: a population-based clinicopathological study. Ann Neurol 2010, submitted.
39.
Ubhi K, Peng K, Lessig S, Estrella J, Adame A, Galasko D, Salmon DP, Hansen LA, Kawas CH, Masliah E: Neuropathology of dementia with Lewy bodies in advanced age: a comparison with Alzheimer disease. Neurosci Lett 2010;485:222–227.
40.
Fujimi K, Sasaki K, Noda K, Wakisaka Y, Tanizaki Y, Matsui Y, Sekita A, Iida M, Kiyohara Y, Kanba S, Iwaki T: Clinicopathological outline of dementia with Lewy bodies applying the revised criteria: the Hisayama study. Brain Pathol 2008;18:317–325.
41.
Oinas M, Polvikoski T, Sulkava R, Myllykangas L, Juva K, Notkola IL, Rastas S, Niinistö L, Kalimo H, Paetau A: Neuropathologic findings of dementia with Lewy bodies (DLB) in a population-based Vantaa 85+ study. J Alzheimers Dis 2009;18:677–689.
42.
Zaccai J, Brayne C, McKeith I, Matthews F, Ince PG: Patterns and stages of α-synucleinopathy: relevance in a population-based cohort. Neurology 2008;70:1042–1048.
43.
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, ed 4, text rev (DSM-IV-TR). Washington, American Psychiatric Association, 2000.
44.
Folstein MF, Folstein SE, McHugh PR: ‘Mini-Mental State’: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189–198.
45.
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: Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology 2005;65:1863–1872.
46.
McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM: 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;34:939–944.
47.
Geser F, Wenning GK, Poewe W, McKeith I: How to diagnose dementia with Lewy bodies: state of the art. Mov Disord 2005;20 (suppl 12):S11–S20.
48.
Hansen LA, Samuel W: Criteria for Alzheimer’s disease and the nosology of dementia with Lewy bodies. Neurology 1997;48:126–132.
49.
Jellinger KA, Attems J: Prevalence and impact of vascular and Alzheimer pathologies in Lewy body disease. Acta Neuropathol 2008;115:427–436.
50.
Jellinger KA, Attems J: Cerebral amyloid angiopathy in Lewy body disease. J Neural Transm 2008;115:473–482.
51.
Braak H, Bohl JR, Müller CM, Rüb U, de Vos RA, del Tredici K: Stanley Fahn Lecture 2005: the staging procedure for the inclusion body pathology associated with sporadic Parkinson’s disease reconsidered. Mov Disord 2006;21:2042–2051.
52.
Braak H, Alafuzoff I, Arzberger T, Kretzschmar H, del Tredici K: Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol 2006;112:389–404.
53.
Hyman BT, Trojanowski JQ: 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 1997;56:1095–1097.
54.
Mirra SS, Heyman A, McKeel D, Sumi SM, Crain BJ, Brownlee LM, Vogel FS, Hughes JP, van Belle G, Berg L: The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). Part 2. Standardization of the neuropathologic assessment of Alzheimer’s disease. Neurology 1991;41:479–486.
55.
Braak H, del Tredici K, Rüb U, de Vos RA, Jansen Steur EN, Braak E: Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 2003;24:197–211.
56.
Beach TG, Adler CH, Lue L, Sue LI, Bachalakuri J, Henry-Watson J, Sasse J, Boyer S, Shirohi S, Brooks R, Eschbacher J, White CL 3rd, Akiyama H, Caviness J, Shill HA, Connor DJ, Sabbagh MN, Walker DG: Unified staging system for Lewy body disorders: correlation with nigrostriatal degeneration, cognitive impairment and motor dysfunction. Acta Neuropathol 2009;117:613–634.
57.
Jellinger KA, Bancher C: Neuropathology of Alzheimer’s disease: a critical update. J Neural Transm Suppl 1998;54:77–95.
58.
Jellinger KA: Con: can neuropathology really confirm the exact diagnosis? Alzheimers Res Ther 2010;2:11.
59.
Uchikado H, Lin WL, DeLucia MW, Dickson DW: Alzheimer disease with amygdala Lewy bodies: a distinct form of α-synucleinopathy. J Neuropathol Exp Neurol 2006;65:685–697.
60.
Attems J, Jellinger KA, Lintner F: Alzheimer’s disease pathology influences severity and topographical distribution of cerebral amyloid angiopathy. Acta Neuropathol 2005;110:222–231.
61.
Jellinger KA, Attems J: Does striatal pathology distinguish Parkinson disease with dementia and dementia with Lewy bodies? Acta Neuropathol 2006;112:253–260.
62.
Kalaitzakis ME, Graeber MB, Gentleman SM, Pearce RK: Striatal β-amyloid deposition in Parkinson disease with dementia. J Neuropathol Exp Neurol 2008;67:155–161.
63.
Kempster PA, O’Sullivan SS, Holton JL, Revesz T, Lees AJ: Relationships between age and late progression of Parkinson’s disease: a clinico-pathological study. Brain 2010;133:1755–1762.
64.
Nelson PT, Jicha GA, Kryscio RJ, Abner EL, Schmitt FA, Cooper G, Xu LO, Smith CD, Markesbery WR: Low sensitivity in clinical diagnoses of dementia with Lewy bodies. J Neurol 2010;257:359–366.
65.
Halliday GM, McCann H: The progression of pathology in Parkinson’s disease. Ann NY Acad Sci 2010;1184:188–195.
66.
Rahkonen T, Eloniemi-Sulkava U, Rissanen S, Vatanen A, Viramo P, Sulkava R: Dementia with Lewy bodies according to the consensus criteria in a general population aged 75 years or older. J Neurol Neurosurg Psychiatry 2003;74:720–724.
67.
Merdes AR, Hansen LA, Jeste DV, Galasko D, Hofstetter CR, Ho GJ, Thal LJ, Corey-Bloom J: Influence of Alzheimer pathology on clinical diagnostic accuracy in dementia with Lewy bodies. Neurology 2003;60:1586–1590.
68.
Attems J, Quass M, Jellinger KA, Lintner F: Topographical distribution of cerebral amyloid angiopathy and its effect on cognitive decline are influenced by Alzheimer disease pathology. J Neurol Sci 2007;257:49–55.
69.
Greenberg SM, Gurol ME, Rosand J, Smith EE: Amyloid angiopathy-related vascular cognitive impairment. Stroke 2004;35:2616–2619.
70.
Tanskanen M, Lindsberg PJ, Tienari PJ, Polvikoski T, Sulkava R, Verkkoniemi A, Rastas S, Paetau A, Kiuru-Enari S: Cerebral amyloid angiopathy in a 95+ cohort: complement activation and apolipoprotein E (ApoE) genotype. Neuropathol Appl Neurobiol 2005;31:589–599.
71.
Thal DR, Ghebremedhin E, Orantes M, Wiestler OD: Vascular pathology in Alzheimer disease: correlation of cerebral amyloid angiopathy and arteriosclerosis/lipohyalinosis with cognitive decline. J Neuropathol Exp Neurol 2003;62:1287–1301.
72.
Zekry D, Duyckaerts C, Belmin J, Geoffre C, Moulias R, Hauw JJ: Cerebral amyloid angiopathy in the elderly: vessel walls changes and relationship with dementia. Acta Neuropathol 2003;106:367–373.
73.
Broderick DF, Schweitzer KJ, Wszolek ZK: Vascular risk factors and dementia: how to move forward? Neurology 2009;73:1934–1935.
74.
Jellinger KA: Prevalence of vascular lesions in dementia with Lewy bodies: a postmortem study. J Neural Transm 2003;110:771–778.
75.
Ghebremedhin E, Rosenberger A, Rüb U, Vuksic M, Berhe T, Bickeböller H, de Vos RA, Thal DR, Deller T: Inverse relationship between cerebrovascular lesions and severity of Lewy body pathology in patients with Lewy body diseases. J Neuropathol Exp Neurol 2010;69:442–448.
76.
Ince PG, McKeith IG: Dementia with Lewy bodies; in Dickson DW (ed): Neurodegeneration. The Molecular Pathology of Dementia and Movement Disorders. Basel, ISN, 2003, pp 188–199.
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.
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 government 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.
You do not currently have access to this content.