{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T11:21:29Z","timestamp":1783596089221,"version":"3.55.0"},"reference-count":35,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Functional decline emerges early in Alzheimer\u2019s disease (AD) and may support clinical staging. However, criterion-referenced thresholds for interpreting the six-minute walk distance (6MWD) across AD stages are lacking. This study aims to derive sex-specific 6MWD cut-off values to differentiate mild cognitive impairment (MCI) from moderate AD dementia. Methods: In this cross-sectional study, 233 community-dwelling adults (128 women) were consecutively recruited from a neurology department and classified using IWG-2 criteria (MCI: MMSE \u2265 26; moderate AD dementia: MMSE 10\u201319). All participants completed a standardized 6 min walk test (6MWT) following American Thoracic Society guidelines. Receiver operating characteristic (ROC) analyses were performed overall and by sex, optimal thresholds were selected using Youden\u2019s index, and diagnostic indices such as area under the curve (AUC), sensitivity, specificity, 95% confidence intervals (CI), likelihood ratios (LR) and odds ratio (OR) were computed. Results: Overall, participants with moderate AD dementia exhibited substantially lower 6MWD values than those with MCI (313.7 \u00b1 46.5 m vs. 461.2 \u00b1 60.1 m, p &lt; 0.001). The optimal overall threshold was 390 m, yielding an AUC of 0.97, sensitivity of 98.0%, and specificity of 79.4%. Sex-specific thresholds were 389 m in men (AUC = 0.96, sensitivity = 96.4%, specificity = 79.3%) and 367 m in women (AUC = 0.98, sensitivity = 97.8%, specificity = 87.7%). Conclusions: The 6MWD demonstrates strong discriminatory ability between MCI and moderate AD dementia in this sample. Sex-specific thresholds may support functional staging and monitoring but require internal and external validation before clinical implementation.<\/jats:p>","DOI":"10.3390\/jcm15145374","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T10:16:22Z","timestamp":1783592182000},"page":"5374","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Criterion-Referenced Sex-Specific Six-Minute Walk Distance Cut-Offs for Staging Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2010-649X","authenticated-orcid":false,"given":"Ines","family":"Ben Ayed","sequence":"first","affiliation":[{"name":"Research Laboratory, Exercise Physiology and Physiopathology: From Integrated to Molecular \u201cBiology, Medicine and Health\u201d, LR19ES09, Faculty of Medicine of Sousse, Sousse University, Sousse 4000, Tunisia"},{"name":"Laboratory of Human and Artificial Cognition (EA 4004), Psychology UFR, University of Vincennes\/Saint-Denis, 93200 Saint-Denis, France"},{"name":"Research Laboratory, Education, Motricity, Sport and Health (EM2S), LR15JS01, High Institute of Sport and Physical Education of Sfax, University of Sfax, Sfax 3000, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emna","family":"Makni","sequence":"additional","affiliation":[{"name":"Research Laboratory, Exercise Physiology and Physiopathology: From Integrated to Molecular \u201cBiology, Medicine and Health\u201d, LR19ES09, Faculty of Medicine of Sousse, Sousse University, Sousse 4000, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0347-8053","authenticated-orcid":false,"given":"Achraf","family":"Ammar","sequence":"additional","affiliation":[{"name":"Department of Training and Movement Science, Institute of Sport Science, Johannes Gutenberg University Mainz, 55122 Mainz, Germany"},{"name":"Research Laboratory, Molecular Bases of Human Pathology, LR19ES13, Faculty of Medicine of Sfax, University of Sfax, Sfax 3000, Tunisia"},{"name":"Department of Nutrition and Food Technology, School of Agriculture, The University of Jordan, Amman 11942, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8439-0429","authenticated-orcid":false,"given":"Mehdi Ben","family":"Brahim","sequence":"additional","affiliation":[{"name":"Sport Sciences and Diagnostics Research Group, GS-HPE Department, Prince Sultan University, Riyadh 11586, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3751-2125","authenticated-orcid":false,"given":"Mohamed","family":"Elloumi","sequence":"additional","affiliation":[{"name":"Sport Sciences and Diagnostics Research Group, GS-HPE Department, Prince Sultan University, Riyadh 11586, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2023). 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