Article Text

Download PDFPDF
Original research
Linking the Mini-Mental State Examination, the Alzheimer’s Disease Assessment Scale–Cognitive Subscale and the Severe Impairment Battery: evidence from individual participant data from five randomised clinical trials of donepezil
  1. Stephen Z Levine1,
  2. Kazufumi Yoshida2,
  3. Yair Goldberg3,
  4. Myrto Samara4,5,
  5. Andrea Cipriani6,
  6. Orestis Efthimiou7,
  7. Takeshi Iwatsubo8,
  8. Stefan Leucht4,
  9. Toshi A Furukawa2
  1. 1Department of Community Mental Health, University of Haifa, Haifa, Israel
  2. 2Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine/ School of Public Health, Kyoto, Japan
  3. 3Faculty of Industrial Engineering and Management, Haifa Technion, Haifa, Israel
  4. 4Department of Psychiatry and Psychotherapy, School of Medicine, Technical University of Munich, Munich, Germany
  5. 5Department of Psychiatry, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
  6. 6Department of Psychiatry, University of Oxford, Oxford, United Kingdom
  7. 7Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland
  8. 8Department of Neuropathology, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan
  1. Correspondence to Professor Stephen Z Levine, University of Haifa, Haifa 31905, Israel; slevine{at}


Background The Mini-Mental State Examination (MMSE), the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog) and the Severe Impairment Battery (SIB) are widely used rating scales to assess cognition in Alzheimer’s disease.

Objective To understand the correspondence between these rating scales, we aimed to examine the linkage of MMSE with the ADAS-Cog and SIB total and change scores.

Methods We used individual-level data on participants with Alzheimer’s disease (n=2925) from five pivotal clinical trials of donepezil. Data were collected at baseline and scheduled visits for up to 6 months. We used equipercentile linking to identify the correspondence between simultaneous measurements of MMSE with ADAS-Cog, and SIB total and change ratings.

Findings Spearman’s correlation coefficients were of strong magnitude between the MMSE total score and the ADAS-Cog (rs from −0.82 to −0.87; p<0.05) and SIB total scores (rs from 0.70 to 0.75; p<0.05). Weaker correlations between the change scores were observed between the MMSE change score and the ADAS-Cog (week 1: r=−0.11, p=0.18; rs thereafter: −0.28 to −0.45; p<0.05) and SIB change scores (rs from 0.31 to 0.44; p<0.05). Linking suggested that the MMSE total scores were sensitive to moderate and severe cognitive impairment levels. Despite weak to moderate correlations for the change scores, moderate change levels linked well, indicating ceiling and floor effects.

Conclusions The current results can be used in meta-analyses, data harmonisation and may contribute to increasing statistical power when pooling data from multiple sources.

Clinical implications The current study results help clinicians to understand these cognitive rating scale scores.

  • adult psychiatry
  • delirium & cognitive disorders

Statistics from


  • SZL and KY are joint first authors.

  • Twitter @szlevine, @And_Cipriani, @Toshi_FRKW

  • Contributors SZL contributed to manuscript drafting, statistical analysis, data management and study conceptualisation. KY contributed to critical manuscript feedback, data management and statistical analysis. YG contributed to critical manuscript feedback and statistical analysis. MS and AC contributed to study conceptualisation, interpretation and critical manuscript feedback. OE contributed to critical manuscript feedback and statistical interpretation. TI and SL contributed to study conceptualisation, interpretation and critical manuscript feedback. SL contributed to study conceptualisation, interpretation and critical manuscript feedback. TAF contributed to critical manuscript feedback, statistical review, study conceptualisation and mentorship.

  • Funding AC is supported by the National Institute for Health Research (NIHR) Oxford Cognitive Health Clinical Research Facility, by an NIHR Research Professorship (grant RP-2017-08-ST2-006), by the NIHR Oxford and Thames Valley Applied Research Collaboration and by the NIHR Oxford Health Biomedical Research Centre (grant BRC-1215-20005). OE is supported by project grant No 180 083 from the Swiss National Science Foundation (SNSF).

  • Competing interests TI has served as a consultant of Eisai, Roche and Biogen in the last 3 years. AC has received research and consultancy fees from INCiPiT (Italian Network for Paediatric Trials), CARIPLO Foundation and Angelini Pharma. In the past 3 years, SL has received honoraria as a consultant or for lectures for LB Pharma, Otsuka, Lundbeck, Boehringer Ingelheim, LTS Lohmann, Janssen, Johnson&Johnson, TEVA, MSD, Sandoz, SanofiAventis, Angelini, Sunovion, Recordati and Geodon Richter. TAF reports personal fees from Mitsubishi-Tanabe, MSD and Shionogi, and a grant from Mitsubishi-Tanabe, outside the submitted work; TAF has a patent 2018-177688 pending.

  • Patient consent for publication Not required.

  • Ethics approval Institutional review boards approved each study, and all patients had given their written informed consent.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request. Data requests can be submitted via

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.