Pre-pandemic cognitive function and COVID-19 mortality: prospective cohort study

BACKGROUND: Poorer performance on standard tests of cognitive function is related to an elevated risk of death from lower respiratory tract infections. Whether pre-pandemic measures of cognition are related to COVID-19 mortality is untested. METHODS: UK Biobank, a prospective cohort study, comprises around half a million people who were aged 40 to 69 years at study induction between 2006 and 2010 when a reaction time test was administered to the full sample, and verbal-numeric reasoning assessed in a subgroup. Death from COVID-19 was ascertained from participant linkage to a UK-wide national registry. RESULTS: Between April 1(st) and September 23(rd) 2020, there were 388 deaths (138 women) ascribed to COVID-19 in the 494,932 individuals (269,602 women) with a reaction time test result, and 125 such deaths (38 women) in the 180,198 (97,794 women) for whom there were data on verbal-numeric reasoning. In analyses adjusted for age, sex, and ethnicity, a one standard deviation (118.2 msec) slower reaction time was related to a higher rate of death from COVID-19 (hazard ratio; 95% confidence interval: 1.18; 1.09, 1.28). A one standard deviation disadvantage (2.16 point) on the verbal-numeric reasoning test was also associated with an elevated risk of death (1.32; 1.09, 1.59). Attenuation after adjustment for additional covariates followed a similar pattern for both measures of cognition. For verbal-numeric reasoning, for instance, the hazard ratios were 1.22 (0.98, 1.51) after control for socioeconomic status, 1.16 (0.96, 1.41) after lifestyle factors, 1.25 (1.04, 1.52) after co-morbidity, and 1.29 (1.01, 1.64) after physiological indices. CONCLUSIONS: In the present study, poorer performance on two pre-pandemic indicators of cognitive function, including reaction time, a knowledge-reduced measure, was related to death ascribed to COVID-19.