{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:24:50Z","timestamp":1791908690832,"version":"4.3.4"},"reference-count":46,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2018,2,20]],"date-time":"2018-02-20T00:00:00Z","timestamp":1519084800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2018,2,20]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Therapeutic research on Alzheimer\u2019s disease (AD) has moved to intercepting the disease at the preclinical phase. Most drugs in late development have focused on the amyloid hypothesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To understand the magnitude of amyloid-related functional decline and to identify the functional domains sensitive to decline in a preclinical AD population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Data were from the Religious Orders Study and the Rush Memory and Aging Project. Cognitive decline was measured by a modified version of the Alzheimer\u2019s Disease Cooperative Study Preclinical Alzheimer Cognitive Composite. The trajectories of functional decline, as measured by the instrumental and basic activities of daily living, were longitudinally modeled in 484 participants without cognitive impairment at baseline and having both a final clinical and a postmortem neuropathology assessment of AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Individuals with different final clinical diagnoses had different trajectories of cognitive and functional decline. Individuals with AD dementia, minor cognitive impairment, and no cognitive impairment had the most, intermediate, and least declines. While individuals with pathologic AD had significantly more cognitive decline over time than those without, the magnitude of difference in functional decline between these two groups was small. Functional domains such as handling finance and handling medications were more sensitive to decline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Demonstrating the functional benefit of an amyloid-targeting drug represents a significant challenge as elderly people experience functional decline due to a wide range of reasons with limited manifestation attributable to AD neuropathology. More sensitive functional scales focusing on the functional domains sensitive to decline in preclinical AD are needed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jad-170903","type":"journal-article","created":{"date-parts":[[2018,2,20]],"date-time":"2018-02-20T18:25:01Z","timestamp":1519151101000},"page":"855-865","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":13,"title":["Longitudinal Modeling of Functional Decline Associated with Pathologic Alzheimer\u2019s Disease in Older Persons without Cognitive Impairment"],"prefix":"10.1177","volume":"62","author":[{"given":"Dai","family":"Wang","sequence":"first","affiliation":[{"name":"R&D Information Technology, Janssen Research and Development, LLC, Titusville, NJ, USA"},{"name":"Neuroscience Therapeutic Area, Janssen Research and Development, LLC, Titusville, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Schultz","sequence":"additional","affiliation":[{"name":"R&D Information Technology, Janssen Research and Development, LLC, Titusville, NJ, USA"},{"name":"Neuroscience Therapeutic Area, Janssen Research and Development, LLC, Titusville, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald P.","family":"Novak","sequence":"additional","affiliation":[{"name":"Neuroscience Therapeutic Area, Janssen Research and Development, LLC, Titusville, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Baker","sequence":"additional","affiliation":[{"name":"Neuroscience Therapeutic Area, Janssen Research and Development, LLC, Titusville, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Bennett","sequence":"additional","affiliation":[{"name":"Rush Alzheimer\u2019s Disease Center, Rush University Medical Center, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaibhav A.","family":"Narayan","sequence":"additional","affiliation":[{"name":"R&D Information Technology, Janssen Research and Development, LLC, Titusville, NJ, USA"},{"name":"Neuroscience Therapeutic Area, Janssen Research and Development, LLC, Titusville, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2018,2,20]]},"reference":[{"key":"ref001","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1312889"},{"key":"ref002","doi-asserted-by":"publisher","DOI":"10.1038\/nbt0515-438"},{"key":"ref003","doi-asserted-by":"publisher","DOI":"10.1007\/s40259-016-0168-3"},{"key":"ref004","doi-asserted-by":"publisher","DOI":"10.1126\/science.1566067"},{"key":"ref005","doi-asserted-by":"publisher","DOI":"10.1126\/science.1072994"},{"key":"ref006","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(00)02031-2"},{"key":"ref007","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201606210"},{"key":"ref008","doi-asserted-by":"publisher","DOI":"10.1097\/01.wad.0000184005.22611.cc"},{"key":"ref009","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1304839"},{"key":"ref010","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.003"},{"key":"ref011","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2014.803"},{"key":"ref012","first-page":"128","volume":"2","author":"Vellas B","year":"2015","journal-title":"J Prev Alzheimers Dis"},{"key":"ref013","first-page":"2","volume":"2","author":"Langbaum JB","year":"2015","journal-title":"J Prev Alzheimers Dis"},{"key":"ref014","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2014.3375"},{"key":"ref015","doi-asserted-by":"publisher","DOI":"10.1093\/geront\/9.3_Part_1.179"},{"key":"ref016","doi-asserted-by":"publisher","DOI":"10.1093\/geront\/10.1_Part_1.20"},{"key":"ref017","doi-asserted-by":"publisher","DOI":"10.1093\/geronj\/37.3.323"},{"key":"ref018","doi-asserted-by":"publisher","DOI":"10.1097\/00002093-199700112-00005"},{"key":"ref019","doi-asserted-by":"publisher","DOI":"10.5014\/ajot.53.5.471"},{"key":"ref020","first-page":"653","volume":"24","author":"Reisberg B","year":"1988","journal-title":"Psychopharmacol Bull"},{"key":"ref021","doi-asserted-by":"publisher","DOI":"10.2174\/156720512801322573"},{"key":"ref022","doi-asserted-by":"publisher","DOI":"10.2174\/156720512801322663"},{"key":"ref023","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181f39adc"},{"key":"ref024","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23964"},{"key":"ref025","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2015.04.006"},{"key":"ref026","doi-asserted-by":"publisher","DOI":"10.1016\/0022-3956(75)90026-6"},{"key":"ref027","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1991.00530150046016"},{"key":"ref028","unstructured":"DavidWechsler (1987)\n                      WMS-R: Wechsler Memory Scale\u2013Revised manual\n                      , Psychological Corporation, San Antonio, TX."},{"key":"ref029","doi-asserted-by":"publisher","DOI":"10.1007\/BF01109053"},{"key":"ref030","unstructured":"DavidWechsler (1981)\n                      WAIS-R: Wechsler adult intelligence scale\u2013Revised manual,\n                      Psychological Corporation, San Antonio, TX."},{"key":"ref031","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.1992.tb01992.x"},{"key":"ref032","doi-asserted-by":"publisher","DOI":"10.1159\/000096129"},{"key":"ref033","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000118211.78503.F5"},{"key":"ref034","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000152982.47274.9E"},{"key":"ref035","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000219668.47116.e6"},{"key":"ref036","doi-asserted-by":"publisher","DOI":"10.1159\/000096129"},{"key":"ref037","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23654"},{"key":"ref038","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.41.4.479"},{"key":"ref039","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308809"},{"key":"ref040","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199710000-00002"},{"key":"ref041","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/34.1-2.28"},{"key":"ref042","first-page":"4","volume":"2","author":"Marson D","year":"2015","journal-title":"J Prev Alzheimers Dis"},{"key":"ref043","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.10.006"},{"key":"ref044","doi-asserted-by":"publisher","DOI":"10.1002\/gps.1367"},{"key":"ref045","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2014.09.002"},{"key":"ref046","doi-asserted-by":"publisher","DOI":"10.2174\/1567205011666141001120903"}],"container-title":["Journal of Alzheimer\u2019s Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-170903","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.3233\/JAD-170903","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-170903","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:05:51Z","timestamp":1777370751000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3233\/JAD-170903"}},"subtitle":[],"editor":[{"given":"Peter","family":"Whitehouse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2018,2,20]]},"references-count":46,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2018,2,20]]}},"alternative-id":["10.3233\/JAD-170903"],"URL":"https:\/\/doi.org\/10.3233\/jad-170903","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2,20]]}}}