{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T06:36:29Z","timestamp":1792046189851,"version":"4.4.0"},"reference-count":88,"publisher":"Elsevier BV","issue":"10","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002565","name":"Alzheimer&apos;s Drug Discovery Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002565","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P20GM109025"],"award-info":[{"award-number":["P20GM109025"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["RO1NS139383"],"award-info":[{"award-number":["RO1NS139383"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Prevention of Alzheimer's Disease"],"published-print":{"date-parts":[[2025,12]]},"DOI":"10.1016\/j.tjpad.2025.100328","type":"journal-article","created":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T01:24:26Z","timestamp":1761528266000},"page":"100328","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":20,"title":["Alzheimer Combination Therapies: Overview and Scenarios"],"prefix":"10.1016","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8944-4158","authenticated-orcid":false,"given":"Jeffrey L","family":"Cummings","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0176-9184","authenticated-orcid":false,"given":"Aaron H","family":"Burstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard","family":"Fillit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"1","key":"10.1016\/j.tjpad.2025.100328_bib0001","doi-asserted-by":"crossref","DOI":"10.1016\/j.tjpad.2024.100001","article-title":"Key considerations for combination therapy in Alzheimer's clinical trials: perspectives from an expert advisory board convened by the Alzheimer's drug discovery foundation","volume":"12","author":"Cummings","year":"2025","journal-title":"J Prev Alzheimers Dis"},{"key":"10.1016\/j.tjpad.2025.100328_bib0002","doi-asserted-by":"crossref","DOI":"10.1016\/j.tjpad.2025.100163","article-title":"Challenges and opportunities for novel combination therapies in Alzheimer's disease: a report from the EU\/US CTAD Task Force","author":"Angioni","year":"2025","journal-title":"J Prev Alzheimers Dis"},{"issue":"8","key":"10.1016\/j.tjpad.2025.100328_bib0003","doi-asserted-by":"crossref","first-page":"5143","DOI":"10.1002\/alz.13859","article-title":"Revised criteria for diagnosis and staging of Alzheimer's disease: alzheimer's Association Workgroup","volume":"20","author":"Jack","year":"2024","journal-title":"Alzheimers Dement"},{"issue":"6","key":"10.1016\/j.tjpad.2025.100328_bib0004","doi-asserted-by":"crossref","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":"10.1016\/j.tjpad.2025.100328_bib0005","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1056\/NEJMoa2212948","article-title":"Lecanemab in early Alzheimer's disease","volume":"388","author":"van Dyck","year":"2023","journal-title":"N Engl J Med"},{"issue":"6","key":"10.1016\/j.tjpad.2025.100328_bib0006","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1038\/s41591-023-02326-3","article-title":"Tau-targeting antisense oligonucleotide MAPT(Rx) in mild Alzheimer's disease: a phase 1b, randomized, placebo-controlled trial","volume":"29","author":"Mummery","year":"2023","journal-title":"Nat Med"},{"issue":"5","key":"10.1016\/j.tjpad.2025.100328_bib0007","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1038\/s43587-023-00403-3","article-title":"Blood biomarkers for Alzheimer's disease in clinical practice and trials","volume":"3","author":"Hansson","year":"2023","journal-title":"Nat Aging"},{"key":"10.1016\/j.tjpad.2025.100328_bib0008","doi-asserted-by":"crossref","DOI":"10.1016\/j.ebiom.2024.105322","article-title":"Insights into the use of biomarkers in clinical trials in Alzheimer's disease","volume":"108","author":"Pascoal","year":"2024","journal-title":"EBioMedicine"},{"key":"10.1016\/j.tjpad.2025.100328_bib0009","doi-asserted-by":"crossref","DOI":"10.1038\/s41573-025-01165-w","article-title":"Biomarker-guided decision making in clinical drug development for neurodegenerative disorders","author":"Cummings","year":"2025","journal-title":"Nat Rev Drug Discov"},{"issue":"8","key":"10.1016\/j.tjpad.2025.100328_bib0010","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1007\/s40263-024-01103-1","article-title":"Alzheimer's disease: combination therapies and clinical trials for combination therapy development","volume":"38","author":"Cummings","year":"2024","journal-title":"CNS Drugs"},{"issue":"3","key":"10.1016\/j.tjpad.2025.100328_bib0011","doi-asserted-by":"crossref","first-page":"779","DOI":"10.3233\/JAD-180766","article-title":"Treatment combinations for Alzheimer's disease: current and future pharmacotherapy options","volume":"67","author":"Cummings","year":"2019","journal-title":"J Alzheimers Dis"},{"key":"10.1016\/j.tjpad.2025.100328_bib0012","series-title":"U.S. department of health and human services, food and drug administration","article-title":"Guidance for industry. Co-development of two or more new investigational drug for use in combination","year":"2013"},{"issue":"9","key":"10.1016\/j.tjpad.2025.100328_bib0013","doi-asserted-by":"crossref","DOI":"10.3390\/ijms21093272","article-title":"Combination drug therapy for the management of Alzheimer's disease","volume":"21","author":"Kabir","year":"2020","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.tjpad.2025.100328_bib0014","doi-asserted-by":"crossref","DOI":"10.1016\/j.pneurobio.2022.102270","article-title":"Amyloid beta, tau, and alpha-synuclein aggregates in the pathogenesis, prognosis, and therapeutics for neurodegenerative diseases","volume":"214","author":"Sengupta","year":"2022","journal-title":"Prog Neurobiol"},{"key":"10.1016\/j.tjpad.2025.100328_bib0015","doi-asserted-by":"crossref","unstructured":"Faridar A., Eid A.M., Thome A.D., et al. A phase 1 open-label pilot study of low-dose interleukine-2 immunotherapy in patients with Alzheimer's disease. Transl Neurodegener. 2023;12(1):54. doi: 10.1186\/s40035-023-00387-5.","DOI":"10.1186\/s40035-023-00387-5"},{"issue":"14","key":"10.1016\/j.tjpad.2025.100328_bib0016","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1056\/NEJMoa013128","article-title":"Memantine in moderate-to-severe Alzheimer's disease","volume":"348","author":"Reisberg","year":"2003","journal-title":"N Engl J Med"},{"issue":"3","key":"10.1016\/j.tjpad.2025.100328_bib0017","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1001\/jama.291.3.317","article-title":"Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial","volume":"291","author":"Tariot","year":"2004","journal-title":"JAMA"},{"issue":"3","key":"10.1016\/j.tjpad.2025.100328_bib0018","doi-asserted-by":"crossref","first-page":"332","DOI":"10.2174\/1381612826666201023144836","article-title":"Enhancing therapeutic efficacy of donepezil by combined therapy: a comprehensive review","volume":"27","author":"Rong","year":"2021","journal-title":"Curr Pharm Des"},{"key":"10.1016\/j.tjpad.2025.100328_bib0019","doi-asserted-by":"crossref","first-page":"3267","DOI":"10.2147\/DDDT.S86463","article-title":"A fixed-dose combination of memantine extended-release and donepezil in the treatment of moderate-to-severe Alzheimer's disease","volume":"10","author":"Deardorff","year":"2016","journal-title":"Drug Des Devel Ther."},{"issue":"1","key":"10.1016\/j.tjpad.2025.100328_bib0020","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1186\/s13063-022-06190-3","article-title":"Noradrenergic add-on therapy with extended-release guanfacine in Alzheimer's Disease (NorAD): study protocol for a randomised clinical trial and COVID-19 amendments","volume":"23","author":"Hoang","year":"2022","journal-title":"Trials"},{"issue":"5","key":"10.1016\/j.tjpad.2025.100328_bib0021","doi-asserted-by":"crossref","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":"10.1016\/j.tjpad.2025.100328_bib0022","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1186\/s13195-024-01441-8","article-title":"Updated safety results from phase 3 lecanemab study in early Alzheimer's disease","volume":"16","author":"Honig","year":"2024","journal-title":"Alzheimers Res Ther"},{"issue":"12","key":"10.1016\/j.tjpad.2025.100328_bib0023","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1001\/jamaneurol.2022.3392","article-title":"Association of donanemab treatment with exploratory plasma biomarkers in early symptomatic Alzheimer disease: a secondary analysis of the TRAILBLAZER-ALZ randomized clinical trial","volume":"79","author":"Pontecorvo","year":"2022","journal-title":"JAMA Neurol"},{"issue":"3","key":"10.1016\/j.tjpad.2025.100328_bib0024","doi-asserted-by":"crossref","first-page":"393","DOI":"10.14283\/jpad.2022.48","article-title":"The future of AD clinical trials with the advent of anti-amyloid therapies: an CTAD Task Force Report","volume":"9","author":"Delrieu","year":"2022","journal-title":"J Prev Alzheimers Dis"},{"key":"10.1016\/j.tjpad.2025.100328_bib0025","article-title":"The Alzheimer\u2019s Tau Platform (ATP): a phase 2, combination amyloid and tau therapy clinical trial for early AD","volume":"20","author":"Boxer","year":"2025","journal-title":"Alzheimer Dement"},{"key":"10.1016\/j.tjpad.2025.100328_bib0026","doi-asserted-by":"crossref","DOI":"10.1177\/1759091420918557","article-title":"Alzheimer drug trials: combination of safe and efficacious biologicals to break the amyloidosis-neuroinflammation vicious cycle","volume":"12","author":"Bartfai","year":"2020","journal-title":"ASN Neuro"},{"issue":"4","key":"10.1016\/j.tjpad.2025.100328_bib0027","article-title":"Targeting immunometabolic pathways for combination therapy in Alzheimer's disease","volume":"9","author":"Erichsen","year":"2023","journal-title":"Alzheimers Dement (N Y)"},{"issue":"1","key":"10.1016\/j.tjpad.2025.100328_bib0029","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1080\/17460441.2023.2277350","article-title":"gamma-Secretase: once and future drug target for Alzheimer's disease","volume":"19","author":"Wolfe","year":"2024","journal-title":"Expert Opin Drug Discov"},{"issue":"1","key":"10.1016\/j.tjpad.2025.100328_bib0030","doi-asserted-by":"crossref","first-page":"25","DOI":"10.14283\/jpad.2022.84","article-title":"Buntanetap, a novel translational inhibitor of multiple neurotoxic proteins, proves to be safe and promising in both Alzheimer's and Parkinson's patients","volume":"10","author":"Fang","year":"2023","journal-title":"J Prev Alzheimers Dis"},{"key":"10.1016\/j.tjpad.2025.100328_bib0031","article-title":"Alzheimer's disease drug development pipeline: 2025","volume":"11","author":"Cummings","year":"2025","journal-title":"Alzheimer Dement"},{"key":"10.1016\/j.tjpad.2025.100328_bib0032","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.jep.2017.12.015","article-title":"Features and outcomes of drugs for combination therapy as multi-targets strategy to combat Alzheimer's disease","volume":"215","author":"Sahoo","year":"2018","journal-title":"J Ethnopharmacol"},{"key":"10.1016\/j.tjpad.2025.100328_bib0033","doi-asserted-by":"crossref","unstructured":"Zhang Y., Guo K., Zhang P., et al. Exploring the mechanism of YangXue QingNao Wan based on network pharmacology in the treatment of Alzheimer's disease. Front genet. 2022;13:942203. doi: 10.3389\/fgene.2022.942203.","DOI":"10.3389\/fgene.2022.942203"},{"key":"10.1016\/j.tjpad.2025.100328_bib0034","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2025.119994","article-title":"Exploring the pharmacological mechanism of Bu-Wang San on Alzheimer's disease through multiple GEO datasets of the human hippocampus, network pharmacology, and metabolomics based on GCMS\u2013 and UPLC-Q\/TOF-MS","volume":"350","author":"Wang","year":"2025","journal-title":"J Ethnopharmacol"},{"issue":"4","key":"10.1016\/j.tjpad.2025.100328_bib0035","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1080\/10408347.2024.2305267","article-title":"Quality consistency evaluation of traditional Chinese medicines: current status and future perspectives","volume":"55","author":"Liu","year":"2025","journal-title":"Crit Rev Anal Chem"},{"key":"10.1016\/j.tjpad.2025.100328_bib0036","article-title":"Advancing herbal medicine: enhancing product quality and safety through robust quality control practices","volume":"14","author":"Wang","year":"2023","journal-title":"Front Pharmacol"},{"issue":"5","key":"10.1016\/j.tjpad.2025.100328_bib0037","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1002\/ana.22093","article-title":"Dextromethorphan plus ultra low-dose quinidine reduces pseudobulbar affect","volume":"68","author":"Pioro","year":"2010","journal-title":"Ann Neurol"},{"issue":"12","key":"10.1016\/j.tjpad.2025.100328_bib0038","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1001\/jama.2015.10214","article-title":"Effect of dextromethorphan-quinidine on agitation in patients with Alzheimer disease dementia: a randomized clinical trial","volume":"314","author":"Cummings","year":"2015","journal-title":"JAMA"},{"issue":"4","key":"10.1016\/j.tjpad.2025.100328_bib0039","doi-asserted-by":"crossref","DOI":"10.4088\/JCP.21m14345","article-title":"Efficacy and safety of AXS-05 (dextromethorphan-bupropion) in patients with major depressive disorder: a phase 3 randomized clinical trial (GEMINI)","volume":"83","author":"Iosifescu","year":"2022","journal-title":"J Clin Psychiatry"},{"key":"10.1016\/j.tjpad.2025.100328_bib0040","series-title":"U.S. department of health and human services, food and drug administration","article-title":"Guidance for industry: co-development of two or more unmarketed investigational drugs for use in combination","year":"2010"},{"issue":"4","key":"10.1016\/j.tjpad.2025.100328_bib0041","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1001\/archneur.1997.00550160091022","article-title":"Effects of xanomeline, a selective muscarinic receptor agonist, on cognitive function and behavioral symptoms in Alzheimer disease","volume":"54","author":"Bodick","year":"1997","journal-title":"Arch Neurol"},{"issue":"1","key":"10.1016\/j.tjpad.2025.100328_bib0042","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s12987-024-00557-1","article-title":"Cellular and molecular mechanisms of the blood-brain barrier dysfunction in neurodegenerative diseases","volume":"21","author":"Chen","year":"2024","journal-title":"Fluids Barriers CNS"},{"key":"10.1016\/j.tjpad.2025.100328_bib0043","doi-asserted-by":"crossref","first-page":"914","DOI":"10.3389\/fphys.2020.00914","article-title":"Structure, function, and regulation of the blood-brain barrier tight junction in central nervous system disorders","volume":"11","author":"Lochhead","year":"2020","journal-title":"Front Physiol"},{"issue":"1","key":"10.1016\/j.tjpad.2025.100328_bib0044","doi-asserted-by":"crossref","DOI":"10.1080\/19420862.2023.2261509","article-title":"Delivery of the Brainshuttle amyloid-beta antibody fusion trontinemab to non-human primate brain and projected efficacious dose regimens in humans","volume":"15","author":"Grimm","year":"2023","journal-title":"MAbs"},{"key":"10.1016\/j.tjpad.2025.100328_bib0045","doi-asserted-by":"crossref","DOI":"10.1016\/j.addr.2022.114583","article-title":"Applications of focused ultrasound-mediated blood-brain barrier opening","volume":"191","author":"Gorick","year":"2022","journal-title":"Adv Drug Deliv Rev"},{"issue":"1","key":"10.1016\/j.tjpad.2025.100328_bib0046","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1056\/NEJMoa2308719","article-title":"Ultrasound blood-brain barrier opening and aducanumab in Alzheimer's disease","volume":"390","author":"Rezai","year":"2024","journal-title":"N Engl J Med"},{"issue":"9984","key":"10.1016\/j.tjpad.2025.100328_bib0047","doi-asserted-by":"crossref","first-page":"2255","DOI":"10.1016\/S0140-6736(15)60461-5","article-title":"A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial","volume":"385","author":"Ngandu","year":"2015","journal-title":"Lancet"},{"issue":"1","key":"10.1016\/j.tjpad.2025.100328_bib0048","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s13195-023-01355-x","article-title":"A multimodal precision-prevention approach combining lifestyle intervention with metformin repurposing to prevent cognitive impairment and disability: the MET-FINGER randomised controlled trial protocol","volume":"16","author":"Barbera","year":"2024","journal-title":"Alzheimers Res Ther"},{"key":"10.1016\/j.tjpad.2025.100328_bib0049","doi-asserted-by":"crossref","DOI":"10.1016\/j.archger.2023.105114","article-title":"Cognitive stimulation and psychosocial results in older adults: a systematic review and meta-analysis","volume":"115","author":"Gomez-Soria","year":"2023","journal-title":"Arch Gerontol Geriatr"},{"issue":"9","key":"10.1016\/j.tjpad.2025.100328_bib0050","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1002\/gps.4247","article-title":"A pilot randomized controlled trial evaluating an integrated treatment of rivastigmine transdermal patch and cognitive stimulation in patients with Alzheimer's disease","volume":"30","author":"D'Onofrio","year":"2015","journal-title":"Int J Geriatr Psychiatry"},{"issue":"1","key":"10.1016\/j.tjpad.2025.100328_bib0051","doi-asserted-by":"crossref","first-page":"222","DOI":"10.14283\/jpad.2024.1","article-title":"The therapeutic effects of noninvasive brain stimulation combined with cognitive training in elders with Alzheimer's disease or amnesic mild cognitive impairment","volume":"11","author":"Wang","year":"2024","journal-title":"J Prev Alzheimers Dis"},{"issue":"1","key":"10.1016\/j.tjpad.2025.100328_bib0052","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1186\/s13195-024-01505-9","article-title":"The cognitive effect of non-invasive brain stimulation combined with cognitive training in Alzheimer's disease and mild cognitive impairment: a systematic review and meta-analysis","volume":"16","author":"Yang","year":"2024","journal-title":"Alzheimers Res Ther"},{"issue":"1","key":"10.1016\/j.tjpad.2025.100328_bib0053","article-title":"Randomized trial of cognitive training and brain stimulation in non-demented older adults","volume":"8","author":"Antonenko","year":"2022","journal-title":"Alzheimers Dement (N Y)"},{"key":"10.1016\/j.tjpad.2025.100328_bib0054","series-title":"Guidance for industry, and fda staff. U.S. department of health and human services food and drug administration. center for devices and radiological health (CDRH) center for drug evaluation and research (CDER)","article-title":"Human factors studies and related clinical study considerations in combination product design and development","year":"2016"},{"key":"10.1016\/j.tjpad.2025.100328_bib0055","unstructured":"Food and Drug Administration. Road map to reducing animal testing in preclinical safety studies. 2025."},{"issue":"7","key":"10.1016\/j.tjpad.2025.100328_bib0056","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1517\/17460441.2015.1041913","article-title":"Rodent models for Alzheimer's disease drug discovery","volume":"10","author":"Puzzo","year":"2015","journal-title":"Expert Opin Drug Discov"},{"key":"10.1016\/j.tjpad.2025.100328_bib0057","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.expneurol.2013.10.001","article-title":"Combination therapy in a transgenic model of Alzheimer's disease","volume":"250","author":"Aytan","year":"2013","journal-title":"Exp Neurol"},{"issue":"27","key":"10.1016\/j.tjpad.2025.100328_bib0058","doi-asserted-by":"crossref","first-page":"11310","DOI":"10.1074\/jbc.M116.762658","article-title":"Combination therapy with octyl gallate and ferulic acid improves cognition and neurodegeneration in a transgenic mouse model of Alzheimer's disease","volume":"292","author":"Mori","year":"2017","journal-title":"J Biol Chem"},{"key":"10.1016\/j.tjpad.2025.100328_bib0059","series-title":"U.S. department of health and human services, food and drug administration","article-title":"Guidance for industry. Nonclinical safety evaluation of drug or biologic combinations","year":"2006"},{"key":"10.1016\/j.tjpad.2025.100328_bib0060","series-title":"US department of health and human services, food and drug administration","article-title":"Guidance for industry. Formal meetings between the FDA and sponsors or applicants of PDUFA products","year":"2023"},{"issue":"1","key":"10.1016\/j.tjpad.2025.100328_bib0061","article-title":"Data-driven discovery of associations between prescribed drugs and dementia risk: a systematic review","volume":"11","author":"Underwood","year":"2025","journal-title":"Alzheimers Dement (N Y)"},{"key":"10.1016\/j.tjpad.2025.100328_bib0062","doi-asserted-by":"crossref","unstructured":"Xu J., Wang F., Zang C., et al. Comparing the effects of four common drug classes on the progression of mild cognitive impairment to dementia using electronic health records. Sci Rep. 2023;13(1):8102. doi: 10.1038\/s41598-023-35258-6.","DOI":"10.1038\/s41598-023-35258-6"},{"issue":"1","key":"10.1016\/j.tjpad.2025.100328_bib0063","doi-asserted-by":"crossref","first-page":"22","DOI":"10.14283\/jpad.2021.62","article-title":"Senolytic therapy to modulate the progression of Alzheimer's Disease (SToMP-AD): a pilot clinical trial","volume":"9","author":"Gonzales","year":"2022","journal-title":"J Prev Alzheimers Dis"},{"issue":"10","key":"10.1016\/j.tjpad.2025.100328_bib0064","doi-asserted-by":"crossref","first-page":"2481","DOI":"10.1038\/s41591-023-02543-w","article-title":"Senolytic therapy in mild Alzheimer's disease: a phase 1 feasibility trial","volume":"29","author":"Gonzales","year":"2023","journal-title":"Nat Med"},{"issue":"21","key":"10.1016\/j.tjpad.2025.100328_bib0065","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.1001\/jama.2023.19793","article-title":"Reporting of factorial randomized trials: extension of the CONSORT 2010 statement","volume":"330","author":"Kahan","year":"2023","journal-title":"JAMA"},{"issue":"7","key":"10.1016\/j.tjpad.2025.100328_bib0066","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1001\/jamaneurol.2023.1526","article-title":"Isosorbide mononitrate and cilostazol treatment in patients with symptomatic cerebral small vessel disease: the Lacunar Intervention Trial-2 (LACI-2) randomized clinical trial","volume":"80","author":"Wardlaw","year":"2023","journal-title":"JAMA Neurol"},{"issue":"1","key":"10.1016\/j.tjpad.2025.100328_bib0067","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1186\/s12916-020-01808-2","article-title":"Adding flexibility to clinical trial designs: an example-based guide to the practical use of adaptive designs","volume":"18","author":"Burnett","year":"2020","journal-title":"BMC Med"},{"issue":"4","key":"10.1016\/j.tjpad.2025.100328_bib0068","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.4269\/ajtmh.20-0995","article-title":"Accelerating clinical evaluation of repurposed combination therapies for COVID-19","volume":"103","author":"Rayner","year":"2020","journal-title":"Am J Trop Med Hyg"},{"issue":"20","key":"10.1016\/j.tjpad.2025.100328_bib0069","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1212\/WNL.0000000000011774","article-title":"Value-generating exploratory trials in neurodegenerative dementias","volume":"96","author":"Friedman","year":"2021","journal-title":"Neurology"},{"issue":"4","key":"10.1016\/j.tjpad.2025.100328_bib0070","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/j.beth.2016.12.005","article-title":"Implementing clinical research using factorial designs: a primer","volume":"48","author":"Baker","year":"2017","journal-title":"Behav Ther"},{"issue":"21","key":"10.1016\/j.tjpad.2025.100328_bib0071","doi-asserted-by":"crossref","first-page":"2687","DOI":"10.1002\/sim.3643","article-title":"Developing multicomponent interventions using fractional factorial designs","volume":"28","author":"Chakraborty","year":"2009","journal-title":"Stat Med"},{"issue":"3","key":"10.1016\/j.tjpad.2025.100328_bib0072","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1080\/10543400701199593","article-title":"Interaction index and different methods for determining drug interaction in combination therapy","volume":"17","author":"Lee","year":"2007","journal-title":"J Biopharm Stat"},{"issue":"1","key":"10.1016\/j.tjpad.2025.100328_bib0073","first-page":"1","article-title":"Design of a Bayesian adaptive phase 2 proof-of-concept trial for BAN2401, a putative disease-modifying monoclonal antibody for the treatment of Alzheimer's disease","volume":"2","author":"Satlin","year":"2016","journal-title":"Alzheimers Dement"},{"issue":"3","key":"10.1016\/j.tjpad.2025.100328_bib0074","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1002\/pst.2194","article-title":"Decision rules for identifying combination therapies in open-entry, randomized controlled platform trials","volume":"21","author":"Meyer","year":"2022","journal-title":"Pharm Stat"},{"issue":"3","key":"10.1016\/j.tjpad.2025.100328_bib0075","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1177\/1535370217750088","article-title":"Biomarker definitions and their applications","volume":"243","author":"Califf","year":"2018","journal-title":"Exp Biol Med (Maywood)"},{"key":"10.1016\/j.tjpad.2025.100328_bib0076","series-title":"BEST (Biomarkers, endpoints, and other tools) resource","year":"2016"},{"issue":"8","key":"10.1016\/j.tjpad.2025.100328_bib0077","doi-asserted-by":"crossref","DOI":"10.3390\/biomedicines12081836","article-title":"P-tau217 as a reliable blood-based marker of Alzheimer's disease","volume":"12","author":"Lai","year":"2024","journal-title":"Biomedicines"},{"issue":"2","key":"10.1016\/j.tjpad.2025.100328_bib0078","doi-asserted-by":"crossref","first-page":"197","DOI":"10.14283\/jpad.2022.30","article-title":"Two randomized phase 3 studies of aducanumab in early Alzheimer's disease","volume":"9","author":"Budd Haeberlein","year":"2022","journal-title":"J Prev Alzheimers Dis"},{"issue":"11","key":"10.1016\/j.tjpad.2025.100328_bib0079","doi-asserted-by":"crossref","first-page":"4414","DOI":"10.1093\/brain\/awad188","article-title":"Amyloid-related imaging abnormalities (ARIA): radiological, biological and clinical characteristics","volume":"146","author":"Hampel","year":"2023","journal-title":"Brain"},{"issue":"18","key":"10.1016\/j.tjpad.2025.100328_bib0080","doi-asserted-by":"crossref","first-page":"e1809","DOI":"10.1212\/WNL.0000000000012778","article-title":"Spontaneous ARIA-like events in cerebral amyloid angiopathy-related inflammation: a multicenter prospective longitudinal cohort study","volume":"97","author":"Antolini","year":"2021","journal-title":"Neurology"},{"issue":"4","key":"10.1016\/j.tjpad.2025.100328_bib0081","doi-asserted-by":"crossref","first-page":"828","DOI":"10.14283\/jpad.2023.83","article-title":"Two-year prognostic utility of plasma p217+tau across the Alzheimer's continuum","volume":"10","author":"Feizpour","year":"2023","journal-title":"J Prev Alzheimers Dis"},{"issue":"8","key":"10.1016\/j.tjpad.2025.100328_bib0082","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1001\/jamaneurol.2024.1612","article-title":"Tau positron emission tomography for predicting dementia in individuals with mild cognitive impairment","volume":"81","author":"Groot","year":"2024","journal-title":"JAMA Neurol"},{"issue":"12","key":"10.1016\/j.tjpad.2025.100328_bib0083","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1002\/psp4.12862","article-title":"Population pharmacokinetic-pharmacodynamic analyses of amyloid positron emission tomography and plasma biomarkers for lecanemab in subjects with early Alzheimer's disease","volume":"11","author":"Hayato","year":"2022","journal-title":"CPT Pharmacometrics Syst Pharmacol"},{"issue":"1","key":"10.1016\/j.tjpad.2025.100328_bib0084","article-title":"The Common Alzheimer's Disease Research Ontology (CADRO) for biomarker categorization","volume":"11","author":"Leisgang Osse","year":"2025","journal-title":"Alzheimers Dement (N Y)"},{"issue":"1","key":"10.1016\/j.tjpad.2025.100328_bib0085","doi-asserted-by":"crossref","first-page":"2691","DOI":"10.1038\/s41467-018-05116-5","article-title":"Network-based approach to prediction and population-based validation of in silico drug repurposing","volume":"9","author":"Cheng","year":"2018","journal-title":"Nat Commun"},{"key":"10.1016\/j.tjpad.2025.100328_bib0086","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1146\/annurev-pharmtox-010818-021511","article-title":"Systems pharmacology: defining the interactions of drug combinations","volume":"59","author":"van Hasselt","year":"2019","journal-title":"Annu Rev Pharmacol Toxicol"},{"issue":"6","key":"10.1016\/j.tjpad.2025.100328_bib0087","doi-asserted-by":"crossref","first-page":"2386","DOI":"10.1002\/med.21709","article-title":"Harnessing endophenotypes and network medicine for Alzheimer's drug repurposing","volume":"40","author":"Fang","year":"2020","journal-title":"Med Res Rev"},{"issue":"1","key":"10.1016\/j.tjpad.2025.100328_bib0088","doi-asserted-by":"crossref","first-page":"8180","DOI":"10.1038\/s41467-023-43929-1","article-title":"High-throughput target trial emulation for Alzheimer's disease drug repurposing with real-world data","volume":"14","author":"Zang","year":"2023","journal-title":"Nat Commun"},{"issue":"6","key":"10.1016\/j.tjpad.2025.100328_bib0089","article-title":"Not a slam dunk (or Free Lunch): the complex future of Alzheimer's combination therapy","volume":"12","author":"C","year":"2025","journal-title":"J Prev Alzheimers Dis"}],"container-title":["The Journal of Prevention of Alzheimer's Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2274580725002717?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2274580725002717?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:52:37Z","timestamp":1785977557000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2274580725002717"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":88,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["S2274580725002717"],"URL":"https:\/\/doi.org\/10.1016\/j.tjpad.2025.100328","relation":{},"ISSN":["2274-5807"],"issn-type":[{"value":"2274-5807","type":"print"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Alzheimer Combination Therapies: Overview and Scenarios","name":"articletitle","label":"Article Title"},{"value":"The Journal of Prevention of Alzheimer's Disease","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.tjpad.2025.100328","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Published by Elsevier Masson SAS on behalf of SERDI Publisher.","name":"copyright","label":"Copyright"}],"article-number":"100328"}}