Neurocognitive disorders (NCDs) are progressive conditions that severely impact cognitive function and daily living. Understanding the transition from mild to major NCD is crucial for personalized early intervention and effective management. Predictive models incorporating demographic variables, clinical data, and scores on neuropsychological and emotional tests can significantly enhance early detection and intervention strategies in primary healthcare settings. We aimed to develop and validate predictive models for the progression from mild NCD to major NCD using demographic, clinical, and neuropsychological data from 132 participants over a two-year period. Generalized Estimating Equations were employed for data analysis. Our final model achieved an accuracy of 83.7%. A higher body mass index and alcohol drinking increased the risk of progression from mild NCD to major NCD, while female sex, higher praxis abilities, and a higher score on the Geriatric Depression Scale reduced the risk. Here, we show that integrating multiple factors—ones that can be easily examined in clinical settings—into predictive models can improve early diagnosis of major NCD. This approach could facilitate timely interventions, potentially mitigating the progression of cognitive decline and improving patient outcomes in primary healthcare settings. Further research should focus on validating these models across diverse populations and exploring their implementation in various clinical contexts.