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Targeting impulsivity in Parkinson's disease using atomoxetine

Kehagia, Angie A; Housden, Charlotte R; Regenthal, Ralf; Barker, Roger A LU ; Müller, Ulrich; Rowe, James; Sahakian, Barbara J and Robbins, Trevor W (2014) In Brain 137(Pt 7). p.97-1986
Abstract

Noradrenergic dysfunction may play a significant role in cognition in Parkinson's disease due to the early degeneration of the locus coeruleus. Converging evidence from patient and animal studies points to the role of noradrenaline in dopaminergically insensitive aspects of the parkinsonian dysexecutive syndrome, yet the direct effects of noradrenergic enhancement have not to date been addressed. Our aim was to directly investigate these, focusing on impulsivity during response inhibition and decision making. To this end, we administered 40 mg atomoxetine, a selective noradrenaline re-uptake inhibitor to 25 patients with Parkinson's disease (12 female /13 male; 64.4 ± 6.9 years old) in a double blind, randomized, placebo controlled... (More)

Noradrenergic dysfunction may play a significant role in cognition in Parkinson's disease due to the early degeneration of the locus coeruleus. Converging evidence from patient and animal studies points to the role of noradrenaline in dopaminergically insensitive aspects of the parkinsonian dysexecutive syndrome, yet the direct effects of noradrenergic enhancement have not to date been addressed. Our aim was to directly investigate these, focusing on impulsivity during response inhibition and decision making. To this end, we administered 40 mg atomoxetine, a selective noradrenaline re-uptake inhibitor to 25 patients with Parkinson's disease (12 female /13 male; 64.4 ± 6.9 years old) in a double blind, randomized, placebo controlled design. Patients completed an extensive battery of neuropsychological tests addressing response inhibition, decision-making, attention, planning and verbal short term memory. Atomoxetine improved stopping accuracy on the Stop Signal Task [F(1,19) = 4.51, P = 0.047] and reduced reflection impulsivity [F(1,9) = 7.86, P = 0.02] and risk taking [F(1,9) = 9.2, P = 0.01] in the context of gambling. The drug also conferred effects on performance as a function of its measured blood plasma concentration: it reduced reflection impulsivity during information sampling [adjusted R(2) = 0.23, F(1,16) = 5.83, P = 0.03] and improved problem solving on the One Touch Stockings of Cambridge [adjusted R(2) = 0.29, F(1,17) = 8.34, P = 0.01]. It also enhanced target sensitivity during sustained attention [F(1,9) = 5.33, P = 0.046]. The results of this exploratory study represent the basis of specific predictions in future investigations on the effects of atomoxetine in Parkinson's disease and support the hypothesis that targeting noradrenergic dysfunction may represent a new parallel avenue of therapy in some of the cognitive and behavioural deficits seen in the disorder.

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Contribution to journal
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published
keywords
Adrenergic Uptake Inhibitors, Aged, Atomoxetine Hydrochloride, Attention, Decision Making, Double-Blind Method, Female, Games, Experimental, Humans, Impulsive Behavior, Inhibition (Psychology), Male, Memory, Short-Term, Middle Aged, Neuropsychological Tests, Parkinson Disease, Propylamines, Reaction Time, Verbal Learning, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
in
Brain
volume
137
issue
Pt 7
pages
12 pages
publisher
Oxford University Press
external identifiers
  • scopus:84903534598
ISSN
1460-2156
DOI
10.1093/brain/awu117
language
English
LU publication?
no
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82f7ec0a-c34f-47a7-bd04-f165fd2bec26
date added to LUP
2016-11-24 15:04:32
date last changed
2017-10-01 05:26:24
@article{82f7ec0a-c34f-47a7-bd04-f165fd2bec26,
  abstract     = {<p>Noradrenergic dysfunction may play a significant role in cognition in Parkinson's disease due to the early degeneration of the locus coeruleus. Converging evidence from patient and animal studies points to the role of noradrenaline in dopaminergically insensitive aspects of the parkinsonian dysexecutive syndrome, yet the direct effects of noradrenergic enhancement have not to date been addressed. Our aim was to directly investigate these, focusing on impulsivity during response inhibition and decision making. To this end, we administered 40 mg atomoxetine, a selective noradrenaline re-uptake inhibitor to 25 patients with Parkinson's disease (12 female /13 male; 64.4 ± 6.9 years old) in a double blind, randomized, placebo controlled design. Patients completed an extensive battery of neuropsychological tests addressing response inhibition, decision-making, attention, planning and verbal short term memory. Atomoxetine improved stopping accuracy on the Stop Signal Task [F(1,19) = 4.51, P = 0.047] and reduced reflection impulsivity [F(1,9) = 7.86, P = 0.02] and risk taking [F(1,9) = 9.2, P = 0.01] in the context of gambling. The drug also conferred effects on performance as a function of its measured blood plasma concentration: it reduced reflection impulsivity during information sampling [adjusted R(2) = 0.23, F(1,16) = 5.83, P = 0.03] and improved problem solving on the One Touch Stockings of Cambridge [adjusted R(2) = 0.29, F(1,17) = 8.34, P = 0.01]. It also enhanced target sensitivity during sustained attention [F(1,9) = 5.33, P = 0.046]. The results of this exploratory study represent the basis of specific predictions in future investigations on the effects of atomoxetine in Parkinson's disease and support the hypothesis that targeting noradrenergic dysfunction may represent a new parallel avenue of therapy in some of the cognitive and behavioural deficits seen in the disorder.</p>},
  author       = {Kehagia, Angie A and Housden, Charlotte R and Regenthal, Ralf and Barker, Roger A and Müller, Ulrich and Rowe, James and Sahakian, Barbara J and Robbins, Trevor W},
  issn         = {1460-2156},
  keyword      = {Adrenergic Uptake Inhibitors,Aged,Atomoxetine Hydrochloride,Attention,Decision Making,Double-Blind Method,Female,Games, Experimental,Humans,Impulsive Behavior,Inhibition (Psychology),Male,Memory, Short-Term,Middle Aged,Neuropsychological Tests,Parkinson Disease,Propylamines,Reaction Time,Verbal Learning,Journal Article,Randomized Controlled Trial,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {Pt 7},
  pages        = {97--1986},
  publisher    = {Oxford University Press},
  series       = {Brain},
  title        = {Targeting impulsivity in Parkinson's disease using atomoxetine},
  url          = {http://dx.doi.org/10.1093/brain/awu117},
  volume       = {137},
  year         = {2014},
}