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

Abstract

Background: Levodopa (L-dopa) is the gold standard treatment of Parkinson’s disease (PD) 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 Ldopa 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 compare it to that in PD. Method: Baseline cognitive and motor function was assessed off L-dopa in patients with PD (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 Ldopa challenge with subsequent subjective and objective analysis of alertness, verbal recall, reaction times and accuracy. The same parameters were measured after three months on Ldopa to assess the prolonged effect. Results: Acute L-dopa challenge significantly 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 PD patients both with and without dementia on L-dopa at three months. However whilst PD patients also had better mean global cognitive function at this time, mean verbal attention and memory deteriorated and PDD patients had slower reaction times in some tests. No individual had a significant deterioration over this time. DLB patients did not experience any adverse cognitive or neuropsychiatric effects after three months of L-dopa therapy. Conclusion: The use of L-dopa in patients with parkinsonism with dementia does not adversely affect cognitive function. INTRODUCTION Dementia occurs six times more frequently in PD than in age-matched controls 1 whilst DLB is recognised as the second commonest form of degenerative dementia in an ageing population. 2 Early cognitive deficits are found in many patients with PD and are typically disorders of verbal memory, dysexecutive syndromes and visuospatial impairment. 3 Dementia in PD characteristically features prominent fluctuating attention and an overall clinical cognitive and neuropsychiatric profile similar to that seen in DLB. Visual hallucinations are common to both conditions and may reflect drug usage. 5 PDD and DLB are currently differentiated by the temporal evolution of motor and cognitive impairment with an arbitrary cut off of 12 months used to differentiate the two dementias. Distinguishing therapeutic features include neuroleptic sensitivity in DLB whilst early diminished verbal fluency and L-dopa induced confusion may be predictive of incident dementia in PD. L-dopa improves extrapyramidal signs in PD, PDD and to a variable extent in DLB but may have both beneficial and deleterious effects on cognitive performance and attention in PD. The influence of this drug on cognition in PDD and DLB has not, to our knowledge, been previously compared but notably, the apparent adverse influence of L-dopa on cognitive and behavioural features has lead to drug withdrawal in DLB. 9 Therefore, the treatment of group.bmj.com on November 5, 2016 Published by http://jnnp.bmj.com/ Downloaded from

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@inproceedings{Molloy2006TheEO, title={The effect of levodopa on cognitive function in Parkinson’s disease with and without dementia and dementia with Lewy bodies}, author={Sophie Molloy and E N Rowan and JT O’Brien and IG McKeith and Keith A Wesnes}, year={2006} }