{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T09:23:02Z","timestamp":1774430582592,"version":"3.50.1"},"reference-count":97,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Public Health"],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Dementia is a neurodegenerative disease that affects more than 45 million patients worldwide. Treatment options for dementia include lecanemab for mild cognitive impairment, acetylcholinesterase inhibitors, which are mainly used for mild to moderate dementia, as well as N-methyl-D-aspartate receptor antagonists for patients with severe dementia or certain antipsychotics. Pharmaceutical approaches are limited by potential side effects. To alleviate symptoms or at least slightly improve cognitive functions, additional herbal medicines (HM) such as\n                      <jats:italic>Ginkgo biloba<\/jats:italic>\n                      and non-pharmacological approaches, e.g., behavioral, exercise, music, and reminiscence therapy, yoga, tai chi, or acupuncture, have been used with heterogeneous results.\n                      <jats:italic>Helleborus niger<\/jats:italic>\n                      , a plant containing multiple bioactive compounds such as ecdysteroids and bufadienolide, is used clinically for its immunomodulatory, anti-inflammatory, analgesic, and antioxidant properties. In a German hospital specializing in geriatric patients, an association between the subcutaneous application of\n                      <jats:italic>Helleborus niger<\/jats:italic>\n                      12x and changes in dementia was observed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Retrospective study on the effect of subcutaneous application of\n                      <jats:italic>Helleborus niger<\/jats:italic>\n                      12x for an average of 3\u202fweeks in patients with dementia. Eligible patients were aged \u2265 60\u202fyears and treated at the Humboldt Clinic in Bad Steben, Bavaria, Germany, with two different treatment regimens: standard care with conventional medication alone (control group, CG) vs. standard care with conventional medication plus\n                      <jats:italic>Helleborus niger<\/jats:italic>\n                      12x preparations (Helleborus group, HG). The primary outcome was the between-group difference in pre-post (T0 vs. T1) changes in the Mini-Mental State Examination (MMSE). Secondary outcomes were pre-post changes in the Dementia Detection test (DemTect), the Shulman clock-drawing test (CDT) and the Geriatric Depression Scale (GDS).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      For the primary outcome, there was a statistically significant difference in MMSE between the groups (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001;\n                      <jats:italic>d<\/jats:italic>\n                      \u202f=\u202f1.5) at T1 with significantly higher values in HG compared to CG. Regarding the secondary outcomes, significantly improved values were seen in HG compared to CG for DemTect, CDT and GDS with medium to high effect sizes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The study gives preliminary evidence that\n                      <jats:italic>Helleborus niger<\/jats:italic>\n                      12x applied subcutaneously might improve cognitive function in patients with dementia at least during the three-week administration. Further randomized, blinded studies with longer follow-up are needed to confirm preliminary results.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration<\/jats:title>\n                    <jats:p>Identifier, DRKS00033972.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fpubh.2026.1758447","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T06:51:37Z","timestamp":1774421497000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Subcutaneous application of Helleborus niger 12x in older patients with dementia\u2014a retrospective cohort study"],"prefix":"10.3389","volume":"14","author":[{"given":"Jan","family":"Vagedes","sequence":"first","affiliation":[{"name":"ARCIM Institute for Academic Research in Complementary and Integrative Medicine","place":["Filderstadt, Germany"]},{"name":"Department of Neonatology, University Hospital T\u00fcbingen","place":["T\u00fcbingen, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelika","family":"Hagen","sequence":"additional","affiliation":[{"name":"Geriatric Rehabilitation Center, Alexander von Humboldt Clinic","place":["Bad Steben, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad Oli Al","family":"Islam","sequence":"additional","affiliation":[{"name":"ARCIM Institute for Academic Research in Complementary and Integrative Medicine","place":["Filderstadt, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohsen","family":"Sobh","sequence":"additional","affiliation":[{"name":"ARCIM Institute for Academic Research in Complementary and Integrative Medicine","place":["Filderstadt, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katrin","family":"Vagedes","sequence":"additional","affiliation":[{"name":"ARCIM Institute for Academic Research in Complementary and Integrative Medicine","place":["Filderstadt, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henrik","family":"Sz\u0151ke","sequence":"additional","affiliation":[{"name":"Department of Integrative Medicine, University of P\u00e9cs","place":["P\u00e9cs, Hungary"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Kohl","sequence":"additional","affiliation":[{"name":"Institute of Precision Medicine, University Furtwangen","place":["Villingen-Schwenningen, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes","family":"Wilkens","sequence":"additional","affiliation":[{"name":"Geriatric Rehabilitation Center, Alexander von Humboldt Clinic","place":["Bad Steben, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"E696","DOI":"10.1016\/S2468-2667(21)00215-2","article-title":"Reinvigorating the public health response to dementia","volume":"6","year":"2021","journal-title":"Lancet Public Health"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s11920-019-1049-5","article-title":"Management of behavioral and psychological symptoms of dementia","volume":"21","author":"Bessey","year":"2019","journal-title":"Curr Psychiatry Rep"},{"key":"ref3","volume-title":"Global action plan on the public health response to dementia 2017-2025","year":"2017"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1186\/s12913-019-4641-9","article-title":"E-learning as valuable caregivers' support for people with dementia - a systematic review","volume":"19","author":"Klimova","year":"2019","journal-title":"BMC Health Serv Res"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"e0196085","DOI":"10.1371\/journal.pone.0196085","article-title":"What does the general public understand about prevention and treatment of dementia? A systematic review of population-based surveys","volume":"13","author":"Cations","year":"2018","journal-title":"PLoS One"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"778","DOI":"10.3389\/fphar.2020.00778","article-title":"Different doses of pharmacological treatments for mild to moderate Alzheimer\u2019s disease: a Bayesian network Meta-analysis","volume":"11","author":"Zhang","year":"2020","journal-title":"Front Pharmacol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1192\/bjp.2020.136","article-title":"Real-world effectiveness, its predictors and onset of action of cholinesterase inhibitors and memantine in dementia: retrospective health record study","volume":"218","author":"Vaci","year":"2020","journal-title":"Br J Psychiatry"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1823","DOI":"10.1021\/acschemneuro.7b00270","article-title":"Classics in chemical neuroscience: memantine","volume":"8","author":"Alam","year":"2017","journal-title":"ACS Chem Neurosci"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1571","DOI":"10.1007\/s00213-018-4867-y","article-title":"The treatment of cognitive dysfunction in dementia: a multiple treatments meta-analysis","volume":"235","author":"Perng","year":"2018","journal-title":"Psychopharmacology"},{"key":"ref10","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":"2023","journal-title":"N Engl J Med"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"2363","DOI":"10.1007\/s00415-019-09200-8","article-title":"Comparative efficacy and safety of therapy for the behavioral and psychological symptoms of dementia: a systemic review and Bayesian network meta-analysis","volume":"266","author":"Jin","year":"2019","journal-title":"J Neurol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"656","DOI":"10.7326\/m19-3887","article-title":"Benefits and harms of prescription drugs and supplements for treatment of clinical Alzheimer-type dementia: a systematic review and meta-analysis","volume":"172","author":"Fink","year":"2020","journal-title":"Ann Intern Med"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1533317519872635","DOI":"10.1177\/1533317519872635","article-title":"Feasibility of conducting nonpharmacological interventions to manage dementia symptoms in community-dwelling older adults: a cluster randomized controlled trial","volume":"35","author":"Park","year":"2020","journal-title":"Am J Alzheimers Dis Other Dement"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/biom11040543","article-title":"Neuroprotective herbs for the Management of Alzheimer's disease","volume":"11","author":"Gregory","year":"2021","journal-title":"Biomolecules"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"105","DOI":"10.51847\/4xc3jpx3u5","article-title":"Phytotherapy in dementia: multi-targeted approaches to neuroprotection and cognitive preservation","volume":"16","author":"Kumar","year":"2025","journal-title":"J Biochem Technol"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/j.fitote.2010.08.012","article-title":"Study on secondary metabolite content of Helleborus niger L. leaves","volume":"82","author":"Vitalini","year":"2011","journal-title":"Fitoterapia"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/S0378-8741(97)00114-1","article-title":"Effects of a phytopreparation from Helleborus niger on immunocompetent cells in vitro","volume":"59","author":"B\u00fcssing","year":"1998","journal-title":"J Ethnopharmacol"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1007\/s11418-021-01481-6","article-title":"Bufadienolides and ecdysteroids from the whole plants of Helleborus niger and their cytotoxicity","volume":"75","author":"Yokosuka","year":"2021","journal-title":"J Nat Med"},{"key":"ref19","first-page":"74","article-title":"Grand rounds: hellebores Niger","volume":"83","author":"Chapman","year":"1992","journal-title":"J Am Inst Homeopathy"},{"key":"ref20","first-page":"152","article-title":"Hellebore in accidents to the head","volume":"64","author":"Hayes","year":"1948","journal-title":"Homeopathic Recorder"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/S0007-0785(59)80002-8","article-title":"The signature of the Christmas rose (Helleborus niger)","volume":"48","author":"K\u00f6nig","year":"1959","journal-title":"Br Homeopath J"},{"key":"ref22","author":"Boericke","year":"1901"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1097\/00001199-199912000-00002","article-title":"Homeopathic treatment of mild traumatic brain injury: a randomized, double-blind, placebo-controlled clinical trial","volume":"14","author":"Chapman","year":"1999","journal-title":"J Head Trauma Rehabil"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"573","DOI":"10.7326\/0003-4819-147-8-200710160-00010","article-title":"The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies","volume":"147","author":"Von Elm","year":"2007","journal-title":"Ann Intern Med"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"113370","DOI":"10.1016\/j.jpba.2020.113370","article-title":"Stability of protoanemonin in plant extracts from Helleborus niger L. and Pulsatilla vulgaris mill","volume":"188","author":"Muller","year":"2020","journal-title":"J Pharm Biomed Anal"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"100424","DOI":"10.1016\/j.phyplu.2023.100424","article-title":"Comparison of cytotoxicity, saponin, and protoanemonin contents of medicinal plant extracts from Helleborus niger L. and Helleborus foetidus L.","volume":"3","author":"M\u00fcller","year":"2023","journal-title":"Phytomed Plus"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0022-3956(75)90026-6","article-title":"\u201cMini-mental state\u201d. A practical method for grading the cognitive state of patients for the clinician","volume":"12","author":"Folstein","year":"1975","journal-title":"J Psychiatr Res"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1176\/ajp.148.1.102","article-title":"Reliability of a standardized mini-mental state examination compared with the traditional mini-mental state examination","volume":"148","author":"Molloy","year":"1991","journal-title":"Am J Psychiatry"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"75","DOI":"10.3233\/jad-141959","article-title":"A phase II trial of tideglusib in Alzheimer's disease","volume":"45","author":"Lovestone","year":"2015","journal-title":"J Alzheimer's Dis"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1097\/WNF.0000000000000109","article-title":"Effect of memantine on cognitive performance in patients under electroconvulsive therapy: a double-blind randomized clinical trial","volume":"38","author":"Alizadeh","year":"2015","journal-title":"Clin Neuropharmacol"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13195-016-0210-1","article-title":"ABT-126 monotherapy in mild-to-moderate Alzheimer\u2019s dementia: randomized double-blind, placebo and active controlled adaptive trial and open-label extension","volume":"8","author":"Gault","year":"2016","journal-title":"Alzheimer's Res Ther"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13195-016-0214-x","article-title":"Effect of concomitant use of memantine on mortality and efficacy outcomes of galantamine-treated patients with Alzheimer\u2019s disease: post-hoc analysis of a randomized placebo-controlled study","volume":"8","author":"Hager","year":"2016","journal-title":"Alzheimer's Res Ther"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1016\/j.jalz.2019.08.197","article-title":"Effects of a combined transcranial magnetic stimulation (TMS) and cognitive training intervention in patients with Alzheimer's disease","volume":"16","author":"Sabbagh","year":"2019","journal-title":"Alzheimers Dement"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1590\/1980-57642021dn15-010013","article-title":"Cognitive performance of older adults with a low level of education with and without depression","volume":"15","author":"Bomfim","year":"2021","journal-title":"Dementia Neuropsychologia"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1002\/0470846410.ch27(ii)","volume-title":"Principles and Practice of Geriatric Psychiatry","author":"Cockrell","year":"2002"},{"key":"ref36","volume-title":"S3-Leitlinie Demenzen. Langversion JanuarS3-Leitlinie Demenzen, Version 4.0., Stand: 28.11.2023","author":"Fachgesellschaften","year":"2016"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"62","DOI":"10.22359\/cswhi","article-title":"Analysis of psychometric features of the Mini-mental state examination and the Montreal cognitive assessment methods","volume":"7","author":"Kab\u00e1tov\u00e1","year":"2016","journal-title":"Clin Soc Work Health Interv"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1002\/gps.1042","article-title":"Demtect: a new, sensitive cognitive screening test to support the diagnosis of mild cognitive impairment and early dementia","volume":"19","author":"Kalbe","year":"2004","journal-title":"Int J Geriatr Psychiatry"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"791","DOI":"10.3389\/fpsyt.2019.00791","article-title":"Prevalence and correlates of cognitive impairment in kidney transplant patients using the DemTect\u2014results of a KTx360 substudy","volume":"10","author":"N\u00f6hre","year":"2019","journal-title":"Front Psychol"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1080\/13607863.2015.1023763","article-title":"DemTect\u00ae\u2013effective to asses MCI and dementia\u2013validation study of the polish language version","volume":"20","author":"Wojty\u0144ska","year":"2016","journal-title":"Aging Ment Health"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"e22","DOI":"10.1002\/gps.4731","article-title":"The test of time: a history of clock drawing","volume":"33","author":"Hazan","year":"2018","journal-title":"Int J Geriatr Psychiatry"},{"key":"ref42","first-page":"648","article-title":"A proposal for application and scoring of the clock drawing test in Alzheimer's disease","volume":"28","author":"Cacho","year":"1999","journal-title":"Rev Neurol"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1002\/gps.930080606","article-title":"Clock-drawing and dementia in the community: a longitudinal study","volume":"8","author":"Shulman","year":"1993","journal-title":"Int J Geriatr Psychiatry"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/0022-3956(82)90033-4","article-title":"Development and validation of a geriatric depression screening scale: a preliminary report","volume":"17","author":"Yesavage","year":"1982","journal-title":"J Psychiatr Res"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1300\/J018v05n01_09","article-title":"Geriatric depression scale (GDS): recent evidence and development of a shorter version","volume":"5","author":"Sheikh","year":"1986","journal-title":"Clin Gerontol"},{"key":"ref46","first-page":"1","volume-title":"Encyclopedia of Gerontology and Population Aging","author":"Stone","year":"2019"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1080\/13607860902861027","article-title":"Criterion-based validity and reliability of the geriatric depression screening scale (GDS-15) in a large validation sample of community-living Asian older adults","volume":"13","author":"Nyunt","year":"2009","journal-title":"Aging Ment Health"},{"key":"ref48","volume-title":"R: A Language and Environment for Statistical Computing","year":"2025"},{"key":"ref49","volume-title":"RStudio: Integrated Development Environment for R","year":"2025"},{"key":"ref50","author":"Torchiano","year":"2020"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"523","DOI":"10.3233\/jad-230710","article-title":"Use of complementary and integrative medicine for Alzheimer\u2019s disease and cognitive decline","volume":"97","author":"Nguyen","year":"2023","journal-title":"J Alzheimer's Dis"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1007\/s11920-022-01355-y","article-title":"Complementary and integrative medicine for neurocognitive disorders and caregiver health","volume":"24","author":"Nguyen","year":"2022","journal-title":"Curr Psychiatry Rep"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"394","DOI":"10.3390\/jcm10143087","article-title":"Acupuncture for behavioral and psychological symptoms of dementia: a systematic review and meta-analysis","volume":"10","author":"Kwon","year":"2021","journal-title":"J Clin Med"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"e26871","DOI":"10.1097\/MD.0000000000026871","article-title":"Effectiveness and safety of acupuncture in treating sleep disturbance in dementia patients: a PRISMA-compliant systematic review and limitations of current evidence","volume":"100","author":"Kwon","year":"2021","journal-title":"Medicine"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"520","DOI":"10.5762\/KAIS.2021.22.1.520","article-title":"Effects of music therapy on cognitive function and agitation, anxiety and depression in dementia elderly: a systematic review and meta-analysis of randomized controlled trials","volume":"22","author":"Gong Ju","year":"2021","journal-title":"J Korea Academia Industrial Cooperation Society"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1891\/1541-6577.33.2.183","article-title":"Use of music therapy to improve cognition in older adults with dementia: an integrative review","volume":"33","author":"Dominguez-Chavez","year":"2019","journal-title":"Res Theory Nurs Pract"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"520","DOI":"10.2174\/1568026615666150813143520","article-title":"Ginkgo Biloba for mild cognitive impairment and Alzheimer's disease: a systematic review and Meta-analysis of randomized controlled trials","volume":"16","author":"Yang","year":"2016","journal-title":"Curr Top Med Chem"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/antiox13060651","article-title":"Ginkgo biloba: a leaf of hope in the fight against Alzheimer's dementia: clinical trial systematic review","volume":"13","author":"Pagotto","year":"2024","journal-title":"Antioxidants (Basel)"},{"key":"ref59","doi-asserted-by":"publisher","first-page":"1639924","DOI":"10.3389\/fneur.2025.1639924","article-title":"Efficacy of Ginkgo biloba extract in amyloid PET-positive patients with mild cognitive impairment","volume":"16","author":"Yang","year":"2025","journal-title":"Front Neurol"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/biomedicines12081812","article-title":"Phytotherapy in Alzheimer's disease-a narrative review","volume":"12","author":"Piekarz","year":"2024","journal-title":"Biomedicine"},{"key":"ref61","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.jgr.2024.02.002","article-title":"Emerging evidence that ginseng components improve cognition in subjective memory impairment, mild cognitive impairment, and early Alzheimer's disease dementia","volume":"48","author":"Lee","year":"2024","journal-title":"J Ginseng Res"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1002\/agm2.12230","article-title":"A pilot randomized controlled trial of WeiNaoKang (SaiLuoTong) in treating vascular dementia","volume":"5","author":"Liu","year":"2022","journal-title":"Aging Med (Milton)"},{"key":"ref63","doi-asserted-by":"publisher","first-page":"e12420","DOI":"10.1002\/trc2.12420","article-title":"A randomized, double-blind, placebo-controlled, parallel-group 12-week pilot phase II trial of SaiLuoTong (SLT) for cognitive function in older adults with mild cognitive impairment","volume":"9","author":"Steiner-Lim","year":"2023","journal-title":"Alzheimer's & Dementia: Translational Res Clin Interventions"},{"key":"ref64","doi-asserted-by":"publisher","first-page":"e18507","DOI":"10.1097\/MD.0000000000018507","article-title":"Danggui-Shaoyao-san for dementia: a PRISMA-compliant systematic review and meta-analysis","volume":"99","author":"Kim","year":"2020","journal-title":"Medicine"},{"key":"ref65","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1080\/19390211.2017.1284970","article-title":"Efficacy and safety of Ashwagandha (Withania somnifera (L.) Dunal) root extract in improving memory and cognitive functions","volume":"14","author":"Choudhary","year":"2017","journal-title":"J Diet Suppl"},{"key":"ref66","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1002\/ptr.6552","article-title":"A systematic review of the clinical use of Withania somnifera (Ashwagandha) to ameliorate cognitive dysfunction","volume":"34","author":"Ng","year":"2020","journal-title":"Phytother Res"},{"key":"ref67","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1126\/science.877552","article-title":"Induction of acetylcholinesterase activity by beta-ecdysone in a Drosophila cell line","volume":"197","author":"Cherbas","year":"1977","journal-title":"Science"},{"key":"ref68","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1007\/BF01538642","article-title":"Acetylcholinesterase induction by \u03b2-ecdysone in Drosophila cell lines and their hybrids","volume":"6","author":"Berger","year":"1980","journal-title":"Somatic Cell Genet"},{"key":"ref69","doi-asserted-by":"publisher","first-page":"824","DOI":"10.3390\/life12060824","article-title":"Ecdysteroids as potent enzyme inhibitors and verification of their activity using in vitro and in silico docking studies","volume":"12","author":"Mamadalieva","year":"2022","journal-title":"Reprod Dev Biol"},{"key":"ref70","first-page":"366","article-title":"Increase in activity of acetylcholinesterase by 20-OH-ecdysone in a Chironomus tentans cell line","volume-title":"Rouxs Arch Dev Biol","author":"Spindler-Barth","year":"1988"},{"key":"ref71","first-page":"1","article-title":"The protective effects of ecdysterone on cognitive impairment through regulating Akt\/GSK-3\u03b2\/Nrf2 signaling pathway and oxidative stress in cognitive mice model and a\u03b2-induced cell neurotoxicity","volume-title":"Front. Biosci.","author":"Xing","year":"2024"},{"key":"ref72","doi-asserted-by":"publisher","first-page":"2090","DOI":"10.1007\/s11064-022-03603-2","article-title":"Therapeutic effects of high-intensity interval training exercise alone and its combination with ecdysterone against amyloid beta-induced rat model of Alzheimer\u2019s disease: a behavioral, biochemical, and histological study","volume":"47","author":"Gholipour","year":"2022","journal-title":"Neurochem Res"},{"key":"ref73","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1007\/978-981-15-4148-3_35","volume-title":"Handbook of Dietary Phytochemicals","author":"Dinan","year":"2021"},{"key":"ref74","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1089\/acm.2020.0243","article-title":"Physicochemical investigations of homeopathic preparations: a systematic review and bibliometric analysis-part 3","volume":"27","author":"Tournier","year":"2021","journal-title":"J Altern Complement Med"},{"key":"ref75","doi-asserted-by":"publisher","first-page":"890","DOI":"10.1089\/acm.2019.0064","article-title":"Physicochemical investigations of homeopathic preparations: a systematic review and bibliometric analysis-part 2","volume":"25","author":"Tournier","year":"2019","journal-title":"J Altern Complement Med"},{"key":"ref76","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1089\/acm.2017.0249","article-title":"Physicochemical investigations of homeopathic preparations: a systematic review and bibliometric analysis-part 1","volume":"24","author":"Klein","year":"2018","journal-title":"J Altern Complement Med"},{"key":"ref77","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1055\/s-0040-1718743","article-title":"Effects of homeopathic preparations of Mercurius corrosivus on the growth rate of moderately mercury-stressed duckweed Lemna gibba L","volume":"110","author":"J\u00e4ger","year":"2021","journal-title":"Homeopathy"},{"key":"ref78","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1055\/s-0038-1676464","article-title":"Effects of homeopathic preparations of Mercurius corrosivus on the growth rate of severely mercury-stressed duckweed Lemna gibba L","volume":"108","author":"J\u00e4ger","year":"2019","journal-title":"Homeopathy"},{"key":"ref79","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/j.homp.2015.06.009","article-title":"The use of plant-based bioassays in homeopathic basic research","volume":"104","author":"J\u00e4ger","year":"2015","journal-title":"Homeopathy"},{"key":"ref80","doi-asserted-by":"publisher","first-page":"680930","DOI":"10.3389\/fsurg.2021.680930","article-title":"Is homeopathic Arnica effective for postoperative recovery? A Meta-analysis of placebo-controlled and active comparator trials","volume":"8","author":"Gaertner","year":"2021","journal-title":"Front Surg"},{"key":"ref81","doi-asserted-by":"publisher","first-page":"895838","DOI":"10.3389\/fphar.2022.895838","article-title":"A scoping review on the therapeutic potential of resin from the species Larix decidua mill. [Pinaceae] to treat ulcerating wounds","volume":"13","author":"Batista","year":"2022","journal-title":"Front Pharmacol"},{"key":"ref82","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1089\/acm.1998.4.371","article-title":"Randomized controlled trials of individualized homeopathy: a state-of-the-art review","volume":"4","author":"Linde","year":"1998","journal-title":"J Altern Complement Med"},{"key":"ref83","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1186\/s13643-017-0445-3","article-title":"Randomised, double-blind, placebo-controlled trials of non-individualised homeopathic treatment: systematic review and meta-analysis","volume":"6","author":"Mathie","year":"2017","journal-title":"Syst Rev"},{"key":"ref84","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1186\/2046-4053-3-142","article-title":"Randomised placebo-controlled trials of individualised homeopathic treatment: systematic review and meta-analysis","volume":"3","author":"Mathie","year":"2014","journal-title":"Syst Rev"},{"key":"ref85","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s002280050716","article-title":"Evidence of clinical efficacy of homeopathy. A meta-analysis of clinical trials. HMRAG. Homeopathic medicines research advisory group","volume":"56","author":"Cucherat","year":"2000","journal-title":"Eur J Clin Pharmacol"},{"key":"ref86","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1186\/s13643-023-02313-2","article-title":"Efficacy of homoeopathic treatment: systematic review of meta-analyses of randomised placebo-controlled homoeopathy trials for any indication","volume":"12","author":"Hamre","year":"2023","journal-title":"Syst Rev"},{"key":"ref87","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1007\/BF02322211","article-title":"Pygmalion in the classroom","volume":"3","author":"Rosenthal","year":"1968","journal-title":"Urban Rev"},{"key":"ref88","doi-asserted-by":"publisher","first-page":"513","DOI":"10.2147\/IJGM.S347439","article-title":"The psychological nursing interventions based on Pygmalion effect could alleviate negative emotions of patients with suspected COVID-19 patients: a retrospective analysis","volume":"15","author":"Zhang","year":"2022","journal-title":"Int J Gen Med"},{"key":"ref89","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1177\/1548051820980428","article-title":"Exploring the bounds of Pygmalion effects: congruence of implicit followership theories drives and binds leader performance expectations and follower work engagement","volume":"28","author":"Veestraeten","year":"2021","journal-title":"J Leadersh Org Stud"},{"key":"ref90","doi-asserted-by":"publisher","first-page":"e42252","DOI":"10.1016\/j.heliyon.2025.e42252","article-title":"The impact of family members on aging persons\u2019 technology use intentions","volume":"11","author":"Van Baelen","year":"2025","journal-title":"Heliyon"},{"key":"ref91","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1002\/1099-1379(200012)21:8<913::AID-JOB62>3.0.CO;2-#","article-title":"Pygmalion in work organizations: a meta-analysis","volume":"21","author":"Kierein","year":"2000","journal-title":"J Organ Behav"},{"key":"ref92","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1002\/bs.3830080302","article-title":"The effect of experimenter bias on the performance of the albino rat","volume":"8","author":"Rosenthal","year":"1963","journal-title":"Behav Sci"},{"key":"ref93","first-page":"708","article-title":"Reviews: Rosenthal, Robert, and Jacobson, Lenore. Pygmalion in the classroom. New York: Holt, Rinehart and Winston, 1968. 240+ xi pp. $3.95","volume":"5","author":"Thorndike","year":"1968","journal-title":"Am Educ Res J"},{"key":"ref94","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1037\/0022-0663.76.1.85","article-title":"Magnitude of teacher expectancy effects on pupil IQ as a function of the credibility of expectancy induction: a synthesis of findings from 18 experiments","volume":"76","author":"Raudenbush","year":"1984","journal-title":"J Educ Psychol"},{"key":"ref95","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1097\/EDE.0b013e31818131e7","article-title":"Why most discovered true associations are inflated","volume":"19","author":"Ioannidis","year":"2008","journal-title":"Epidemiology"},{"key":"ref96","doi-asserted-by":"publisher","first-page":"1676","DOI":"10.1001\/jama.2012.13444","article-title":"Empirical evaluation of very large treatment effects of medical interventions","volume":"308","author":"Pereira","year":"2012","journal-title":"JAMA"},{"key":"ref97","doi-asserted-by":"publisher","first-page":"100415","DOI":"10.1016\/j.lansea.2024.100415","article-title":"Observational studies: practical tips for avoiding common statistical pitfalls","volume":"25","author":"Sterrantino","year":"2024","journal-title":"Lancet Reg Health Southeast Asia"}],"container-title":["Frontiers in Public Health"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpubh.2026.1758447\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T06:51:44Z","timestamp":1774421504000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpubh.2026.1758447\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,25]]},"references-count":97,"alternative-id":["10.3389\/fpubh.2026.1758447"],"URL":"https:\/\/doi.org\/10.3389\/fpubh.2026.1758447","relation":{},"ISSN":["2296-2565"],"issn-type":[{"value":"2296-2565","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,25]]},"article-number":"1758447"}}