The following article is based on a poster presentation from ADPD 2025, “RBANS as a predictor of disease progression in early symptomatic Alzheimer’s Disease.”
Download the poster here.
Alzheimer’s Disease (AD) is a relentless neurodegenerative disorder that affects millions globally. Early detection and intervention are key to managing the disease and enhancing patients’ quality of life. In the quest for effective treatments, clinical trials often rely on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) as a primary endpoint. This semi-structured interview is also a crucial inclusion criterion in most trials. However, these trials typically require large participant samples and extended follow-up periods to observe significant placebo decline and detect treatment effects.
To streamline these trials, identifying clinical factors that predict placebo decline is essential. These factors can help enrich trial samples or serve as stratification variables for earlier phase trials with smaller samples. In this study, we examined the utility of common screening measures used in early symptomatic AD trials to determine their predictive value for progression on the CDR-SB.
Study Overview
We analyzed data from 3,606 participants across six early symptomatic AD studies. These studies included the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) delayed Memory Index (DMI) cutoff of 85 or less, and the Mini Mental Status Examination (MMSE) cutoff of 20+ for inclusion. Using forward and backward stepwise regressions, we identified the best model for predicting change in CDR-SB from screening to month 18. The predictor variables included RBANS total scale index score, RBANS DMI, MMSE total, CDR-SB, and age. The final model was evaluated using linear regression to determine the magnitude and direction of the predictor variables.
Key Findings
The final model, identified by both forward and backward stepwise regressions, included all variables except RBANS DMI. The linear regression analysis revealed that the model was statistically significant (adjusted R2 = 0.1216; p-value < 0.0001). Subject age was positively associated with change in CDR-SB (coefficient = 0.007), while RBANS total scale index score (coefficient = -0.057), MMSE total (coefficient = -0.121), and screening CDR-SB (coefficient = -0.087) were negatively associated.
Implications for Clinical Trials
Our findings indicate that screening measures such as RBANS, MMSE, and CDR are valuable tools in predicting disease progression in early symptomatic AD. The RBANS total scale index score showed the strongest relationship to progression on CDR-SB. Participants in the lowest quartile on this measure progressed more than 2.5 times the rate of those in the highest quartile. These insights can be instrumental in designing future clinical trials, either by enriching study samples for faster progression or for stratification purposes.
Conclusion
The study underscores the importance of using clinical screening data, including RBANS total scale index score, MMSE total, CDR-SB, and age, in predicting disease progression in early symptomatic AD. By leveraging these measures, researchers can enhance the efficiency and effectiveness of clinical trials, ultimately paving the way for better treatment options for Alzheimer’s Disease.
References:
- Morris JC. The clinical dementia rating (CDR): current version and scoring rules. Neurology 1993; 43: 2412-4.
- Randolph, C. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). NCS Pearson, 1998, 2012.
- Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatry Res 12(3):189–198.