Air pollution may accelerate cognitive aging, it is unclear whether large-scale interventions by Clean Air Act can mitigate the cognitive deterioration. Here, we conducted a difference-in-differences analysis based on Chinese Longitudinal Healthy Longevity Survey during 2014 and 2018. Intervention group came from where the government set a strict target of reducing air pollution, whereas control group lived in areas without reduction target. Global cognitive functions were measured using the Mini-Mental State Examination (MMSE). We found the intervention group with implementing Clean Air Act had a significantly smaller decline in MMSE score compared to the control group. Interquartile increases in PM2.5 and SO2 concentrations were significantly associated with a faster decline of MMSE score by 1.78 and 0.92 points, respectively. Implementing stringent clean air policies, especially in low- and middle-income countries may mitigate the risk of cognitive aging in older people.

Alzheimer’s disease (AD) is a dementia-related disease with cognitive deterioration and memory impairment. Catalpol was reported to relieve impairments in learning and memory. The present study assessed the functional mechanism of catalpol in AD via miR-124/STIM2-mediated mitochondrial function. Primary hippocampal neurons were isolated and cultured. AD cell model was induced by Aβ1−42 and treated with catalpol. APP/PS1 mouse model was established and treated with catalpol and miR-124 agomir. Aβ1−42 induced mitochondrial damage and reactive oxygen species (ROS) generation in AD cell model. Catalpol alleviated mitochondrial damage and reduced ROS generation in hippocampal neurons. miR-124 was highly expressed in AD cell model and catalpol inhibited miR-124 expression. Catalpol alleviated Aβ1−42 induced mitochondrial damage and ROS generation in hippocampal neurons by inhibiting miR-124 expression. miR-124 overexpression after catalpol treatment promoted mitochondrial damage and ROS generation in hippocampal neurons. miR-124 targeted STIM2. Silencing STIM2 after catalpol treatment promoted mitochondrial damage and ROS generation in hippocampal neurons. Catalpol slowed AD progression via the miR-124/STIM2 axis in vivo. The results of the present study indicated that catalpol alleviated mitochondrial damage and ROS generation and thus attenuated AD by regulating miR-124-mediated STIM2.