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Fortschr Neurol Psychiatr 2002; 70(9): 476-494
DOI: 10.1055/s-2002-33858
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© Georg Thieme Verlag Stuttgart · New York

Demenzen mit Lewy-Körperchen

Dementias with Lewy BodiesC.  J.  G.  Lang1 , M.  Bergmann2
  • 1Neurologische Klinik der Friedrich-Alexander-Universität Erlangen (Direktor: Prof. Dr. B. Neundörfer)
  • 2Institut für klinische Neuropathologie, Zentralkrankenhaus Bremen-Ost (Leiter: PD Dr. M. Bergmann)
Die Klinik für Psychiatrie und Psychotherapie des Bezirkskrankenhauses Bayreuth (Chefarzt: Prof. Dr. M. Wolfersdorf) übermittelte freundlicherweise klinische Daten und Computertomogramme. Herrn Prof. Dr. K. H. Plate und Dr. T. Acker von der Neuropathologischen Abteilung des Pathologischen Instituts und Herrn Dr. S. Probst-Cousin von der Neurologischen Klinik der Friedrich-Alexander-Universität Erlangen danken wir für überlassene Hirnschnitte, Herrn Prof. Dr. T. Kuwert und Dr. A. Schwarz von der Nuklearmedizinischen Klinik der Friedrich-Alexander-Universität Erlangen für SPECT- und Herrn Prof. Dr. P. Bartenstein von der Johannes-Gutenberg-Universität Mainz für PET-Abbildungen.
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Publication History

Publication Date:
05 September 2002 (online)

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Zusammenfassung

Demenzen mit Lewy-Körperchen sind eine nicht seltene Ursache kognitiver und motorischer Beeinträchtigungen im höheren Lebensalter. Sie müssen je nach Ausbreitung und Begleitpathologie in diffuse Lewy-Körperchen-Erkrankung bzw. Demenz mit Lewy-Körperchen, Morbus Parkinson mit begleitender Alzheimer-Pathologie und die Lewy-Körperchen-Variante des Morbus Alzheimer differenziert werden. Als bisher zuverlässigste diagnostische Merkmale der Demenzen mit Lewy-Körperchen haben sich fluktuierende kognitive und Bewusstseinsbeeinträchtigungen, visuelle Störungen (Halluzinationen, visuell-perzeptive und visuokonstruktive Auffälligkeiten) und frühzeitig einsetzende extrapyramidalmotorische Symptome vom hypokinetisch-rigiden Typ mit einer Neigung zu häufigen Stürzen erwiesen. Maßgeblich sind derzeit die Konsensus-Kriterien nach McKeith u. Mitarb. [48]. Zusätzlich scheinen nach jüngsten Untersuchungen in erster Linie morphologisch und funktionell bildgebende Verfahren (SPECT, PET), in zweiter Linie Liquoruntersuchungen (Homovanillinsäure) einen Beitrag leisten zu können. Selbst unter Ausschöpfung aller Möglichkeiten ist aber eine diagnostische Treffsicherheit von 85 % derzeit kaum zu erzielen. Die Diagnose der Lewy-Körperchen-Variante des Morbus Alzheimer ist, wie an einem Fallbeispiel gezeigt wird, ante mortem oft nicht verlässlich möglich. Klinisch ist diese Gruppe von Demenzen vor allem dadurch bedeutsam, dass eine erhebliche Neuroleptikaüberempfindlichkeit besteht und moderne zentralcholinerg wirksame Medikamente eine viel versprechende Therapieform darstellen.

Abstract

Dementias with Lewy bodies are no rare cause of cognitive and motor impairments in old age. Neuropathologically, they must be distinguished into diffuse Lewy body disease resp. dementia with Lewy bodies, Parkinson's disease with concomitant Alzheimer's pathology, and the Lewy body variant of Alzheimer's disease according to extent and concomitant pathology. The most reliable diagnostic features of dementia with Lewy bodies are fluctuating disturbances of cognition and consciousness, visual disorders (hallucinations, visuoperceptive and visuoconstructive impairments), and early extrapyramidal signs of the hypokinetic-rigid type with a propensity to frequent falls. The pertinent diagnostic criteria are the consensus criteria according to McKeith et al. [48]. Additional contributions are to be expected by functional neuroimaging (SPECT, PET) and CSF examination (homovanillic acid). However, even assuming the most favorable conditions a diagnostic accuracy of 85 % is presently hard to achieve. Particularly, as is demonstrated using a case example, reliable antemortem diagnosis of Lewy body variant of Alzheimer's disease is hardly possible. Clinically, this group of diseases is important, since increased neuroleptic sensitivity must be taken into account and modern central cholinergic agents seem to be a promising therapeutic option.

Literatur

  • 1 Luis C A, Mittenberg W, Gass C S, Duara R. Diffuse Lewy body disease: Clinical, pathological, and neuropsychological review.  Neuropsychol Rev. 1999;  9 137-150
    CrossrefPubMedGoogle Scholar
  • 2 Papka M, Rubio A, Schiffer R B. A review of Lewy body disease, an emerging concept of cortical dementia.  J Neuropsychiatry Clin Neurosci. 1998;  10 267-279
    PubMedGoogle Scholar
  • 3 Robles A. Demencia con cuerpos de Lewy: nuevas aportaciones a su conocimiento clínico.  Rev Neurol. 2000;  30 701-707
    PubMedGoogle Scholar
  • 4 Farina E, Cannatà A P, Mariani C. Non-Alzheimer forms of cortical degeneration: Frequency in clinical practice and clinical report of six cases.  Aging Clin Exp Res. 1996;  8 235-242
    PubMedGoogle Scholar
  • 5 Perry R, McKeith I, Perry E. (Hrsg) .Dementia with Lewy Bodies. Cambridge, UK: Cambridge University Press 1996
    Google Scholar
  • 6 McKeith I G. Clinical Lewy body syndromes.  Ann N Y Acad Sci. 2000;  920 1-8
    PubMedGoogle Scholar
  • 7 Hansen L A. Dementia with Lewy bodies. In: Terry RD, Katzman R, Bick KL, Sisodia SS (Hrsg). Alzheimer Disease. 2. Aufl Philadelphia, USA: Lippincott Williams & Wilkins 1999: 181-185
    Google Scholar
  • 8 Lang C. Demenzen: Diagnose und Differentialdiagnose. London: Chapman & Hall 1994: 152-167
    Google Scholar
  • 9 Lennox G, Lowe J, Landon M, Byrne E J, Mayer R J, Godwin-Austen R B. Diffuse Lewy body disease: correlative neuropathology using anti-ubiquitin immunocytochemistry.  J Neurol Neurosurg Psychiatry. 1989;  52 1236-1247
    PubMedGoogle Scholar
  • 10 Lennox G G, Lowe J S. Dementia with Lewy bodies.  Baillieres Clin Neurol. 1997;  6 147-166
    PubMedGoogle Scholar
  • 11 Jackson M, Lennox G, Balsitis M, Lowe J. Lewy body dysphagia.  J Neurol Neurosurg Psychiatry. 1995;  58 756-757
    PubMedGoogle Scholar
  • 12 Lennox G G, Lowe J S. Dementia with Lewy bodies. In: Markesberry WR (Hrsg). Neuropathology of dementing disorders. London: Arnold 1998: 181-192
    Google Scholar
  • 13 Mori H, Yoshimura M, Tomonaga M, Yamanouchi H. Progressive supranuclear palsy with Lewy bodies.  Acta Neuropathol (Berlin). 1986;  71 344-346
    CrossrefPubMedGoogle Scholar
  • 14 Fearnley J M, Revesz T, Brooks D J, Frackowiak R S, Lees A J. Diffuse Lewy body disease presenting with a supranuclear gaze palsy.  J Neurol Neurosurg Psychiatry. 1991;  54 159-161
    PubMedGoogle Scholar
  • 15 Mark M H, Sage J I, Dickson D W, Heikkila R E, Manzino L, Schwarz K O, Duvoisin R C. Meige syndrome in the spectrum of Lewy body disease.  Neurology. 1994;  44 1432-1436
    PubMedGoogle Scholar
  • 16 Hansen L, Salmon D, Galasko D, Masliah E, Katzman R, DeTeresa R, Thal L, Pay M M, Hofstetter R, Klauber M, Rice V, Butters N, Alford M. The Lewy body variant of Alzheimer's disease: A clinical and pathologic entity.  Neurology. 1990;  40 1-8
    PubMedGoogle Scholar
  • 17 Galasko D, Salmon D P, Thal L J. The nosological status of Lewy body dementia. In: Perry R, McKeith I, Perry E (Hrsg). Dementia with Lewy Bodies Cambridge, UK: Cambridge University Press 1996: 21-32
    Google Scholar
  • 18 Ince P G, Perry E K, Morris C M. Dementia with Lewy bodies. A distinct non-Alzheimer dementia syndrome?.  Brain Pathol. 1998;  8 299-324
    PubMedGoogle Scholar
  • 19 McKeith I G. Spectrum of Parkinson's disease, Parkinson's dementia, and Lewy body dementia.  Neurol Clin. 2000;  18 865-902
    CrossrefPubMedGoogle Scholar
  • 20 Förstl H. The Lewy body variant of Alzheimer's disease: clinical, pathophysiological and conceptual issues.  Eur Arch Psychiatry Clin Neurosci. 1999;  249 (Suppl 3) III/64-III/67
    PubMedGoogle Scholar
  • 21 Crystal H A, Dickson D, Davies P, Masur D, Grober E, Lipton R B. The relative frequency of “dementia of unknown etiology” increases with age and is nearly 50 % in nonagenarians.  Arch Neurol. 2000;  57 713-719
    CrossrefPubMedGoogle Scholar
  • 22 Byrne E J, Lowe J, Godwin-Austen R B, Arie T, Jones R. Dementia and Parkinson's disease associated with diffuse cortical Lewy bodies.  Lancet. 1987;  I (8531) 501
    PubMedGoogle Scholar
  • 23 Dale G E, Probst A, Luthert P, Martin J, Anderton B H, Leigh P N. Relationships between Lewy bodies and pale bodies in Parkinson's disease.  Acta Neuropathol (Berl). 1992;  83 525-529
    CrossrefPubMedGoogle Scholar
  • 24 Goldman J E, Yen S H, Chiu F C, Peress N S. Lewy bodies of Parkinson's disease contain neurofilament antigens.  Science. 1983;  221 1082-1084
    PubMedGoogle Scholar
  • 25 Pollanen M S, Dickson D W, Bergeron C. Pathology and biology of the Lewy body.  J Neuropathol Exp Neurol. 1993;  52 183-191
    PubMedGoogle Scholar
  • 26 Lowe J. Lewy bodies. In: Calne DB (Hrsg). Neurodegenerative Diseases. Philadelphia: Saunders 1994: 51-69
    Google Scholar
  • 27 Mouradian M M. Recent advances in the genetics and pathogenesis of Parkinson disease.  Neurology. 2002;  58 179-185
    PubMedGoogle Scholar
  • 28 Lowe J, Blanchard A, Morrell K, Lennox G, Reynolds L, Billet M, Landon M, Mayer R J. Ubiquitin is a common factor in intermediate filament inclusion bodies of diverse type in man, including those of Parkinson's disease, and Alzheimer's disease, as well as Rosenthal fibres in cerebellar astrocytomas, cytoplasmatic bodies in muscle, and mallory bodies in alcoholic liver disease.  J Pathol. 1988;  155 9-15
    PubMedGoogle Scholar
  • 29 Lowe J, McDermott H, Landon M, Mayer R J, Wilkinson K D. Ubiquitin carboxyl-terminal hydrolase (PGP 9.5) is selectively present in ubiquitinated inclusion bodies characteristic of human neurodegenerative diseases.  J Pathol. 1990;  161 153-160
    PubMedGoogle Scholar
  • 30 Lowe J, McDermott H, Pike I, Spendlove I, Landon M, Mayer R J. Alpha B crystallin expression in non-lenticular tissues and selective presence in ubiquitinated inclusion bodies in human disease.  J Pathol. 1992;  166 61-68
    PubMedGoogle Scholar
  • 31 Lowe J, Mayer R J, Landon M. Ubiquitin in neurodegenerative diseases.  Brain Pathol. 1993;  3 55-65
    PubMedGoogle Scholar
  • 32 Haroutunian V, Serby M, Purohit D P, Perl D P, Marin D, Lantz M, Mohs R C, Davis K L. Contribution of Lewy body inclusions to dementia in patients with and without Alzheimer disease neuropathological conditions.  Arch Neurol. 2000;  57 1145-1150
    CrossrefPubMedGoogle Scholar
  • 33 Stern Y, Jacobs D, Goldman J, Gomez-Tortosa E, Hyman B T, Liu Y, Troncoso J, Marder K, Tang M X, Brandt J, Albert M. An investigation of clinical correlates of Lewy bodies in autopsy-proven Alzheimer disease.  Arch Neurol. 2001;  58 460-465
    CrossrefPubMedGoogle Scholar
  • 34 Samuel W, Galasko D, Masliah E, Hansen L A. Neocortical Lewy body counts correlate with dementia in the Lewy body variant of Alzheimer's disease.  J Neuropathol Exp Neurol. 1996;  55 44-52
    PubMedGoogle Scholar
  • 35 Hurtig H I, Trojanowski J Q, Galvin J, Ewbank D, Schmidt M L, Lee V M-Y, Clark C M, Glosser G, Stern M B, Gollomp S M, Arnold S E. Alpha-synuclein cortical Lewy bodies correlate with dementia in Parkinson's disease.  Neurology. 2000;  54 1916-1921
    PubMedGoogle Scholar
  • 36 Anonymus. Obituaries. Frederic H. Lewey, M.D. 1885 - 1950.  Arch Neurol Psychiatry. 1951;  66 114-115
    PubMedGoogle Scholar
  • 37 Gibb W RG, Poewe W H. The centenary of Friederich H. Lewy 1885 - 1950.  Neuropathol Appl Neurobiol. 1986;  12 217-221
    PubMedGoogle Scholar
  • 38 Cohn D F. Biographical note on F. H. Lewy. In: Perry R, McKeith I, Perry E (Hrsg). Dementia with Lewy Bodies Cambridge, UK: Cambridge University Press 1996: XXV-XXIX
    Google Scholar
  • 39 Schiller F. Fritz Lewy and his bodies.  J History Neurosci. 2000;  9 148-151
    PubMedGoogle Scholar
  • 40 Holdorff B. Friedrich Heinrich Lewy (1885 - 1950) and his work.  J Hist Neurosci. 2002;  11 19-28
    PubMedGoogle Scholar
  • 41 Lewy F H. I. Pathologische Anatomie. In: Forster E, Lewy FH. Paralysis agitans. In: Lewandowsky M (Hrsg). Handbuch der Neurologie. Dritter Band. Spezielle Neurologie II. Berlin: Springer 1912: 920-933
    Google Scholar
  • 42 Lewy F H. Zur pathologischen Anatomie der Paralysis agitans.  Dt Zsch Nervenheilk. 1914;  50 50-55
    PubMedGoogle Scholar
  • 43 Lewy F H. Die Lehre vom Tonus und der Bewegung. Zugleich systematische Untersuchungen zur Klinik, Physiologie, Pathologie und Pathogenese der Paralysis agitans. Berlin: Springer 1923
    Google Scholar
  • 44 Okazaki H, Lipkin L E, Aronson S M. Diffuse intracytoplasmatic ganglionic inclusions (Lewy type) associated with progressive dementia and quadriparesis in flexion.  J Neuropathol Exp Neurol. 1961;  20 237-244
    CrossrefPubMedGoogle Scholar
  • 45 Kosaka K, Yoshimura M, Ikeda K, Budka H. Diffuse Lewy body disease: progressive dementia with abundant Lewy bodies and senile changes of varying degree - a new disease?.  Clin Neuropathol. 1984;  3 185-192
    PubMedGoogle Scholar
  • 46 Byrne E J, Lennox G, Lowe J, Godwin-Austen R B. Diffuse Lewy body disease: clinical features in 15 cases.  J Neurol Neurosurg Psychiatry. 1989;  52 709-717
    PubMedGoogle Scholar
  • 47 McKeith I G, Perry R H, Fairbairn A F, Jabeen S, Perry E K. Operational criteria for senile dementia of Lewy body type (SDLT).  Psychol Med. 1992;  22 911-922
    PubMedGoogle Scholar
  • 48 McKeith I G, Galasko D, Kosaka K, Perry E K, Dickson D W, Hansen L A, Salmon D P, Lowe J, Mirra S S, Byrne E J, Lennox G, Quinn N P, Edwardson J A, Inc E PG, Bergeron C, Burns A, Miller B L, Lovestone S, Collerton D, Jansen E N, Ballard C, de Vos R A, Wilcock G K, Jellinger K A, Perry R H. 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
    CrossrefPubMedGoogle Scholar
  • 49 Holmes C, Cairns N, Lantos P, Mann A. Validity of current clinical criteria for Alzheimer's disease, vascular dementia and dementia with Lewy bodies.  Br J Psychiatry. 1999;  174 45-50
    CrossrefPubMedGoogle Scholar
  • 50 Londos E, Passant U, Brun A, Gustafson L. Clinical Lewy body dementia and the impact of vascular components.  Int J Geriatr Psychiatry. 2000;  15 40-49
    CrossrefPubMedGoogle Scholar
  • 51 McKeith I, O’Brien J. Dementia with Lewy bodies.  Austr N Z J Psychiatry. 1999;  33 800-808
    PubMedGoogle Scholar
  • 52 Forno L S, Langston J W. The amygdala-hippocampal region: a predilection site for Lewy bodies.  J Neuropathol Exp Neurol. 1988;  47 354
    PubMedGoogle Scholar
  • 53 Lennox G, Lowe J, Byrne E J, Landon M, Mayer R J, Godwin-Austen . Diffuse Lewy body disease.  Lancet. 1989;  I (8633) 323-324
    PubMedGoogle Scholar
  • 54 Dickson D W, Feany M B, Yen S H, Mattiace L A, Davies P. Cytoskeletal pathology in non-Alzheimer degenerative dementia: new lesions in diffuse Lewy body disease, Pick's disease, and corticobasal degeneration.  J Neural Transm Suppl. 1996;  47 31-46
    PubMedGoogle Scholar
  • 55 Neuropathology Group of the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS) . Pathological correlates of late-onset dementia in a multicentre, community-based population in England and Wales.  Lancet. 2001;  357 169-175
    CrossrefPubMedGoogle Scholar
  • 56 Cercy S P, Bylsma F W. Lewy bodies and progressive dementia: a critical review and meta-analysis.  J Int Neuropsychol Soc. 1997;  3 179-194
    PubMedGoogle Scholar
  • 57 Papka M, Rubio A, Schiffer R B, Cox C. Lewy body disease: can we diagnose it?.  J Neuropsychiatry Clin Neurosci. 1998;  10 405-412
    PubMedGoogle Scholar
  • 58 Klatka L A, Louis E D, Schiffer R B. Psychiatric features in diffuse Lewy body disease: A clinicopathologic study using Alzheimer’s disease and Parkinson's disease comparison groups.  Neurology. 1996;  47 1148-1152
    PubMedGoogle Scholar
  • 59 Rosenberg C K, Cummings T J, Saunders A M, Widico C, McIntyre L M, Hulette C M. Dementia with Lewy bodies and Alzheimer's disease.  Acta Neuropathol. 2001;  102 621-626
    PubMedGoogle Scholar
  • 60 Saitoh T, Xia Y, Chen X, Masliah E, Galasko D, Shults C, Thal L J, Hansen L A, Katzman R. The CYP2D6B mutant allele is overrepresented in the Lewy body variant of Alzheimer's disease.  Ann Neurol. 1995;  37 110-112
    CrossrefPubMedGoogle Scholar
  • 61 Galasko D, Saitoh T, Xia Y, Thal L J, Katzman R, Hill L R, Hansen L. The apolipoprotein E allele epsilon 4 is overrepresented in patients with the Lewy body variant of Alzheimer's disease.  Neurology. 1994;  44 1950-1951
    PubMedGoogle Scholar
  • 62 Tiraboschi P, Hansen L A, Alford M, Sabbagh M N, Schoos B, Masliah E, Thal L J, Corey-Bloom . Cholinergic dysfunction in diseases with Lewy bodies.  Neurology. 2000;  54 407-411
    CrossrefPubMedGoogle Scholar
  • 63 Chinnery P F, Taylor G A, Howell N, Andrews R M, Morris C M, Taylor R W, McKeith I G, Perry R H, Edwardson J A, Turnbull D M. Mitochondrial DNY haplogroups and susceptibility to AD and dementia with Lewy bodies.  Neurology. 2000;  55 302-304
    PubMedGoogle Scholar
  • 64 Lowe J S, Mayer R J, Landon M. Pathological significance of Lewy bodies in dementia. In: Perry R, McKeith I, Perry E (Hrsg). Dementia with Lewy Bodies. Cambridge, UK: Cambridge University Press 1996: 195-203
    Google Scholar
  • 65 Cummings J L. Lewy body diseases with dementia: Pathophysiology and treatment.  Brain Cogn. 1995;  28 266-280
    PubMedGoogle Scholar
  • 66 Liberini P, Valerio A, Memo M, Spano P. Lewy-body dementia and responsiveness to cholinesterase inhibitors: a paradigm for heterogeneity of Alzheimer's disease?.  Trends Pharmacol Sci. 1996;  17 155-160
    CrossrefPubMedGoogle Scholar
  • 67 Perry E K, Morris C M, Court J A, Cheng A, Fairbairn A F, McKeith I G, Irving D, Brown A, Perry R H. Alteration in nicotine binding sites in Parkinson's disease, Lewy body dementia and Alzheimer's disease: possible index of early neuropathology.  Neuroscience. 1995;  64 385-395
    CrossrefPubMedGoogle Scholar
  • 68 Martin-Ruiz C, Court J, Lee M, Piggott M, Johnson M, Ballard C, Kalaria R, Perry R, Perry E. Nicotinic receptors in dementia of Alzheimer, Lewy body and vascular types.  Acta Neurol Scand. 2000;  Suppl 176 34-41
    PubMedGoogle Scholar
  • 69 Sabbagh M N, Reid R T, Hansen L A, Alford M, Thal L J. Correlation of nicotinic receptor binding with clinical and neuropathological changes in Alzheimer's disease and dementia with Lewy bodies.  J Neural Transm. 2001;  108 1149-1157
    CrossrefPubMedGoogle Scholar
  • 70 Weiner M F, Risser R C, Cullum M, Honig L, White III C, Speciale S, Rosenberg R N. Alzheimer's disease and its Lewy body variant: A clinical analysis of postmortem verified cases.  Am J Psychiatry. 1996;  153 1269-1273
    PubMedGoogle Scholar
  • 71 Leverenz J B, Miller M A, Dobie D J, Peskind E R, Raskind M A. Increased alpha 2-adrenergic receptor binding in locus coeruleus projection areas in dementia with Lewy bodies.  Neurobiol Aging. 2001;  22 555-561
    CrossrefPubMedGoogle Scholar
  • 72 Leake A, Perry E K, Perry R H, Jabeen S, Fairbairn A F, McKeith I G, Ferrier I N. Neocortical concentrations of neuropeptides in senile dementia of the Alzheimer and Lewy body type: Comparison with Parkinson's disease and severity correlations.  Biol Psychiatry. 1991;  29 357-364
    CrossrefPubMedGoogle Scholar
  • 73 McKeith I G, Ballard C G, Perry R H, Ince P G, O'Brien J T, Neill D, Lowery K, Jaros E, Barber R, Thompson P, Swann A, Fairbairn A F, Perry E K. Prospective validation of Consensus criteria for the diagnosis of dementia with Lewy bodies.  Neurology. 2000;  54 1050-1058
    PubMedGoogle Scholar
  • 74 Markesberry W K. Neuropathology of dementing disorders. London: Arnold 1998: 64
    Google Scholar
  • 75 Harding A J, Halliday G M. Cortical Lewy body pathology in the diagnosis of dementia.  Acta Neuropathol. 2001;  102 355-363
    PubMedGoogle Scholar
  • 76 de Vos R AI, Jansen E NH, Stam F C, Ravid R, Swaab D F. ‘Lewy body disease’: clinico-pathologial correlations in 18 consecutive cases of Parkinson’s disease with and without dementia.  Clin Neurol Neurosurg. 1995;  97 13-22
    CrossrefPubMedGoogle Scholar
  • 77 Chu C T, Caruso J L, Cummings T J, Ervin J, Rosenberg C, Hulette C M. Ubiquitin immunochemistry as a diagnostic aid for community pathologists evaluating patients who have dementia.  Mod Pathol. 2000;  13 420-426
    CrossrefPubMedGoogle Scholar
  • 78 Hansen L A, Masliah E, Quijada-Fawcett S, Rexin D. Entorhinal neurofibrillary tangles in Alzheimer disease with Lewy bodies.  Neurosci Lett. 1991;  129 269-272
    CrossrefPubMedGoogle Scholar
  • 79 Hansen L A. Tautological tangles in neuropathologic criteria for dementias associated with Lewy bodies. In: Perry R, McKeith I, Perry E (Hrsg). Dementia with Lewy Bodies Cambridge, UK: Cambridge University Press 1996: 204-211
    Google Scholar
  • 80 Del Ser T, Hachinski V, Merskey H, Munoz D G. Clinical and pathological features of two groups of patients with dementia with Lewy bodies: Effect of coexisting Alzheimer-type lesion load.  Alzh Dis Assoc Disord. 2001;  15 31-44
    PubMedGoogle Scholar
  • 81 Broe M, Shepherd C E, Milward E A, Halliday G M. Relationship between DNA fragmentation, morphological changes and neuronal loss in Alzheimer's disease and dementia with Lewy bodies.  Acta Neuropathol. 2001;  101 616-624
    PubMedGoogle Scholar
  • 82 Shepherd C E, Thiel E, McCann H, Harding A J, Halliday G M. Cortical inflammation in Alzheimer disease but not dementia with Lewy bodies.  Arch Neurol. 2000;  57 817-822
    CrossrefPubMedGoogle Scholar
  • 83 Lopez O L, Hamilton R L, Becker T, Wisniewski S, Kaufer D I, DeKosky S T. Severity of cognitive impairment and the clinical diagnosis of AD with Lewy bodies.  Neurology. 2000;  54 1780-1787
    PubMedGoogle Scholar
  • 84 McKeith I G, Fairbairn A F, Perry R H, Thompson P. The clinical diagnosis and misdiagnosis of senile dementia of Lewy body type (SDLT).  Br J Psychiatry. 1994;  165 324-332
    CrossrefPubMedGoogle Scholar
  • 85 Walker M P, Ayre G A, Cummings J L, Wesnes K, McKeith I G, O'Brien J T, Ballard C G. Quantifying fluctuation in dementia with Lewy bodies, Alzheimer's disease, and vascular dementia.  Neurology. 2000;  54 1616-1624
    PubMedGoogle Scholar
  • 86 Gomez-Isla T, Growdon W B, McNamara M, Newell K, Gomez-Tortosa E, Hedley-White E T, Hyman B T. Clinicopathological correlates in temporal cortex in dementia with Lewy bodies.  Neurology. 1999;  53 2003-2009
    PubMedGoogle Scholar
  • 87 Verghese J, Crystal H A, Dickson D W, Lipton R B. Validity of clinical criteria for the diagnosis of dementia with Lewy bodies.  Neurology. 1999;  53 1974-1982
    PubMedGoogle Scholar
  • 88 Hohl U, Tiraboschi P, Hansen L A, Thal L J, Corey-Bloom J. Diagnostic accuracy of dementia with Lewy bodies.  Arch Neurol. 2000;  57 347-351
    CrossrefPubMedGoogle Scholar
  • 89 Serby M, Samuels S C. Visual hallucinations and dementia with Lewy bodies.  Arch Neurol. 2000;  57 1792
    CrossrefPubMedGoogle Scholar
  • 90 Burns A. Clinical features of patients with Alzheimer's disease and Lewy bodies. In: Perry R, McKeith I, Perry E (Hrsg). Dementia with Lewy Bodies. Cambridge, UK: Cambridge University Press 1996: 46-56
    Google Scholar
  • 91 McShane R, Keene J, Gedling K, Hope T. Hallucinations, cortical Lewy body pathology, cognitive function and neuroleptic use in dementia. In: Perry R, McKeith I, Perry E (Hrsg). Dementia with Lewy Bodies. Cambridge, UK: Cambridge University Press 1996: 85-98
    Google Scholar
  • 92 Förstl H, Burns A, Luthert P, Cairns N, Levy R. The Lewy-body variant of Alzheimer's disease.  Br J Psychiatry. 1993;  162 385-392
    PubMedGoogle Scholar
  • 93 Heyman A, Fillenbaum G G, Gearing M, Mirra S S, Welsh-Bohmer K A, Peterson B, Pieper C. Comparison of Lewy body variant of Alzheimer's disease with pure Alzheimer's disease.  Neurology. 1999;  52 1839-1844
    PubMedGoogle Scholar
  • 94 Lopez O L, Wisniewski S, Hamilton R L, Becker J T, Kaufer D I, DeKosky S T. Predictors of progression in patients with AD and Lewy bodies.  Neurology. 2000;  54 1774-1779
    PubMedGoogle Scholar
  • 95 Louis E D, Klatka L A, Liu Y, Fahn S. Comparison of extrapyramidal features in 31 pathologically confirmed cases of diffuse Lewy body disease and 34 pathologically confirmed cases of Parkinson's disease.  Neurology. 1997;  48 376-380
    PubMedGoogle Scholar
  • 96 Galasko D, Katzman R, Salmon D P, Hansen L. Clinical and neuropathological findings in Lewy body dementias.  Brain Cogn. 1996;  31 166-175
    CrossrefPubMedGoogle Scholar
  • 97 Gnanalingham K K, Byrne E J, Thornton A. Motor and cognitive function in Lewy body dementia: comparison with Alzheimer's and Parkinson's disease.  J Neurol Neurosurg Psychiatry. 1997;  62 243-252
    CrossrefPubMedGoogle Scholar
  • 98 Imamura T, Hirono N, Hashimoto M, Kazui H, Tanimukai S, Hanihara T, Takahara A, Mori E. Fall-related injuries in dementia with Lewy bodies (DLB) and Alzheimer's disease.  Eur J Neurol. 2000;  7 77-79
    CrossrefPubMedGoogle Scholar
  • 99 McShane R H, Nagy Z, Esiri M M, King E, Joachim C, Sullivan N, Smith A D. Anosmia in dementia is associated with Lewy bodies rather than Alzheimer's pathology.  J Neurol Neurosurg Psychiatry. 2001;  70 739-743
    CrossrefPubMedGoogle Scholar
  • 100 Daum R F, Sekinger B, Kobal G, Lang C JG. Riechprüfung mit „sniffin’ sticks” zur klinischen Diagnostik des Morbus Parkinson.  Nervenarzt. 2000;  71 643-650
    CrossrefPubMedGoogle Scholar
  • 101 Mann D M. Anosmia in dementia is associated with Lewy bodies rather than Alzheimer's pathology.  J Neurol Neurosurg Psychiatry. 2001;  70 720-721
    CrossrefPubMedGoogle Scholar
  • 102 Watanabe H, Ieda T, Katayama T, Takeda A, Aiba I, Doyu M, Hirayama M, Sobue G. Cardiac 123I-meta-iodobenzylguanidine (MIBG) uptake in dementia with Lewy bodies: comparison with Alzheimer's disease.  J Neurol Neurosurg Psychiatry. 2001;  70 781-783
    CrossrefPubMedGoogle Scholar
  • 103 Ballard C, Lowery K, Harrison R, McKeith I G. Noncognitive symptoms in Lewy body dementia. In: Perry R, McKeith I, Perry E (Hrsg). Dementia with Lewy Bodies Cambridge, UK: Cambridge University Press 1996: 67-84
    Google Scholar
  • 104 Beck B J. Neuropsychiatric manifestations of diffuse Lewy body disease.  J Geriatr Psychiatry Neurol. 1995;  8 189-196
    PubMedGoogle Scholar
  • 105 Filley C M. Neuropsychiatric features of Lewy body disease.  Brain Cogn. 1995;  28 229-239
    PubMedGoogle Scholar
  • 106 Ferman T J, Boeve B F, Smith G E, Silber M H, Kokmen E, Petersen R C, Ivnik R J. REM sleep behavior disorder and dementia: cognitive differences when compared with AD.  Neurology. 1999;  23 951-957
    PubMedGoogle Scholar
  • 107 Boeve B F, Silber M H, Ferman T J, Kokmen E, Smith G E, Ivnik R J, Parisi J E, Olson E J, Petersen R C. REM sleep behavior disorder and degenerative dementia: an association likely reflecting Lewy body disease.  Neurology. 1998;  51 363-370
    PubMedGoogle Scholar
  • 108 Byrne E J. The nature of cognitive decline in Lewy body dementia. In: Perry R, McKeith I, Perry E (Hrsg). Dementia with Lewy Bodies Cambridge, UK: Cambridge University Press 1996: 57-66
    Google Scholar
  • 109 Galloway P G, Mulvihill P, Perry G. Filaments of Lewy bodies contain insoluble cytoskeletal elements.  Am J Pathol. 1992;  140 809-822
    PubMedGoogle Scholar
  • 110 Salmon D P, Galasko D. Neuropsychological aspects of Lewy body dementia. In: Perry R, McKeith I, Perry E (Hrsg). Dementia with Lewy Bodies Cambridge, UK: Cambridge University Press 1996: 96-113
    Google Scholar
  • 111 Salmon D P, Galasko D, Hansen L A, Masliah E, Butters N, Thal L J, Katzman R. Neuropsychological deficits associated with diffuse Lewy body disease.  Brain Cogn. 1996b;  31 148-165
    CrossrefPubMedGoogle Scholar
  • 112 Ala T A, Hughes L F, Kyrouac G A, Ghobrial M W, Elble R J. Pentagon copying is more impaired in dementia with Lewy bodies than in Alzheimer's disease.  J Neurol Neurosurg Psychiatry. 2001;  70 483-488
    CrossrefPubMedGoogle Scholar
  • 113 Gnanalingham K K, Byrne E J, Thornton A, Sambrook M A, Bannister P. Clock-face drawing to differentiate Lewy body and Alzheimer type dementia syndromes.  Lancet. 1996;  347 696-697
    PubMedGoogle Scholar
  • 114 Mori E, Shimomura T, Fujimori M, Hirono N, Imamura T, Hashimoto M, Tanimukai S, Kazui H, Hanihara T. Visuoperceptual impairment in dementia with Lewy bodies.  Arch Neurol. 2000;  57 489-493
    CrossrefPubMedGoogle Scholar
  • 115 Walker Z, Allen R L, Shergill S, Katona C LE. Neuropsychological performance in Lewy body dementia and Alzheimer's disease.  Br J Psychiatry. 1997;  170 156-158
    PubMedGoogle Scholar
  • 116 Connor D J, Salmon D P, Sandy T J, Galasko D, Hansen L A, Thal L J. Cognitive profiles of autopsy-confirmed Lewy body variant vs. pure Alzheimer disease.  Arch Neurol. 1998;  55 994-1000
    CrossrefPubMedGoogle Scholar
  • 117 Sahgal A. The neuroanatomical basis of cognitive deficits in Lewy body dementia. In: Perry R, McKeith I, Perry E (Hrsg). Dementia with Lewy Bodies Cambridge, UK: Cambridge University Press 1996: 114-131
    Google Scholar
  • 118 Olichney J M, Galasko D, Salmon D P, Hofstetter C R, Hansen L A, Katzman R, Thal L J. Cognitive decline is faster in Lewy body variant than in Alzheimer's disease.  Neurology. 1998;  51 351-357
    PubMedGoogle Scholar
  • 119 Galasko D R, Gould R L, Abramson I S, Salmon D P. Measuring cognitive change in a cohort of patients with Alzheimer's disease.  Stat Med. 2000;  19 1421-1432
    CrossrefPubMedGoogle Scholar
  • 120 Ballard C, Patel A, Oyebode F, Wilcock G. Cognitive decline in patients with Alzheimer's disease, vascular dementia and senile dementia of Lewy body type.  Age Ageing. 1996;  25 209-213
    PubMedGoogle Scholar
  • 121 Kanemaru K, Kameda N, Yamanouchi H. Decreased CSF amyloid β42 and normal tau levels in dementia with Lewy bodies.  Neurology. 2000;  54 1875-1876
    PubMedGoogle Scholar
  • 122 Tschampa H J, Schulz-Schaeffer W, Wiltfang J, Poser S, Otto M, Neumann M, Kretzschmar H A. Decreased CSF amyloid β42 and normal tau levels in dementia with Lewy bodies.  Neurology. 2001;  56 576
    PubMedGoogle Scholar
  • 123 Briel R C, McKeith I G, Barker W A, Hewitt Y, Perry R H, Ince P G, Fairbairn A F. EEG findings in dementia with Lewy bodies and Alzheimer's disease.  J Neurol Neurosurg Psychiatry. 1999;  66 401-403
    PubMedGoogle Scholar
  • 124 Tschampa H J, Neumann M, Zerr I, Henkel K, Schröter A, SchulzSchaeffer W J, Steinhoff B J, Kretzschmar H A, Poser S. Patients with Alzheimer's disease and dementia with Lewy bodies mistaken for Creutzfeldt-Jakob disease.  J Neurol Neurosurg Psychiatry. 2001;  71 33-39
    CrossrefPubMedGoogle Scholar
  • 125 Hashimoto M, Kitagaki H, Imamura T, Hirono N, Shimomura T, Kazui H, Tanimukai S, Hanihara T, Mori E. Medial temporal and whole-brain atrophy in dementia with Lewy bodies: a volumetric MRI study.  Neurology. 1998;  51 357-362
    CrossrefPubMedGoogle Scholar
  • 126 Lippa C F, Johnson R, Smith T W. The medial temporal lobe in dementia with Lewy bodies: a comparative study with Alzheimer's disease.  Ann Neurol. 1998;  43 102-106
    CrossrefPubMedGoogle Scholar
  • 127 Barber R, Ballard C, McKeith I G, Gholkar A, O'Brien J T. MRI volumetric study of dementia with Lewy bodies.  Neurology. 2000;  54 1304-1309
    CrossrefPubMedGoogle Scholar
  • 128 Barber R, McKeith I G, Ballard C, Gholkar A, O'Brien J T. A comparison of medial and lateral temporal lobe atrophy in dementia with Lewy bodies and Alzheimer's disease: Magnetic resonance imaging volumetric study.  Dement Geriatr Cogn Disord. 2001;  12 198-205
    CrossrefPubMedGoogle Scholar
  • 129 Middelkoop H AM, van der Flier W M, Burton E J, Lloyd A J, Paling S, Barber R, Ballard C, McKeith I G, O'Brien J T. Dementia with Lewy bodies and AD are not associated with occipital atrophy on MRI.  Neurology. 2001;  57 2117-2120
    CrossrefPubMedGoogle Scholar
  • 130 Imamura T, Ishii K, Sasaki M, Kitagaki H, Yamaji S, Hirono N, Shimomura T, Hashimoto M, Tanimukai S, Kazui H, Mori E. Regional cerebral glucose metabolism in dementia with Lewy bodies and Alzheimer's disease: a comparative study using positron emission tomography.  Neurosci Lett. 1997;  235 49-52
    CrossrefPubMedGoogle Scholar
  • 131 Imamura T, Ishii K, Hirono N, Hashimoto M, Tanimukai S, Kazui H, Hanihara T, Sasaki M, Mori E. Occipital glucose metabolism in dementia with Lewy bodies with and without Parkinsonism: A study using positron emission tomography.  Dementia Geriatr Cogn Disord. 2001;  12 194-197
    PubMedGoogle Scholar
  • 132 Donnemiller E, Heilmann J, Wenning G K, Berger W, Decristoforo C, Moncayo R, Poewe W, Ransmayr G. Brain perfusion scintigraphy with 99mTc-HMPAO or 99mTc-ECD and 123I-β-CIT single-photon emission tomography in dementia of the Alzheimer-type and diffuse Lewy body disease.  Eur J Nuclear Med. 1997;  24 320-325
    PubMedGoogle Scholar
  • 133 Velakoulis D, Lloyd J H. The role of SPECT scanning in a neuropsychiatry unit.  Aust N Z J Psychiatry. 1998;  32 511-522
    CrossrefPubMedGoogle Scholar
  • 134 Varma A R, Talbot P R, Snowden J S, Lloyd J J, Testa H J, Neary D. A 99mTc-HMPAO single-photon emisson computed tomography study of Lewy body disease.  J Neurol. 1997;  244 349-359
    CrossrefPubMedGoogle Scholar
  • 135 Lobotesis K, Fenwick J D, Phipps A, Ryman A, Swann A, Ballard C, McKeith I G, O'Brien J T. Occipital hypoperfusion on SPECT in dementia with Lewy bodies but not AD.  Neurology. 2001;  56 643-649
    CrossrefPubMedGoogle Scholar
  • 136 Ransmayr G, Seppi K, Donnemiller E, Luginger E, Marksteiner J, Riccabona G, Poewe W, Wenning G K. Striatal dopamine transporter function in dementia with Lewy bodies and Parkinson's disease.  Eur J Nucl Med. 2001;  28 1523-1528
    CrossrefPubMedGoogle Scholar
  • 137 Graham C, Ballard C, Saad K. Variables which distinguish patients fulfilling clinical criteria for dementia with Lewy bodies from those with Alzheimer's disease.  Int J Geriatr Psychiatry. 1997;  12 314-318
    PubMedGoogle Scholar
  • 138 Hely M A, Reid W G, Halliday G M, McRitchie D A, Leicester J, Joffe R, Brooks W, Broe G A, Morris J G. Diffuse Lewy body disease: clinical features in nine cases without coexistent Alzheimer's disease.  J Neurol Neurosurg Psychiatry. 1996;  60 531-538
    PubMedGoogle Scholar
  • 139 Lennox G G, Lowe J S. The clinical diagnosis and misdiagnosis of Lewy body dementia. In: Perry R, McKeith I, Perry E (Hrsg). Dementia with Lewy Bodies Cambridge, UK: Cambridge University Press 1996: 9-20
    Google Scholar
  • 140 Campbell S, Stephens S, Ballard C. Dementia with Lewy bodies: clinical features and treatment.  Drugs Aging. 2001;  18 397-407
    PubMedGoogle Scholar
  • 141 McKeith I G, Fairbairn A F, Bothwell R A, Moore P B, Ferrier I N, Thompson P, Perry R H. An evaluation of the predictive validity and interrater reliability of clinical diagnostic criteria for senile dementia of Lewy body type.  Neurology. 1994;  44 872-877
    PubMedGoogle Scholar
  • 142 Ballard C, Grace J, McKeith I, Holmes C. Neuroleptic sensitivity in dementia with Lewy bodies and Alzheimer's disease.  Lancet. 1998;  351 1032-1033
    CrossrefPubMedGoogle Scholar
  • 143 McKeith I G, Del Ser T, Spano P, Emre M, Wesnes K, Anand R, Cicin-Sain A, Ferrara R, Spiegel R. Efficacy of rivastigmine in dementia with Lewy bodies: a randomised, double-blind, placebo-controlled international study.  Lancet. 2000;  356 2031-2036
    CrossrefPubMedGoogle Scholar
  • 144 Grace J, Daniel S, Stevens T, Shankar K K, Walker Z, Byrne E J, Butler S, Wilkinson D, Woolford J, Waite J, McKeith I G. Long-term use of rivastigmine in patients with dementia with Lewy bodies: an open-label trial.  Int Psychogeriatr. 2001;  13 199-205
    CrossrefPubMedGoogle Scholar
  • 145 Skjerve A, Nygaard H A. Improvement in sundowning in dementia with Lewy bodies after treatment with donepezil.  Int J Geriatr Psychiatry. 2000;  15 1147-1151
    PubMedGoogle Scholar
  • 146 Rojas-Fernandez C H. Successful use of donepezil for the treatment of dementia with Lewy bodies.  Ann Pharmacother. 2001;  35 202-205
    CrossrefPubMedGoogle Scholar
  • 147 Lebert F, Pasquier F, Souliez L, Petit H. Tacrine efficacy in Lewy body dementia.  Int J Geriatr Psychiatry. 1998;  13 516-519
    PubMedGoogle Scholar
  • 148 Querfurth H W, Allam G J, Geffroy M A, Schiff H B, Kaplan R F. Acetylcholinesterase inhibition in dementia with Lewy bodies: results of a prospective pilot trial.  Dement Geriatr Cogn Disord. 2000;  11 314-321
    CrossrefPubMedGoogle Scholar
  • 149 Byrne E J, Burns A, Waite J. Neuroleptic sensitivity in dementia with cortical Lewy bodies.  Br Med J. 1992;  305 1158-1159
    PubMedGoogle Scholar
  • 150 McKeith I G, Fairbairn A, Perry R, Thompson P, Perry E. Neuroleptic sensitivity in patients with senile dementia of Lewy body type.  Br Med J. 1992;  305 673-678
    CrossrefPubMedGoogle Scholar
  • 151 Walker Z, Grace J, Overshot R, Satarasinghe S, Swan A, Katona C L, MCKeith I G. Olanzapine in dementia with Lewy bodies: a clinical study.  Int J Geriatr Psychiatry. 1999;  14 459-466
    PubMedGoogle Scholar
  • 152 Burke W J, Pfeiffer R F, McComb R D. Neuroleptic sensitivity to clozapine in dementia with Lewy bodies.  J Neuropsychiatry Clin Neurosci. 1998;  10 227-229
    PubMedGoogle Scholar
  • 153 Lowery K, Mynt P, Aisbett J, Dixon L, O'Brien J, Ballard C. Depression in the careers of dementia sufferers: a comparison of the careers of patients suffering from dementia with Lewy bodies and the careers of patients with Alzheimer's disease.  J Affect Disord. 2000;  59 61-65
    CrossrefPubMedGoogle Scholar
  • 154 Lang C JG, Bozikake-Leisch E, Spambalg M, Bartelsen P, Treig T. Psychometrische Sprachstudien bei Alzheimer-Demenz mit dem Aachener Aphasie-Test.  Nervenarzt. 1991;  62 621-628
    PubMedGoogle Scholar
  • 155 McKeith I G. Dementia with Lewy bodies.  Br J Psychiatry. 2002;  180 144-147
    CrossrefPubMedGoogle Scholar

Prof. Dr. med. Dipl.-Psych. C. J. G. Lang

Neurologische Universitätsklinik

Schwabachanlage 6

91054 Erlangen

Email: christoph.lang@neuro.imed.uni-erlangen.de