{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T10:38:24Z","timestamp":1760524704176,"version":"3.32.0"},"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T00:00:00Z","timestamp":1735516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Despite several studies having correlated Alzheimer\u2019s disease with mental health conditions, the extent to which they have been incorporated into Alzheimer\u2019s disease clinical trials remains unclear.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Objective<\/jats:title>\n<jats:p>This study aimed to assess the temporal trends in mental health-related terminology in Alzheimer\u2019s disease clinical trials as a proxy measure of research interest. Additionally, it sought to determine the effect of the COVID-19 pandemic on the frequency of these terms through pre-pandemic and post-pandemic trend assessment.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Methods<\/jats:title>\n<jats:p>In this retrospective descriptive analysis, we included 2243 trials with a start date between 1988 and 2022 by searching for the keyword \u201cAlzheimer Disease\u201d in the U.S. National Library of Medicine ClinicaTrials.gov database. A Python program was created to extract and count the frequency of four mental health terms (loneliness, depression, anxiety, and distress) by year and trial status (e.g., completed, active, recruiting). Binary logistic regression analyses were conducted to examine the yearly patterns in the appearance of the four mental health terms. A multivariable logistic regression analysis was performed to identify trial characteristics associated with each mental health term.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Results<\/jats:title>\n<jats:p>Our results depicted a statistically significant increasing trend in three (i.e., loneliness, anxiety, distress) of the four mental health conditions by year. A comparison between pre-pandemic and post-pandemic trials showed an increase in the mention of the same three words over time.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Interpretation<\/jats:title>\n<jats:p>These results may suggest a growing awareness of mental health conditions and a greater interest in considering these conditions in Alzheimer\u2019s disease trials, particularly after the onset of COVID-19. Future researchers should conduct more in-depth analyses to examine how mental health variables are operationalized in these trials, with consideration for their subsequent success.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0310264","type":"journal-article","created":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T18:40:04Z","timestamp":1735584004000},"page":"e0310264","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Temporal trends in mental health terminology in Alzheimer\u2019s disease clinical trials"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0384-8472","authenticated-orcid":true,"given":"Amir-Ali","family":"Golrokhian-Sani","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1561-6746","authenticated-orcid":true,"given":"Maya","family":"Morcos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1208-7842","authenticated-orcid":true,"given":"Alecco","family":"Philippi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reem","family":"Al-Rawi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3744-9930","authenticated-orcid":true,"given":"Marc","family":"Morcos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Fu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,12,30]]},"reference":[{"key":"pone.0310264.ref001","volume-title":"In: StatPearls","author":"A Kumar","year":"2022"},{"key":"pone.0310264.ref002","doi-asserted-by":"crossref","first-page":"937486","DOI":"10.3389\/fnagi.2022.937486","article-title":"Global, regional, and national burden of Alzheimer\u2019s disease and other dementias, 1990\u20132019","volume":"14","author":"X Li","year":"2022","journal-title":"Front Aging Neurosci"},{"issue":"12","key":"pone.0310264.ref003","first-page":"e50522","article-title":"The Latest Advances in the Diagnosis and Treatment of Dementia","volume":"15","author":"R Hafiz","year":"2023","journal-title":"Cureus"},{"key":"pone.0310264.ref004","volume-title":"In: StatPearls","author":"N Cloak","year":"2024"},{"issue":"3","key":"pone.0310264.ref005","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.3233\/JAD-215198","article-title":"Behavioral and Psychological Symptoms of Dementia in Different Dementia Disorders: A Large-Scale Study of 10,000 Individuals","volume":"87","author":"E Schwertner","year":"2022","journal-title":"J Alzheimers Dis"},{"issue":"2","key":"pone.0310264.ref006","first-page":"619","article-title":"Caregiver Stress and the Patient With Dementia","volume":"22","author":"AE Sanders","year":"2016","journal-title":"Continuum (Minneap Minn)"},{"issue":"12","key":"pone.0310264.ref007","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1080\/13607863.2017.1387760","article-title":"Psychosocial risk factors and Alzheimer\u2019s disease: the associative effect of depression, sleep disturbance, and anxiety","volume":"22","author":"SL Burke","year":"2018","journal-title":"Aging Ment Health"},{"issue":"3\u20134","key":"pone.0310264.ref008","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1177\/0898264320977309","article-title":"Psychological Distress and Alzheimer\u2019s Disease Mortality in the United States: Results from the 1997\u20132014 National Health Interview Survey-National Death Index Record Linkage Study","volume":"33","author":"GK Singh","year":"2021","journal-title":"J Aging Health"},{"issue":"7","key":"pone.0310264.ref009","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1093\/geronb\/gby112","article-title":"Loneliness and Risk of Dementia","volume":"75","author":"AR Sutin","year":"2020","journal-title":"J Gerontol Ser B"},{"key":"pone.0310264.ref010","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.3389\/fpsyg.2020.01226","article-title":"Mental Health and Well-Being of University Students: A Bibliometric Mapping of the Literature","volume":"11","author":"D Hern\u00e1ndez-Torrano","year":"2020","journal-title":"Front Psychol"},{"issue":"4","key":"pone.0310264.ref011","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1097\/WAD.0000000000000454","article-title":"Cognitive Behavioral Therapy for Mood and Insomnia in Persons With Dementia: A Systematic Review","volume":"35","author":"JW Jin","year":"2021","journal-title":"Alzheimer Dis Assoc Disord"},{"key":"pone.0310264.ref012","first-page":"1","article-title":"Behavioral and Psychological Symptoms in Alzheimer\u2019s Disease","volume":"2014","author":"XL Li","year":"2014","journal-title":"BioMed Res Int"},{"issue":"10","key":"pone.0310264.ref013","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1002\/alz.12327","article-title":"Associations of loneliness with risk of Alzheimer\u2019s disease dementia in the Framingham Heart Study","volume":"17","author":"SC Akhter\u2010Khan","year":"2021","journal-title":"Alzheimers Dement"},{"issue":"1","key":"pone.0310264.ref014","doi-asserted-by":"crossref","first-page":"171","DOI":"10.3233\/ADR-210294","article-title":"The Relationship Between Anxiety and Alzheimer\u2019s Disease","volume":"5","author":"MF Mendez","year":"2021","journal-title":"J Alzheimers Dis Rep"},{"key":"pone.0310264.ref015","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.ynstr.2018.04.002","article-title":"The relationship between stress and Alzheimer\u2019s disease","volume":"8","author":"NJ Justice","year":"2018","journal-title":"Neurobiol Stress"},{"issue":"7","key":"pone.0310264.ref016","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1093\/geronb\/gby112","article-title":"Loneliness and risk of dementia","volume":"75","author":"AR Sutin","year":"2020","journal-title":"J Gerontol B Psychol Sci Soc Sci"},{"key":"pone.0310264.ref017","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.jad.2015.09.069","article-title":"The prevalence of neuropsychiatric symptoms in Alzheimer\u2019s disease: Systematic review and meta-analysis","volume":"190","author":"QF Zhao","year":"2016","journal-title":"J Affect Disord"},{"issue":"3","key":"pone.0310264.ref018","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1159\/000095761","article-title":"Chronic psychological distress and risk of Alzheimer\u2019s disease in old age","volume":"27","author":"RS Wilson","year":"2006","journal-title":"Neuroepidemiology"},{"key":"pone.0310264.ref019","volume-title":"WHO Director-General\u2019s opening remarks at the media briefing on COVID-19\u201311 March 2020Internet","author":"World Health Organization","year":"2020"},{"key":"pone.0310264.ref020","unstructured":"Centers for Disease Control and Prevention. Timeline of CDC\u2019s Response to COVID-19 [Internet]. CDC; last reviewed 2023 Mar 15 [cited 2024 May 15]. Available from: https:\/\/www.cdc.gov\/museum\/timeline\/covid19.html."},{"key":"pone.0310264.ref021","volume-title":"World mental health report: Transforming mental health for all","author":"World Health Organization","year":"2022"},{"issue":"6","key":"pone.0310264.ref022","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1111\/j.1600-0447.2012.01826.x","article-title":"Evolution of public attitudes about mental illness: a systematic review and meta-analysis: Evolution of public attitudes","volume":"125","author":"G Schomerus","year":"2012","journal-title":"Acta Psychiatr Scand"},{"issue":"5\u20136","key":"pone.0310264.ref023","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1159\/000494921","article-title":"Effects of Light Treatment on Sleep, Cognition, Mood, and Behavior in Alzheimer\u2019s Disease: A Systematic Review","volume":"46","author":"M Mitolo","year":"2018","journal-title":"Dement Geriatr Cogn Disord"},{"issue":"18","key":"pone.0310264.ref024","doi-asserted-by":"crossref","first-page":"e29145","DOI":"10.1097\/MD.0000000000029145","article-title":"On Covid-19 and mental health: An observational study on depression, anxiety, and loneliness during the second lockdown in patients with Alzheimer disease","volume":"101","author":"M El Haj","year":"2022","journal-title":"Medicine (Baltimore)"},{"issue":"5","key":"pone.0310264.ref025","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1111\/inm.12601","article-title":"Post\u2010traumatic stress disorder and dementia in veterans: A scoping literature review","volume":"28","author":"K Ritchie","year":"2019","journal-title":"Int J Ment Health Nurs"},{"issue":"6","key":"pone.0310264.ref026","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1177\/0020764020922269","article-title":"Social isolation in covid-19: The impact of loneliness","volume":"66","author":"D Banerjee","year":"2020","journal-title":"Int J Soc Psychiatry"},{"issue":"4","key":"pone.0310264.ref027","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1002\/acp.3821","article-title":"Social isolation during COVID-19 lockdown impairs cognitive function","volume":"35","author":"J Ingram","year":"2021","journal-title":"Appl Cogn Psychol"},{"issue":"11","key":"pone.0310264.ref028","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1097\/JGP.0b013e318211c219","article-title":"Life space and risk of alzheimer disease, mild cognitive impairment, and cognitive decline in old age","volume":"19","author":"BD James","year":"2011","journal-title":"Am J Geriatr Psychiatry"},{"key":"pone.0310264.ref029","volume-title":"COVID-19 pandemic triggers 25% increase in prevalence of anxiety and depression worldwide","author":"World Health Organization","year":"2022"},{"issue":"1","key":"pone.0310264.ref030","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1080\/03071022.2017.1256093","article-title":"The rise of living alone and loneliness in history","volume":"42","author":"KD Snell","year":"2017","journal-title":"Soc Hist"},{"key":"pone.0310264.ref031","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.jrurstud.2021.01.014","article-title":"The rural exodus of young people from empty Spain. socio-educational aspects","volume":"82","author":"V Llorent-Bedmar","year":"2021","journal-title":"J Rural Stud"},{"issue":"3","key":"pone.0310264.ref032","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1002\/j.1839-4655.2004.tb01178.x","article-title":"\u2018you don\u2019t want to be a check\u2010out chick all your life\u2019: The out\u2010migration of young people from Australia\u2019s small rural towns","volume":"39","author":"M. Alston","year":"2004","journal-title":"Aust J Soc Issues"},{"issue":"2","key":"pone.0310264.ref033","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1007\/s11205-020-02304-z","article-title":"Disconnected lives: Trends in time spent alone in Finland","volume":"150","author":"T Anttila","year":"2020","journal-title":"Soc Indic Res"},{"issue":"11","key":"pone.0310264.ref034","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1176\/ajp.137.11.1399","article-title":"A clinic for the impaired elderly and their families","volume":"137","author":"BV Reifler","year":"1980","journal-title":"Am J Psychiatry"},{"key":"pone.0310264.ref035","unstructured":"Alzheimer\u2019s Society. Talking therapies [Internet]. London: Alzheimer\u2019s Society; last revised 2024 [cited 2024 May 15]. Available from: https:\/\/www.alzheimers.org.uk\/about-dementia\/symptoms-and-diagnosis\/talking-therapies."}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0310264","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T18:40:17Z","timestamp":1735584017000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0310264"}},"subtitle":[],"editor":[{"given":"Thiago P.","family":"Fernandes","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,12,30]]},"references-count":35,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,12,30]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0310264","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,30]]}}}