High-sensitivity cardiac troponin I and risk of dementia: the 25-year longitudinal Whitehall II study

Abstract Background and Aims This study hypothesizes that subclinical myocardial injury during midlife, indexed by increases in cardiac troponin I, is associated with accelerated cognitive decline, smaller structural brain volume, and higher risk of dementia. Methods Overall, 5985 participants in the Whitehall II study, aged 45–69 who had cardiac troponin I measured by a high-sensitivity assay at baseline (1997–99), were followed until March 2023. The outcome measure was incident dementia; cognitive testing was performed at six waves; and neuroimaging metrics were obtained from magnetic resonance imaging scans in 2012–16. Cox model and linear mixed model were used to examine the association of cardiac troponin with incident dementia and cognitive trajectory. A nested case–control sample of 3475 participants (695 dementia cases and 2780 matched controls) was used for backward trajectory analysis for cardiac troponin, measured at three waves (1997–99, 2007–09, 2012–13). Results A total of 606 (10.1%) cases of dementia were recorded over a median follow-up of 24.8 years. Doubling of cardiac troponin was associated with 10% (95% confidence interval 3%–17%) higher risk of dementia. Participants with increased cardiac troponin at baseline had a faster decline of cognitive function. Participants with dementia had increased cardiac troponin concentrations compared with those without dementia between 7 and 25 years before diagnosis. Compared with those with cardiac troponin levels < 2.5 ng/L at baseline, those with concentrations > 5.2 ng/L had lower grey matter volume and higher hippocampal atrophy 15 years later, equivalent to ageing effects of 2.7 and 3 years, respectively. Conclusions Subclinical myocardial injury at midlife was associated with higher dementia risk in later life.