Summary
Neuronal loss was estimated semiquantitatively in the substantia nigra (SN) and locus coeruleus (LC), and by cell counts in the nucleus basalis of Meynert (NBM), in 32 patients with idiopathic Parkinson's disease (14 non-demented and 18 demented). The number of senile plaques (SP) and neurofibrillary tangles (NFT) was rated in four cortical areas. Neuronal loss in the SN seemed in dependent of mental impairment, while severe lesions of the LC were more frequent in demented patients. In the NBM, neuronal loss and Lewy bodies were observed in most cases (95%) and were associated with significant reductions of choline acetyltransferase (CAT) activity both in the NBM and the cortex (measurements available for 13 cases). This confirms that the cholinergic innominatocortical pathway is damaged in Parkinson's disease and that the lesion is severer in subjects with dementia. SP and NFT were present in the cortex in 75% of the cases and significantly more numerous in demented patients. However, in 37% of the cases (six cases with dementia), the score for cortical changes was low and could be related to age. Cortical SP and NFT were not correlated to the degree of cell loss in LC and NBM, or to CAT activity in the cortex or NBM. Damage to coeruleocortical, innominato-cortical and intra-cortical neurones could each play a role in the appearance of dementia in Parkinsonism. The lesions in the different neuronal systems do not seem to evolve in parallel, but may be additive or potentiate one another in terms of functional expression. Also, the variety in extent and degree of lesions encountered in Parkinson's disease may offer a pathological substrate for the wide variety of mental symptoms described in this illness.
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References
Arendt T, Gigl V, Arendt A, Tennstedt A (1983) Loss of neurons in the nucleus basalis of Meynert in Alzheimer's disease, paralysis agitans and Korsakoff's disease. Acta Neuropathol (Berl) 61:101–108
Berger B, Escourolle R, Moyne MA (1976) Axones catecholaminergiques du cortex cérébral humain observation en histofluorescence de biopsies cérébrales dont 2 cas de maladie d'Alzheimer. Rev Neurol (Paris) 132:183–194
Berger B, Tassin JP, Rancurel G, Blanc G (1980) Catecholaminergic innervation of the human cerebral cortex in presenile and senile dementia. Histochemical and biochemical studies. In: Usdin E, Sourkes TL, Youdim BH (eds) Enzymes and neurotransmitters in mental disease. Wiley, New York, pp 317–328
Bethlem J, Den Hartog Jager WA (1960) The incidence and characteristics of Lewy bodies in idiopathic paralysis agitans (Parkinson's disease). J Neurol Neurosurg Psychiatry 23:74–80
Boller F, Mizutani R, Roessmann U, Gambetti P (1980) Parkinson's disease, dementia and Alzheimer's disease: clinico pathological correlations. Ann Neurol 1:329–355
Bondareff W, Mountjoy CQ, Roth M (1982) Loss of neurons of origin of the adrenergic projection to the cerebral cortex (nucleus locus coeruleus) in senile dementia. Neurology 32:165–168
Buttlar-Brentano K (1955) Das Parkinson-Syndrom in Lichte der lebensgeschichtlichen Veränderungen des Nucleus basalis. J Hirnforsch 2:26–76
Candy JM, Perry RH, Perry EK, Irving D, Blessed G, Fairbairn AF, Tomlinson BE (1983) Pathological changes in the nucleus of Meynert in Alzheimer's and Parkinson's disease. J Neurol Sci 54:277–289
Corsellis JAN (1962) Mental illness and the ageing brain. Oxford University Press, London
Davies P, Katzman R, Terry RD (1980) Reduced somatostatin-like immunoreactivity in cerebral cortex from cases of Alzheimer's disease and Alzheimer's senile dementia. Nature 288:279–280
Dayan AD (1970) Quantitative histological studies on the aged human brain. I. Senile plaques and neurofibrillary tangles in “normal” patients. Acta Neuropathol (Berl) 16:85–94
Dubois B, Ruberg M, Javoy-Agid F, Ploska A, Agid Y (1983) A subcortico-cortical cholinergic system is affected in Parkinson's disease. Brain Res 288:213–218
Epelbaum J, Ruberg M, Moyse E, Havoy-Agid F, Dubois B, Agid Y (1983) Somatostatin and dementia in Parkinson's disease. Brain Res 278:376–379
Escourolle R, de Recondo J, Gray F (1970) Etude anatomopathologique des syndromes parkinsoniens. Dans. Monoamines et noyaux gris centraux. Rapport au IVéme Symposium de Bel Air, Genève, pp 173–229
Foix C, Nicolesco J (1925) Les noyaux gris centraux et la région mésencéphalo-sous-optique. Paris, Masson
Fonnum F (1969) Radiochemical micro assays for the determination of choline acetyl transferase and acetylcholinesterase activities Biochem J 115:465–472
Forno LS (1969) Concentric hyaline intraneuronal inclusion of Lewy type in the brains of elderly persons (50 incidental cases). Relationship to parkinsonism. J Am Geriat Soc 17:557–575
Forno LS (1982) Pathology of Parkinson's disease. In: Marsden D, Fahn S (eds) Movement disorders. Butterworth Scientific, London, pp 25–40
Forno LS, Barbour PJ, Norville RL (1978) Presenile dementia with Lewy bodies and neurofibrillary tangles. Arch Neurol 35:818–822
Goldman JE, Yen SH, Chiu FC, Peress NS (1983) Lewy bodies of Parkinson's disease contain neurofilament antigens. Science 221:1082–1084
Hakim AH, Mathieson G (1979) Dementia in Parkinson's disease: A neuropathologic study. Neurology 29:1209–1214
Hassler R (1938) Zur Pathologie der Paralysis agitans und des postencephalitischen Parkinsonismus. J Psychol Neurol (Lpz) 48:387–476
Hornykiewicz O (1982) Brain neurotransmitter changes in Parkinson's disease. In: Marsden D, Fahn S (eds) Movement disorders. Butterworth Scientific, London, pp 41–58
Ischii T (1966) Distribution of Alzheimer's neurofibrillary changes in the brain stem and hypothalamus of senile dementia. Acta Neuropathol (Berl) 6:181–187
Javoy-Agid F, Agid Y (1980) Is the mesocortical dopaminergic system involved in Parkinson's disease? Neurology 30:1326–1330
Javoy-Agid F, Ruberg M, Taquet H, Bokobza B, Agid Y, Gaspar P, Berger B, N'Guyen-Legros J, Alvarez C, Gray F, Hauw JJ, Scatton B, Rouquier L (1983) Biochemical neuropathology of Parkinson's disease. Adv Neurol 40:189–198
Jellinger K (1983) Hirnatrophie bei Morbus Parkinson and (prä)-seniler Demenz. In: Schnaberth G, Pateisky K (Hrsg) Fortschritte der Klinischen Neurologie. Thieme, Stuttgart New York S 151–164
Jellinger K, Riederer P (1983) Dementia in Parkinson's disease and (pre)-senile dementia of Alzheimer type: Morphological aspects and changes in the intracerebral MAO activity. In: Hassler R, Christ JF (eds) Advances in neurology. Raven Press, pp 199–210
Lewy FH (1913) Zur pathologischen Anatomie der Paralysis agitans. Dtsch Z Nervenheilkd 50:50–55
Liebermann A, Dziatolowski M, Kupersmith M, Serby M, Goodgold A, Korein J, Goldstein M (1979) Dementia in Parkinson's disease. Ann Neurol 6:355–359
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the folin-phenol reagent. J Biol Chem 193:265–275
Mann DMA, Yates PO (1982) Is the loss of cerebral cortical choline acetyl transferase activity in Alzheimer's disease due to degeneration of ascending cholinergic nerve cells. J Neurol Neurosurg Psychiatry 45:936
Mann DMA, Yates PO (1983) Pathological basis for neurotransmitter changes in Parkinson's disease. Neuropathol Appl Neurobiol 9:3–19
marsden CD (1982) The mysterious motor function of the basal ganglia: the Robert Wartenberg lecture. Neurology (NY) 32:514–539
Marttila RJ, Rinne UK (1976) Dementia in Parkinson's disease. Acta Neurol Scand 54:431–441
Mayeux R, Stern Y, Rosen J, Leventhal J (1981) Depression, intellectual impairment and Parkinson's disease. Neurology (NY) 31:645–650
Mindham RHS, Ahmed SWA, Clough CG (1982) A controlled study of dementia in Parkinson's disease. J Neurol Neurosurg Psychiatry 45:969–974
Ohama E, Ikuta F (1976) Distribution of Lewy bodies and monoamine neuron system. Acta Neuropathol (Berl) 34:311–319
Perry EK, Tomlinson BE, Blessed G, Perry RH, Cross JA, Crow TJ (1981) Neuropathological and biochemical observations on the noradrenergic system in Alzheimer's disease. J Neurol Sci 51:279–287
Perry RH, Candy JM, Perry EK, Irving D, Blessed G, Fairbairn AF, Tomlinson BE (1982) Extensive loss of choline acetyltransferase activity is not reflected by neuronal loss in the nucleus of Meyner in Alzheimer's disease. Neurosci Lett 33:311–315
Riederer P, Jellinger K (1982) Morphological and biochemical changes in the aging brain: pathophysiological and possible therapeutic consequences. Exp Brain Res 5:158–165
Riederer R, Jellinger K (1983) Morphologie und Pathobiochemie der Parkinson-Krankheit, Bd 13. Neurologie-Symposium, Heidelberg S 33–52
Rossor MN (1981) Parkinson's disease and Alzheimer's disease as disorders of the isodendritic core. Br Med J 283:1588–1590
Rossor MN(1982) Dementia. Lancet II 1200–1204
Rossor MN, Svenssen C, Hunt SP, Mountjoy CQ, Roth M, Iversen LL (1982) The substantia inominata in Alzheimer's disease: an histochemical and biochemical study of cholinergic marker enzymes. Neurosci Lett 28:217–222
Ruberg M, Ploska A, Javoy-Agid F, Agid Y (1982) Muscarinic binding and choline acetyltransferase activity in parkinsonian subjects with reference to dementia. Brain Res 232:129–139
Ruberg M, Dubois B, Javoy-Agid F, Epelbaum J, Scatton B, Agid Y (1983) Dementia in patients with Parkinson's disease. Review of biochemical data. Proceedings of the VIIIth World Congress of Psychiatry, Vienna Plenum Production Co, (in press)
Scatton JB, Rouquier L, Javoy-Agid F, Agid Y (1982) Dopamine deficiency in the cerebral cortex in Parkinson's disease. Neurology 32:1039–1040
Scatton B, Javoy-Agid F, Rouquier L, Dubois B, Agid Y (1983) Reduction of cortical dopamine noradrenalin, serotonin and their metabolites in Parkinson's disease. Brain Res 275:321–328
Tomlinson BE, Blessed G, Roth M (1968) Observations on the brains non-demented old people. J Neurol Sci 11:205–242
Ulrich J (1982) Senile plaques and neurofibrillary tangles of the Alzheimer type in non-demented individuals at presenile age. Gerontology 28:86–90
Whitehouse PJ, Price DL, Clark AW, Coyle JT, De Long MR (1981) Alzheimer's disease: Evidence for selective loss of cholinergic neurons in the nucleus basalis. Ann Neurol 10:122–126
Whitehouse PJ, Price DL, Struble RG, Clark AW, Coyle JT, De Long MR (1982) Alzheimer's disease and senile dementia loss of neurons in the basal forebrain. Science 215:1227–1229
Whitehouse PJ, Hedreer JC, White CL, Price DL (1983) Basal forebrain neurons in the dementia of Parkinson's disease. Ann Neurol 13:243–248
Wilcock GK, Esiri MM, Bowen DM, Smith CCT (1983) The nucleus basalis in Alzheimer's disease: cell counts and cortical biochemistry. Neuropathol Appl Neurobiol 9:175–179
Yoshimura M (1983) Cortical changes in the parkinsonian brain: a contribution to the delineation of “diffuse Lewy body disease”. J Neurol 229:17–32
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This work is dedicated to the memory of Pr. R. Escourolle. As the head of the laboratoire Charles Foix, he had followed this work with great interest
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Gaspar, P., Gray, F. Dementia in idiopathic Parkinson's disease. Acta Neuropathol 64, 43–52 (1984). https://doi.org/10.1007/BF00695605
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DOI: https://doi.org/10.1007/BF00695605