Reaction Time Variability as a Marker of Aging

There are many easily measured biomarkers that correlate to various degrees with mortality risk and aging, such as grip strength, heart rate variability, as so forth. Given enough of them, it may be possible to build a much more accurate biomarker of aging through a weighted combination algorithm, but this has yet to be accomplished well enough to compete with the DNA methylation approach to measuring biological age. It is important to establish some useful form of biomarker of aging, however it is accomplished, as this can then be used to assess potential rejuvenation therapies far more cost-effectively than any of the other alternative options, such as running lengthy life span studies. Lack of a quick, cost-effective method of rating the outcome such therapies in both animal and human studies is holding back the field.

In addition to average performance level, there is an increasing focus in ageing research on intraindividual variability or inconsistency in cognitive performance. Such variability in performance is often measured by the trial-to-trial within-person variation in reaction times (RT) on a single cognitive task and is known as intraindividual reaction time variability (IIVRT). IIVRT has received considerable attention as a useful indicator of neurobiological disturbance. Consistent with this, several studies indicate that IIVRT is greater in older age and in a variety of neuropathological conditions of old age. Associations have been found with measures of brain integrity, including white matter hyperintensities, brain connectivity, and dopaminergic neuromodulation.

Our present interest is whether this measure can predict mortality in old age. It is possible that neurobiogical changes that are related to eventual mortality are captured by variability measures and are present many years in advance. A few studies have reported that increased variability predicts mortality up to 19 years before eventual death in older populations but it is unknown whether this association is independent of general age-related cognitive decline, an established risk factor for mortality. Moreover, the potential influence of incipient dementia on this relationship has not been addressed adequately in previous studies.

Hence, IIVRT warrants investigation as a specific predictor of impending death in older age independently of global cognitive level and other mortality risk factors. Therefore, the aim of this study was to investigate the association of IIVRT with mortality over 8 years in a large, well-characterised population-based cohort of older adults aged 70 years and over. In this large community-based old age cohort, greater variability in RT performance but not slower mean RT predicted all-cause mortality while adjusting for conventional mortality risk factors of age, sex, cardiovascular risk and APOE ɛ4 status and important potential confounders. Our findings broadly support and extend the small extant literature by providing further support for a strong association between IIVRT and all-cause mortality. The findings supports the view of IIVRT as a behavioural marker of neurobiological integrity.



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