Pre‐diagnostic cognitive and functional impairment in multiple sporadic neurodegenerative diseases

Introduction The pathophysiological processes of neurodegenerative diseases begin years before diagnosis. However, pre-diagnostic changes in cognition and physical function are poorly understood, especially in sporadic neurodegenerative disease. Methods UK Biobank data were extracted. Cognitive and functional measures in individuals who subsequently developed Alzheimer's disease (AD), Parkinson disease, frontotemporal dementia, progressive supranuclear palsy, dementia with Lewy bodies, or multiple system atrophy were compared against individuals without neurodegenerative diagnoses. The same measures were regressed against time to diagnosis, after adjusting for the effects of age. Results There was evidence for pre-diagnostic cognitive impairment and decline with time, particularly in AD. Pre-diagnostic functional impairment and decline were observed in multiple diseases. Discussion The scale and longitudinal follow-up of UK Biobank participants provides evidence for cognitive and functional decline years before symptoms become obvious in multiple neurodegenerative diseases. Identifying pre-diagnostic functional and cognitive changes could improve selection for preventive and early disease-modifying treatment trials.