Cognitive impairment and its neurobiological correlates in adults experiencing long-term homelessness: an exploratory observational cross-sectional study protocol.

Introduction Homelessness is an escalating global crisis. Research suggests that people experiencing homelessness (PEH) have high rates of cognitive impairment (CI), which demonstrate domain-specific patterns. Additionally, a high lifetime prevalence of traumatic brain injury (TBI) has been identified in this population. However, the relationships between cognitive impairment, head injury exposure, brain structure, and biological markers of neurodegeneration in PEH remain poorly characterised. This study aims to investigate cognitive impairment in long-term homeless adults (LTHAs) and to examine its associations with neuroimaging measures and fluid biomarkers. Protocol An exploratory cross-sectional observational study of cognitive function and its neuroimaging and biomarker associations in 80 LTHAs and matched housed controls will be performed. Participants will complete a detailed biopsychosocial assessment and a multidomain neurocognitive battery, provide blood samples for fluid biomarker analysis and will undergo contrast-enhanced brain magnetic resonance imaging (MRI). Cognitive performance, neuroimaging measures and fluid biomarker levels will be compared between LTHAs and controls. Within the LTHA group, associations between cognitive impairment, TBI exposure, neuroimaging findings, and biomarker measures will be explored. Ethics and Dissemination Ethical Approval for this study (project number 3759) was granted by the St James’s Hospital/Tallaght University Hospital Joint Research Ethics Committee (SJH/TUH JREC) prior to the first recruitment of human subjects. Study results will be disseminated to participants via gatekeeper organisations and to professionals working in homeless services. Findings will also be disseminated to the scientific community through open-access publication and presentation at conferences.