Effect of levodopa on cognitive function in Parkinson’s disease with and without dementia and dementia with Lewy bodies

Background: Levodopa (L-dopa) is the gold standard treatment for Parkinson’s disease, but a lack of clear efficacy combined with a perceived liability to neuropsychiatric side effects has limited L-dopa use in patients with parkinsonism and dementia. Therefore, the effect of L-dopa on the cognitive profile of dementia with Lewy bodies (DLB) and Parkinson’s disease with dementia (PDD) is unclear. Aim: To ascertain the acute and long-term effects of L-dopa on aspects of attention and cognition in patients with DLB and PDD, and to compare these with the effects in Parkinson’s disease. Method: Baseline cognitive and motor function was assessed off L-dopa in patients with Parkinson’s disease (n = 22), PDD (n = 27) and DLB (n = 11) using standard “bedside” measures and a computerised programme detecting reaction times and accuracy. All patients then underwent an acute L-dopa challenge with subsequent subjective and objective analysis of alertness, verbal recall, reaction times and accuracy. The same parameters were measured after 3 months on L-dopa to assess the prolonged effect. Results: Acute L-dopa challenge considerably improved motor function and subjective alertness in all patients without compromising either reaction times or accuracy, but increased fluctuations were noted in both groups with dementia. Neuropsychiatric scores improved in patients with Parkinson’s disease both with and without dementia on L-dopa at 3 months. Although patients with Parkinson’s disease also had better mean global cognitive function at this time, mean verbal attention and memory deteriorated, and patients with PDD had slower reaction times in some tests. No patient had a marked deterioration over this time. Patients with DLB did not experience any adverse cognitive or neuropsychiatric effects after 3 months of L-dopa treatment. Conclusion: The use of L-dopa in patients with parkinsonism with dementia does not adversely affect cognitive function.

[1]  I G McKeith,et al.  The role of levodopa in the management of dementia with Lewy bodies , 2005, Journal of Neurology, Neurosurgery & Psychiatry.

[2]  P. Kelly,et al.  Bilateral Lesions of the Habenula Induce Attentional Disturbances in Rats , 2005, Neuropsychopharmacology.

[3]  M. Mehta,et al.  Cognitive and motor effects of dopaminergic medication withdrawal in Parkinson’s disease , 2004, Neuropsychologia.

[4]  Günther Deuschl,et al.  Rivastigmine for dementia associated with Parkinson's disease. , 2004, The New England journal of medicine.

[5]  Dinesh Kumar,et al.  Concurrent administration of donepezil HCl and levodopa/carbidopa in patients with Parkinson's disease: assessment of pharmacokinetic changes and safety following multiple oral doses. , 2004, British journal of clinical pharmacology.

[6]  T. Fujita.  [Mechanism of intracerebral calcification in hypoparathyroidism]. , 2004, Clinical calcium.

[7]  T. Robbins,et al.  l-Dopa medication remediates cognitive inflexibility, but increases impulsivity in patients with Parkinson’s disease , 2003, Neuropsychologia.

[8]  C. Caltagirone,et al.  Dopaminergic Modulation of Visual-Spatial Working Memory in Parkinson’s Disease , 2003, Dementia and Geriatric Cognitive Disorders.

[9]  D. Manoach,et al.  Cognitive slowing in Parkinson’s disease resolves after practice , 2002, Journal of neurology, neurosurgery, and psychiatry.

[10]  N. Fukumitsu,et al.  Imaging of Bilateral Striopallidodentate Calcinosis , 2002, Clinical nuclear medicine.

[11]  Takashi Hanakawa,et al.  Cognitive Slowing in Parkinson's Disease: A Behavioral Evaluation Independent of Motor Slowing , 2002, The Journal of Neuroscience.

[12]  T. Goldberg,et al.  Dopaminergic modulation of cortical function in patients with Parkinson's disease , 2002, Annals of neurology.

[13]  I. McKeith,et al.  A comparative study of psychiatric symptoms in dementia with Lewy bodies and Parkinson's disease with and without dementia , 2001, International journal of geriatric psychiatry.

[14]  D. Aarsland,et al.  Risk of dementia in Parkinson’s disease , 2001, Neurology.

[15]  D. Aarsland,et al.  Risk of dementia in Parkinson’s disease: A community-based, prospective study , 2001 .

[16]  M Zappia,et al.  Consensus statement on the role of acute dopaminergic challenge in Parkinson's disease , 2001, Movement disorders : official journal of the Movement Disorder Society.

[17]  Murat Emre,et al.  Efficacy of rivastigmine in dementia with Lewy bodies: a randomised, double-blind, placebo-controlled international study , 2000, The Lancet.

[18]  H. Przuntek,et al.  Choice reaction time after levodopa challenge in parkinsonian patients , 2000, Journal of the Neurological Sciences.

[19]  C. Clarke,et al.  Systematic review of acute levodopa and apomorphine challenge tests in the diagnosis of idiopathic Parkinson's disease , 2000, Journal of neurology, neurosurgery, and psychiatry.

[20]  I G McKeith,et al.  The Clinician Assessment of Fluctuation and the One Day Fluctuation Assessment Scale. Two methods to assess fluctuating confusion in dementia. , 2000, The British journal of psychiatry : the journal of mental science.

[21]  J. Nutt.  Response to l-dopa in PD , 2000, Neurology.

[22]  T. Robbins,et al.  Chemical neuromodulation of frontal-executive functions in humans and other animals , 2000, Experimental Brain Research.

[23]  R. Dixon,et al.  Age-related cognitive deficits mediated by changes in the striatal dopamine system. , 2000, The American journal of psychiatry.

[24]  Juan Fernández-Ruiz,et al.  Spatial memory improvement by levodopa in parkinsonian MPTP-treated monkeys , 1999, Psychopharmacology.

[25]  J. Cummings,et al.  Range of neuropsychiatric disturbances in patients with Parkinson’s disease , 1999, Journal of neurology, neurosurgery, and psychiatry.

[26]  K. Kowdley,et al.  Cognitive impairment and intracranial calcification in chronic hypoparathyroidism. , 1999, The American journal of the medical sciences.

[27]  A. Arnsten.  Catecholamine modulation of prefrontal cortical cognitive function , 1998, Trends in Cognitive Sciences.

[28]  R. Schiffer,et al.  A review of Lewy body disease, an emerging concept of cortical dementia. , 1998, The Journal of neuropsychiatry and clinical neurosciences.

[29]  A. Flahault,et al.  Neuropsychological prediction of dementia in Parkinson’s disease , 1998, Journal of neurology, neurosurgery, and psychiatry.

[30]  K. Kosaka,et al.  Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB) , 1996, Neurology.

[31]  T. Aigner,et al.  Long-term cognitive impairment in MPTP-treated Rhesus monkeys , 1995, Neuroreport.

[32]  M. Mega,et al.  The Neuropsychiatric Inventory , 1994, Neurology.

[33]  Y. Agid,et al.  Impaired simultaneous cognitive task performance in Parkinson's disease , 1994, Neurology.

[34]  C D Marsden,et al.  The effect of withdrawal of dopaminergic medication on simple and choice reaction time and the use of advance information in Parkinson's disease. , 1992, Journal of neurology, neurosurgery, and psychiatry.

[35]  Keith Wesnes,et al.  The cognitive drug research computerized assessment system for demented patients: A validation study , 1991 .

[36]  W. Gibb,et al.  The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease. , 1988, Journal of neurology, neurosurgery, and psychiatry.

[37]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[38]  A. Bond,et al.  The use of analogue scales in rating subjective feelings , 1974 .

[39]  C. Marsden,et al.  l-Dopa withdrawal in Parkinson's disease selectively impairs cognitive performance in tests sensitive to frontal lobe dysfunction , 2005, Psychopharmacology.

[40]  Joseph E Parisi,et al.  Parkinson disease neuropathology: later-developing dementia and loss of the levodopa response. , 2002, Archives of neurology.

[41]  A. Bonnet,et al.  [The Unified Parkinson's Disease Rating Scale]. , 2000, Revue neurologique.

[42]  K. Jellinger,et al.  Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. , 1996, Neurology.

[43]  S. Fahn.  Members of the UPDRS Development Committee. Unified Parkinson's Disease Rating Scale , 1987 .

[44]  C. Marsden,et al.  Recent Developments in Parkinson's Disease , 1986 .