Cognitive deficits in Parkinson's disease: A cognitive neuroscience perspective

Progress in characterization of the nature, neural basis, and treatment of cognitive deficits in Parkinson's disease is reviewed from the perspective of cognitive neuroscience. An initial emphasis on fronto‐striatal executive deficits is surveyed along with the discoveries of disruption as well as remediation of certain impairments by dopaminergic mediation and their association with theories of reinforcement learning. Subsequent focus on large cohorts has revealed considerable heterogeneity in the cognitive impairments as well as a suggestion of at least two distinct syndromes, with the dopamine‐dependent fronto‐striatal deficits being somewhat independent of other signs commonly associated with Parkinson's disease dementia. The utility is proposed of a new, integrated cognitive neuroscience approach based on combining genetic and neuroimaging methodologies with neuropsychological and, ultimately, psychopharmacological approaches. © 2014 International Parkinson and Movement Disorder Society

[1]  T. Robbins,et al.  Striatal contributions to working memory: a functional magnetic resonance imaging study in humans , 2004, The European journal of neuroscience.

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

[3]  A. M. Owen,et al.  Visuospatial memory deficits at different stages of Parkinson's disease , 1993, Neuropsychologia.

[4]  T. Robbins,et al.  Enhanced or impaired cognitive function in Parkinson's disease as a function of dopaminergic medication and task demands. , 2001, Cerebral cortex.

[5]  T. Robbins,et al.  Evolution of cognitive dysfunction in an incident Parkinson's disease cohort. , 2007, Brain : a journal of neurology.

[6]  T. Robbins,et al.  Dopaminergic modulation of high-level cognition in Parkinson's disease: the role of the prefrontal cortex revealed by PET. , 2002, Brain : a journal of neurology.

[7]  N. Bohnen,et al.  Cortical cholinergic function is more severely affected in parkinsonian dementia than in Alzheimer disease: an in vivo positron emission tomographic study. , 2003, Archives of neurology.

[8]  S. Munshi,et al.  Neuropsychiatric non-motor aspects of Parkinson’s disease , 2003, Postgraduate medical journal.

[9]  Kenneth Hugdahl,et al.  Neuropsychological Profile of Patients with Parkinson’s Disease without Dementia , 2003, Dementia and Geriatric Cognitive Disorders.

[10]  M. Hallett,et al.  Mechanisms Underlying Dopamine-Mediated Reward Bias in Compulsive Behaviors , 2010, Neuron.

[11]  A. Lawrence,et al.  Factors influencing susceptibility to compulsive dopaminergic drug use in Parkinson disease , 2005, Neurology.

[12]  M. Egan,et al.  Catechol O-methyltransferase val158-met genotype and individual variation in the brain response to amphetamine , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[13]  Trevor W. Robbins,et al.  Time-limited modulation of appetitive Pavlovian memory by D1 and NMDA receptors in the nucleus accumbens , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[14]  C. Marsden,et al.  The performance on learning tasks of patients in the early stages of Parkinson's disease , 1989, Neuropsychologia.

[15]  T. Robbins,et al.  A role for mesencephalic dopamine in activation: commentary on Berridge (2006) , 2007, Psychopharmacology.

[16]  V. Haroutunian,et al.  The neuropathological basis for depression in Parkinson's disease. , 2009, Parkinsonism & related disorders.

[17]  Yves Agid,et al.  A subcortico-cortical cholinergic system is affected in Parkinson's disease , 1983, Brain Research.

[18]  W. Todd Maddox,et al.  Rule-based category learning in patients with Parkinson's disease , 2009, Neuropsychologia.

[19]  T. Robbins,et al.  Planning ability in Parkinson's disease is influenced by the COMT val158met polymorphism , 2004, Movement disorders : official journal of the Movement Disorder Society.

[20]  J. Saint-Cyr,et al.  Procedural learning and neostriatal dysfunction in man. , 1988, Brain : a journal of neurology.

[21]  M. Gluck,et al.  l-dopa impairs learning, but spares generalization, in Parkinson's disease , 2006, Neuropsychologia.

[22]  A. Lawrence,et al.  Apathy blunts neural response to money in Parkinson's disease , 2011, Social neuroscience.

[23]  T. Robbins,et al.  Contrasting mechanisms of impaired attentional set-shifting in patients with frontal lobe damage or Parkinson's disease. , 1993, Brain : a journal of neurology.

[24]  C. E. Polkey,et al.  Impaired dimensional selection but intact use of reward feedback during visual discrimination learning in Parkinson's disease , 2006, Neuropsychologia.

[25]  Roshan Cools,et al.  Aberrant reward processing in Parkinson's disease is associated with dopamine cell loss , 2012, NeuroImage.

[26]  Karl J. Friston,et al.  Frontal, midbrain and striatal dopaminergic function in early and advanced Parkinson's disease A 3D [(18)F]dopa-PET study. , 1999, Brain : a journal of neurology.

[27]  D. Eckstein,et al.  Parkinson's disease and dopaminergic therapy—differential effects on movement, reward and cognition , 2008, Brain : a journal of neurology.

[28]  T R Ten Have,et al.  Atomoxetine for depression and other neuropsychiatric symptoms in Parkinson disease , 2010, Neurology.

[29]  Catherine E. Myers,et al.  A neural model of hippocampal–striatal interactions in associative learning and transfer generalization in various neurological and psychiatric patients , 2010, Brain and Cognition.

[30]  T. Robbins,et al.  Reliance on habits at the expense of goal-directed control following dopamine precursor depletion , 2011, Psychopharmacology.

[31]  A. Dagher,et al.  The role of the striatum and hippocampus in planning: a PET activation study in Parkinson's disease. , 2001, Brain : a journal of neurology.

[32]  Thomas Foltynie,et al.  The distinct cognitive syndromes of Parkinson's disease: 5 year follow-up of the CamPaIGN cohort. , 2009, Brain : a journal of neurology.

[33]  M. Gluck,et al.  Dissociating Hippocampal versus Basal Ganglia Contributions to Learning and Transfer , 2003, Journal of Cognitive Neuroscience.

[34]  L. Squire.  Memory systems of the brain: A brief history and current perspective , 2004, Neurobiology of Learning and Memory.

[35]  A. Faure,et al.  Lesion to the Nigrostriatal Dopamine System Disrupts Stimulus-Response Habit Formation , 2005, The Journal of Neuroscience.

[36]  Richard B. Ivry,et al.  Rule-based categorization deficits in focal basal ganglia lesion and Parkinson's disease patients , 2010, Neuropsychologia.

[37]  C. Marsden,et al.  'Frontal' cognitive function in patients with Parkinson's disease 'on' and 'off' levodopa. , 1988, Brain : a journal of neurology.

[38]  Jennifer A. Mangels,et al.  A Neostriatal Habit Learning System in Humans , 1996, Science.

[39]  Adrian M. Owen,et al.  Visuo-spatial short-term recognition memory and learning after temporal lobe excisions, frontal lobe excisions or amygdalo-hippocampectomy in man , 1995, Neuropsychologia.

[40]  C. Marsden,et al.  Internal versus external cues and the control of attention in Parkinson's disease. , 1988, Brain : a journal of neurology.

[41]  M. Gluck,et al.  Reward-learning and the novelty-seeking personality: a between- and within-subjects study of the effects of dopamine agonists on young Parkinson's patients. , 2009, Brain : a journal of neurology.

[42]  M. Egan,et al.  The BDNF val66met Polymorphism Affects Activity-Dependent Secretion of BDNF and Human Memory and Hippocampal Function , 2003, Cell.

[43]  K. Marder,et al.  Memory and executive function impairment predict dementia in Parkinson's disease , 2002, Movement disorders : official journal of the Movement Disorder Society.

[44]  F. Boller,et al.  Visuospatial impairment in Parkinson's disease. Role of perceptual and motor factors. , 1984, Archives of neurology.

[45]  T. Robbins,et al.  Dopaminergic basis for deficits in working memory but not attentional set-shifting in Parkinson's disease , 2005, Neuropsychologia.

[46]  M. Pessiglione,et al.  Pharmacological modulation of subliminal learning in Parkinson's and Tourette's syndromes , 2009, Proceedings of the National Academy of Sciences.

[47]  Michael J. Frank,et al.  By Carrot or by Stick: Cognitive Reinforcement Learning in Parkinsonism , 2004, Science.

[48]  H. E. Rosvold,et al.  Cognitive deficit caused by regional depletion of dopamine in prefrontal cortex of rhesus monkey. , 1979, Science.

[49]  V Kaasinen,et al.  Increased frontal [(18)F]fluorodopa uptake in early Parkinson's disease: sex differences in the prefrontal cortex. , 2001, Brain : a journal of neurology.

[50]  C. Marsden,et al.  'Subcortical dementia': the neuropsychological evidence. , 1988, Neuroscience.

[51]  K. Jellinger,et al.  Pathology of Parkinson's disease. Changes other than the nigrostriatal pathway. , 1991, Molecular and chemical neuropathology.

[52]  J. O'Doherty,et al.  Annals of the New York Academy of Sciences Contributions of the Ventromedial Prefrontal Cortex to Goal-directed Action Selection , 2022 .

[53]  H. Braak,et al.  Staging of brain pathology related to sporadic Parkinson’s disease , 2003, Neurobiology of Aging.

[54]  M. Gluck,et al.  Role of the basal ganglia in category learning: how do patients with Parkinson's disease learn? , 2004, Behavioral neuroscience.

[55]  T. Robbins,et al.  The BDNF Val66Met polymorphism has a gender specific influence on planning ability in Parkinson’s disease , 2005, Journal of Neurology.

[56]  D. Aarsland,et al.  A systematic review of prevalence studies of dementia in Parkinson's disease , 2005, Movement disorders : official journal of the Movement Disorder Society.

[57]  A J Lees,et al.  Bradyphrenia in Parkinson's disease and psychomotor retardation in depressive illness. An experimental study. , 1987, Brain : a journal of neurology.

[58]  Roshan Cools,et al.  Habitual versus Goal-directed Action Control in Parkinson Disease , 2011, Journal of Cognitive Neuroscience.

[59]  R. H. Perry,et al.  Acetylcholine and Hallucinations - Disease-Related Compared to Drug-Induced Alterations in Human Consciousness , 1995, Brain and Cognition.

[60]  J. Saint-Cyr,et al.  Parkinson's disease. Cognitive changes in relation to treatment response. , 1987, Brain : a journal of neurology.

[61]  Angie A. Kehagia,et al.  Neuropsychological and clinical heterogeneity of cognitive impairment and dementia in patients with Parkinson's disease , 2010, The Lancet Neurology.

[62]  S. Kapur.  Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia. , 2003, The American journal of psychiatry.

[63]  T. Robbins,et al.  Heterogeneity of Parkinson’s disease in the early clinical stages using a data driven approach , 2005, Journal of Neurology, Neurosurgery & Psychiatry.

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

[65]  Melissa Gerstenhaber,et al.  Atomoxetine for the treatment of executive dysfunction in Parkinson's disease: A pilot open‐label study , 2009, Movement disorders : official journal of the Movement Disorder Society.

[66]  T. Robbins,et al.  The CamPaIGN study of Parkinson's disease: 10-year outlook in an incident population-based cohort , 2013, Journal of Neurology, Neurosurgery & Psychiatry.

[67]  M. Ban,et al.  Tau and α‐synuclein in susceptibility to, and dementia in, Parkinson's disease , 2007 .

[68]  James Parkinson,et al.  An essay on the shaking palsy. 1817. , 2002, The Journal of neuropsychiatry and clinical neurosciences.

[69]  H J Sagar,et al.  Remote memory function in Alzheimer's disease and Parkinson's disease. , 1988, Brain : a journal of neurology.

[70]  T. Robbins,et al.  Probabilistic learning and reversal deficits in patients with Parkinson’s disease or frontal or temporal lobe lesions: possible adverse effects of dopaminergic medication , 2000, Neuropsychologia.

[71]  R. Dolan,et al.  Neural systems engaged by planning: a PET study of the Tower of London task , 1996, Neuropsychologia.

[72]  T. Robbins,et al.  The cognitive ability of an incident cohort of Parkinson's patients in the UK. The CamPaIGN study. , 2004, Brain : a journal of neurology.

[73]  M. Rieger,et al.  Inhibition of ongoing responses in patients with Parkinson’s disease , 2004, Journal of Neurology, Neurosurgery & Psychiatry.

[74]  Mark A. Gluck,et al.  A Neurocomputational Model of Dopamine and Prefrontal–Striatal Interactions during Multicue Category Learning by Parkinson Patients , 2011, Journal of Cognitive Neuroscience.

[75]  P. Dayan,et al.  Dopamine and performance in a reinforcement learning task: evidence from Parkinson's disease. , 2012 .

[76]  S. Kish,et al.  Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson's disease. Pathophysiologic and clinical implications. , 1988, The New England journal of medicine.

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

[78]  T. Robbins,et al.  A comparative study of visuospatial memory and learning in Alzheimer-type dementia and Parkinson's disease. , 1988, Brain : a journal of neurology.

[79]  G. E. Alexander,et al.  Parallel organization of functionally segregated circuits linking basal ganglia and cortex. , 1986, Annual review of neuroscience.

[80]  A. Lees,et al.  Cognitive deficits in the early stages of Parkinson's disease. , 1983, Brain : a journal of neurology.

[81]  James M. Shine,et al.  Fronto-striatal gray matter contributions to discrimination learning in Parkinson's disease , 2013, Front. Comput. Neurosci..

[82]  Michael J. Frank,et al.  Dynamic Dopamine Modulation in the Basal Ganglia: A Neurocomputational Account of Cognitive Deficits in Medicated and Nonmedicated Parkinsonism , 2005, Journal of Cognitive Neuroscience.

[83]  T. Robbins,et al.  Characterizing mild cognitive impairment in incident Parkinson disease , 2014, Neurology.

[84]  Y. Agid,et al.  Reduction of cortical dopamine, noradrenaline, serotonin and their metabolites in Parkinson's disease , 1983, Brain Research.

[85]  R. Cools.  Dopaminergic modulation of cognitive function-implications for l-DOPA treatment in Parkinson's disease , 2006, Neuroscience & Biobehavioral Reviews.

[86]  M. Gluck,et al.  Dopaminergic Drugs Modulate Learning Rates and Perseveration in Parkinson's Patients in a Dynamic Foraging Task , 2009, The Journal of Neuroscience.

[87]  V. Chan‐Palay,et al.  Alterations in catecholamine neurons of the locus coeruleus in senile dementia of the Alzheimer type and in Parkinson's disease with and without dementia and depression , 1989, The Journal of comparative neurology.

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

[89]  W. Schultz.  Getting Formal with Dopamine and Reward , 2002, Neuron.

[90]  A. C. Roberts,et al.  Impaired extra-dimensional shift performance in medicated and unmedicated Parkinson's disease: Evidence for a specific attentional dysfunction , 1989, Neuropsychologia.

[91]  T. Robbins,et al.  L-DOPA Disrupts Activity in the Nucleus Accumbens during Reversal Learning in Parkinson's Disease , 2007, Neuropsychopharmacology.

[92]  J. Saint-Cyr,et al.  Frontal lobe dysfunction in Parkinson's disease. The cortical focus of neostriatal outflow. , 1986, Brain : a journal of neurology.

[93]  H J Sagar,et al.  Temporal ordering and short-term memory deficits in Parkinson's disease. , 1988, Brain : a journal of neurology.

[94]  T. Robbins,et al.  Catechol O-Methyltransferase val158met Genotype Influences Frontoparietal Activity during Planning in Patients with Parkinson's Disease , 2007, The Journal of Neuroscience.

[95]  A. Dickinson,et al.  Disrupted prediction-error signal in psychosis: evidence for an associative account of delusions. , 2007, Brain : a journal of neurology.

[96]  Michael X. Cohen,et al.  A Role for Dopamine in Temporal Decision Making and Reward Maximization in Parkinsonism , 2008, The Journal of Neuroscience.

[97]  B. Dubois,et al.  Motivation, reward, and Parkinson’s disease: influence of dopatherapy , 2002, Neuropsychologia.

[98]  E. Sullivan,et al.  Cognitive impairment in early, untreated Parkinson's disease and its relationship to motor disability. , 1991, Brain : a journal of neurology.

[99]  D. Shohamy,et al.  The role of the basal ganglia in learning and memory: Insight from Parkinson’s disease , 2011, Neurobiology of Learning and Memory.

[100]  M. D’Esposito,et al.  Reversal learning in Parkinson's disease depends on medication status and outcome valence , 2006, Neuropsychologia.

[101]  C. Marsden,et al.  Fronto-striatal cognitive deficits at different stages of Parkinson's disease. , 1992, Brain : a journal of neurology.

[102]  S. Lewis,et al.  The role of learned irrelevance in attentional set-shifting impairments in Parkinson's disease. , 2006, Neuropsychology.

[103]  M. Piccirilli,et al.  Frontal lobe dysfunction in Parkinson's disease: prognostic value for dementia? , 1989, European neurology.

[104]  K. Berridge.  The debate over dopamine’s role in reward: the case for incentive salience , 2007, Psychopharmacology.

[105]  B. Balleine,et al.  Human and Rodent Homologies in Action Control: Corticostriatal Determinants of Goal-Directed and Habitual Action , 2010, Neuropsychopharmacology.

[106]  R. Dolan,et al.  Dopamine Enhances Model-Based over Model-Free Choice Behavior , 2012, Neuron.

[107]  P. Smittenaar,et al.  Decomposing effects of dopaminergic medication in Parkinson’s disease on probabilistic action selection – learning or performance? , 2012, The European journal of neuroscience.