Identification of circulating risk biomarkers for cognitive decline in a large community‐based population in Chongqing China

Abstract INTRODUCTION This study aims to investigate the relationship between blood‐based pathologies and established risk factors for cognitive decline in the community‐based population of Chongqing, a region with significant aging. METHODS A total of 26,554 residents aged 50 years and older were recruited. Multinomial logistic regression models were applied to assess the risk factors of cognition levels. Propensity score matching and linear mixed effects models were used to evaluate the relationship between key risk factors and the circulating biomarkers. RESULTS Shared and distinct risk factors for MCI and dementia were identified. Age, lower education, medical history of stroke, hypertension, and epilepsy influenced mild cognitive impairment (MCI) progression to dementia. Correlations between key risk factors and circulating neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), amyloid β protein (Aβ)40, and Aβ42/Aβ40 ratio suggest underlying mechanisms contributing to cognitive impairment. DISCUSSION The common and distinct risk factors across cognitive decline stages emphasize the need for tailored interventions. The correlations with blood biomarkers provide insights into potential management targets. Highlights From a large community‐based cohort study on the residents in Chongqing, we have identified that mild cognitive impairment (MCI) and dementia share several common risk factors, including age, female gender, rural living, lower education levels, and a medical history of stroke. However, each condition also has its own unique risk factors. Several factors contribute to the progression of MCI into dementia including age, education levels, occupation, and a medical history of hypertension and epilepsy. We discover the correlations between the risk factors for dementia and blood biomarkers that indicate the presence of axonal damage, glial activation, and Aβ pathology.