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Neurochemical Basis of Dementia in Parkinson’s Disease

Published online by Cambridge University Press:  18 September 2015

Oleh Hornykiewicz  and
Stephen J. Kish
Oleh Hornykiewicz
Affiliation:
The Institute of Biochemical Pharmacology, University of Vienna, Austria
Stephen J. Kish
Affiliation:
Human Brain Laboratory, Clarke Institute of Psychiatry, Toronto, Ontario
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Abstract

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According to their mental status, patients with Parkinson’s disease can be subdivided into three groups: (1) mentally normal patients; (2) patients with severe cognitive impairment and Alzheimer-type brain pathology (neuritic plaques, neurofibrillary tangles, granulovacuolar changes); and (3) demented patients without any evidence of Alzheimer changes. Neurochemically, irrespective of the presence or absence of Alzheimer-type brain pathology, demented Parkinson patients seem to have the same disturbance of cortical cholinergic neuron function as patients with Alzheimer-type dementia (Alzheimer’s disease), namely, reduced levels of cortical acetylcholine esterase and choline acetyltransferase activity. At present, the question whether the “cortical cholinergic deficiency” is the only (or sufficient) neurochemical basis for the cognitive impairment in Parkinson patients with dementia cannot be answered with certainty; the additional role of other neurotransmitter changes known to occur in the Parkinson brain, especially loss of cortical, hippocampal and subcortical noradrenaline and/or dopamine cannot be ruled out.

Type
6. Dementia in Parkinson’s Disease
Information
Canadian Journal of Neurological Sciences , Volume 11 , Issue S1: Current Concepts and Controversies in Parkinson’s Disease , February 1984 , pp. 185 - 190
Copyright
Copyright © Canadian Neurological Sciences Federation 1984

References

Adolfsson, R, Gottfries, CG, Roos, BE, Winblad, B (1979) Changes in the brain catecholamines in patients with dementia of Alzheimer type. Brit. J. Psychiat. 135:216–223.CrossRefGoogle ScholarPubMed
Albert, ML (1978) Subcortical dementia. In : Alzheimer’s Disease : Senile Dementia and Related Disorders, ed. Fatzman, R, Terry, RD, and Bick, KL.173–180. Raven Press, N.Y.Google Scholar
Alvord, E, Forno, LS, Kusse, JA, Kauffman, RJ, Rhodes, JS, Goetowski, CR (1974) The pathology of Parkinsonism: a comparison of degenerations in cerebral cortex and brainstem. Adv. Neurol. 5:175–193.Google ScholarPubMed
Asso, D (1969) W.A.I.S. scores in a group of Parkinson patients. Brit. J. Psychiat. 115:555–556.CrossRefGoogle Scholar
Bartus, RT, Dean III, RL, Beer, B, Lippa, AS (1982) The cholinergic hypothesis of geriatric memory dysfunction. Science 217:408–417.CrossRefGoogle ScholarPubMed
Boiler, F, Mizutani, T, Roessmann, U, Gambetti, P (1980) Parkinson’s disease: clinicopathological correlations. Ann. Neurol. 7:329–335.CrossRefGoogle Scholar
Bondareff, W, Mountjoy, CQ, Roth, M (1981) Selective loss of neurones of origin of adrenergic projection to cerebral cortex (nucleus locus caeruleus) in senile dementia. Lancet i:783–784.CrossRefGoogle Scholar
Bowen, DM, Sims, NR, Benton, JS, Curzon, G, Davison, AN, Neary, D, Thomas, DJ (1981) Treatment of Alzheimer’s disease: a cautionary note. New Engl. J. Med. 305:1016.Google ScholarPubMed
Buttlar-Brentano, K von (1955) Das Parkinsonsyndrom im Lichte der lebensgeschichtlichen Veranderungen des Nucleus basilis. J. Hirnforsch. 2:55–77.Google Scholar
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. 59:277–289.CrossRefGoogle Scholar
Celesia, GG, Wanamaker, WM (1972) Psychiatric disturbances in Parkinson’s disease. Dis. Nerv. Syst. 33:577–583.Google ScholarPubMed
Coyle, JT, Price, DL, Delong, MR (1983) Alzheimer’s disease: a disorder of cortical cholinergic innervation. Science 219:1184–1190.CrossRefGoogle ScholarPubMed
Cross, AJ, Crow, TJ, Perry, EK, Perry, RH, Blessed, G, Tomlinson, BE (1981) Reduced dopamine-beta-hydroxylase activity in Alzheimer’s disease. Brit. Med. J. 282:93–94.CrossRefGoogle ScholarPubMed
Danielczyk, W (1983) Various mental behavioural disorders in Parkinson’s disease, primary degenerative senile dementia, and multiple infarction dementia. J. Neural Transm. 56:161–176.CrossRefGoogle ScholarPubMed
Davies, P, Maloney, AJR (1976) Selective loss of central cholinergic neurons in Alzheimer’s disease. Lancet ii: 1403.Google Scholar
Ehringer, H, Hornykiewicz, O (1960) Distribution of noradrenaline and dopamine (3-hydroxytyramine) in human brain: their behaviour in extrapyramidal system diseases. Klin. Wschr. 38:1236–1239.CrossRefGoogle Scholar
Farley, IJ, Hornykiewicz, O (1976) Noradrenaline in subcortical brain regions of patients with Parkinson’s disease and control subjects. In: Advances in Parkinsonism. Eds. Birkmayer, W., Hornykiewicz, O.. 178–185, Editiones Roche, Basel.Google Scholar
Garron, DC, Klawans, HL, Narin, F (1972) Intellectual functioning of persons with idiopathic Parkinsonism. J. Nerv. Ment. Dis. 154:445–452.CrossRefGoogle ScholarPubMed
Gibson, CJ, Ball, MJ (1983) Hippocampal monoamine deficits in Alzheimer’s disease. J. Neurochem. Supp. 41:S20B.Google Scholar
Greenfield, JG, Bosanquet, FD (1953) The brain-stem lesions in Parkinsonism. J. Neurol. Neurosurg. Psychiat. 16:213–226.CrossRefGoogle ScholarPubMed
Hakim, AM, Mathieson, G (1979) Dementia in Parkinson’s disease: a neuropathological study. Neurology 29:1209–1214.CrossRefGoogle Scholar
Hassler, R (1938) Zur Pathologie der Paralysis agitans und des post-encephalitischen Parkinsonismus. J. Psychol, u. Neurol. 8:387–476.Google Scholar
Heston, LL (1980) Dementia associated with Parkinson’s disease: a genetic study. J. Neurol. Neurosurg. Psychiat. 43:846–848.CrossRefGoogle ScholarPubMed
Hornykiewicz, O (1981) Brain neurotransmitter changes in Parkinson’s disease. In: Movement Disorders. Ed. Marsden, CD and Fahn, S, Butterworth Int. Med. Rev., 41–58, Butterworth Sci., London.Google Scholar
Hornykiewicz, O (1982) Imbalance of brain monoamines and clinical disorders. Progr. Brain Res. 55:419–429.CrossRefGoogle ScholarPubMed
Johnston, MV, McKinney, M, Coyle, JT (1979) Evidence for a cholinergic projection to neocortex from neurons in basal forebrain. Proc. Natl. Acad. Sci. 76:5392–5396.CrossRefGoogle ScholarPubMed
Kety, SS (1970) The biogenic amines in the central nervous system: their possible roles in arousal, emotion, and learning. In: The Neurosciences, Second Study Program, O Schmitt, editor-in-chief. 324–336. Rockefeller Univ. Press, New York.Google Scholar
Kish, SJ, Shannak, KS, Rajput, AH, Gilbert, JJ, Hornykiewicz, O (1984) Reduction of cerebellar noradrenaline in Parkinson’s disease. Arch. Neurol., in press.Google Scholar
Lieberman, A, Dziatolowski, M, Kupersmith, M, Serby, M, Goodgold, A, Korein, J, Goldstein, M (1979) Dementia in Parkinson’s disease. Ann. Neurol. 6:355–359.CrossRefGoogle Scholar
Mair, RG, McEntee, WJ (1983) Korsakoff’s psychosis: noradrenergic systems and cognitive movement. Behav. Brain Res. 9:1–32.CrossRefGoogle Scholar
Mann, DMA, Lincoln, J, Yates, PO, Stamp, JE, Toper, S (1980) Changes in the monoamine containing neurones of the human CNS in senile dementia. Brit. J. Psychiat. 136:533–541.CrossRefGoogle ScholarPubMed
Marttila, RJ, Rinne, UK (1976) Dementia in Parkinson’s disease. Acta Neurol. Scand. 54:431–441.CrossRefGoogle ScholarPubMed
Mayeux, R, Stern, Y, Rosen, J, Leventhal, J (1981) Depression, intellectual impairment, and Parkinson disease. Neurology 31:645–650.CrossRefGoogle ScholarPubMed
McEntee, WJ, Mair, RG (1978) Memory impairment in Korsakoff’s psychosis: a correlation with brain noradrenergic activity. Science 202:905–907.CrossRefGoogle ScholarPubMed
Mindham, R, Ahmed, S, Clough, CG (1982) A controlled study of dementia in Parkinson’s disease. J. Neurol. Neurosurg. Psychiat. 45:969–974.CrossRefGoogle ScholarPubMed
Mjones, H (1949) Paralysis agitans. Acta Psychiat. Neurol. Scand. Suppl. 54:1–195.Google Scholar
Moore, RY, Bloom, FE (1979) Central catecholamine neuron system: anatomy and physiology of the norepinephrine and epinephrine systems. Ann. Rev. Neurosci. 2:113–168.CrossRefGoogle ScholarPubMed
Mortimer, JA, Pirozzolo, FJ, Hansch, EC and Webster, DD (1982) Relationship of motor symptoms to intellectual deficits in Parkinson disease. Neurology 32:133–137.CrossRefGoogle ScholarPubMed
Nagai, T, McGeer, PL, Peng, JH, McGeer, EG, Dolman, CE (1983) Choline acetyltransferase immunohistochemistry in brains of Alzheimer’s disease patients and controls. Neurosci. Lett. 36:195–199.CrossRefGoogle ScholarPubMed
Parhad, IM, Clark, AW, Folstein, S, Whitehouse, PJ, Hedreen, JC, Price, DL, Chase, GA (1982) The nucleus basalis in Huntington disease. Neurol. 32:A168.Google Scholar
Patrick, HT, Levy, DM (1922) Parkinson’s Disease: a clinical study of one hundred and forty-six cases. Arch. Neurol. Psychiat. 7:711–720.CrossRefGoogle Scholar
Perry, EK, Perry, RH (1980) The cholinergic system in Alzheimer’s disease. In: Biochemistry of Dementia. Ed. Roberts, PJ.135–183. John Wiley and Sons, Chichester.Google Scholar
Perry, EK, Perry, RH, Blessed, G, Tomlinson, BE (1977a) Necropsy evidence of central cholinergic deficits in senile dementia. Lancet i:189.CrossRefGoogle Scholar
Perry, EK, Gibson, PH, Blessed, G, Perry, RH, Tomlinson, BE (1977b) Neurotransmitter enzyme abnormalities in senile dementia. J. Neurol. Sci. 34:247–265.CrossRefGoogle ScholarPubMed
Perry, EK, Tomlinson, BE, Blessed, G, Bergmann, K, Gibson, PH, Perry, RH (1978) Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Brit. Med. J. 2:1457–1459.CrossRefGoogle ScholarPubMed
Perry, EK, Tomlinson, BE, Blessed, G, Perry, RH, Cross, AJ, Crow, TJ (1981) Noradrenergic and cholinergic systems in senile dementia of Alzheimer type. Lancet ii: 149.CrossRefGoogle Scholar
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 Meynert in Alzheimer’s disease. Neurosci. Lett. 33:311–315.CrossRefGoogle Scholar
Perry, RH, Tomlinson, BE, Candy, JM, Blessed, G, Foster, JF, Bloxham, CA, Perry, EK (1983) Cortical cholinergic deficit in mentally impaired parkinsonian patients. Lancet ii:789–790.CrossRefGoogle Scholar
Pollock, M, Hornabrook, RW (1966) The prevalence, natural history and dementia of Parkinson’s disease. Brain 89:429–448.CrossRefGoogle ScholarPubMed
Pope, A, Hess, HH, Lewin, E (1965) Microchemical pathology of the cerebral cortex in pre-senile dementia. Trans. Am. Neurol. Assn. 89:15–16.Google Scholar
Price, KS, Farley, U and Hornykiewicz, O (1978) Neurochemistry of Parkinson’s disease: relation between striatal and limbic dopamine. Adv. Biochem. Psychopharmacol. 19:293–300.Google ScholarPubMed
Richter, JA, Perry, EK, Tomlinson, BE (1980) Acetycholine and choline levels in post-mortem human brain tissue: preliminary observations in Alzheimer’s disease. Life Sci. 26:1683–1689.CrossRefGoogle Scholar
Rinne, UK, Sonninen, V (1973) Brain catecholamines and their metabolites in Parkinsonian patients. Arch. Neurol. 28:107–110.CrossRefGoogle ScholarPubMed
Rossor, MN, Garrett, NJ, Johnson, AL, Mountjoy, CQ, Roth, M, Iversen, LL (1982) A post-mortem study of the cholinergic and GABA systems in senile dementia. Brain 105:313–330.CrossRefGoogle ScholarPubMed
Rubert, M, Ploska, A, Javoy-Agid, F, Agid, Y (1982) Muscarinic binding and choline acetyletransferase activity in Parkinsonian subjects with reference to dementia. Brain Res. 232:129–139.CrossRefGoogle Scholar
Sacks, SW, Kohl, MS, Messeloff, CR, Schwartz, WF (1972) Effects of levodopa in parkinsonian patients with dementia. Neurology 22:516–519.CrossRefGoogle ScholarPubMed
Scatton, V, Javoy-Agid, F, Rouquier, L, Dubois, B, Agid, Y (1983) Reduction of cortical dopamine, noradrenaline, serotonin and their metabolites in Parkinson’s disease. Brain Res. 275:321–328.CrossRefGoogle ScholarPubMed
Shute, CCD, Lewis, PR (1967) The ascending cholinergic reticular system: neocortical, olfactory and subcortical projections. Brain 90:497–520.CrossRefGoogle ScholarPubMed
Sims, NR, Bowen, DM, Smith, CCT, Flack, RHA, Davison, AN, Snowdon, JS, Neary, D (1980) Glucose metabolism and acetycholine synthesis in relation to neuronal activity in Alzheimer’s disease. Lancet i:333–335.CrossRefGoogle Scholar
Sweet, RD, McDowell, H, Fergenson, JS, Loranger, AW, Goodell, H (1976) Mental symptoms in Parkinson’s disease during chronic treatment with levodopa. Neurology 26:305–310.CrossRefGoogle ScholarPubMed
Talland, GA (1962) Cognitive function in Parkinson’s disease. J. Nerv. Ment. Dis. 135:196–205.CrossRefGoogle ScholarPubMed
Terry, RD, Davies, P (1980) Dementia of the Alzheimer type. Ann. Rev. Neurosci. 3:77–95.CrossRefGoogle ScholarPubMed
Tomlinson, BE, Irving, D, Blessed, G (1981) Cell loss in the locus caeruleus in senile dementia of Alzheimer type. J. Neurol. Sci. 49:419–428.CrossRefGoogle ScholarPubMed
Whitehouse, PJ, Price, DL, Clark, AW, Coyle, JT, DeLong, MR (1981) Alzheimer disease: evidence for selective loss of cholinergic neurons in the nucleus basalis. Ann. Neurol. 10:122–126.CrossRefGoogle ScholarPubMed
Whitehouse, PJ, Price, DL, Struble, RG, Clark, AW, Coyle, JT, Delong, MR (1982) Alzheimer’s disease and senile dementia: loss of neurons in the basal forebrain. Science 215:1237–1239.CrossRefGoogle ScholarPubMed
Whitehouse, PJ, Hedreen, JC, White, CL, Price, DL (1983) Basal forebrain neurons in the dementia of Parkinson’s disease. Ann. Neurol. 13:243–248.CrossRefGoogle Scholar