Sepsis increases the risk of dementia in middle-aged and elderly adults: a large prospective cohort study.

Background & aims: Sepsis is associated with dementia; however, there is little real-world evidence to study the long-term risk of sepsis for dementia. This study investigated the long-term risk of dementia after sepsis, combined with genetic data, to identify the effects of apolipoprotein E (APOE) on the relationship between sepsis and dementia and provide data support for the later management of sepsis.

Methods: This large-scale, prospective cohort study evaluated participants from the UK Biological Sample Bank. A multivariate Cox proportional hazards model was used to examine the relationship between sepsis and the risk of long-term dementia. A stratified analysis was conducted to elucidate the relationship between sepsis and dementia in different sex and age groups, as well as in APOE gene populations.

Results: Among 499,238 participants, sepsis was associated with higher dementia risk than chronic diseases. Although the risk of dementia after sepsis increased, this association gradually decreases over time with the progressive exclusions of follow-up. Subgroup analysis revealed that sepsis was an independent risk factor for dementia among aged 45 and above. Compared without sepsis patients, sepsis patients carrying APOE ε2 and APOE ε3 alleles had a 2.863 and 2.815 fold increased risk of dementia, respectively (all P < 0.001). However, no significant correlation was found between sepsis and dementia among participants carrying APOE ε4 (P = 0.097).

Conclusions: Sepsis increases the short-term dementia risk but not long-term risk. Attention should be paid to people aged 45 and above after sepsis. Notably, The APOE gene affects the sepsis-dementia relationship.