{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:25:11Z","timestamp":1787495111856,"version":"build-2736575974"},"reference-count":29,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T00:00:00Z","timestamp":1764806400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T00:00:00Z","timestamp":1764806400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100013420","name":"Tsumura and Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013420","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Psychogeriatrics"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>No effective agents currently exist for treating loss of appetite and apathy in patients with dementia. This multicentre, randomised, comparative study aimed to evaluate the effect and safety of Ninjin'yoeito (NYT) for these symptoms in patients with Alzheimer's disease (AD) or dementia with Lewy Bodies (DLB).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 16 sites, including clinics and hospitals, participated in this study. The primary outcome measure was the 12\u2010week change in the loss of appetite score in the \u2018eating behaviour\u2019 subcategory of the Neuropsychiatric Inventory\u201012 (NPI\u201012). Secondary outcome measures included changes in food intake, the NPI\u201012 score, the Japanese Version of the Zarit Caregiver Burden Interview, Vitality Index, Mini\u2010Mental State Examination, Frontal Assessment Battery, body weight, red blood cell count, haemoglobin, albumin, and Controlling Nutritional Status Score.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Regarding the efficacy evaluation, 24 and 25 patients were assigned to the NYT and control groups, respectively. Regarding the primary outcome\u2014the change in the loss of appetite score\u2014no significant difference was observed between the two groups at 12\u2009weeks after the start of administration. Among the secondary outcomes, food intake showed a significant increase in the NYT group compared to the control group at both 4 and 12\u2009weeks. In the NYT group, significant decreases were recorded in the NPI\u201012 total score at 4 and 8\u2009weeks; in depression at 12\u2009weeks; in apathy at 4, 8, and 12\u2009weeks; and in eating behaviour at 4, 8, and 12\u2009weeks. However, these changes were not different from those in the control group. In a post hoc subgroup analysis of participants with a loss of appetite score of \u2265\u20096, significant decreases from baseline at 8 and 12\u2009weeks were observed in the NYT group compared to the control group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Although the primary endpoint did not reach statistical significance, likely due to insufficient sample size, the NYT group showed a significant improvement in food intake, a secondary outcome measure. Furthermore, exploratory post hoc subgroup analysis suggested that NYT may improve appetite in patients with more severe appetite loss at baseline. These findings indicate the potential role of NYT in appetite improvement in patients with AD or DLB, warranting further investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/psyg.70120","type":"journal-article","created":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T14:51:09Z","timestamp":1764859869000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Efficacy and Safety of Tsumura Ninjin'yoeito for Loss of Appetite and Apathy in Patients With Alzheimer's Disease or Dementia With Lewy Bodies: A Multicentre, Open\u2010Label, Randomised, Comparative Study"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0959-1499","authenticated-orcid":false,"given":"Masashi","family":"Tamura","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Division of Clinical Medicine Institute of Medicine, University of Tsukuba  Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taro","family":"Shindo","sequence":"additional","affiliation":[{"name":"Rainbow &amp; Sea Hospital  Saga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazunori","family":"Okahara","sequence":"additional","affiliation":[{"name":"Keimei Memorial Hospital  Miyazaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Fukasawa","sequence":"additional","affiliation":[{"name":"Seinan Hospital  Aomori Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Asada","sequence":"additional","affiliation":[{"name":"Memory Clinic Toride  Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takafumi","family":"Jinnouchi","sequence":"additional","affiliation":[{"name":"Jinnnouchi Neurosurgical Clinic  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Ohsawa","sequence":"additional","affiliation":[{"name":"Ooido Clinic  Isesaki Gunma Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsutoshi","family":"Furukawa","sequence":"additional","affiliation":[{"name":"Division of Geriatric and Community Medicine, Faculty of Medicine Tohoku Medical and Pharmaceutical University  Sendai Miyagi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshige","family":"Sato","sequence":"additional","affiliation":[{"name":"Sato Clinic of Internal Medicine and Neurosurgery  Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masa\u2010aki","family":"Higuchi","sequence":"additional","affiliation":[{"name":"Youmei\u2010kai Foundation and Higuchi Hospital  Saga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Ikeda Neurosurgical Clinic  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Suzuki Kei Yasuragi Clinic  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kengo","family":"Uemura","sequence":"additional","affiliation":[{"name":"Ishiki Hospital  Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4355-3900","authenticated-orcid":false,"given":"Tetsuaki","family":"Arai","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Division of Clinical Medicine Institute of Medicine, University of Tsukuba  Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,4]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"Government of Japan Annual Report on the Ageing Society 2021 Chapter\u00a01: Situation of the Ageing Population (Full Text). Accessed June 28 2024(2021) https:\/\/cao.go.jp\/."},{"key":"e_1_2_11_3_1","unstructured":"The Ministry of Health Labour and Welfare Health Labour Sciences Research Study on Future Projections of the Elderly Population With Dementia in Japan. Report of the 2014 Summary and Assigned Research. Study Group on Future Projections of the Elderly Population With Dementia in Japan(2015)."},{"key":"e_1_2_11_4_1","first-page":"461","volume-title":"Handbook of Dementing Illnesses","author":"Tariot P.","year":"1994"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.maturitas.2013.07.013"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCO.0000000000000880"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2013.06.004"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12603-012-0401-9"},{"issue":"4","key":"e_1_2_11_9_1","doi-asserted-by":"crossref","first-page":"839","DOI":"10.3233\/JAD-150869","article-title":"Classification of Neuropsychiatric Symptoms Requiring Antipsychotic Treatment in Patients With Alzheimer's Disease: Analysis of the CATIE\u2010AD Study","volume":"50","author":"Nagata T.","year":"2016","journal-title":"Journal of Alzheimer's Disease"},{"key":"e_1_2_11_10_1","volume-title":"Practice Guideline for the Treatment of Dementia","author":"Japanese Society of Neurology","year":"2017"},{"issue":"4","key":"e_1_2_11_11_1","first-page":"277","article-title":"Utility of Olanzapine in Geriatric Patients, Focusing on Its Pharmacological Profile and Cognitive Function","volume":"18","author":"Imanaka A.","year":"2013","journal-title":"Japanese Journal of Psychiatry"},{"key":"e_1_2_11_12_1","first-page":"60","volume-title":"Guidelines for Safe Drug Therapy in the Elderly 2015","author":"The Japan Geriatrics Society","year":"2015"},{"issue":"6","key":"e_1_2_11_13_1","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1055\/a-0637-9760","article-title":"Kampo, a Japanese Traditional Medicinal System for Psychiatric Conditions: A Narrative Review","volume":"52","author":"Tatsumi L.","year":"2019","journal-title":"Pharmacopsychiatry"},{"key":"e_1_2_11_14_1","unstructured":"TJ\u2010108 Ninjin'yoeito Extract Granules for Ethical Use Package Insert Revised December 2023 (1st Ed)."},{"issue":"1","key":"e_1_2_11_15_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3233\/ADR-170026","article-title":"A Possibility of Simultaneous Treatment With the Multicomponent Drug, Ninjin'yoeito, for Loss of Appetite, Apathy, and Cognitive Dysfunction in Frail Alzheimer's Disease Patients: An Open\u2010Label Study","volume":"1","author":"Ohsawa M.","year":"2017","journal-title":"Journal of Alzheimer's Disease Reports"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.books.9780890425596"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.004"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004058"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.21507"},{"issue":"1","key":"e_1_2_11_20_1","first-page":"38","article-title":"CONUT: A Tool for Controlling Nutritional Status. First Validation in a Hospital Population","volume":"20","author":"Ignacio de Ul\u00edbarri J.","year":"2005","journal-title":"Nutrici\u00f3n Hospitalaria"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.44.12.2308"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1819.1997.tb03199.x"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1444-1586.2002.00016.x"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-3956(75)90026-6"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.55.11.1621"},{"key":"e_1_2_11_26_1","doi-asserted-by":"crossref","first-page":"5","DOI":"10.3389\/fnut.2020.00005","article-title":"Japanese Herbal Medicine Ninjinyoeito Mediates Its Orexigenic Properties Partially by Activating Orexin 1 Receptors","volume":"7","author":"Miyano K.","year":"2020","journal-title":"Frontiers in Nutrition"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/bbb\/zbab162"},{"key":"e_1_2_11_28_1","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.npep.2019.03.001","article-title":"Ninjin\u2010Yoeito Activates Ghrelin\u2010Responsive and Unresponsive NPY Neurons in the Arcuate Nucleus and Counteracts Cisplatin\u2010Induced Loss of Appetite","volume":"75","author":"Goswami C.","year":"2019","journal-title":"Neuropeptides"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/WNR.0000000000001667"},{"issue":"2","key":"e_1_2_11_30_1","first-page":"207","article-title":"Ninjinyoeito Ameliorates Loss of Appetite and Decrease in the Nest Building via a Dopamine D2 Receptor\u2010Dependent Manner in a Novel Murine Apathy Model","volume":"46","author":"Yamada C.","year":"2018","journal-title":"Japanese Pharmacology & Therapeutics"}],"container-title":["Psychogeriatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/psyg.70120","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/psyg.70120","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/psyg.70120","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T10:21:39Z","timestamp":1768386099000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/psyg.70120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,4]]},"references-count":29,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1111\/psyg.70120"],"URL":"https:\/\/doi.org\/10.1111\/psyg.70120","archive":["Portico"],"relation":{},"ISSN":["1346-3500","1479-8301"],"issn-type":[{"value":"1346-3500","type":"print"},{"value":"1479-8301","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,4]]},"assertion":[{"value":"2025-03-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70120"}}