An Assessment of Cognition in Healthy Individuals to Inform the Assessment of Cognition in Transient Ischemic Attack Patients Danielle Lambert June 2017 Research submitted in partial fulfilment of the requirements for the degree of Doctor in Clinical Psychology (DClinPsy), Royal Holloway, University of London. 1 Abstract It is known that people can suffer from cognitive impairments following a TIA. Yet, currently, the methods for measuring this impairment are not very accurate or feasible. Whilst there is a gold standard battery to test for cognitive impairment, there are no up-to-date cohesive UK norms. Furthermore, current screening tools, it has been shown, have ceiling effects, and they are not sensitive in detecting mild cognitive impairments seen in a TIA profile. This study aims to explore whether a brief battery (BICAMS), which is used in MS could be an improvement on current tools. The sensitivity and specificity of the BICAMS were compared with a gold standard measure of cognitive impairment in TIA (NINDS-VCI; Hachinski et al., 2006). Furthermore, the study develops cohesive UK norms for the full NINDS-VCI battery to determine whether these would provide different outcomes to the available norm sources. Sixty-seven healthy UK participants were recruited to complete a 90-minute battery of tests – the MoCA, MMSE, BICAMS and NINDS-VCI 60-minute battery and a measure of estimated IQ, fatigue, anxiety and depression. Different norm sources were compared for the NINDS-VCI battery (published and current study). The numbers of participants falling below the expected level on the NINDS-VCI battery were compared with those identified by the three different screening tools. Finally, regression analyses were conducted to show which clinical and demographic factors contributed to performance on the NINDS-VCI and BICAMS. The study found that different numbers of participants fell below the expected levels on the NINDS-VCI battery, depending on which norm sources were used, with a trend towards more participants being identified with published norms. Years of 2 education was a significant predictor of NINDS-VCI scores and age was a significant unique contributor to BICAMS scores. BICAMS significantly correlated with NINDS-VCI performance and was found to be more sensitive and specific than the MoCA or MMSE. Relevant and up-to date cohesive norms are important to evaluate performance accurately on the NINDS-VCI –VCI 60-minute battery. BICAMS shows promise as a suitable screening tool to measure mild cognitive impairment after a TIA. Further research should focus on comparing TIA participants with UK matched controls. 3 List of Tables TABLE 1. DEMOGRAPHIC AND CLINICAL CHARACTERISTICS OF THE PILOT GROUP (N=94). ........................................ 60 TABLE 2. CLASSIFICATIONS AND SCORES ON THE FATIGUE SEVERITY RATING SCALE (FSS) ......................................... 61 TABLE 3. CLASSIFICATION AND SCORES ON THE HOSPITAL ANXIETY AND DEPRESSION SCALE (HADS) FOR PILOT DATA (N=94). .......................................................................................................................................... 62 TABLE 4. MEANS, STANDARD DEVIATIONS (SD) AND RANGES FOR SUB-DOMAINS OF EACH NEUROPSYCHOLOGICAL MEASURE IN THE PILOT GROUP (N=94). ............................................................................................... 64 TABLE 5. PARTICIPANTS FALLING BELOW ESTABLISHED CUT-OFF SCORES ON THE MONTREAL COGNITIVE ASSESSMENT (MOCA), MINI-MENTAL STATE EXAMINATION (MMSE) AND BRIEF INTERNATIONAL COGNITIVE ASSESSMENT MEASURE (BICAMS) IN THE PILOT GROUP (N=94). ............................................................................... 66 TABLE 6. SUMMARIES OF CORRELATIONS BETWEEN NEUROPSYCHOLOGICAL MEASURES AND FATIGUE, ANXIETY AND DEPRESSION FOR PILOT GROUP (N=94). ............................................................................................... 67 TABLE 7. ORDER OF TEST DELIVERY. ............................................................................................................... 80 TABLE 8. DEMOGRAPHIC AND CLINICAL CHARACTERISTICS OF THE 90-MINUTE BATTERY (N=67). ............................... 87 TABLE 9. CLASSIFICATION AND SCORES ON THE FATIGUE SEVERITY SCALE (FSS) FOR 90-MINUTE BATTERY (N=67). ...... 88 TABLE 10. CLASSIFICATION AND SCORES ON THE HOSPITAL ANXIETY AND DEPRESSION SCALE (HADS) FOR 90-MINUITE BATTERY (N=67). ............................................................................................................................. 90 TABLE 11. MEANS AND STANDARD DEVIATIONS FOR ALL NEUROPSYCHOLOGICAL TESTS WITHIN THE 90-MINUTE BATTERY (N=67). .......................................................................................................................................... 91 TABLE 12. COMPARISON OF MEANS ON BICAMS ACROSS DIFFERENT HEALTHY UK CONTROL SAMPLES. .................... 93 TABLE 13. PARTICIPANTS FALLING BELOW THE ESTABLISHED CUT-OFF SCORES ON THE MOCA, MMSE AND BICAMS (N=67). .......................................................................................................................................... 94 TABLE 14. CLASSIFICATION OF DIFFERENT PARTICIPANTS USING DIFFERENT IMPAIRMENT CRITERIA ............................ 96 TABLE 15. FREQUENCY OF PARTICIPANTS SCORING MORE THAN 1.5 SD BELOW THE MEAN ACROSS ALL NEUROPSYCHOLOGICAL MEASURE OF THE 90-MINUTE BATTERY FROM PUBLISHED NORMS AND MEANS AND NORMS OF THE CURRENT FROM THE CURRENT GROUP. ............................................................................ 97 TABLE 16. SUMMARY OF CORRELATIONS BETWEEN NEUROPSYCHOLOGICAL MEASURES AND CLINICAL AND DEMOGRAPHIC FACTORS IN THE 90-MINUTE BATTERY (N=67). ...................................................................................... 99 4 TABLE 17. SENSITIVITY AND SPECIFICITY FOR BICAMS, MOCA AND MMSE. ....................................................... 106 5 List of Figures FIGURE 1 ROC CURVE SENSITIVITY AND SPECIFICITY OF BICAMS COMPARED WITH NINDS-VCI BATTERY ................. 104 6 Table of Contents Abstract……………………………………………………………………………………………………….…….2 List of Tables……………………………………………………………………………………………………….4 List of Figures……………………………………………………………………………………………….…….6 1.1 Recommended Neuropsychological Testing in Stroke and TIA .............................. 13 1.1.1 Overview .............................................................................................. 13 1.1.2 The National Institute of Neurological Disorders and Stroke-Canadian Stroke and Vascular Cognitive Impairment Harmonisation Standards (NINDS-VCI). ..... 13 1.1.3 Current Norms and the Importance of Cohesive Norms ...................... 16 1.1.4 Summary ............................................................................................... 18 1.2 TIA and Mild Stroke Synopsis ................................................................................ 18 1.2.1 Overview .............................................................................................. 18 1.2.2 Epidemiology of TIA .............................................................................. 19 1.2.3 Prevalence of Cognitive Impairments after TIA .................................... 22 1.2.4 The Impact of Cognitive Impairments after TIA on Daily Life ............... 24 1.2.5 Treatment of TIA in UK NHS ................................................................. 25 1.2.6 The Case for Cognitive Screening ......................................................... 26 1.2.7 Summary .............................................................................................. 27 1.3 The Neuropsychological Profile of TIA and Mild Stroke ......................................... 28 1.3.1 Overview .............................................................................................. 28 1.3.2 Processing Speed .................................................................................. 28 1.3.3 Learning and Memory .......................................................................... 30 1.3.4 Executive Function ............................................................................... 32 1.3.5 Language .............................................................................................. 33 1.3.6 Visuospatial Deficits ............................................................................. 34 7 1.3.7 Summary .............................................................................................. 34 1.4 Challenges in Detecting Cognitive Impairment in TIA ............................................ 35 1.4.1 Overview .............................................................................................. 35 1.4.2 Heterogeneity of Studies ...................................................................... 35 1.4.3 Factors Impacting Cognitive Testing after a TIA ................................... 38 1.4.4 Summary .............................................................................................. 39 1.5 Evaluation of Current Screening Tools .................................................................. 40 1.5.1 Summary .............................................................................................. 43 1.6 Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) ............ 44 1.7 Summary and Synthesis ........................................................................................ 45 1.8 Study Aim and Hypotheses ..................................................................................