title: Disease-modifying approaches to Alzheimer's disease: challenges and opportunities-Lessons from donepezil therapy.
abstract: The era of disease modification as a therapeutic option for Alzheimer's disease (AD) is upon us. With dozens of novel drugs in development, there is more need than ever to develop biomarkers that distinguish normal aging from AD and AD from other dementias, track changes over time as disease progresses, and respond to interventions. Future trials will need to weight biomarker outcomes equal to cognitive outcomes especially when the biomarkers are linked to specific mechanisms, such as changes to beta amyloid (Abeta) deposition or brain volume. Since the advent of donepezil as a treatment for AD, new mechanisms of action of this molecule have been discovered. In this perspective, we review trial design and discuss the use of biomarkers by using lessons learned from previous trials conducted with cholinergic therapy.
authors.affiliation: Cleo Roberts Center for Clinical Research, Sun Health Research Institute, Sun City, AZ, USA. Marwan. sabbagh@sunhealth.org
authors.forename: Marwan N
authors.initials: MN
authors.lastname: Sabbagh
authors.forename: Sharon
authors.initials: S
authors.lastname: Richardson
authors.forename: Norman
authors.initials: N
authors.lastname: Relkin
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D015415:Biomarkers; D001921:Brain / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D000077265:Donepezil; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use*; D012107:Research Design
chemical_list: D015415:Biomarkers; D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil