Title: An Investigation of Auditory Processes in Parkinson's Disease: Risk Factors and the Potential Utility of Corrective Hearing Treatments.
Funder: Economic and Social Research Council

Abstract: The proposed fellowship contains three strands: i. Enhance my academic profile and skill set (~56%): I will submit two PhD manuscripts to leading peer-reviewed journals to enhance my publication record. I will also disseminate these findings, via oral presentations, at several large national/international conferences (e.g. International Parkinson's and Movement Disorders Society Congress, and the British Neuropsychology Society Meeting). Conference participation will enable me to gain feedback on the work, develop novel research ideas, build on my existing networks, and develop new connections. In collaboration with leading researchers in Parkinson's Disease (PD), auditory neuroscience, and perception (Prof. Christopher Plack, Prof. Trevor Crawford and Dr Sally Lineknauger), I will spend 3 months conducting further research. This secondary data analysis (using the UK Biobank), will explore the relatedness of hearing loss, the diagnosis of PD, the severity of symptomology, medication consumption, and participant demographics (e.g. sex, race, socioeconomic status and nationality). With support from previous and current faculty colleagues (Dr Stefanie Doebler and Dr Neil McLatchie; 1, 2) who specialise in 'big-data' and Bayesian statistics, the data will be analysed using advanced techniques (Bayesian linear mixed-effects modeling). This analysis will serve as a basis for a grant (see iii). Conducting this research will enhance my data analysis skills, enable me to obtain pilot data to strengthen funding applications, and develop new collaborations with experts in the field, including the Manchester Centre for Audiology and Deafness (ManCAD) and SENSE-Cog, both of which my mentor is a member of. ii. Generate non-academic impact (~25%): My PhD revealed that perceptual-motor calibration is intact in mild-moderate PD. Therefore, in line with a growing body of literature, these results suggest that perceptual-motor training may be useful in slowing motor impairment in PD. Consequently, the obtained results are of interest to both academics and clinicians, and people with PD. From previous discussions with the Research Operations Manager at Royal Preston Hospital, it is clear that clinicians/physiotherapists often are not aware of such therapeutic developments. Therefore, as part of this fellowship, in collaboration with Prof. Hedley Emsley (Consultant neurologist and Honorary Lecturer at Lancashire Teaching Hospitals NHS FT) and Lancashire Neuroscience, I will organise a research symposium (targeted to individuals working with people with PD) in which the advances in the understanding of the utility of perceptual-motor training for neurorehabilitation in PD will be discussed. I will also create an infographic summarising this content, for dissemination at this event. As findings are also of interest to individuals with PD, I will also organise a research workshop (in collaboration with Parkinson's UK and The NW Parkinson's Research Interest Group; of which I am a member) in which I, along with one other researcher will present our findings and provide an interactive workshop displaying how perceptual-motor training may work and benefit individuals with PD. I will also publish a lay summary of one study in the Parkinson's UK research magazine. iii. Apply for further funding (~33%): During the fellowship, I will develop two funding applications: the ESRC New Investigator grant and the Secondary Data Analysis Initiative. These grants will investigate the propensity and effects of hearing loss in individuals with both early stage and advanced PD. Moreover, the potential utility of treatments to correct hearing loss, on not only the correcting of hearing loss but also in improving cognitive performance and reducing symptomology in PD, will be explored. The research questions posed will be co-developed with key stakeholders (e.g. clinicians, physiotherapists and individuals with Parkinson's) to ensure that they address clinical need.

Lay abstract: Parkinson's Disease (PD), the second most pervasive neurodegenerative disorder after Alzheimer's Disease (3), is a multifaceted movement disorder, which currently affects ~137,000 people in the UK (4,5). While we know that PD occurs due to the progressive loss of dopamine neurons in the basal ganglia of the brain (6), we do not know what causes the loss of dopamine neurons to occur. Subsequently, PD is currently incurable (7). Therefore, the management, and identification of potential risk factors associated with PD is of particular clinical importance. PD and dementia, particularly dementia with Lewy bodies, share similar neuropathologies, brain chemistry, and symptoms (8). Importantly, approximately 80% of people with PD are affected by dementia (9). Hearing loss is a potentially modifiable risk factor for dementia, such that even mild hearing loss doubles dementia risk (10). Given the interrelatedness of dementia and PD, it may be that hearing loss is also a potentially modifiable risk factor for PD. While some studies have begun to acknowledge the relatedness of PD and hearing loss, large scale analyses are needed to fully determine whether hearing loss is a risk factor of PD or whether hearing loss is a secondary consequence of impaired sensory processing or medication consumption that occurs over the course of PD progression. Therefore, I propose to conduct a large-scale secondary data analysis, using the UK Biobank, of the relatedness of hearing loss, the diagnosis of PD the severity of Parkinsonian symptomology, anti-Parkinsonian medication consumption, and demographics (e.g. race, sex, and nationality). This analysis will be conducted in collaboration with renowned researchers in the fields of auditory neuroscience (Prof. Plack; ManCAD, SENSE-Cog, C4AR), neurodegeneration (Prof. Crawford; C4AR), and perception (Dr Linkenauger). Health inequalities are disparities in our understanding, and treatment, of health conditions. Although, North African and Ashkenazi Jewish individuals are more likely to develop PD, ethnic minorities are grossly underrepresented in research. Akin to the ESRC objectives, Parkinson's UK has launched an initiative that aims to tackle health inequalities. In line with these objectives, the proposed study will also analyse the influence of demographic characteristics including race, nationality and sex, on (a) the overall occurrence of PD and (b) the relatedness of hearing loss and PD. The proposed fellowship aims to:(i) Disseminate findings with academics: Previous PhD findings, and new findings will be presented at large international conferences and through peer-reviewed publications. (ii) Generate non-academic output: In collaboration with Professor Hedley Emsley, I will organise a research symposium (targeted to individuals working with people with PD). I will also organise a research workshop for individuals with PD. In addition to these workshops, a summary infographic will be developed and shared with workshop/symposium attendees, members of Lancashire Teaching Hospitals NHS Foundation Trust, Lancashire Neuroscience, and the C4AR. (iii) Conduct a large-scale secondary data analysis investigating the relatedness of hearing loss and PD (using the UK Biobank). The results of these exploratory analyses will form the basis of funding applications.(iv) Enhance my research skills and collaborative networks: By completing additional research, I will enhance my data analysis skills and develop new collaborations with experts in the field. These skills and collaborations will allow me to conduct further research in the future. (v) Develop funding applications: During the fellowship, I will develop funding applications: The ESRC New Investigator grant, and the ESRC Secondary Data Analysis Initiative. These grants will investigate the propensity and effects of hearing loss in individuals with both early stage and advanced PD, and the potential utility of treatments to correct hearing loss in PD

Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: EAR;NEUROLOGICAL