To unravel the combined effect of risk and protective factors that may contribute to preserve or impair cognitive status, this prospective cohort study systematically investigated a cluster of factors in elders aged 75 years and older from Guangxi Longitudinal Cohort (GLC) dataset. GLC has tracked 630 oldest-elders for two times within 2 years and will continue to follow two times in the next 4 years. At baseline geriatric assessment, sociodemographic information (e.g., education, Mandarin, marriage, and income), physical status [body mass index (BMI), chronic disease/medicine], lifestyle factors (smoking, alcohol, and exercise), and self-rated mental health (self-care, well-being, anxiety) were recorded by online interview. With 2 years' follow-up, Mini-Mental State Examination (MMSE) and memory test were performed through person-to-person interview. The performance of MMSE was applied to represent the responder's cognitive status which classified into cognitive impairment and normal group based on a cutoff point of 20. An age-related cognitive declining trend of 15 stratified factors was observed, though with a small effect size (Rsquare: 0.001-0.15). The odds of exposure or non-exposure on factors (memory, self-care, exercise, income, education, and literacy) had a significantly different effect on cognitive impairment through multivariate analysis after adjusting other confounding variables. Through stepwise multiple logistic regression analysis, the following 12 factors/index would be integrated to predict cognitive impairment: gender, physical health factors (BMI, chronic disease), socioeconomic and lifestyle factors (education, literacy, Mandarin, marriage, income, and exercise), and psychological health factors (memory, self-care cognition, and anxiety). Related clinical and nursing applications were also discussed.