Differential sensitivity of the MMSE and MoCA for staging and longitudinal cognitive change in Huntington's disease

Objective

To compare the sensitivity of the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) for detecting cognitive change in Huntington's disease (HD) subjects stratified by baseline performance quartiles and the Huntington's Disease Integrated Staging System (HD-ISS).

Methods

Participants (age 25–65; CAG 40–50) from an observational cohort completed MMSE and MoCA at baseline, with follow-up visits at least six months after baseline, and observations truncated at five years.

We analyzed the full cohort (n = 246) and an HD-ISS–staged subset (n = 132). Longitudinal change was evaluated using mixed-effects models, adjusted for baseline age, gender, education, CAG, and age × CAG interaction. Baseline discrimination between HD-ISS stages was assessed with ROC curves and AUC comparisons.

Results

Annual decline was nearly identical for MMSE and MoCA (–0.334 vs. −0.331). Adjusted quartile analyses revealed differential sensitivity: MoCA showed greater decline in lower and higher performance levels (Quartiles 1, 3, and 4), while MMSE was most sensitive at mid-range (Quartile 2). In HD-ISS analyses, MMSE demonstrated more consistent decline across stages, particularly Stages 1 and 3, indicating sensitivity to early and moderate disease phases. Baseline ROC analyses favored MoCA for stage discrimination (Stage 0 vs. all: AUC 0.789 vs. 0.686, p = 0.011).

Conclusion

The MMSE and MoCA exhibit complementary strengths. MoCA demonstrates superior sensitivity for baseline staging and early disease detection, while MMSE better captures longitudinal decline. These findings suggest that combined use of both instruments may provide a more complete assessment of cognitive progression in HD.