Exercise delayed cognitive decline in Chinese seniors: a new causal inference method for ordered multi-categorical exposures

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Abstract Background The cognitive problems are prominent in the context of global aging, and the traditional Mendelian randomization method is not applicable to ordered multi-categorical exposures. Therefore, we aimed to address this issue through the development of a new method and to investigate the causal inference of cognitive-related lifestyle factors. Method The study sample was derived from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), which included 897 seniors aged 65+. This study used genome-wide association analysis to screen genetic loci as instrumental variables and innovatively combined maximum likelihood estimation to infer causal associations between ordered multi-categorical exposures (diet, exercise, etc.) and continuous outcomes (cognitive level). Results The new causal inference method for ordered multi-categorical exposures developed in this study was simple, easy to implement, and able to effectively and reliably discover the potential causal associations between variables. Through this method, we found a potential positive causal association between exercise status and cognitive level in Chinese seniors ( = 1.883, 95%CI: 0.260–3.564), in which there was no horizontal pleiotropy (p = 0.370). Conclusion The study provided a new causal inference method applicable to ordered multi-categorical exposures, that addressed the limitations of the traditional Mendelian randomization method.

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