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We conducted a systematic review of public data sources from 1990 to 2008 for all available AChE inhibitor studies, as well as clinical studies that evaluated the rate of deterioration in AD patients. Unique to this analysis, we developed a model based on literature data to describe the longitudinal response in the Alzheimer's Disease Assessment Scale\u2010Cognitive (ADAS\u2010cog) (change from baseline) in mild to moderate severity AD patients. The model was used to estimate disease progression for both placebo\u2010treated patients and acetylcholinesterase (AChE)\u2010inhibitor treated patients, and factors that affected disease progression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We collected 576 mean ADAS\u2010cog changes from baseline data points of 52 trials, representing data from approximately 19,972 patients and more than 84,000 individual observations. The model described the rate of disease progression, the evident placebo effect, and the symptomatic effect of AChE\u2010inhibitors. Baseline ADAS\u2010cog, Mini\u2010Mental State Examination score, age, and year of publication were tested as covariates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The disease progression in mild to moderate AD patients across all available and relevant literature sources was estimated as 5.5 points per year. An Emax\u2010type model best described the symptomatic drug effect of AChE inhibitors. The rate of disease progression (underlying disease progression) was no different between placebo and AChE\u2010inhibitors groups. Baseline ADAS\u2010cog is a significant covariate in disease progression. Baseline age was also tested as a covariate in the rate of disease progression, but the model was unable to describe any effects of age, likely because of the narrow distribution of mean age (literature\u2010level analysis). There was no significant impact of publication year in the model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Baseline ADAS\u2010cog is a significant covariate affecting the rate of disease progression, and it describes or at least explains the different rates of deterioration evident in early or late stages of the disease. There was no significant impact of publication year in the model, suggesting that disease progression has not slowed in more recent trials.<\/jats:p><\/jats:sec>","DOI":"10.1016\/j.jalz.2009.05.665","type":"journal-article","created":{"date-parts":[[2009,7,10]],"date-time":"2009-07-10T06:00:10Z","timestamp":1247205610000},"page":"39-53","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":163,"title":["Disease progression meta\u2010analysis model in Alzheimer's disease"],"prefix":"10.1002","volume":"6","author":[{"given":"Kaori","family":"Ito","sequence":"first","affiliation":[{"name":"Pfizer Global Research and Development New London CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sima","family":"Ahadieh","sequence":"additional","affiliation":[{"name":"Pfizer Global Research and Development New London CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Corrigan","sequence":"additional","affiliation":[{"name":"Pfizer Global Research and Development New London CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"French","sequence":"additional","affiliation":[{"name":"Pfizer Global Research and Development New London CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terence","family":"Fullerton","sequence":"additional","affiliation":[{"name":"Pfizer Global Research and Development New London CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Tensfeldt","sequence":"additional","affiliation":[{"name":"Pfizer Global Research and Development New London CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Alzheimer's Disease Working Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,7,10]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2009.03.001"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.151.3.390"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002093-200110000-00003"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.23.11466"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.23.11471"},{"key":"e_1_2_7_7_2","first-page":"17","article-title":"The effect of tacrine and lecithin in Alzheimer's disease. 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