{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:37:11Z","timestamp":1791844631556,"version":"4.3.4"},"reference-count":32,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T00:00:00Z","timestamp":1669766400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>An Alzheimer's disease (AD) dementia disease progression model was developed based on the integrated Alzheimer's Disease Rating Scale (iADRS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data from 3483 placebo participants in six AD trials were used to develop the disease progression model with NONMEM (version 7.4.2) and examined for mild cognitive impairment, and mild and moderate dementia due to AD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Baseline iADRS score was significantly influenced by AD symptomatic medication use, EXPEDITION2 enrollment (included moderate AD participants), age, and baseline Mini\u2010Mental State Examination (MMSE) score. Rate of disease progression increased across disease stage and was significantly influenced by AD medication use, age, and baseline MMSE score. Apolipoprotein E \u03b54 carrier status did not influence baseline iADRS score or disease progression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These results demonstrate a disease progression model describing the time course of the iADRS across the AD severity spectrum. This model can assist future clinical trials in study design optimization and treatment effect interpretation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>A disease progression model described the integrated Alzheimer's Disease Rating Scale (iADRS) time course in mild cognitive impairment to moderate Alzheimer's disease.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Using the linear regression model, iADRS scores can be calculated for Mini\u2010Mental State Examination scores.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Results can help optimize future clinical trial design and aid in understanding treatment effects.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.12876","type":"journal-article","created":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T14:53:29Z","timestamp":1669820009000},"page":"2253-2264","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Disease progression model using the integrated Alzheimer's Disease Rating Scale"],"prefix":"10.1002","volume":"19","author":[{"given":"Ivelina","family":"Gueorguieva","sequence":"first","affiliation":[{"name":"Eli Lilly and Company  Bracknell UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laiyi","family":"Chua","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian A.","family":"Willis","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Sims","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alette M.","family":"Wessels","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,11,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40495\u2010016\u20100066\u2010x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928\u2010014\u20109375\u2010z"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.2147\/ndt.s62323"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928\u2010012\u20109263\u20103"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.01.005"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.14283\/jpad.2018.2"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.14283\/jpad.2022.30"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1312889"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.141.11.1356"},{"issue":"1","key":"e_1_2_7_11_1","first-page":"22","article-title":"Outcomes assessment in clinical trials of Alzheimer's disease and its precursors: readying for short\u2010term and long\u2010term clinical trial needs","volume":"14","author":"Posner H","year":"2017","journal-title":"Innov Clin Neurosci"},{"key":"e_1_2_7_12_1","unstructured":"US Food and Drug Administration. Guidance for Industry Alzheimer's Disease: Developing Drugs for the Treatment of Early Stage Disease. Draft Guidance. (2013).Available at. 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