Neuropsychological Aspects of Apathy in Parkinson's Disease
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Neuropsychological Aspects of Apathy in Parkinson's Disease Graham Christopher Pluck Thesis submitted in fulfilment of the requirements for the degree of Doctor of Philosophy The Institute of Neurology University College London ProQuest Number: U643345 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest. ProQuest U643345 Published by ProQuest LLC(2016). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code. Microform Edition © ProQuest LLC. ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 Abstract Patients with Parkinson's disease (PD) are often described as failing to show a normal range of goal directed behaviours. Among explanations that have been proposed for this apathy are effects of personality, depression and disability. This thesis investigated the phenomena from a neuropsychological perspective. It was found that PD patients are significantly more apathetic than equally disabled osteoarthritis patients, indicating that their apathy is a primary symptom of the disease. No evidence was found relating apathy in PD to personality, depression, anxiety or anhedonia. It was found that the PD patients with high levels of apathy were impaired on cognitive tests, but only those that required executive control. Using visual-search tasks it was shown that this association could not be accounted for by a reduction in effort applied. It was also shown that attention to novelty or curiosity arousing stimuli were not reduced in PD patients with apathy. However, it was shown that they persevered on task for longer than patients with low apathy in conditions in which there was no prompt to stop. This may be due to a willed action deficit that retards actions in situations that lack formal guidance. To test this hypothesis further, a task was developed to record response times for stimuli and will driven actions and was validated in a single case study of an akinetic patient. Although PD patients with high apathy appeared to show a willed action deficit, it was also found that other executive impairments might confound interpretation. It is concluded that apathy in PD may be an expression of executive impairment, but further research is needed to assess the relative contributions of cognitive and motivational dysfunction. There are significant implications to the findings, including the conceptualisation of apathy as a symptom and the potential for therapeutic interventions with apathetic patients. Contents ABSTRACT 2 CONTENTS 3 LIST OF TABLES 7 LIST OF FIGURES 9 ACKNOWLEDGEMENTS 11 THE EXTENT OF MY PERSONAL CONTRIBUTION 12 CHAPTER 1: PARKINSON’S DISEASE 13 Basic Features of Parkinson’s Disease 13 Anatomy and Connections of the Basal Ganglia 22 Non-Motor Aspects of Parkinson’s Disease 30 The Significance of Apathy in Parkinson’s Disease 45 CHAPTER 2: THE CONCEPTS OF MOTIVATION, THE WILL AND GOAL DIRECTED BEHAVIOUR 48 Cognitive Models of Motivation, the Will and Goal Directed Behaviour 51 A Framework for Understanding Goal Directed Behaviour 53 Patterns of Disturbance of Goal Directed Behaviour 58 Clinical Syndromes Related to Reduced Goal Directed Behaviour 60 Diseases Associated with Symptoms of Reduced Goal Directed Behaviour 69 Approaches to the Study of Goal Directed Behaviour 75 CHAPTER 3: DISABILITY, COGNITION, MOOD AND PERSONALITY IN RELATION TO APATHY IN PARKINSON'S DISEASE 90 Introduction 90 Method 95 Results of Disability and Apathy 99 Discussion of Disability and Apathy 103 Results of Cognition and Apathy 106 Discussion of Cognition and Apathy 114 Results of Mood and Apathy 119 Discussion of Mood and Apathy 124 Results of Personality and Apathy 126 Discussion of Personality and Apathy 129 General Discussion 132 CHAPTER 4: EFFORT APPLIED AND INFORMATION PROCESSING SPEED IN PARKINSON'S DISEASE PATIENTS WITH APATHY 139 Introduction 139 Method 145 Results 148 Discussion 156 CHAPTER 5: ATTENTION TO NOVEL STIMULI AND ITS RELATIONSHIP TO APATHY IN PARKINSON'S DISEASE 162 Introduction 162 Method 166 Results 171 Discussion 180 CHAPTER 6: CURIOSITY AND ITS RELATIONSHIP TO APATHY IN PARKINSON'S DISEASE 187 Introduction 187 Pilot Study: Method and Results 191 Main Study: Method 192 Results 198 Discussion 205 CHAPTER 7: WILLED AND STIMULUS DRIVEN ACTION: A SINGLE CASE STUDY OF AN AKINETIC PATIENT 212 Introduction 212 Case history 217 Neuropsychological examination 218 Experiment 1 223 Results of Experiment 1 226 Discussion of Experiment 1 229 Experiment 2 230 Results of Experiment 2 233 Discussion of Experiment 2 234 Experiment 3 236 Results of Experiment 3 237 Discussion of Experiment 3 238 General Discussion 239 CHAPTER 8: WILLED ACTION, EXECUTIVE FUNCTION AND APATHY IN PARKINSON'S DISEASE 247 Introduction 247 Experiment 1 256 Results of Experiment 1 259 Discussion of Experiment 1 267 Experiment 2 269 Results of Experiment 2 270 Discussion of Experiment 2 273 General Discussion 274 CHAPTERS: GENERAL DISCUSSION 283 Summary of Findings 283 Potential Limitations of the Studies 288 Implications for Cognitive Neuroscience 290 A Note on Neurophilosophy 298 Implications for Therapeutic Interventions 299 Implications for the Concept of Apathy 303 Suggestions for Future Research 304 Conclusions 306 REFERENCES 307 APPENDIX A: GUIDE TO ABBREVIATIONS USED IN THIS THESIS 360 APPENDIX B: STRUCTURE AND ADMINISTRATION OF THE APATHY EVALUATION SCALE 362 APPENDIX C: DETAILS OF THE HOEHN AND YAHR PARKINSON'S DISEASE PROGRESSION SCALE 365 APPENDIX D: DETAILS OF THE ADL ASSESMENT USED IN CHAPTER 3 367 APPENDIX E: DESCRIPTION AND SCOREING METHODS OF COGNITIVE ASSESMENTS USED IN CHAPTER 3 369 Verbal Fluency (FAS) 369 Category Fluency 369 Stroop Task 370 Wisconsin Card Sorting Test (WCST) 371 CAMCOG and MMSE 372 APPENDIX F: COMPLETION RATES OF ASSESSMENTS DESCRIBED IN CHAPTER 3 376 List of Tables CHAPTER 2 Table 1: Neurological diseases associated with GDB impairment. 74 CHAPTER 3 Table 2: Percentage of the PD-HA and PD LA group members at each Hoehn and Yahr stage. 102 Table 3: Correlational statistics for the relationship between apathy and MMSE and CAMCOG derived measures in the PD patients. 109 Table 4: Means (and SDs) for the PD-HA, PD-LA and OA groups on tests of executive skills. 112 Table 5: Correlational statistics for the relationship between apathy and executive function in the PD patients. 114 Table 6: Mean (and SD) scores on anhedonia (Likert scale), depression and anxiety for the PD-HA, PD-LA and OA groups. 122 Table 7: Correlational statistics for the relationship between apathy and mood variables in the PD patients. 124 Table 8: Mean (and SD) scores on the TPQ for the PD-HA, PD-LA and OA patients. 127 Table 9: Correlational statistics for the relationship between apathy and personality variables in the PD patients. 128 Table 10: Correlation values for personality scores and cognitive measures in the full PD sample. 128 CHAPTER 4 Table 11 : Means (and SDs) for the characteristics of the PD-HA and PD-LA patients. 147 Table 12: Linear regressions of response times on display size for the parallel search task. 151 Table 13: Mean number (and SE) of errors made in the parallel search task. 152 Table 14: Linear regression of response times on display size in the serial search task. 155 Table 15: Mean number (and SE) of errors made in the serial search task. 156 CHAPTER 5 Table 16: Means (and SDs) for the characteristics of the PD-HA and PD-LA patients. 170 Table 17: Response times (and SEMs) for the PD-HA, PD-LA and control subjects in the novelty attention task. 173 Table 18: Mean and SEM number of errors made by each group and the percentage of blank trials that were affected. 176 Table 19: Correlations between the distracting effect of the novel stimuli and psychometrically derived scores of personality and apathy. 180 CHAPTER 6 Table 20: Means (and SDs) for the characteristics of the PD-HA and PD-LA patients. 194 Table 21: Mean (and SD) of the total errors made in each condition of the word search task by the PD-HA, PD-LA and control subjects. 199 Table 22: Correlations between apathy scores and response times in the word search task. 204 Table 23: Correlations between personality trait scores and response times in the word search task. 205 CHAPTER 7 Table 24: Performance by TYR on standard tests of executive performance. 222 Table 25: Order and temporal sequence of events in the delay detection task. 232 CHAPTER 8 Table 26: Means (and SDs) for the characteristics of the PD-HA and PD-LA patients. 258 Table 27: Correlational r (and p) values for the analysis between response times on the will driven, stimulus driven and the difference between the two with executive function test scores. 266 Table 28: Correlational r (and p) values for the analysis between response times on the will driven, stimulus driven and the difference between the two with personality scores. 267 Table 29: Correlation statistics for the relationship between errors made in the duration judgement experiment and executive task performance. 273 List of Figures CHAPTER 1 Figure 1: The five proposed cortical-basal ganglia-thalamic-cortical loops from Alexander et al. (1986). 28 CHAPTER 2 Figure 2: A Framework for interpreting goal directed behaviour. 55 CHAPTER 3 Figure 3: The distribution of AES-R scores in the PD and OA groups. 101 Figure 4: Mean scores (and SEMs) on the sub-scales of the CAMCOG examination for the PD-HA, PD-LA and OA patients. 108 Figure 5: The distribution of binary SHPS scores for the PD-HA, PD-LA and OA groups.