Extension and external validation of mapping between the Mini-Mental State Examination and the Clinical Dementia Rating scale in patients with Alzheimer's disease

INTRODUCTIONWe aimed to develop and externally validate a mapping to translate Mini-Mental State Examination (MMSE) scores to Clinical Dementia Rating scale Sum of Boxes (CDR-SB) scores in patients with Alzheimer's disease (AD).METHODSWe extended a previously published CDR-SB to MMSE mapping to include later stages of AD and validated it using the US National Alzheimer's Coordinating Centers (NACC) database. Calibration and discrimination metrics were evaluated, and the mapping was validated in clinically relevant subgroups of the AD population.RESULTSA linear MMSE to CDR-SB mapping (CDRSB=-0.6809xMMSE+20.1982)${\mathrm{CD}}{{{\mathrm{R}}}_{{\mathrm{SB}}}} = - 0.6809 \times {\mathrm{MMSE}} + 20.1982)$ demonstrated high goodness of fit and satisfied all validation metrics. The extended mapping performed well across subgroups, though calibration was less accurate for severe dementia patients.DISCUSSIONThis MMSE to CDR-SB MMSE mapping performed generally well though caution is needed when applying this mapping to people with severe AD dementia. It could be used to help contextualize outcomes in AD clinical trials and real-world health research studies.Highlights We developed a mapping between the CDR-SB and MMSE instruments, by obtaining the optimal functional form of a mapping previously published using data from the Alzheimer's Disease Neuroimaging Initiative dataset and extending it to the full range of clinical severities for Alzheimer's disease. The resulting mapping was externally validated using 26,729 MMSE and CDR-SB pairs from participants recruited to the US National Alzheimer's Coordinating Centers database. The selected model satisfied the pre-specified selection criteria and the extended mapping demonstrated good performance, especially in the earlier clinical stages. However, caution is advised when inferring mapped scores in more severe dementia. The extension and subsequent validation of the mapping can support the translation of AD severity assessments between datasets using CDR-SB and MMSE, bridging a common information gap between clinical trials, real-world evidence studies, and clinical practice.