[Joint effects of heatwave exposure and apolipoprotein E genotype on risk for cognitive impairment in older adults]

Objective: To investigate the associations of heatwave exposure and apolipoprotein E (ApoE) genotype, as well as their interaction, with the risk for cognitive impairment in older adults. Methods: Study participants were from the Chinese Longitudinal Healthy Longevity Survey. Individuals aged ≥65 years who completed ApoE genotyping and the Mini-Mental State Examination in 2008 were enrolled as the baseline cohort and follow up was conducted until 2021. Annual mean heatwave days were defined using daily maximum temperature (T_max) data matched to the latitude and longitude of the areas where the study participants lived. A time-dependent Cox proportional hazards regression model and restricted cubic splines were used to evaluate the associations of ApoE ε4 genotype status and heatwave exposure with the risk for cognitive impairment, and multiplicative and additive interactions were examined. Results: A total of 4 412 older adults with normal cognition at baseline were included. The mean follow-up duration was 7.38 years, during which 1 317 cases of cognitive impairment were newly identified. After adjusting for confounders, ApoE ε4 genotype carriers had a higher risk for cognitive impairment compared with non-carriers (HR=1.23, 95%CI: 1.08-1.40). Heatwave exposure was positively associated with cognitive impairment risk; each 10-day increase in annual mean heatwave days was associated with an 11% higher risk for cognitive impairment (HR=1.11, 95%CI: 1.02-1.20). Restricted cubic spline analyses showed a stable positive association between annual mean heatwave days and cognitive impairment risk in 0-20 days, followed by a plateau, with no significant nonlinear relationship (P for nonlinearity=0.186). Joint analyses indicated that individuals who were ApoE ε4 genotype carriers and exposed to high levels of heatwaves had higher risk for cognitive impairment; however, no significant interaction was observed, either on the multiplicative scale (P=0.296) or the additive scale (95%CIs of the relative excess risk due to interaction included 0). Conclusions: Both ApoE ε4 genotype carriage and heatwave exposure were independently associated with increased risk for cognitive impairment in older adults. In the context of climate warming, it is necessary to strengthen heatwave prevention and health management in old population to reduce potential cognitive health risks.