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Abstract Background The potential difference in the impacts of unhealthy lifestyle factors (LFs) on progression from healthy to first neurological and psychiatric disorders (NPDs), subsequently to neuropsychiatric multimorbidity (NPM), and further to death is unclear. We aimed to evaluate the associations between unhealthy lifestyle and dynamic transitions of NPDs. Materials and Methods This prospective study included 317,163 participants from the UK Biobank cohort. NPM was defined as the coexistence of at least two NPDs, including dementia, Parkinson disease, anxiety, depression and sleep disorders. We used multi-state model to analyse the impacts of unhealthy LFs (current smoking, unhealthy sleep duration and physical inactivity) on the progression of NPDs. Results During a median follow-up of 12.85 years, 35,010 participants developed at least one NPD, 5,865 developed NPM and 20,932 died afterwards. Unhealthy LFs played crucial but different roles in all transitions from healthy to NPD, to NPM, and then to death. The hazard ratios (95% confidence intervals) per one-factor increase were 1.08 (1.07, 1.10) and 1.04 (1.00, 1.16) for transitions from healthy to NPD, and from first NPD to NPM, and 1.34 (1.32, 1.37), 1.23 (1.18, 1.28) and 1.26 (1.15, 1.39) for mortality risk from healthy, NPD and NPM, respectively. When we further divided NPD into dementia, Parkinson disease, anxiety, depression and sleep disorders, the associations of single and combined unhealthy LFs with NPD transitions varied depending on disease types and specific combinations of unhealthy LFs, even within the same transition stage. Conclusion Unhealthy LFs play important roles in nearly all transitions of NPD progression, highlighting the significance of LFs management for the prevention and control of NPDs.
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