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Nervenheilkunde 2005; 24(02): 129-136
DOI: 10.1055/s-0038-1629940
Original Article
Schattauer GmbH

Kognitive Veränderungen bei spontan auftretendem Morbus Parkinson

Klinisch-neuropathologische KorrelationCognitive changes in sporadic Parkinson’s diseaseA cliniconeuropathological correlation
H. Braak
1   Institut für Klinische Neuroanatomie, Dr. Senkenbergische Anatomie, J. W. Goethe-Universität, Frankfurt am Main
,
U. Rüb
1   Institut für Klinische Neuroanatomie, Dr. Senkenbergische Anatomie, J. W. Goethe-Universität, Frankfurt am Main
,
K. Del Tredici
1   Institut für Klinische Neuroanatomie, Dr. Senkenbergische Anatomie, J. W. Goethe-Universität, Frankfurt am Main
› Author Affiliations
Further Information

Publication History

Eingegangen am: 18 October 2004

angenommen am: 22 October 2004

Publication Date:
30 January 2018 (online)

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Zusammenfassung

Der dem Morbus Parkinson unterliegende pathologische Prozess entwickelt sich über viele Jahre. Erste Veränderungen entstehen noch vor dem Erscheinen klinischer Symptome. Der Prozess befällt in vorbestimmter Weise übergeordnete Zentren des olfaktorischen, limbischen, viszeromotorischen und somatomotorischen Systems. Die zeitlich gestaffelte und räumlich geordnete Ausbreitung der Veränderungen über das zentrale Nervensystem ermöglicht eine Zuordnung individueller Autopsiefälle zu sechs neuropathologischen Stadien. Kognitive Beeinträchtigungen variablen Schweregrades ergänzen die klassische Symptomentrias des Morbus Parkinson. Diese Beeinträchtigungen kognitiver Fähigkeiten, ermittelt mit Hilfe des MMSE-Testes, korrelieren mit den Stadien der neurodegenerativen Veränderungen. Der Abbau kognitiver Fähigkeiten gehört zu den Kernsymptomen der Parkinsonschen Krankheit wie Bradykinesie, Rigor und Tremor und kann gelegentlich das klinische Bild beherrschen. Das pathomorphologische Korrelat der dementiven Veränderungen wird diskutiert.

Summary

In sporadic Morbus Parkinson, the disease-process usually requires years to reach its full extent. The neuronal damage, however, begins before the appearance of the initial clinical symptoms, and recent findings show that the brain pathology develops in a predictable manner and sequence with the result that superordinate portions of the olfactory, limbic, visceromotor, and somatomotor systems sustain heavy damage. The topographic advance of the lesions is so characteristic that autopsy cases can be assigned to one of six neuropathological stages. In addition to the classical symptom triad associated with Parkinson’s disease, patients can manifest signs of cognitive decline ranging from subtle mental dysfunction to overt dementia. Results of a new clinicopathological correlation study show for the first time that cognitive decline assessed by using the MMSE Test is associated with the recently proposed neuropathological stages. Thus, cognitive decline leading to dementia is as much a major symptom of sporadic M. Parkinson as bradykinesia, rigor, and tremor and may even come to dominate the clinical picture. Some possible pathomorphological correlates of dementia are discussed.

Schlüsselwörter

Demenz - Lewy-Körper/Lewy-Neuriten - Morbus Parkinson - Synukleinopathien

Keywords

Dementia - Lewy bodies/Lewy neurites - Parkinson’s disease - synucleinopathies
 

  • Literatur

  • 1 Aarsland D, Andersen K, Larsen JP, Lolk A, Kragh-Sorensen P. Prevalence and characteristics of dementia in Parkinson disease. An 8-year prospective study. Arch Neurol 2003; 60: 387-92.
    CrossrefPubMedGoogle Scholar
  • 2 Albin RL, Young AB, Peney JB. The functional anatomy of disorders of the basal ganglia. Trends Neurosci 1995; 18: 63-4.
    CrossrefPubMedGoogle Scholar
  • 3 Alexander GE, Crutcher MD, DeLong MR. Basal ganglia-thalamocortical circuits: Parallel substrates for motor, oculomotor, »prefrontal,« and »limbic« functions. Progr Brain Res 1990; 85: 119-46.
    Google Scholar
  • 4 Apaydin H, Ahlskog E, Parisi JE, Boeve BF, Dickson DW. Parkinson disease neuropathology. Arch Neurol 2002; 59: 102-12.
    CrossrefPubMedGoogle Scholar
  • 5 Bortz J, Lienert GA, Boehnke K. Verteilungsfreie Methoden in der Biostatistik. Berlin: Springer; 1990
    Google Scholar
  • 6 Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 1991; 82: 239-59.
    CrossrefPubMedGoogle Scholar
  • 7 Braak H, Braak E. Pathoanatomy of Parkinson’s disease. J Neurol 2000; 247 (Suppl. 02) 3-10
    CrossrefPubMedGoogle Scholar
  • 8 Braak H, Del Tredici K. Presymptomatic and symptomatic stages of inclusion body pathology in Parkinson’s disease. In: Schmidt W, Reith M. (eds). Dopamine and Glutamate in Psychiatric Disorders. Totowa, NJ: The Humana Press; 2004: 469-96.
    Google Scholar
  • 9 Braak H, Braak E, Yilmazer D, de Vos RAI, Jansen ENH, Bohl J, Jellinger K. Amygdala pathology in Parkinson’s disease. Acta Neuropathol 1994; 88: 493-500.
    CrossrefPubMedGoogle Scholar
  • 10 Braak H, de Vos RAI, Jansen ENH, Bratzke HJ, Braak E. Neuropathological hallmarks of Alzheimer’s and Parkinson’s diseases. Progr Brain Res 1998; 117: 267-85.
    Google Scholar
  • 11 Braak H, Rüb U, Sandmann-Keil D, Gai WP, de Vos RAI, Jansen Steur ENH, Arai K, Braak E. Parkinson’s disease: affection of brain stem nuclei controlling premotor and motor neurons of the somatomotor system. Acta Neuropathol 2000; 99: 489-95.
    CrossrefPubMedGoogle Scholar
  • 12 Braak H, Del Tredici K, Rüb U, de Vos RAI, Jansen Steur ENH, Braak E. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 2003; 24: 197-210.
    CrossrefPubMedGoogle Scholar
  • 13 Braak H, Rüb U, Del Tredici K. Idiopathic Parkinson’s disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. J Neural Transm 2003; 110: 517-36.
    CrossrefPubMedGoogle Scholar
  • 14 Braak H, Del Tredici K, Braak E. Spectrum of pathology. In: Petersen RC. (ed). Mild cognitive impairment. Aging to Alzheimer’s disease. Oxford: University Press; 2003: 149-89.
    Google Scholar
  • 15 Braak H, Ghebremedhin E, Rüb U, Bratzke H, Del Tredici K. Stages in the development of Parkinson’s disease-related pathology. Cell Tissue Res 2004; 318: 121-34.
    CrossrefPubMedGoogle Scholar
  • 16 Chan-Palay V. Depression and dementia in Parkinson’s disease. Adv Neurol 1993; 60: 438-46.
    Google Scholar
  • 17 Cole NB, Murphy DD. The cell-biology of alpha-synuclein: a sticky problem?. Neuromol Med 2002; 1: 95-109.
    CrossrefPubMedGoogle Scholar
  • 18 Colosimo C, Hughes AJ, Kilford L, Lees AJ. Lewy body cortical involvement may not always predict dementia in Parkinson’s disease. J Neurol Neurosurg Psychiatry 2003; 74: 852-6.
    CrossrefPubMedGoogle Scholar
  • 19 Davis DG, Schmitt FA, Wekstein DR, Markesbery WR. Alzheimer neuropathologic alteration in aged cognitively normal subjects. J Neuropathol Exp Neurol 1999; 58: 376-88.
    CrossrefPubMedGoogle Scholar
  • 20 Del Tredici K, Braak H. Idiopathic Parkinson’s disease: Staging an α-synucleinopathy with a predictable pathoanatomy. In: Kahle P, Haass C. (eds). Molecular Mechanisms in Parkinson’s Disease. Georgetown, TX: Landes Bioscience; 2004: 1-32.
    Google Scholar
  • 21 Del Tredici K, Rüb U, de Vos RAI, Bohl JRE, Braak H. Where does Parkinson disease pathology begin in the brain?. J Neuropathol Exp Neurol 2002; 61: 413-26.
    CrossrefPubMedGoogle Scholar
  • 22 Dickson DW. Alpha-synuclein and the Lewy body disorders. Curr Opin Neurol 2001; 14: 423-32.
    CrossrefPubMedGoogle Scholar
  • 23 Doty RL. Olfaction. Ann Rev Psych 2001; 52: 423-52.
    CrossrefPubMedGoogle Scholar
  • 24 Dubois B, Pillon B. Dementia in Parkinson’s disease. In: Wolters EC, Scheltens P, Berendse HW. (eds). Mental Dysfunction in Parkinson’s Disease. Utrecht: Netherlands Academic Pharmaceutical Productions; 1999: 165-76.
    Google Scholar
  • 25 Folstein MF, Folstein SE, McHugh PR. »Minimental state.« A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12: 189-98.
    CrossrefPubMedGoogle Scholar
  • 26 Galvin JE, Lee VMY, Trojanowski JQ. Synucleinopathies. Clinical and pathological implications. Arch Neurol 2001; 58: 186-90.
    CrossrefPubMedGoogle Scholar
  • 27 Gelb DJ, Oliver E, Gilman S. Diagnostic criteria for Parkinson’s disease. Arch Neurol 1999; 56: 33-9.
    CrossrefPubMedGoogle Scholar
  • 28 German DC, Manaye KF, White CL. Diseasespecific patterns of locus coeruleus cell loss. Ann Neurol 1992; 32: 667-76.
    CrossrefPubMedGoogle Scholar
  • 29 Golbe LI. Alpha-synuclein and Parkinson’s disease. Mov Disord 1999; 14: 6-9.
    CrossrefPubMedGoogle Scholar
  • 30 Hawkes C. Olfaction in neurodegenerative disorder. Mov Disord 2003; 18: 364-72.
    CrossrefPubMedGoogle Scholar
  • 31 Heimer L, de Olmos J, Alheid GF, Zaborszky L. »Perestroika« in the basal forebrain: Opening the border between neurology and psychiatry. Progr Brain Res 1991; 87: 109-65.
    Google Scholar
  • 32 Huang XF, Törk I, Paxinos G. Dorsal motor nucleus of the vagus nerve: a cyto- and chemoarchitectonic study in the human. J Comp Neurol 1993; 330: 158-82.
    CrossrefPubMedGoogle Scholar
  • 33 Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 1992; 55: 181-4.
    CrossrefPubMedGoogle Scholar
  • 34 Hughes AJ, Daniel SE, Blankson S, Lees AJ. A clinicopathologic study of 100 cases of Parkinson’s disease. Arch Neurol 1993; 50: 140-8.
    CrossrefPubMedGoogle Scholar
  • 35 Hughes TA, Ross HF, Musa S, Bhattacherjee S, Nathan RN, Mindham RH, Spokes EG. A 10-year study of the incidence of and factors predicting dementia in Parkinson’s disease. Neurology 2000; 54: 1596-1602.
    CrossrefPubMedGoogle Scholar
  • 36 Hyman BT, van Hoesen GW, Damasio AR. Memory-related systems in Alzheimer’s disease: an anatomic study. Neurology 1990; 40: 1721-30.
    CrossrefPubMedGoogle Scholar
  • 37 Insausti R, Amaral DG. Hippocampal formation. In: Paxinos G, Mai KJ. (eds). The Human Nervous System. 2nd edition. San Diego, London: Elsevier Academic Press; 2004: 872-915.
    Google Scholar
  • 38 Inzelberg R, Plotnik M, Flash T, Schechtman E, Shahar I, Korczyn AD. Switching abilities in Parkinson’s disease. Adv Neurol 1996; 69: 361-9.
    Google Scholar
  • 39 Jellinger KA. Morphological substrates of mental dysfunction in Lewy body disease: an update. J Neural Transm 2000; 59 (Suppl): 185-212.
    Google Scholar
  • 40 Jellinger KA, Seppi K, Wenning GK, Poewe W. Impact of coexistent Alzheimer pathology on the natural history of Parkinson’s disease. J Neural Transm 2002; 109: 329-39.
    CrossrefPubMedGoogle Scholar
  • 41 Jensen PH, Gai WP. Alpha-synuclein. Axonal transport, ligand interaction, and neurodegeneration. In: Tolnay M, Probst A. (eds). Neuropathology and Genetics of Dementia. New York: Kluwer Academic/Plenum; 2001: 129-34.
    Google Scholar
  • 42 Knopman DS, Boeve BF, Petersen RC. Essentials of the proper diagnoses of mild cognitive impairment, dementia, and major subtypes of dementia. Mayo Clin Proc 2003; 78: 1290-1308.
    CrossrefPubMedGoogle Scholar
  • 43 Kövari E, Gold G, Herrmann FR. et al. Lewy body densities in the entorhinal and anterior cingulate cortex predict cognitive deficits in Parkinson’s disease. Acta Neuropathol 2003; 106: 83-8.
    PubMedGoogle Scholar
  • 44 Korczyn AD. Dementia in Parkinson’s disease. J Neurol 2001; 248 (Suppl. 03) 1-4.
    CrossrefPubMedGoogle Scholar
  • 45 Kuusisto E, Parkkinen L, Alafuzoff I. Morphogenesis of Lewy bodies: dissimilar incorporation of alpha-synuclein, ubiquitin, and p62. J Neuropathol Exp Neurol 2003; 62: 1241-53.
    CrossrefPubMedGoogle Scholar
  • 46 Lowe J. Lewy bodies. In: Calne DP. (ed). Neurodegenerative Diseases. Philadelphia: Saunders; 1994: 51-69.
    Google Scholar
  • 47 Noe E, Marder K, Bell KL, Jacobs DM, Manly JJ, Stern Y. Comparison of dementia with Lewy bodies to Alzheimer’s disease and Parkinson’s disease with dementia. Mov Disord 2004; 19: 60-7.
    CrossrefPubMedGoogle Scholar
  • 48 Perry RH, Jaros EB, Irving D. et al. What is the neuropathological basis of dementia associated with Lewy bodies?. In: Perry RH, McKeith IG, Perry EK. (eds). Dementia with Lewy bodies. Cambridge, New York: Cambridge University Press; 1996: 212-23.
    Google Scholar
  • 49 Perry E, Walker M, Grace J, Perry R. Acetylcholine in mind: a neurotransmitter correlate of consciousness?. Trends Neurosci 1999; 22: 273-80.
    CrossrefPubMedGoogle Scholar
  • 50 Petersen RC, Doody R, Kurz A. et al. Current concepts in mild cognitive impairment. Arch Neurol 2001; 58: 1985-92.
    CrossrefPubMedGoogle Scholar
  • 51 Petersen RC, Morris JC. Clinical features. In: Petersen RC. (ed). Mild Cognitive Impairment. Aging to Alzheimer’s disease. Oxford: University Press; 2003: 15-40.
    Google Scholar
  • 52 Petrides M, Pandya DN. The frontal cortex. In: Paxinos G, Mai JK. (eds). The Human Nervous System. 2nd edition. San Diego, London: Elsevier Academic Press; 2004: 951-74.
    Google Scholar
  • 53 Price JL. Olfaction. In: Paxinos G, Mai JM. (eds). The Human Nervous System. 2nd edition. San Diego, London: Elsevier Academic Press; 2004: 1198-1212.
    Google Scholar
  • 54 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: 567-77.
    CrossrefPubMedGoogle Scholar
  • 55 Saper CB. Diffuse cortical projection systems: Anatomical organization and role in cortical function. In: Plum F. (ed). Handbook of Physiology, vol. 5. The Nervous System. Bethesda: Am Physiol Soc; 1987: 169-210.
    Google Scholar
  • 56 Thal DR, Del Tredici K, Braak H. Neurodegeneration in normal brain aging and disease. SAGE KE 2004; 23: 26.
    Google Scholar
  • 57 Vertesi A, Lever JA, Molloy DW, Sanderson B, Tuttle I, Pokoradi L, Principi E. Standardized Mini-Mental State Examination. Use and interpretation. Can Fam Physician 2001; 47: 2018-23.
    PubMedGoogle Scholar
  • 58 Wakabayashi K, Hansen LA, Masliah E. Cortical Lewy body-containing neurons are pyramidal cells. Laser confocal imaging of double-immunolabeled sections with anti-ubiquitin and SMI32. Acta Neuropathol 1995; 89: 404-8.
    CrossrefPubMedGoogle Scholar
  • 59 Wolters EC, Francot CMJE. The concept of mental dysfunction in Parkinson’s disease. In: Wolters EC, Scheltens P, Berendse HW. (eds). Mental Dysfunction in Parkinson’s Disease. Utrecht: Netherlands Academic Pharmaceutical Productions; 1999: 35-48.
    Google Scholar
  • 60 Woods SP, Tröster AI. Prodromal frontal/executive dysfunction predicts incident dementia in Parkinson’s disease. J Intern Neuropsychol Soc 2003; 9: 17-24.
    Google Scholar
  • 61 Zilles K. Architecture of the human cortex. In: Paxinos G, Mai JK. (eds). The Human Nervous System. 2nd edition. San Diego, London: Elsevier Academic Press; 2004: 997-1060.
    Google Scholar
  • 62 Zweig RM, Cardillo JE, Cohen M, Giere S, Hedreen JC. The locus ceruleus and dementia in Parkinson’s disease. Neurology 1993; 43: 986-91.
    CrossrefPubMedGoogle Scholar