Development and Validation of the “Addenbrooke’s Cognitive Examination” as a Screening Test for Mild Cognitive Impairment in Hearing Impaired Individuals Courtney North D.Clin.Psy. thesis (Volume 1), 2020 University College London 1 UCL Doctorate in Clinical Psychology Thesis declaration form I confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis. Signature: Name: Courtney North Date: 19th June 2020 2 Overview This thesis examined the utility of different neuropsychological tests in the detection of cognitive impairment in older adult populations. Limitations, directions for research and clinical implications have been highlighted. Part One: Meta-Analysis - The literature review sought to identify, for the first time, the cognitive tests that best discriminate between Posterior Cortical Atrophy (PCA) and typical Alzheimer’s Disease (tAD), as well as PCA and healthy controls (HC). The most discriminating cognitive tests for PCA and tAD presentations were found to be measures of perception and verbal memory. Part Two: Empirical Paper - The objectives were to develop a hearing-impaired version of the Addenbrooke’s Cognitive Examination (HI-ACE-III) and assess whether it can be used as a screening tool for mild cognitive impairment (MCI), as well as accurately distinguish cognitively impaired people from healthy controls. It was found to be a sensitive and specific screening tool, with a good ability to diagnose individuals with and without MCI in hearing-impaired populations. This was a joint project with Nattawan Utoomprurkporn, PhD student and qualified audiologist, and Mary Heatley, Trainee Clinical Psychologist Part Three: Critical Appraisal - The critical appraisal, considers the challenges of the project, including the barriers to recruitment, the navigation of the scientist- practitioner role and the impact of conducting research during a pandemic. It offers personal reflections on the research process and considers how my personal experiences fit with the issues that are commonly cited in the literature. 3 Impact Statement The present findings indicate that researchers and clinicians could benefit from updating their approach to neuropsychological testing in certain aging populations. In line with increasing recognition for the role of neuropsychology in differential diagnosis, this study highlights the need for nuanced approaches in rarer dementias and in older adults with sensory impairments. The literature review took a meta-analytic approach to identify cognitive tests that best discriminate between Posterior Cortical Atrophy (PCA) and typical Alzheimer’s Disease (tAD), as well as PCA and healthy controls (HC). When compared with other dementias, PCA is relatively under-researched, and until recently, the majority of research into PCA has concentrated around establishing the neuroimaging profile(s) of those with the diagnosis. The academic contributions of this review are therefore towards the understanding of the role of neuropsychology in the diagnosis of PCA. Outside of academia, this review recognises the need to understand the tests that are best suited to distinguishing between dementia subtypes, and their importance in improving the accuracy of clinical classification or clinical diagnosis. At present there is no established common framework for the selection of cognitive outcome measures for trials involving individuals with PCA. Findings from this review suggest that measures of perception and delayed & immediate verbal memory should form an important part of this emerging framework. 4 Part 2 of this thesis addressed a recognised need for cognitive screening tests adapted to individuals with hearing loss. This is the first study to develop a hearing-impaired version of the Addenbrooke’s Cognitive Examination (HI-ACE-III) and validate it as a screening tool for people with MCI and comorbid hearing loss. Whilst other tools have been adapted, no studies have yet reported the sensitivity or specificity of those tools in clinical populations. This study validates the use of the HI-ACE-III amongst populations with MCI and comorbid hearing loss and suggests that, in instances where clinicians are aware of diagnosed hearing impairments, the HI-ACE-III could be considered an appropriate tool for use in clinical settings. 5 Table of Contents Contents of Tables and Figures ............................................................................... 10 Appendices ................................................................................................................. 11 Acknowledgements ................................................................................................... 12 Part 1: Literature Review - Neuropsychological Deficits in Posterior Cortical Atrophy and Alzheimer's Disease: A Meta-Analytic Review ............................... 13 Abstract ..................................................................................................................... 14 1.0 Introduction ......................................................................................................... 16 1.1 The Impact of Dementia .................................................................................. 16 1.2 Typical Alzheimer’s Disease (tAD) and Other Dementias ............................. 16 1.3 Posterior Cortical Atrophy (PCA) ................................................................... 17 1.4 The Importance of differential diagnosis ......................................................... 19 1.5 The Role of Neuropsychology ......................................................................... 21 1.6 Review Aims ................................................................................................... 22 2.0 Method ................................................................................................................. 23 2.1 Data Sources and study inclusion .................................................................... 23 2.2 Risk of bias ...................................................................................................... 24 2.3 Data collection and analytic strategy ............................................................... 25 2.4 Effect size calculation ...................................................................................... 26 2.5 Statistical procedures ....................................................................................... 26 3.0. Results ................................................................................................................. 30 3.1 Corpus of studies ............................................................................................. 30 3.2 Study quality .................................................................................................... 30 6 3.3 Meta-Analyses ................................................................................................. 39 3.3.1 Cognitive domains that discriminated between PCA and tAD ................. 40 3.3.2 Cognitive domains that did not discriminate between PCA and tAD ...... 42 3.3.3 Cognitive domains that discriminated between PCA and HC .................. 43 4.0 Discussion ............................................................................................................ 50 4.1 Summary of findings ....................................................................................... 50 4.1.1. PCA vs tAD ............................................................................................. 50 4.1.2 PCA vs HC ............................................................................................... 53 4.2 Limitations and Research Implications ............................................................ 54 5. 0 References ........................................................................................................... 57 Part 2: Empirical Paper - Development and Validation of the "Addenbrooke's Cognitive Examination" as a Screening Test for Mild Cognitive Impairment in Hearing Impaired Individuals ................................................................................ 76 Abstract ..................................................................................................................... 77 1.0 Introduction ......................................................................................................... 79 1.1 Mild Cognitive Impairment ............................................................................. 79 1.2 Hearing impairment ......................................................................................... 80 1.3 MCI and Hearing Impairment .......................................................................... 80 1.4 Hearing impaired screening measures ............................................................. 82 1.5 Addenbrooke’s Cognitive Examination ........................................................... 84 1.6 Research aims .................................................................................................. 86 2.0 Method ................................................................................................................. 86 2.1 Joint working ................................................................................................... 86 2.2 Ethics ............................................................................................................... 87 7 2.3 Power calculation