title: Currents of memory: recent progress, translational challenges, and ethical considerations in fornix deep brain stimulation trials for Alzheimer's disease.
abstract: The serendipitous discovery of triggered autobiographical memories and eventual memory improvement in an obese patient who received fornix deep brain stimulation in 2008 paved the way for several phase I and phase II clinical trials focused on the safety and efficacy of this potential intervention for people with Alzheimer's disease. In this article, we summarize clinical trials and case reports on fornix deep brain stimulation for Alzheimer's disease and review experiments on animal models evaluating the physiological or behavioral effects of this intervention. Based on information from these reports and studies, we identify potential translational challenges of this approach and determine practical and ethical considerations for clinical trials, focusing on issues regarding selection criteria, trial design, and outcome evaluation. Based on initial results suggesting greater benefit for those with milder disease stage, we find it essential that participant expectations are carefully managed to avoid treatment disenchantment and/or frustration from participants and caregivers. Finally, we urge for collaboration between centers to establish proper clinical standards and to promote better trial results comparison.
authors.affiliation: Ethics, Policy & Public Engagement (EPPE) Program, Australian Research Council Centre of Excellence for Electromaterials Science, Hobart, Tasmania, Australia; Philosophy and Gender Studies Program, School of Humanities, Faculty of Arts and Law, University of Tasmania, Hobart, Tasmania, Australia. Electronic address: John.viana@utas.edu.au.
authors.forename: John Noel M
authors.initials: JNM
authors.lastname: Viaña
authors.affiliation: Wicking Dementia Research and Education Centre, Faculty of Health, University of Tasmania, Hobart, Tasmania, Australia.
authors.forename: James C
authors.initials: JC
authors.lastname: Vickers
authors.affiliation: Department of Medicine, St. Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia; Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Cook
authors.affiliation: Ethics, Policy & Public Engagement (EPPE) Program, Australian Research Council Centre of Excellence for Electromaterials Science, Hobart, Tasmania, Australia; Philosophy and Gender Studies Program, School of Humanities, Faculty of Arts and Law, University of Tasmania, Hobart, Tasmania, Australia.
authors.forename: Frederic
authors.initials: F
authors.lastname: Gilbert
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000523:psychology* / Q000628:therapy*; D000818:Animals; D002986:Clinical Trials as Topic / Q000941:ethics; D046690:Deep Brain Stimulation / Q000941:ethics* / Q000639:trends*; D004195:Disease Models, Animal; D005260:Female; D020712:Fornix, Brain; D006801:Humans; D008297:Male; D008568:Memory; D008875:Middle Aged; D012720:Severity of Illness Index; D016896:Treatment Outcome
keywords: Alzheimer disease; Clinical trials; Deep brain stimulation; Ethics; Fornix; Memory