{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T04:50:41Z","timestamp":1790484641005,"version":"4.1.0"},"reference-count":27,"publisher":"American Medical Association (AMA)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Alzheimer disease (AD) biomarker and genetic testing results are increasingly disclosed to cognitively unimpaired adults in research and could in the future inform clinical treatment decisions in this population.<\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n \n To assess psychological outcomes after returning 3 categories of amyloid biomarker results as well as apolipoprotein E (\n APOE<\/jats:italic>\n ) genotypes.\n <\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This cohort study was a secondary analysis of data collected as part of screening for the multisite AHEAD preclinical AD trial. Participants were individuals aged 55 to 80 years undergoing screening from July 14, 2020, to October 15, 2024.<\/jats:p>\n <\/jats:sec>\n \n Exposure<\/jats:title>\n \n Participants were informed whether they had not-detected, intermediate, or elevated amyloid positron emission tomography levels, as well as their\n APOE<\/jats:italic>\n genotype, which were categorized as noncarrier, \u03b54 heterozygote, or \u03b54 homozygote.\n <\/jats:p>\n <\/jats:sec>\n \n Main outcomes and measures<\/jats:title>\n Impact of Events Scale (IES; 15 items to assess intrusive thoughts and avoidance; each item is scored as not at all [0], rarely [1], sometimes [3], or often [5]; total range, 0-75), collected 24 to 72 hours after disclosure, and change in a scale measuring concerns about AD dementia (adapted scale using 6 items in which participants indicated their level of agreement with statements related to their perceived probability of developing AD dementia; items scored as strongly disagree [1] through strongly agree [5]; total range, 6-30), calculated by subtracting the score collected before biomarker testing from 1 collected after biomarker and genetic test results disclosure.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Among 3414 included individuals, the mean (SD) age was 68.8 (6.0) years and 2116 (62%) were female. Group mean IES scores were below clinically significant thresholds. Nevertheless, across genetic groups, learning an elevated amyloid result (1184 participants) was associated with higher IES (mean [SD], 10.5 [10.9]) than intermediate amyloid (482 participants; mean [SD] IES, 8.8 [9.8]), and intermediate amyloid was associated with higher scores than not-detected amyloid (1748 participants; mean [SD] IES, 6.5 [8.4]). Across amyloid groups, learning\n APOE<\/jats:italic>\n \u03b54 homozygosity (337 participants) was associated with higher mean (SD) IES (12.7 [11.6]) than heterozygosity (1609 participants; 9.1 [10.2]), and heterozygosity was associated with higher IES than noncarrier status (1468 participants; mean [SD] IES, 6.2 [8.1]). Both types of information were significant in an analysis of covariance model; no interaction effect was observed. In contrast, only biomarker disclosure was associated with differential change in concerns about AD dementia. Those with elevated amyloid showed a mean (SD) increase in concern (0.8 [3.5]), those with intermediate amyloid showed a smaller increase (0.4 [3.7]), and those with not-detected amyloid showed decreased concerns (\u22121.1 [4.2]).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this cohort study of cognitively unimpaired adults, associations with intrusive thoughts were observed to differ among genetic and biomarker subgroups; such associations were limited to biomarker subgroups for measures of perceived dementia risk.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2026.3845","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T15:30:28Z","timestamp":1774884628000},"page":"e263845","source":"Crossref","is-referenced-by-count":3,"title":["Amyloid Imaging and\n APOE<\/i>\n Genotype Disclosure and Short-Term Psychological Distress"],"prefix":"10.1001","volume":"9","author":[{"given":"Joshua D.","family":"Grill","sequence":"first","affiliation":[{"name":"Institute for Memory Impairments and Neurological Disorders, University of California, Irvine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rema","family":"Raman","sequence":"additional","affiliation":[{"name":"Epstein Family Alzheimer's Therapeutic Research Institute, University of Southern California, San Diego"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunran","family":"Wang","sequence":"additional","affiliation":[{"name":"Epstein Family Alzheimer's Therapeutic Research Institute, University of Southern California, San Diego"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Ernstrom","sequence":"additional","affiliation":[{"name":"Epstein Family Alzheimer's Therapeutic Research Institute, University of Southern California, San Diego"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia S.","family":"Andrews","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian S.","family":"Appleby","sequence":"additional","affiliation":[{"name":"Departments of Neurology, Psychiatry, and Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio"},{"name":"University Hospitals Cleveland Medical Center, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaspreet","family":"Bhangu","sequence":"additional","affiliation":[{"name":"St Joseph\u2019s Health Care London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shobha","family":"Dhadda","sequence":"additional","affiliation":[{"name":"Eisai, Nutley, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Irizarry","sequence":"additional","affiliation":[{"name":"Eisai, Nutley, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Johnson","sequence":"additional","affiliation":[{"name":"Center for Alzheimers, Harvard, Brigham and Women\u2019s Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Lenio","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston University, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Michigan, Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay K.","family":"Ramanan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul B.","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"Department of Psychology, Johns Hopkins University, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Weisman","sequence":"additional","affiliation":[{"name":"Abington Neurologic Associates, Abington, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Aisen","sequence":"additional","affiliation":[{"name":"Epstein Family Alzheimer's Therapeutic Research Institute, University of Southern California, San Diego"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reisa","family":"Sperling","sequence":"additional","affiliation":[{"name":"Center for Alzheimers, Harvard, Brigham and Women\u2019s Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Sultzer","sequence":"additional","affiliation":[{"name":"Institute for Memory Impairments and Neurological Disorders, University of California, Irvine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Karlawish","sequence":"additional","affiliation":[{"name":"University of Pennsylvania, Philadelphia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"issue":"8","key":"zoi260152r1","doi-asserted-by":"publisher","first-page":"5143","DOI":"10.1002\/alz.13859","article-title":"Revised criteria for diagnosis and staging of Alzheimer\u2019s disease: Alzheimer\u2019s Association Workgroup.","volume":"20","author":"Jack","year":"2024","journal-title":"Alzheimers Dement"},{"issue":"12","key":"zoi260152r2","doi-asserted-by":"publisher","first-page":"1304","DOI":"10.1001\/jamaneurol.2024.3770","article-title":"Alzheimer disease as a clinical-biological construct-an international working group recommendation.","volume":"81","author":"Dubois","year":"2024","journal-title":"JAMA Neurol"},{"issue":"22","key":"zoi260152r3","doi-asserted-by":"publisher","first-page":"4757","DOI":"10.1016\/j.cell.2023.09.023","article-title":"Accelerating Alzheimer\u2019s therapeutic development: the past and future of clinical trials.","volume":"186","author":"Boxer","year":"2023","journal-title":"Cell"},{"key":"zoi260152r4","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12748","article-title":"The AHEAD 3-45 study: design of a prevention trial for Alzheimer\u2019s disease.","volume":"\u2022\u2022\u2022","author":"Rafii","year":"2022","journal-title":"Alzheimers Dement"},{"issue":"1","key":"zoi260152r5","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1186\/s13195-021-00807-6","article-title":"Early detection of amyloid load using 18F-florbetaben PET.","volume":"13","author":"Bullich","year":"2021","journal-title":"Alzheimers Res Ther"},{"issue":"17","key":"zoi260152r6","doi-asserted-by":"publisher","first-page":"e1452","DOI":"10.1212\/WNL.0000000000005354","article-title":"Memory decline accompanies subthreshold amyloid accumulation.","volume":"90","author":"Landau","year":"2018","journal-title":"Neurology"},{"issue":"6","key":"zoi260152r7","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1001\/jama.2023.13239","article-title":"Donanemab in early symptomatic Alzheimer disease: the TRAILBLAZER-ALZ 2 randomized clinical trial.","volume":"330","author":"Sims","year":"2023","journal-title":"JAMA"},{"issue":"1","key":"zoi260152r8","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1056\/NEJMoa2212948","article-title":"Lecanemab in early Alzheimer\u2019s disease.","volume":"388","author":"van Dyck","year":"2022","journal-title":"N Engl J Med"},{"issue":"5","key":"zoi260152r9","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1001\/jamaneurol.2025.0065","article-title":"Amyloid-related imaging abnormalities with donanemab in early symptomatic Alzheimer disease: secondary analysis of the TRAILBLAZER-ALZ and ALZ 2 randomized clinical trials.","volume":"82","author":"Zimmer","year":"2025","journal-title":"JAMA Neurol"},{"issue":"1","key":"zoi260152r10","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1186\/s13195-015-0112-7","article-title":"Development of a process to disclose amyloid imaging results to cognitively normal older adult research participants.","volume":"7","author":"Harkins","year":"2015","journal-title":"Alzheimers Res Ther"},{"issue":"12","key":"zoi260152r11","doi-asserted-by":"publisher","first-page":"1504","DOI":"10.1001\/jamaneurol.2020.2734","article-title":"Short-term psychological outcomes of disclosing amyloid imaging results to research participants who do not have cognitive impairment.","volume":"77","author":"Grill","year":"2020","journal-title":"JAMA Neurol"},{"issue":"2","key":"zoi260152r12","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.1002\/alz.13542","article-title":"Plasma Abeta42\/Abeta40 and phospho-tau217 concentration ratios increase the accuracy of amyloid PET classification in preclinical Alzheimer\u2019s disease.","volume":"20","author":"Rissman","year":"2023","journal-title":"Alzheimers Dement"},{"issue":"3","key":"zoi260152r13","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1097\/00006842-197905000-00004","article-title":"Impact of event scale: a measure of subjective stress.","volume":"41","author":"Horowitz","year":"1979","journal-title":"Psychosom Med"},{"issue":"6","key":"zoi260152r14","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1016\/j.jalz.2008.04.007","article-title":"Comparing test-specific distress of susceptibility versus deterministic genetic testing for Alzheimer\u2019s disease.","volume":"4","author":"Cassidy","year":"2008","journal-title":"Alzheimers Dement"},{"issue":"1","key":"zoi260152r15","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2022.50921","article-title":"Analysis of psychological symptoms following disclosure of amyloid-positron emission tomography imaging results to adults with subjective cognitive decline.","volume":"6","author":"Caprioglio","year":"2023","journal-title":"JAMA Netw Open"},{"issue":"3","key":"zoi260152r16","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1097\/00002093-200007000-00003","article-title":"Illness representations among first-degree relatives of people with Alzheimer disease.","volume":"14","author":"Roberts","year":"2000","journal-title":"Alzheimer Dis Assoc Disord"},{"issue":"12","key":"zoi260152r17","doi-asserted-by":"publisher","first-page":"1296","DOI":"10.1038\/ejhg.2010.119","article-title":"The role of disease perceptions and results sharing in psychological adaptation after genetic susceptibility testing: the REVEAL Study.","volume":"18","author":"Ashida","year":"2010","journal-title":"Eur J Hum Genet"},{"issue":"1","key":"zoi260152r18","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1038\/nrneurol.2012.241","article-title":"Preclinical Alzheimer disease-the challenges ahead.","volume":"9","author":"Sperling","year":"2013","journal-title":"Nat Rev Neurol"},{"issue":"14","key":"zoi260152r19","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1212\/WNL.0000000000207438","article-title":"Implications of the approval of lecanemab for Alzheimer disease patient care: incremental step or paradigm shift?","volume":"101","author":"Knopman","year":"2023","journal-title":"Neurology"},{"issue":"1","key":"zoi260152r20","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/s13195-016-0212-z","article-title":"Psychological, behavioral and social effects of disclosing Alzheimer\u2019s disease biomarkers to research participants: a systematic review.","volume":"8","author":"Bemelmans","year":"2016","journal-title":"Alzheimers Res Ther"},{"key":"zoi260152r21","doi-asserted-by":"publisher","DOI":"10.1017\/S1041610217002204","author":"Wake","year":"2018","journal-title":"Int Psychogeriatr"},{"issue":"9","key":"zoi260152r22","doi-asserted-by":"publisher","first-page":"6579","DOI":"10.1002\/alz.14153","article-title":"Psychosocial implications of learning amyloid PET results in an observational cohort.","volume":"20","author":"Clark","year":"2024","journal-title":"Alzheimers Dement"},{"key":"zoi260152r23","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0809578","author":"Green","year":"2009","journal-title":"N Engl J Med"},{"issue":"3","key":"zoi260152r24","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1177\/0891988721993575","article-title":"Safety and tolerability of APOE genotyping and disclosure in cognitively normal volunteers from the Butler Alzheimer\u2019s prevention registry.","volume":"35","author":"Alber","year":"2022","journal-title":"J Geriatr Psychiatry Neurol"},{"key":"zoi260152r25","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.103","author":"Christensen","year":"2018","journal-title":"Genet Med"},{"issue":"2","key":"zoi260152r26","doi-asserted-by":"publisher","DOI":"10.1212\/CPJ.0000000000200265","article-title":"Immediate reactions to Alzheimer biomarker disclosure in cognitively unimpaired individuals in a global truncated randomized trial.","volume":"14","author":"Grill","year":"2024","journal-title":"Neurol Clin Pract"},{"issue":"2","key":"zoi260152r27","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0229137","article-title":"Cognitively unimpaired adults\u2019 reactions to disclosure of amyloid PET scan results.","volume":"15","author":"Largent","year":"2020","journal-title":"PLoS One"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2847125\/grill_2026_oi_260152_1774285973.17272.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T15:30:28Z","timestamp":1774884628000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2847125"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,30]]},"references-count":27,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3,2]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2026.3845","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,30]]}}}