Abstract
A group of ten patients with idiopathic Parkinson's disease (PD) was tested on a series of automated tests of learning, memory, planning and attention whilst either on or offl-dopa medication. Controlled with-drawal ofl-dopa interfered with aspects of performance on three of the tests that had previously been shown to be sensitive to frontal lobe dysfunction; a spatial working memory task, the Tower of London planning test, and a visual discrimination paradigm that also included intra- and extra-dimensional shift tests of selective attention. More specifically, errors were increased in the spatial working memory test, and both the accuracy and latency of thinking were impaired. Thinking time was significantly slowed followingl-dopa withdrawal, even though the possible contaminating effects on motor slowing were fully controlled by a yoked control procedure. Nine out of ten patients reached a further stage of the visual discrimination, set-shifting paradigm when on, rather than off,l-dopa medication. Spatial span was also impaired off medication, but there were no effects ofl-dopa withdrawal on tests of pattern and spatial recognition memory, simultaneous and delayed matching to sample or visuospatial conditional associative learning. Comparisons with a large control group confirmed previous findings that PD is associated with deficits on the majority of these tests. The results are discussed in terms of the fronto-striatal, dopamine dependent nature of some of the cognitive deficits found in PD, but the apparent dopamine-independent nature of deficits in other aspects of cognitive functioning, notably in tests of visual recognition memory and associative learning.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abas M, Sahakian BJ, Levy R (1990) Neuropsychological deficits and CT scan changes in elderly depressives. Psychol Med 20:507–520
Agid Y, Ruberg M, Dubois B, Pillon B (1987) Anatomoclinical and biochemical concepts of subcortical dementia. In: Stahl SM, Iversen SD, Goodman EC (eds) Cognitive Neurochemistry. Oxford University Press, Oxford, pp 248–271
Alexander GE, Delong MR, Strick PL (1986) Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci 9:357–381
Berger B, Gaspar P, Verney C (1991) Dopaminergic innervation of the cerebral cortex: unexplained differences between rodents and primates. TINS 14:21–27
Björklund A, Lindvall O (1984) Dopamine containing systems in the CNS. In: Bjorklund A, Hokfelt T (eds) Handbook of chemical neuroanatomy vol 2, Classical transmitters in the CNS, Part 1. Elsevier, London, pp 55–122
Bowen FP, Kamienny MA, Burns MM, Yahr M (1975) Parkinsonism: effects ofl-dopa on concept formation. Neurology 25:701–704
Brown RG, Marsden CD (1988) “Subcortical dementia”. The neuropsychological evidence. Neuroscience 25:363–387
Brown RG, Marsden CD, Quinn N, Wyke MA (1984) Alterations in cognitive performance and affect-arousal state during fluctuations in motor function in Parkinson's disease. J Neurol Neurosurg Psychiatry 47:454–465
Brozoski TJ, Brown RM, Rosvold HE, Goldman PS (1979) Cognitive deficit caused by regional depletion of dopamine in prefrontal cortex of rhesus monkey. Science 205:929–932
Canavan A, Passingham RE, Marsden CD, Quinn N, Wyke M, Polkey CE (1989) The performance on learning tasks of patients in the early stages of Parkinson's disease. Neuropsychologia 27:141–156
Cools AR, van der Berken JHL, Horstink MWI, van Spaendonck KPM, Berger HJC (1984) Cognitive and motor shifting aptitude disorder in Parkinson's disease. J Neurol Neurosurg Psychiatry 47:443–453
Cooper J, Sagar H, Jordan N, Harvey NS, Sullivan E (1991) Cognitive impairment in early, untreated Parkinson's disease and its relationship to motor disability. Brain 114:2095–2122
Divac I, Rosvold HE, Szwarcbart MK (1967) Behavioral effects of selective ablation of the caudate nucleus. J Comp Physiol Psychol 63:184–190
Downes JJ, Roberts AC, Sahakian BJ, Evenden JL, Morris RG, Robbins TW (1989) Impaired extra-dimensional shift performance in medicated and unmedicated Parkinson's disease: evidence for a specific attentional dysfunction. Neuropsychologia 27:1329–1343
El-Awar M, Becker JT, Hammond KM, Nebes RD, Boller F (1987) Learning deficit in Parkinson's disease: comparison with Alzheimer's disease and normal aging. Arch Neurol 44:180–184
Flowers KA, Robertson C (1985) The effect of Parkinson's disease on the ability to maintain a mental set. J Neurol Neurosurg Psychiatry 48:517–529
Gotham A-M, Brown RG, Marsden CD (1988) “Frontal” cognitive functions in patients with Parkinson's disease “on” and “off”l-dopa. Brain 111:299–332
Hoehn MM, Yahr M (1967) Parkinsonism: onset, progression and mortality. Neurology 17:427–442
Kendrick DC (1985) Kendrick cognitive tests for the elderly. NFER Nelson, Windsor
Lees AJ (1990) The behavioural neurology of Parkinson's disease. In: Stern G (ed) Parkinson's disease. Chapman and Hall, London, pp 389–413
Lees AJ, Smith E (1983) Cognitive deficits in the early stages of Parkinson's disease. Brain 106:257–270
Milner B (1964) Some effects of frontal lobectomy in man. In: Warren JM, Akert K (eds) The frontal granular cortex and behaviour. McGraw-Hill, New York, pp 313–331
Milner B (1982) Some cognitive effects of frontal-lobe lesions in man. Philos Trans R Soc Lond B298:211–226
Mishkin M (1982) A memory system in the monkey. Philos Trans R Soc B298:85–92
Morris RG, Downes JJ, Evenden JL, Sahakian BJ, Heald A, Robbins TW (1988) Planning and spatial working memory in Parkinson's disease. J Neurol Neurosurg Psychiatry 51:757–766
Nelson HE (1982) National adult reading test manual. NFER Nelson, Windsor
Owen AM, Downes JJ, Sahakian BJ, Polkey CE, Robbins TW (1990a) Planning and spatial working memory following frontal lobe lesions in man. Neuropsychologia 28:1021–1034
Owen AM, Galton M, Leigh PNL, Marsden CD, Quinn N, Sahakian BJ, Summers B, Robbins TW (1990b) Planning and spatial working memory in Parkinson's disease. Soc Neurosci Abstr 16:453–10
Owen AM, Roberts AC, Polkey C, Sahakian BJ, Robbins TW (1991) Extra-dimensional versus intradimensional set shifting performance following frontal lobe excisions, temporal lobe excisions or amygdalo-hippocampectomy in man. Neuropsychologia 29:993–1006
Petrides M (1985) Deficits on conditional associative-learning tasks after frontal and temporal lobe lesions in man. Neuropsychologia 23:601–614
Roberts AC, Everitt BJ, Robbins TW (1988) Extra- and intradimensional shifts in man and marmoset. Q J Exp Psychol 40B:321–342
Sahakian BJ, Morris RG, Evenden JL, Heald A, Levy R, Philpot M, Robbins TW (1988) A comparative study of visuospatial memory and learning in Alzheimer type dementia and Parkinson's disease. Brain 111:695–718
Sahakian BJ, Downes JJ, Eagger S, Evenden JL, Levy R, Philpot M, Roberts AC, Robbins TW (1990) Sparing of attentional relative to mnemonic function in a subgroup of patients with dementia of the Alzheimer type. Neuropsychologia 28:1197–1213
Shallice T (1982) Specific impairments of planning. Philos Trans R Soc Lond B298:199–209
Weingartner H, Burns S, Debel R, Lewitt PA (1984) Cognitive impairment in Parkinson's disease: distinguishing between effort-demanding and autonomic processes. Psychiat Res 11:223–235
Winer BJ (1971) Statistical principles in experimental design, 2nd edn. McGraw Hill, New York
Yahr M (1990) Principles of medical treatment. In: Stern G (ed) Parkinson's disease. Chapman and Hall, London, pp 495–508
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lange, K.W., Robbins, T.W., Marsden, C.D. et al. l-Dopa withdrawal in Parkinson's disease selectively impairs cognitive performance in tests sensitive to frontal lobe dysfunction. Psychopharmacology 107, 394–404 (1992). https://doi.org/10.1007/BF02245167
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02245167