{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T15:48:54Z","timestamp":1790869734654,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T00:00:00Z","timestamp":1722211200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Recent clinical trials of amyloid beta (A\u03b2)\u2010targeting therapies in Alzheimer's disease (AD) have demonstrated a clinical benefit over 18 months, but their long\u2010term impact on disease trajectory is not yet understood. We propose a framework for evaluating realistic long\u2010term scenarios.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Results from recent phase 3 trials of A\u03b2\u2010targeting antibodies were integrated with an estimate of the long\u2010term patient\u2010level natural history trajectory of the Clinical Dementia Rating\u2010Sum of Boxes (CDR\u2010SB) score to explore realistic long\u2010term efficacy scenarios.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Three distinct long\u2010term efficacy scenarios were examined, ranging from conservative to optimistic. These extrapolations of positive phase 3 trials suggested treatments delayed onset of severe dementia by 0.3 to 0.6 years (conservative), 1.1 to 1.9 years (intermediate), and 2.0 to 4.2 years (optimistic).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Our study provides a common language for long\u2010term impact of disease\u2010modifying treatments. Our work calls for studies with longer follow\u2010up and results from early intervention trials to provide a comprehensive assessment of these therapies' true long\u2010term impact.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>We present long\u2010term scenarios of the efficacy of AD therapies.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>In this framework, scenarios are defined relative to the natural history of AD.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Long\u2010term projections with different levels of optimism can be compared.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>It provides a common language for expressing beliefs about long\u2010term efficacy.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.14134","type":"journal-article","created":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T06:49:34Z","timestamp":1722235774000},"page":"6374-6383","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Scenarios for the long\u2010term efficacy of amyloid\u2010targeting therapies in the context of the natural history of Alzheimer's disease"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7099-2314","authenticated-orcid":false,"given":"Lars Lau","family":"Raket","sequence":"first","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"},{"name":"Clinical Memory Research Unit Department of Clinical Sciences Lund University  Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Cummings","sequence":"additional","affiliation":[{"name":"Chambers\u2010Grundy Center for Transformative Neuroscience Pam Quirk Brain Health and Biomarker Laboratory Department of Brain Health School of Integrated Health Sciences University of Nevada Las Vegas (UNLV)  Las Vegas Nevada USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Moscoso","sequence":"additional","affiliation":[{"name":"Wallenberg Centre for Molecular and Translational Medicine and the Department of Psychiatry and Neurochemistry University of Gothenburg Huvudbyggnad Vasaparken, Universitetsplatsen 1  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Villain","sequence":"additional","affiliation":[{"name":"Department of Neurology Institute of Memory and Alzheimer's Disease AP\u2010HP Sorbonne Universit\u00e9 Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital  Paris France"},{"name":"Sorbonne Universit\u00e9 INSERM U1127 Institut du Cerveau \u2010 ICM  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Sch\u00f6ll","sequence":"additional","affiliation":[{"name":"Wallenberg Centre for Molecular and Translational Medicine and the Department of Psychiatry and Neurochemistry University of Gothenburg Huvudbyggnad Vasaparken, Universitetsplatsen 1  Gothenburg Sweden"},{"name":"Department of Clinical Physiology Sahlgrenska University Hospital  Gothenburg Sweden"},{"name":"Dementia Research Centre Queen Square Institute of Neurology University College London  London 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