Prodromal markers of neurodegenerative disease: Insights from the UK Biobank dataset

Abstract

AbstractBackgroundAbnormal quantitative motor testing and subtle cognitive deficits are associated with increased neurodegenerative disease risk although assessment methods and outcomes vary. Understanding how and when these deficits develop will improve early detection and clarify prodromal disease course. We set out to determine markers predictive of two common neurodegenerative diseases, Alzheimer’s Disease (AD) and Parkinson’s Disease (PD), in a prospective cohort study.MethodThe UK Biobank dataset includes demographics, medical history, cognitive function tests and physical measures collected from 500,000 adults aged 40‐69 between 2006‐2010. Ongoing follow‐up includes repeat testing, death registry and hospital diagnostic coding. Cases were identified from hospital coding data and death registry and were matched with age and gender‐similar controls (2:1). Those with a known diagnosis at baseline were excluded.Result2248 AD cases (male=48%, mean age 65.3±4.2 years, mean time to diagnosis 8.4±2.5 years) and 2212 PD cases (male=62%, mean age 63.8±5.2 years, mean time to diagnosis 7.7±2.7 years) were identified. 537/2248 (male=51%) AD cases had died by June 2020 (mean assessment to death 9.8±2.0 years) and 357/2212 (male=70%) PD cases (mean assessment to death 9.4±2.2 years). The AD group had shown poorer performance on tasks of fluid intelligence (p<0.0001) and numeric memory (p<0.0001) at baseline than both controls and the PD group. Both AD and PD groups had had slower reaction times (p<0.0001) and weaker hand grip strength at baseline (p<0.0001) than controls. There were no significant effects of age or sex.ConclusionPoor performance on tasks of cognitive function are established features of AD at diagnosis, however it is unknown when during the prodromal disease course they begin. Our data demonstrate subtle changes in markers of these features many years prior to diagnosis in a large, prospective cohort.