Are MMSE and ACE-R useful for detecting the earliest stages of Alzheimer's disease? A comparative study

Subjective cognitive decline (SCD) is an at-risk condition for future cognitive decline, making its early identification crucial. We examined whether two widely used screening tools, the Addenbrooke's Cognitive Examination-Revised (ACE-R) and the Mini Mental State Examination (MMSE), can distinguish SCD individuals from healthy elderly (HS) and from individuals with objective cognitive impairment. 110 participants were recruited: 22 HS, 25 SCD, 31 amnestic mild cognitive impairment (aMCI), and 32 Alzheimer's disease (AD) patients. All participants underwent an extensive neuropsychological battery and the ACE-R, which incorporates the MMSE. Partial ACE-R (ACER_P) scores were derived. Between-group comparisons were performed and discriminant analyses were run to evaluate sensitivity, specificity, and accuracy of total ACE-R (ACER_TOT), ACER_P, and MMSE. Despite no screening test significantly distinguishing SCD from HS, a progressive downward trend emerged across groups, with AD performing worst, followed by aMCI, then SCD and HS. Discriminant analyses indicated ACER_TOT had the highest sensitivity for AD (84.4%), with overall accuracy of 59.1%. Sensitivity for HS (68.2%) and aMCI (51.6%) was good but weaker. ACER_P and MMSE yielded similar or lower accuracy. Importantly, all measures poorly detected SCD, with sensitivity below 30%, leading to frequent misclassification as HS or aMCI. Although ACE-R and MMSE are moderately effective for identifying AD, HS and aMCI, they fail to distinguish SCD from other groups. Given the higher risk of SCD of being in AD continuum, such misclassification may prevent appropriate clinical follow-up. More sensitive screening instruments are needed to capture subtle cognitive changes and support early intervention strategies.