{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T13:34:36Z","timestamp":1787578476205,"version":"build-2736575974"},"reference-count":107,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Revista de Investigaci\u00f3n Cl\u00ednica"],"published-print":{"date-parts":[[2026,7]]},"DOI":"10.1016\/j.ric.2026.100050","type":"journal-article","created":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T11:45:18Z","timestamp":1783770318000},"page":"100050","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["Precision therapeutics and innovative clinical trial design in neurodegenerative diseases"],"prefix":"10.1016","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2831-3394","authenticated-orcid":false,"given":"Ariadna","family":"Dom\u00ednguez-Garc\u00eda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3896-6612","authenticated-orcid":false,"given":"Juan Carlos","family":"Delgado-Uriarte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3935-9278","authenticated-orcid":false,"given":"Amin","family":"Cervantes-Arriaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"2","key":"10.1016\/j.ric.2026.100050_bib0540","doi-asserted-by":"crossref","first-page":"e105","DOI":"10.1016\/S2468-2667(21)00249-8","article-title":"Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the Global Burden of Disease Study 2019","volume":"7","year":"2022","journal-title":"Lancet Public Health"},{"issue":"s1","key":"10.1016\/j.ric.2026.100050_bib0545","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.3233\/JPD-181474","article-title":"The emerging evidence of the Parkinson pandemic","volume":"8","author":"Dorsey","year":"2018","journal-title":"J Parkinsons Dis"},{"issue":"1","key":"10.1016\/j.ric.2026.100050_bib0550","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s13024-019-0333-5","article-title":"The neuropathological diagnosis of Alzheimer's disease","volume":"14","author":"DeTure","year":"2019","journal-title":"Mol Neurodegener"},{"issue":"3","key":"10.1016\/j.ric.2026.100050_bib0555","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1212\/CON.0000000000001137","article-title":"Neuropathology of dementia disorders","volume":"28","author":"Schneider","year":"2022","journal-title":"Continuum (Minneap Minn)"},{"key":"10.1016\/j.ric.2026.100050_bib0560","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.vhri.2023.09.008","article-title":"Economic burden of Alzheimer's disease: a systematic review","volume":"40","author":"Tay","year":"2024","journal-title":"Value Health Reg Issues"},{"issue":"2","key":"10.1016\/j.ric.2026.100050_bib0565","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1038\/s41591-024-03469-7","article-title":"Toward a biological definition of neuronal and glial synucleinopathies","volume":"31","author":"Soto","year":"2025","journal-title":"Nat Med"},{"key":"10.1016\/j.ric.2026.100050_bib0570","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2024.1432342","article-title":"Inflammation and heterogeneity in synucleinopathies","volume":"15","author":"Freuchet","year":"2024","journal-title":"Front Immunol"},{"issue":"12","key":"10.1016\/j.ric.2026.100050_bib0575","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.3390\/brainsci15121260","article-title":"Alpha-synuclein neurobiology in Parkinson's disease: a comprehensive review of its role, mechanisms, and therapeutic perspectives","volume":"15","author":"Pitton Rissardo","year":"2025","journal-title":"Brain Sci"},{"issue":"Pt B","key":"10.1016\/j.ric.2026.100050_bib0580","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.nbd.2017.07.018","article-title":"Distinct \u03b1-synuclein strains and implications for heterogeneity among \u03b1-synucleinopathies","volume":"109","author":"Peng","year":"2018","journal-title":"Neurobiol Dis"},{"issue":"5","key":"10.1016\/j.ric.2026.100050_bib0585","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.1093\/cercor\/bhz280","article-title":"LRRK2 and GBA variants exert distinct influences on Parkinson's disease-specific metabolic networks","volume":"30","author":"Schindlbeck","year":"2020","journal-title":"Cereb Cortex"},{"issue":"12","key":"10.1016\/j.ric.2026.100050_bib0590","doi-asserted-by":"crossref","first-page":"9079","DOI":"10.1002\/alz.14340","article-title":"2024 AA criteria for Alzheimer's disease diagnosis: mainly anchored at A\u03b2 not tau","volume":"20","author":"Moscoso","year":"2024","journal-title":"Alzheimers Dement"},{"issue":"1","key":"10.1016\/j.ric.2026.100050_bib0595","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1007\/s13311-022-01185-z","article-title":"Heterogeneity in Alzheimer's disease diagnosis and progression rates: implications for therapeutic trials","volume":"19","author":"Duara","year":"2022","journal-title":"Neurotherapeutics"},{"issue":"13","key":"10.1016\/j.ric.2026.100050_bib0600","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.2174\/1567205018666210212160902","article-title":"The contribution of cerebral vascular neuropathology to mild stage of Alzheimer's dementia using the NACC database","volume":"17","author":"Liu","year":"2020","journal-title":"Curr Alzheimer Res"},{"issue":"10004","key":"10.1016\/j.ric.2026.100050_bib0605","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.1016\/S0140-6736(15)00461-4","article-title":"Frontotemporal dementia","volume":"386","author":"Bang","year":"2015","journal-title":"Lancet"},{"issue":"8","key":"10.1016\/j.ric.2026.100050_bib0610","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1007\/s00415-019-09363-4","article-title":"An update on genetic frontotemporal dementia","volume":"266","author":"Greaves","year":"2019","journal-title":"J Neurol"},{"issue":"10","key":"10.1016\/j.ric.2026.100050_bib0615","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2020.22847","article-title":"Rates of brain atrophy across disease stages in familial frontotemporal dementia associated with MAPT, GRN, and C9orf72 pathogenic variants","volume":"3","author":"Staffaroni","year":"2020","journal-title":"JAMA Netw Open"},{"issue":"4","key":"10.1016\/j.ric.2026.100050_bib0620","doi-asserted-by":"crossref","DOI":"10.1016\/j.omtm.2025.101622","article-title":"Intrathalamic delivery of adeno-associated viral vector expressing progranulin as gene therapy for GRN-related frontotemporal dementia","volume":"33","author":"Lee","year":"2025","journal-title":"Mol Ther Methods Clin Dev"},{"key":"10.1016\/j.ric.2026.100050_bib0625","doi-asserted-by":"crossref","first-page":"335","DOI":"10.3389\/fnins.2019.00335","article-title":"The pathobiology of TDP-43 C-terminal fragments in ALS and FTLD","volume":"13","author":"Berning","year":"2019","journal-title":"Front Neurosci"},{"issue":"1","key":"10.1016\/j.ric.2026.100050_bib0630","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s40035-023-00389-3","article-title":"Novel data-driven subtypes and stages of brain atrophy in the ALS-FTD spectrum","volume":"12","author":"Shen","year":"2023","journal-title":"Transl Neurodegener"},{"issue":"7\u20138","key":"10.1016\/j.ric.2026.100050_bib0635","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1080\/21678421.2021.1903506","article-title":"Comparison of the ability of the King's and MiToS staging systems to predict disease progression and survival in amyotrophic lateral sclerosis","volume":"22","author":"Luna","year":"2021","journal-title":"Amyotroph Lateral Scler Frontotemporal Degener"},{"issue":"7","key":"10.1016\/j.ric.2026.100050_bib0640","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/S1474-4422(22)00120-X","article-title":"A biological classification of Huntington's disease: the integrated staging system","volume":"21","author":"Tabrizi","year":"2022","journal-title":"Lancet Neurol"},{"key":"10.1016\/j.ric.2026.100050_bib0645","doi-asserted-by":"crossref","DOI":"10.1016\/j.ebiom.2025.106090","article-title":"Brain atrophy staging in spinocerebellar ataxia type 3 for clinical prognosis and trial enrichment","volume":"123","author":"Baumeister","year":"2026","journal-title":"EBioMedicine"},{"issue":"4","key":"10.1016\/j.ric.2026.100050_bib0650","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1002\/ana.26200","article-title":"Brain structure and degeneration staging in Friedreich ataxia: magnetic resonance imaging volumetrics from the ENIGMA-Ataxia Working Group","volume":"90","author":"Harding","year":"2021","journal-title":"Ann Neurol"},{"issue":"2","key":"10.1016\/j.ric.2026.100050_bib0655","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.pathol.2024.10.006","article-title":"Current concepts and molecular pathology of neurodegenerative diseases","volume":"57","author":"Forrest","year":"2025","journal-title":"Pathology"},{"issue":"12","key":"10.1016\/j.ric.2026.100050_bib0660","doi-asserted-by":"crossref","first-page":"6442","DOI":"10.3390\/ijms22126442","article-title":"Brain disposition of antibody-based therapeutics: dogma, approaches and perspectives","volume":"22","author":"Kouhi","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"20","key":"10.1016\/j.ric.2026.100050_bib0665","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.129240","article-title":"Brain pharmacology of intrathecal antisense oligonucleotides revealed through multimodal imaging","volume":"4","author":"Mazur","year":"2019","journal-title":"JCI Insight"},{"key":"10.1016\/j.ric.2026.100050_bib0670","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s40035-017-0077-5","article-title":"Protein misfolding in neurodegenerative diseases: implications and strategies","volume":"6","author":"Sweeney","year":"2017","journal-title":"Transl Neurodegener"},{"issue":"1","key":"10.1016\/j.ric.2026.100050_bib0675","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s00415-024-12770-x","article-title":"An update on immune-based alpha-synuclein trials in Parkinson's disease","volume":"272","author":"Alfaidi","year":"2024","journal-title":"J Neurol"},{"issue":"5","key":"10.1016\/j.ric.2026.100050_bib0680","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1056\/NEJMoa2202867","article-title":"Trial of prasinezumab in early-stage Parkinson's disease","volume":"387","author":"Pagano","year":"2022","journal-title":"N Engl J Med"},{"issue":"5","key":"10.1016\/j.ric.2026.100050_bib0685","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1056\/NEJMoa2203395","article-title":"Trial of cinpanemab in early Parkinson's disease","volume":"387","author":"Lang","year":"2022","journal-title":"N Engl J Med"},{"key":"10.1016\/j.ric.2026.100050_bib0690","doi-asserted-by":"crossref","DOI":"10.1016\/j.parkreldis.2024.107257","article-title":"A phase 2b, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of intravenous prasinezumab in early-stage Parkinson's disease (PADOVA): rationale, design, and baseline data","volume":"132","author":"Nikolcheva","year":"2025","journal-title":"Parkinsonism Relat Disord"},{"issue":"6","key":"10.1016\/j.ric.2026.100050_bib0695","doi-asserted-by":"crossref","first-page":"595","DOI":"10.15252\/emmm.201606210","article-title":"The amyloid hypothesis of Alzheimer's disease at 25 years","volume":"8","author":"Selkoe","year":"2016","journal-title":"EMBO Mol Med"},{"issue":"1","key":"10.1016\/j.ric.2026.100050_bib0700","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.ric.2026.100050_bib0705","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":"12","key":"10.1016\/j.ric.2026.100050_bib0710","doi-asserted-by":"crossref","DOI":"10.1002\/alz.70905","article-title":"Long-term safety and efficacy of lecanemab in early Alzheimer's disease: results from the clarity AD open-label extension study","volume":"21","author":"van Dyck","year":"2025","journal-title":"Alzheimers Dement"},{"issue":"2","key":"10.1016\/j.ric.2026.100050_bib0715","doi-asserted-by":"crossref","DOI":"10.1016\/j.tjpad.2025.100446","article-title":"Donanemab in early symptomatic Alzheimer's disease: results from the TRAILBLAZER-ALZ 2 long-term extension","volume":"13","author":"Zimmer","year":"2026","journal-title":"J Prev Alzheimers Dis"},{"issue":"6","key":"10.1016\/j.ric.2026.100050_bib0720","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.3390\/ph3061812","article-title":"Non-steroidal anti-inflammatory drugs in Alzheimer's disease and Parkinson's disease: reconsidering the role of neuroinflammation","volume":"3","author":"Moore","year":"2010","journal-title":"Pharmaceuticals (Basel)"},{"issue":"3","key":"10.1016\/j.ric.2026.100050_bib0725","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1212\/WNL.54.3.588","article-title":"A randomized controlled trial of prednisone in Alzheimer's disease","volume":"54","author":"Aisen","year":"2000","journal-title":"Neurology"},{"issue":"2","key":"10.1016\/j.ric.2026.100050_bib0730","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1001\/jamaneurol.2019.3762","article-title":"Minocycline at 2 different dosages vs placebo for patients with mild Alzheimer disease: a randomized clinical trial","volume":"77","author":"Howard","year":"2020","journal-title":"JAMA Neurol"},{"issue":"10103","key":"10.1016\/j.ric.2026.100050_bib0735","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1016\/S0140-6736(17)31585-4","article-title":"Exenatide once weekly versus placebo in Parkinson's disease: a randomised, double-blind, placebo-controlled trial","volume":"390","author":"Athauda","year":"2017","journal-title":"Lancet"},{"issue":"13","key":"10.1016\/j.ric.2026.100050_bib0740","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1056\/NEJMoa2312323","article-title":"Trial of lixisenatide in early Parkinson's disease","volume":"390","author":"Meissner","year":"2024","journal-title":"N Engl J Med"},{"issue":"10479","key":"10.1016\/j.ric.2026.100050_bib0745","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/S0140-6736(24)02808-3","article-title":"Exenatide once a week versus placebo as a potential disease-modifying treatment for people with Parkinson's disease in the UK: a phase 3, multicentre, double-blind, parallel-group, randomised, placebo-controlled trial","volume":"405","author":"Vijiaratnam","year":"2025","journal-title":"Lancet"},{"issue":"3","key":"10.1016\/j.ric.2026.100050_bib0750","doi-asserted-by":"crossref","DOI":"10.1016\/j.immuni.2017.08.008","article-title":"The TREM2-APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases","volume":"47","author":"Krasemann","year":"2017","journal-title":"Immunity"},{"issue":"1","key":"10.1016\/j.ric.2026.100050_bib0755","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1186\/s12883-025-04241-1","article-title":"Mitotherapy in Alzheimer's and Parkinson's diseases: a systematic review of preclinical studies","volume":"25","author":"Modiri","year":"2025","journal-title":"BMC Neurol"},{"issue":"4","key":"10.1016\/j.ric.2026.100050_bib0760","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1136\/heart.87.4.346","article-title":"Idebenone and reduced cardiac hypertrophy in Friedreich's ataxia","volume":"87","author":"Hausse","year":"2002","journal-title":"Heart"},{"issue":"8","key":"10.1016\/j.ric.2026.100050_bib0765","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1001\/archneurol.2010.168","article-title":"A phase 3, double-blind, placebo-controlled trial of idebenone in Friedreich ataxia","volume":"67","author":"Lynch","year":"2010","journal-title":"Arch Neurol"},{"issue":"2","key":"10.1016\/j.ric.2026.100050_bib0770","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1002\/ana.25934","article-title":"Safety and efficacy of omaveloxolone in Friedreich ataxia: the MOXIe study","volume":"89","author":"Lynch","year":"2021","journal-title":"Ann Neurol"},{"key":"10.1016\/j.ric.2026.100050_bib0775","doi-asserted-by":"crossref","first-page":"100862","DOI":"10.1016\/j.lanepe.2024.100862","article-title":"Long-term efficacy and safety of nusinersen in adults with 5q spinal muscular atrophy: a prospective European multinational observational study","volume":"39","author":"G\u00fcnther","year":"2024","journal-title":"Lancet Reg Health Eur"},{"issue":"11","key":"10.1016\/j.ric.2026.100050_bib0780","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1007\/s40265-023-01904-6","article-title":"Tofersen: first approval","volume":"83","author":"Blair","year":"2023","journal-title":"Drugs"},{"issue":"12","key":"10.1016\/j.ric.2026.100050_bib0785","doi-asserted-by":"crossref","first-page":"3242","DOI":"10.1111\/bcp.16202","article-title":"Pharmacokinetics and pharmacodynamics of PTC518, an oral huntingtin lowering splicing modifier: a first-in-human study","volume":"90","author":"Gao","year":"2024","journal-title":"Br J Clin Pharmacol"},{"issue":"8","key":"10.1016\/j.ric.2026.100050_bib0790","article-title":"Emerging gene therapies for Alzheimer's and Parkinson's diseases: an overview of clinical trials and promising candidates","volume":"16","author":"Roberts","year":"2024","journal-title":"Cureus"},{"key":"10.1016\/j.ric.2026.100050_bib0795","article-title":"Significance of gene therapy in neurodegenerative diseases","volume":"19","author":"Wang","year":"2025","journal-title":"Front Neurosci"},{"key":"10.1016\/j.ric.2026.100050_bib0800","first-page":"567","article-title":"CRISPR\/Cas9 genome editing for neurodegenerative diseases","volume":"22","author":"Nouri Nojadeh","year":"2023","journal-title":"EXCLI J"},{"key":"10.1016\/j.ric.2026.100050_bib0805","doi-asserted-by":"crossref","DOI":"10.3389\/fnins.2023.1223777","article-title":"CRISPR\/Cas9: implication for modeling and therapy of amyotrophic lateral sclerosis","volume":"17","author":"Shi","year":"2023","journal-title":"Front Neurosci"},{"issue":"4","key":"10.1016\/j.ric.2026.100050_bib0810","doi-asserted-by":"crossref","DOI":"10.1016\/j.neurot.2024.e00435","article-title":"Immune responses to central nervous system directed adeno-associated virus gene therapy: does direct CNS delivery make a difference?","volume":"21","author":"Harkins","year":"2024","journal-title":"Neurotherapeutics"},{"issue":"3","key":"10.1016\/j.ric.2026.100050_bib0815","doi-asserted-by":"crossref","DOI":"10.1016\/j.omtn.2025.102635","article-title":"Trends and challenges of AAV-delivered gene editing therapeutics for CNS disorders: implications for neurodegenerative disease","volume":"36","author":"Kantor","year":"2025","journal-title":"Mol Ther Nucleic Acids"},{"issue":"1","key":"10.1016\/j.ric.2026.100050_bib0820","first-page":"1","article-title":"Challenges and opportunities in the application of CRISPR-Cas9: a review on genomic editing and therapeutic potentials","volume":"35","author":"Karimi","year":"2026","journal-title":"Med Princ Pract"},{"issue":"4","key":"10.1016\/j.ric.2026.100050_bib0825","doi-asserted-by":"crossref","first-page":"230","DOI":"10.62347\/GZVM7194","article-title":"Innovative approaches in neural stem cell therapy: a comprehensive review of mechanisms and applications","volume":"14","author":"Panin","year":"2025","journal-title":"Am J Stem Cells"},{"issue":"24","key":"10.1016\/j.ric.2026.100050_bib0830","doi-asserted-by":"crossref","DOI":"10.3390\/ijms20246305","article-title":"The challenge of bringing iPSCs to the patient","volume":"20","author":"Ortu\u00f1o-Costela","year":"2019","journal-title":"Int J Mol Sci"},{"issue":"2","key":"10.1016\/j.ric.2026.100050_bib0835","doi-asserted-by":"crossref","first-page":"146","DOI":"10.2174\/011574888X313112240510160102","article-title":"The role of stem cell therapies in the treatment of neurodegenerative diseases","volume":"20","author":"Jayaprakash","year":"2025","journal-title":"Curr Stem Cell Res Ther"},{"issue":"11","key":"10.1016\/j.ric.2026.100050_bib0840","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1002\/sctm.19-0020","article-title":"Neuronal stem cell and drug interactions: a systematic review and meta-analysis: concise review","volume":"8","author":"Ikhsan","year":"2019","journal-title":"Stem Cells Transl Med"},{"issue":"11","key":"10.1016\/j.ric.2026.100050_bib0845","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1001\/jamaneurol.2025.2781","article-title":"Long-term personalized adaptive deep brain stimulation in Parkinson disease: a nonrandomized clinical trial","volume":"82","author":"Bronte-Stewart","year":"2025","journal-title":"JAMA Neurol"},{"key":"10.1016\/j.ric.2026.100050_bib0850","doi-asserted-by":"crossref","DOI":"10.3389\/fnana.2024.1469250","article-title":"Therapeutic ultrasound: an innovative approach for targeting neurological disorders affecting the basal ganglia","volume":"18","author":"Singh","year":"2024","journal-title":"Front Neuroanat"},{"key":"10.1016\/j.ric.2026.100050_bib0855","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/bs.irn.2021.06.004","article-title":"Focused ultrasound neuromodulation","volume":"159","author":"Meng","year":"2021","journal-title":"Int Rev Neurobiol"},{"key":"10.1016\/j.ric.2026.100050_bib0860","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/j.jconrel.2024.07.006","article-title":"The road ahead to successful BBB opening and drug-delivery with focused ultrasound","volume":"372","author":"L\u00f3pez-Aguirre","year":"2024","journal-title":"J Control Release"},{"issue":"4","key":"10.1016\/j.ric.2026.100050_bib0865","doi-asserted-by":"crossref","DOI":"10.1016\/j.omtm.2025.101622","article-title":"Intrathalamic delivery of adeno-associated viral vector expressing progranulin as gene therapy for GRN-related frontotemporal dementia","volume":"33","author":"Lee","year":"2025","journal-title":"Mol Ther Methods Clin Dev"},{"issue":"165","key":"10.1016\/j.ric.2026.100050_bib0870","first-page":"51","article-title":"Lewy bodies dementia and primary progressive aphasias: current diagnostic criteria","volume":"35","author":"Ollari","year":"2024","journal-title":"Vertex"},{"key":"10.1016\/j.ric.2026.100050_bib0875","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.socscimed.2017.12.005","article-title":"Understanding and misunderstanding randomized controlled trials","volume":"210","author":"Deaton","year":"2018","journal-title":"Soc Sci Med"},{"issue":"1","key":"10.1016\/j.ric.2026.100050_bib0880","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1177\/02537176241297953","article-title":"Poorly recognized and uncommonly acknowledged limitations of randomized controlled trials","volume":"47","author":"Andrade","year":"2025","journal-title":"Indian J Psychol Med"},{"key":"10.1016\/j.ric.2026.100050_bib0885","doi-asserted-by":"crossref","DOI":"10.3389\/fneur.2023.1098454","article-title":"Study design challenges and strategies in clinical trials for rare diseases: lessons learned from pantothenate kinase-associated neurodegeneration","volume":"14","author":"Videnovic","year":"2023","journal-title":"Front Neurol"},{"issue":"1","key":"10.1016\/j.ric.2026.100050_bib0890","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1186\/s12874-024-02386-0","article-title":"Barriers and facilitators to conducting randomised controlled trials within routine care of neurorehabilitation centres: a qualitative study","volume":"24","author":"Hotz","year":"2024","journal-title":"BMC Med Res Methodol"},{"issue":"11","key":"10.1016\/j.ric.2026.100050_bib0895","doi-asserted-by":"crossref","first-page":"629","DOI":"10.3390\/curroncol32110629","article-title":"A narrative review of the strengths and limitations of real-world evidence in comparison to randomized clinical trials: what are the opportunities in thoracic oncology for real-world evidence to shine?","volume":"32","author":"Ellis","year":"2025","journal-title":"Curr Oncol"},{"issue":"5646","key":"10.1016\/j.ric.2026.100050_bib0900","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1126\/science.1090349","article-title":"Looking backward to move forward: early detection of neurodegenerative disorders","volume":"302","author":"DeKosky","year":"2003","journal-title":"Science"},{"issue":"4","key":"10.1016\/j.ric.2026.100050_bib0905","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","article-title":"NIA-AA research framework: toward a biological definition of Alzheimer's disease","volume":"14","author":"Jack","year":"2018","journal-title":"Alzheimers Dement"},{"issue":"15","key":"10.1016\/j.ric.2026.100050_bib0910","doi-asserted-by":"crossref","DOI":"10.3390\/ijms26157268","article-title":"Circulating biomarkers for the early diagnosis of Alzheimer's disease","volume":"26","author":"Nunkoo","year":"2025","journal-title":"Int J Mol Sci"},{"issue":"6","key":"10.1016\/j.ric.2026.100050_bib0915","doi-asserted-by":"crossref","first-page":"107","DOI":"10.3390\/clinpract15060107","article-title":"Alpha-synuclein seed amplification assays in Parkinson's disease: a systematic review and network meta-analysis","volume":"15","author":"Rissardo","year":"2025","journal-title":"Clin Pract"},{"issue":"6","key":"10.1016\/j.ric.2026.100050_bib0920","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1038\/s41591-024-02937-4","article-title":"Plasma extracellular vesicle tau and TDP-43 as diagnostic biomarkers in FTD and ALS","volume":"30","author":"Chatterjee","year":"2024","journal-title":"Nat Med"},{"issue":"2","key":"10.1016\/j.ric.2026.100050_bib0925","doi-asserted-by":"crossref","DOI":"10.1002\/alz.14482","article-title":"Plasma p-tau217 and neurofilament\/p-tau217 ratio in differentiating Alzheimer's disease from syndromes associated with frontotemporal lobar degeneration","volume":"21","author":"Benussi","year":"2025","journal-title":"Alzheimers Dement"},{"issue":"3","key":"10.1016\/j.ric.2026.100050_bib0930","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1038\/s41591-024-03424-6","article-title":"Somatic CAG repeat expansion in blood associates with biomarkers of neurodegeneration in Huntington's disease decades before clinical motor diagnosis","volume":"31","author":"Scahill","year":"2025","journal-title":"Nat Med"},{"issue":"5","key":"10.1016\/j.ric.2026.100050_bib0935","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.3390\/ijms26052231","article-title":"Molecular biomarkers in neurological diseases: advances in diagnosis and prognosis","volume":"26","author":"Myrou","year":"2025","journal-title":"Int J Mol Sci"},{"issue":"5","key":"10.1016\/j.ric.2026.100050_bib0940","doi-asserted-by":"crossref","DOI":"10.3390\/s24051572","article-title":"Machine learning and digital biomarkers can detect early stages of neurodegenerative diseases","volume":"24","author":"Chudzik","year":"2024","journal-title":"Sensors (Basel)"},{"key":"10.1016\/j.ric.2026.100050_bib0945","doi-asserted-by":"crossref","DOI":"10.3389\/fninf.2025.1557177","article-title":"Advancements in deep learning for early diagnosis of Alzheimer's disease using multimodal neuroimaging: challenges and future directions","volume":"19","author":"Raza","year":"2025","journal-title":"Front Neuroinform"},{"issue":"1","key":"10.1016\/j.ric.2026.100050_bib0950","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1002\/med.70005","article-title":"Digital therapeutics for Alzheimer's and Parkinson's diseases: current trends and future perspectives","volume":"46","author":"Jeong","year":"2026","journal-title":"Med Res Rev"},{"key":"10.1016\/j.ric.2026.100050_bib0955","doi-asserted-by":"crossref","DOI":"10.2196\/46992","article-title":"Digital health technology for real-world clinical outcome measurement using patient-generated data: systematic scoping review","volume":"25","author":"Pyper","year":"2023","journal-title":"J Med Internet Res"},{"key":"10.1016\/j.ric.2026.100050_bib0960","doi-asserted-by":"crossref","DOI":"10.3389\/fneur.2023.1210974","article-title":"Digital endpoints in clinical trials of Alzheimer's disease and other neurodegenerative diseases: challenges and opportunities","volume":"14","author":"Brem","year":"2023","journal-title":"Front Neurol"},{"issue":"2","key":"10.1016\/j.ric.2026.100050_bib0965","doi-asserted-by":"crossref","first-page":"102","DOI":"10.3390\/bios15020102","article-title":"Development of neurodegenerative disease diagnosis and monitoring from traditional to digital biomarkers","volume":"15","author":"Song","year":"2025","journal-title":"Biosensors (Basel)"},{"key":"10.1016\/j.ric.2026.100050_bib0970","doi-asserted-by":"crossref","DOI":"10.3389\/fdgth.2025.1727707","article-title":"Merging multimodal digital biomarkers into \u201cDigital Neuro Fingerprints\u201d for precision neurology in dementias: the promise of the right treatment for the right patient at the right time in the age of AI","volume":"7","author":"Tarnanas","year":"2026","journal-title":"Front Digit Health"},{"key":"10.1016\/j.ric.2026.100050_bib0975","article-title":"Innovative oncology trial designs: time to act \u2013 a review with recommendations of the Cancer Drug Development Forum","volume":"47","author":"Giuliani","year":"2025","journal-title":"J Cancer Policy"},{"issue":"12 suppl","key":"10.1016\/j.ric.2026.100050_bib0980","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0929-6646(09)60002-4","article-title":"A regulatory view of adaptive trial design","volume":"107","author":"Wang","year":"2008","journal-title":"J Formos Med Assoc"},{"issue":"1","key":"10.1016\/j.ric.2026.100050_bib0985","doi-asserted-by":"crossref","DOI":"10.1111\/1742-6723.14532","article-title":"Review article: primer for clinical researchers on innovative trial designs for emergency medicine","volume":"37","author":"Lee","year":"2025","journal-title":"Emerg Med Australas"},{"issue":"3","key":"10.1016\/j.ric.2026.100050_bib0990","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0119632","article-title":"A novel approach to delayed-start analyses for demonstrating disease-modifying effects in Alzheimer's disease","volume":"10","author":"Liu-Seifert","year":"2015","journal-title":"PLoS One"},{"issue":"7","key":"10.1016\/j.ric.2026.100050_bib0995","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1001\/jamaneurol.2023.0815","article-title":"Advocating for demonstration of disease modification \u2013 have we been approaching clinical trials in early alzheimer disease incorrectly?","volume":"80","author":"Planche","year":"2023","journal-title":"JAMA Neurol"},{"issue":"1","key":"10.1016\/j.ric.2026.100050_bib1000","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/s41392-024-01760-0","article-title":"New clinical trial design in precision medicine: discovery, development and direction","volume":"9","author":"Duan","year":"2024","journal-title":"Signal Transduct Target Ther"},{"issue":"9","key":"10.1016\/j.ric.2026.100050_bib1005","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1093\/jnci\/djad103","article-title":"Seamless phase II\/III design: a useful strategy to reduce the sample size for dose optimization","volume":"115","author":"Jiang","year":"2023","journal-title":"J Natl Cancer Inst"},{"issue":"6","key":"10.1016\/j.ric.2026.100050_bib1010","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1177\/0962280210379035","article-title":"Seamless phase II\/III designs","volume":"20","author":"Stallard","year":"2011","journal-title":"Stat Methods Med Res"},{"issue":"7","key":"10.1016\/j.ric.2026.100050_bib1015","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1111\/epi.17621","article-title":"Time-to-event clinical trial designs: existing evidence and remaining concerns","volume":"64","author":"Kerr","year":"2023","journal-title":"Epilepsia"},{"key":"10.1016\/j.ric.2026.100050_bib1020","first-page":"1","article-title":"The temporal event-based model: learning event timelines in progressive diseases","volume":"1","author":"Wijeratne","year":"2023","journal-title":"Imaging Neurosci (Camb)"},{"issue":"5","key":"10.1016\/j.ric.2026.100050_bib1025","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1155\/2011\/465281","article-title":"A comparison between enriched and nonenriched enrollment randomized withdrawal trials of opioids for chronic noncancer pain","volume":"16","author":"Furlan","year":"2011","journal-title":"Pain Res Manag"},{"issue":"1","key":"10.1016\/j.ric.2026.100050_bib1030","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1161\/HYPERTENSIONAHA.114.04035","article-title":"Randomized withdrawal study of patients with symptomatic neurogenic orthostatic hypotension responsive to droxidopa","volume":"65","author":"Biaggioni","year":"2015","journal-title":"Hypertension"},{"issue":"1","key":"10.1016\/j.ric.2026.100050_bib1035","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pdig.0001191","article-title":"Decentralized clinical trials: a comprehensive analysis of trends, technologies, and global challenges","volume":"5","author":"Kijewski","year":"2026","journal-title":"PLoS Digit Health"},{"issue":"5","key":"10.1016\/j.ric.2026.100050_bib1040","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1002\/cpt.70070","article-title":"Operationalizing decentralized clinical trials: technology insights from the Trials@Home RADIAL Proof-of-Concept Trial","volume":"118","author":"Hanke","year":"2025","journal-title":"Clin Pharmacol Ther"},{"issue":"1","key":"10.1016\/j.ric.2026.100050_bib1045","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1056\/NEJMra1510062","article-title":"Master protocols to study multiple therapies, multiple diseases, or both","volume":"377","author":"Woodcock","year":"2017","journal-title":"N Engl J Med"},{"issue":"1","key":"10.1016\/j.ric.2026.100050_bib1050","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1186\/s13063-019-3664-1","article-title":"Systematic review of basket trials, umbrella trials, and platform trials: a landscape analysis of master protocols","volume":"20","author":"Park","year":"2019","journal-title":"Trials"},{"issue":"2","key":"10.1016\/j.ric.2026.100050_bib1055","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1002\/ana.26285","article-title":"Adaptive platform trials to transform amyotrophic lateral sclerosis therapy development","volume":"91","author":"Paganoni","year":"2022","journal-title":"Ann Neurol"},{"issue":"9","key":"10.1016\/j.ric.2026.100050_bib1060","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1002\/mds.29899","article-title":"Advantages and challenges of platform trials for disease modifying therapies in Parkinson's disease","volume":"39","author":"Fabbri","year":"2024","journal-title":"Mov Disord"},{"issue":"7","key":"10.1016\/j.ric.2026.100050_bib1065","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1039\/C5IB00031A","article-title":"Systems biology of neurodegenerative diseases","volume":"7","author":"Wood","year":"2015","journal-title":"Integr Biol (Camb)"},{"issue":"1","key":"10.1016\/j.ric.2026.100050_bib1070","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s13024-026-00934-4","article-title":"Systems biology of Alzheimer's Disease: a scoping review of key pathways and mechanisms","volume":"21","author":"Bice","year":"2026","journal-title":"Mol Neurodegener"}],"container-title":["Revista de Investigaci\u00f3n Cl\u00ednica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0034837626000173?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0034837626000173?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T13:10:32Z","timestamp":1787577032000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0034837626000173"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":107,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["S0034837626000173"],"URL":"https:\/\/doi.org\/10.1016\/j.ric.2026.100050","relation":{},"ISSN":["0034-8376"],"issn-type":[{"value":"0034-8376","type":"print"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Precision therapeutics and innovative clinical trial design in neurodegenerative diseases","name":"articletitle","label":"Article Title"},{"value":"Revista de Investigaci\u00f3n Cl\u00ednica","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ric.2026.100050","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Author(s). Published by Elsevier Espa\u00f1a, S.L.U. on behalf of Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubiran.","name":"copyright","label":"Copyright"}],"article-number":"100050"}}