3/4/2014 Overview • Journal and Researchers • Purpose of paper “Dopaminergic modulation of memory and affective processing in Parkinson • General Background Information depression” • Parkinson Disease (PD) • Depression within PD patients • Methods Lee X. Blonder, John T.Slevin, Richard J. Kryscio, Catherine A. • Testing Conditions Martin, Anders H.Andersen, Charles D. Smith and Frederick A.Schmitt • Results • Discussion Presented by Zoloo Enkhbayar and Adam Katz • Further Research BIONB 4410 Spring 2014 • UPenn, 1986 Lee X. • Professor at Department of Behavioral Science and The Journal Blonder Neurology and Sanders- • Psychiatry Research Journal Brown Center on Aging at published by Elsevier University of Kentucky • Impact Factor of 2.456 • Research on neural substrates according to Thomson Reuters of mental and emotional Journal Citation Reports 2013. processing in humans. • Reports on basic psychiatric • effects of strokes in right studies, clinical studies on hemisphere and associated “flat human behavior, clinical affect” on social and marital laboratory techniques, and behavior. advances in research • PI in “Neural Substrates of Facial and Lexical Emotion Using fMRI” methodology. 1997-2000 • Monthly Publication • “Brain and emotion relations in • 1961- Present culturally diverse populations.” (1999) John T. Richard J. • Professor at Sanders- Brown Center on Aging Slevin Kryscio • Chair in Department of • MD at West Virginia University Statistics and Biostatistics at (1975) University of Kentucky • Professor of Neurology, • Research and lab focus on Molecular and Biomedical providing expert advice on Pharmacology at University of data analysis to investigators Kentucky in Center on Aging • Research Associate at Morris K. • Longitudinal analysis of Markov Udall Parkinson’s Disease transition states, prevention in Research Center of Excellence Alzheimer’s disease, screening for early detection of ovarian cancer. • Interested in movement • Recent Publication: “Modeling the disorders, Parkinson’s disease, association between 43 different clinical and pathological variables and the severity of and deep brain stimulation cognitive impairment in a large autopsy cohort of elderly persons. (2010) 1
3/4/2014 Catherine Anders H. • Purdue University (1983) • Assistant Professor of A. Martin Andersen Anatomy and Neurobiology • Research focus on functional • MD from University of neuroimaging at Magnetic Kentucky (1976) Resonance Imaging & • Department of Psychiatry Spectroscopy Center at the University of • Overall detectability issues, Kentucky. mathematical modeling, data- pre and post • Research focus on child processing, etc. psychiatry. • Publications: “Functional • Research Publication: fMRI of apomorphine “Measurement of the Subjective Effects activation of the basal ganglia of Methylphenidate in 11- to 15-Year- Old Children with ADHD” (2007) in rhesus monkeys.” (2000) Charles D. Frederick A. • Robert P. and Mildred Smith Schmitt • Professor at Sanders- Brown Center Moore’s Professor in on Aging and Dept. of Neurology at Alzheimer’s Research in Dept. the University of Kentucky of Neurology at University of • Research Focus: Brain behaviors Kentucky. associations in neurological diseases • Research Focus: Application • Early detection of dementia of fMRI techniques in • Results of therapeutic predicting, quantifying, and interventions in Alzheimer’s disease diagnosing patients with • PI in clinical trials in Alzheimer’s Alzheimer’s disease other disease and Mild Cognitive related dementias. Impairment • Research Publications: • Research Publications: • “Comprehensive cognitive neurological assessment in • “Age and gender effects on human brain anatomy: voxel- stroke” (2009) based morphometric study in healthy elderly.” (2007) General Information Research Locations Parkinson's disease: a disorder of the University of Kentucky Dept of Neurology specializing in brain that leads to shaking (tremors) treating neuromuscular and neurological diseases and difficulty with walking, movement, (Parkinson's and stroke) through collaboration with: and coordination. • Kentucky Neuroscience Institute, Lexington, KY, USA • Sanders Brown Center on Aging, Lexington, KY, USA • Veterans Administration Medical Center, Lexington, KY USA 2
3/4/2014 Common symptoms include: • T.R.A.P.: Acronym for four primary PD symptoms: • • Decrease in facial expressions T remor: Shaking of limb (usually hand) while at rest • Difficulty starting and controlling movement • Loss or weakness of movement (paralysis) R igidity: Muscle stiffness and resistance to movement • Soft voice • Stiffness of the trunk, arms, or legs A kinesia/bradykinesia: • Tremor i) Inability to move spontaneously ii) Slowed movement P ostural instability: Impaired balance & coordination Secondary parkinsonism may be caused by health problems, including: • • AIDS • • Encephalitis • • Meningitis carbidopa/levodopa: Medication to relieve PD symptoms • Stroke • dopamine: Acts as one of the brain's messengers to signal • Diffuse Lewy body disease movement and maintain balance and coordination • Multiple system atrophy • dyskinesia : Abnormal involuntary movements • Progressive supranuclear palsy • PD: Parkinson’s disease • PWP: Person (or people) with Parkinson’s disease 3
3/4/2014 Veterans who develop Parkinson's disease and were exposed to Agent Orange or other herbicides during military service do not have to prove a connection between their disease and service to be eligible to receive VA health care and disability compensation. The Experiment Hypothesis Purpose of this experiment: - DSM-IV diagnostic criteria “..was to examine dopaminergic modulation of cognitive and affective task 7 major performance in depressed Parkinson’s Disease patients.” 3 minor DSM - V (2013) - Hoehn and Yahr scale 1-5 scale patients with Hypothesis: idiopathic PD eligible (<3) “..Withdrawal of dopaminergic medications is associated with increased - All treated with levodopa depressive mood as well as impairment in cognitive and affective task performance. carbidopa either alone or _______ ___ ___ combined with dopamine agonist Based on previous studies that point to dopaminergic pathways playing a role in supporting • working memory • affective (i.e. emotional) processing • dopamine agonist as an agent of alleviating depression in PD patients? 4
3/4/2014 The Experiment The Experiment • 3 visits to University of Kentucky Medical Center • Clinical evaluations based on the scores of the Unified Parkinson’s Disease • 1st Visit - consisted of cognitive tests and screenings Rating Scale; on and off-scores and motor UPDRS on and off scores. • DSM IV, Hamilton Depression Scale- 21 item version, Hoehn and Yahr Scale, neurological examination, and the Unified Parkinson’s Disease Rating Scale (UPDRS) • Prior to visit 2 or 3, patients stopped taking anti-PD medication after last dose of • Tests conducted during visit 2 or 3 were performed in an operationally previous evening (before midnight), allowing test to commence at minimum 9 hrs defined “off” condition after last dose • Anti-PD medication withheld for two times the lifespan of the half life of • On the other visit, patients took normal prescribed PD medication morning of the each drug. session. • Testing done prior to patient’s first regular dose of medication on the • Neuropsychological tests during visits 2 and 3 day of testing. • Hopkins Verbal Learning Test- Revised • Purdue Pegboard • Tests performed in an operationally “on” condition • Benton Test of Facial Recognition • Tests conducted within 1- 2 hours after PD patient’s first dose of medication of the day • Brief Visuospatial Memory Test - Revised • Wechsler Adult Intelligence Scale - Revised • Positive and Negative Affect Scale • A facial affect naming task consisting of photos with varied emotions. • National Adult Reading test Results Results • No statistical difference between dPD and non-dPD patients on • gender (chi square test) , There was a significant difference between depression and • education, Dementia Rating Scale scores (t-test) medication status for • Hoehn/Yahr stage of PD • Unified PD Rating Scale Motor/Tremor subscales • activities of daily living abilities • facial affect naming test (p=0.016) • % PD patients taking DA and levodopa daily dose • Significant differences btwn dPD and non-dPD patients • Hopkins Verbal Learning Revised Total Recall (p=0.011), • dPD patients younger and scored lower in National Adult delayed recall, and recognition subscores. Reading Test- Revised, measure of pre-morbid intelligence • dPD patients sig. more depressed on Hamilton depression and GDS. • Higher levels of depression in dPD patients while on dopaminergic medications • No statistical difference among non-dPD patients while on versus off medication 5
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