{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T12:39:28Z","timestamp":1784205568980,"version":"3.55.0"},"reference-count":32,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T00:00:00Z","timestamp":1612224000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2021,2,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>This study evaluated whether the apolipoprotein \u025b4 ( APOE4) allele, a genetic marker associated with increased risk of developing late-onset Alzheimer\u2019s disease (AD), was associated with differences in evoked pain responsiveness in cognitively healthy subjects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>The aim was to determine whether individuals at increased risk of late-onset AD based on APOE allele genotype differ phenotypically in their response to experimentally-induced painful stimuli compared to those who do not have at least one copy of the \u025b4 allele.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Forty-nine cognitively healthy subjects aged 30\u201389 years old with the APOE4 allele ( n\u200a=\u200a12) and without ( n\u200a=\u200a37) were assessed for group differences in pain thresholds and affective (unpleasantness) responses to experimentally-induced thermal pain stimuli.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Statistically significant main effects of APOE4 status were observed for both the temperature at which three different pain intensity percepts were reached ( p\u200a=\u200a0.040) and the level of unpleasantness associated with each ( p\u200a=\u200a0.014). APOE4 positive participants displayed lower overall pain sensitivity than those who were APOE4 negative and also greater overall levels of pain unpleasantness regardless of intensity level.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Cognitively healthy APOE4 carriers at increased risk of late-onset AD demonstrated reduced thermal pain sensitivity but greater unpleasantness to thermal pain stimuli relative to individuals at lower risk of late-onset AD. These results suggest that altered evoked pain perception could potentially be used as a phenotypic biomarker of late-onset AD risk prior to disease onset. Additional studies of this issue may be warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jad-201293","type":"journal-article","created":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T12:43:50Z","timestamp":1608036230000},"page":"1227-1233","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Could Altered Evoked Pain Responsiveness Be a Phenotypic Biomarker for Alzheimer\u2019s Disease Risk? A Cross-Sectional Analysis of Cognitively Healthy Individuals"],"prefix":"10.1177","volume":"79","author":[{"given":"Raymond R.","family":"Romano","sequence":"first","affiliation":[{"name":"College of Graduate Health Sciences, University of Tennessee Health Science Center, Memphis, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Carter","sequence":"additional","affiliation":[{"name":"College of Nursing, University of Tennessee Health Science Center, Memphis, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary S.","family":"Dietrich","sequence":"additional","affiliation":[{"name":"School of Medicine (Biostatistics, Psychiatry) and School of Nursing, Vanderbilt University, Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald L.","family":"Cowan","sequence":"additional","affiliation":[{"name":"Departments of Psychiatry and Anatomy and Neurobiology,College of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen P.","family":"Bruehl","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd B.","family":"Monroe","sequence":"additional","affiliation":[{"name":"College of Nursing, The Ohio State University, Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,2,5]]},"reference":[{"key":"ref001","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12068"},{"key":"ref002","doi-asserted-by":"publisher","DOI":"10.1177\/147323000403200207"},{"key":"ref003","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.47.1.56"},{"key":"ref004","doi-asserted-by":"publisher","DOI":"10.1177\/1099800420947176"},{"key":"ref005","doi-asserted-by":"publisher","DOI":"10.1002\/gps.2204"},{"key":"ref006","unstructured":"MatlinMW, FoleyHJ (1992) Sensation and perception, 3rd ed, Allyn & Bacon, Needham Heights, MA, US."},{"key":"ref007","doi-asserted-by":"publisher","DOI":"10.1177\/0891988712466457"},{"key":"ref008","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-161187"},{"key":"ref009","first-page":"1737","volume":"19","author":"Monroe TB","year":"2018","journal-title":"Pain Med"},{"key":"ref010","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-016-0619-1"},{"key":"ref011","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-190142"},{"key":"ref012","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-019-0324-6"},{"key":"ref013","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-019-1299-4"},{"key":"ref014","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-019-0228-7"},{"key":"ref015","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0060970"},{"key":"ref016","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genom.1.1.507"},{"key":"ref017","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70325-2"},{"key":"ref018","doi-asserted-by":"publisher","DOI":"10.1159\/000334607"},{"key":"ref019","doi-asserted-by":"publisher","DOI":"10.1016\/0022-3956(75)90026-6"},{"key":"ref020","unstructured":"HollingsheadAB (1975) Four factor index of social status. 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