Population-Based Mini-Mental State Examination Norms in Adults of Mexican Heritage in the Cameron County Hispanic Cohort

Background: Accurately identifying cognitive changes in Mexican American (MA) adults using the Mini-Mental State Examination (MMSE) requires knowledge of population-based norms for the MMSE, a scale which has widespread use in research settings. Objective: To describe the distribution of MMSE scores in a large cohort of MA adults, assess the impact of MMSE requirements on their clinical trial eligibility, and explore which factors are most strongly associated with their MMSE scores. Methods: Visits between 2004-2021 in the Cameron County Hispanic Cohort were analyzed. Eligible participants were >= 18 years old and of Mexican descent. MMSE distributions before and after stratification by age and years of education (YOE) were assessed, as was the proportion of trial-aged (50-85-year-old) participants with MMSE <24, a minimum MMSE cutoff most frequently used in Alzheimer's disease (AD) clinical trials. As a secondary analysis, random forest models were constructed to estimate the relative association of the MMSE with potentially relevant variables. Results: The mean age of the sample set (n = 3,404) was 44.4 (SD, 16.0) years old and 64.5% female. Median MMSE was 28 (IQR, 28-29). The percentage of trial-aged participants (n = 1,267) with MMSE <24 was 18.6% overall and 54.3% among the subset with 0-4 YOE (n = 230). The five variables most associated with the MMSE in the study sample were education, age, exercise, C-reactive protein, and anxiety. Conclusion: The minimum MMSE cutoffs in most phase III prodromal-to-mild AD trials would exclude a significant proportion of trial-aged participants in this MA cohort, including over half of those with 0-4 YOE.