Anchor-Based Estimation of Minimal Clinically Important Decline on ACE-III in MCI and Dementia

Background:

Dementia is a progressive neurodegenerative condition characterized by cognitive and functional decline, making accurate monitoring of change essential. The Minimal Clinically Important Difference (MCID) provides a threshold to determine whether observed decline on cognitive measures is clinically meaningful. This study aimed to estimate anchor-based MCIDs for Addenbrooke’s Cognitive Examination-III (ACE-III), a commonly used tool for cognitive assessment using change in the Clinical Dementia Rating–Sum of Boxes (CDR-SB) as the clinical anchor.

Methods

375 individuals with cognitive impairment were followed for a median of 1.17 years (IQR 1.1–1.6) between April 2021 and November 2025. Cognitive performance was assessed using ACE-III and clinical severity using CDR-SOB; patients with baseline severe dementia (CDR-Global ≥3) were excluded. Change in ACE-III (ΔACE) was defined as follow-up minus baseline. Clinically meaningful worsening was anchored to ΔCDR-SOB ≥ 0.5 for MCI and ≥ 1.0 for dementia. Anchor-based MCID was calculated as the difference in mean ΔACE between anchor-defined groups. Complete paired ACE-III data were available for 98 participants and were used for MCID estimation.

Results

The analysed cohort (n=156) had a mean age of 62 years (SD 10), was predominantly male (64.1%), and had moderate education (median 12 years, IQR 9–15). Significant decline occurred over follow-up: median ACE-III decreased from 59 (30, 76) to 52 (16, 72) (p<0.001) and median CDR-SOB increased from 7.5 (3, 11) to 10 (3, 16) (p<0.001). Disease severity progressed, with the proportion of severe dementia rising from 10.3% to 28.9%. Anchor analyses showed that ACE-III change differentiated participants with and without meaningful CDR-SOB worsening. In MCI (n=22), ΔACE was 1.5±1.49 in the worsened group versus −0.36±0.60 in the stable group (mean difference −1.86; 95% CI −2.79 to −0.93; p<0.001). In dementia (n=114), ΔACE was 4.94± 2.90 versus −1.21±1.60 (mean difference −6.15; 95% CI −7.08 to −5.22; p<0.001).

Conclusions

Anchor-based estimates indicate that an ACE-III decline of approximately 2 points in MCI and 6 points in dementia corresponds to clinically meaningful deterioration. These stage-specific thresholds demonstrate a graded relationship between ACE-III change and progression on CDR-SB and may enhance interpretation of cognitive outcomes in trials and routine dementia care.