AbstractDementia progression is characterised by a lengthy pre-symptomatic phase, where pathology may be accumulating, followed by a more rapid decline evidenced by onset of clinical symptoms and eventually functional impairment. The rate of decline in symptoms from cognitive impairment to dementia greatly varies between individuals, complicating prognosis and the assessment of much needed disease-modifying drugs. As a result there is a huge demand for greater understanding of the between-subject variability in progression and a need to understand biomarkers and risk factors for predicting future cognitive decline.
In cohorts derived from two of the largest NHS foundation trust mental health service providers in the UK and multiple Alzheimer’s cohorts, this thesis explores methods for modelling disease progression and investigates the relationship between blood based proteins, genetic variants, health indicators and potential repurposing medications with cognitive decline.
Through applying approaches that tackle three areas that require consideration for modelling of cognitive decline and disease progression, this thesis identified associations of antidepressant medication and psychotic symptoms associated with faster cognitive decline in dementia, in two separate cohorts.
|Date of Award
|Stephen Newhouse (Supervisor), Mizanur Khondoker (Supervisor) & Richard Dobson (Supervisor)