title: Can commonly prescribed drugs be repurposed for the prevention or treatment of Alzheimer's and other neurodegenerative diseases? Protocol for an observational cohort study in the UK Clinical Practice Research Datalink.
abstract: Current treatments for Alzheimer's and other neurodegenerative diseases have only limited effectiveness meaning that there is an urgent need for new medications that could influence disease incidence and progression. We will investigate the potential of a selection of commonly prescribed drugs, as a more efficient and cost-effective method of identifying new drugs for the prevention or treatment of Alzheimer's disease, non-Alzheimer's disease dementias, Parkinson's disease and amyotrophic lateral sclerosis. Our research will focus on drugs used for the treatment of hypertension, hypercholesterolaemia and type 2 diabetes, all of which have previously been identified as potentially cerebroprotective and have variable levels of preclinical evidence that suggest they may have beneficial effects for various aspects of dementia pathology.
  
  
  
  We will conduct a hypothesis testing observational cohort study using data from the Clinical Practice Research Datalink (CPRD). Our analysis will consider four statistical methods, which have different approaches for modelling confounding. These are multivariable adjusted Cox regression; propensity matched regression; instrumental variable analysis and marginal structural models. We will also use an intention-to-treat analysis, whereby we will define all exposures based on the first prescription observed in the database so that the target parameter is comparable to that estimated by a randomised controlled trial.
  
  
  
  This protocol has been approved by the CPRD's Independent Scientific Advisory Committee (ISAC). We will publish the results of the study as open-access peer-reviewed publications and disseminate findings through national and international conferences as are appropriate.
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.|MRC University of Bristol Integrative Epidemiology Unit, Bristol, UK.
authors.forename: Venexia M
authors.identifier: 0000-0001-5064-446X
authors.initials: VM
authors.lastname: Walker
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.|MRC University of Bristol Integrative Epidemiology Unit, Bristol, UK.
authors.forename: Neil M
authors.initials: NM
authors.lastname: Davies
authors.affiliation: NIHR CLAHRC West, Bristol, UK.
authors.forename: Tim
authors.initials: T
authors.lastname: Jones
authors.affiliation: Dementia Research Group, School of Clinical Sciences, University of Bristol, Bristol, UK.
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Kehoe
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.|MRC University of Bristol Integrative Epidemiology Unit, Bristol, UK.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Martin
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000517:prevention & control; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000517:prevention & control; D015331:Cohort Studies; D003362:Cost-Benefit Analysis; D016208:Databases, Factual; D003704:Dementia / Q000188:drug therapy* / Q000517:prevention & control; D058492:Drug Repositioning; D006801:Humans; D015999:Multivariate Analysis; D010300:Parkinson Disease / Q000188:drug therapy* / Q000517:prevention & control; D016016:Proportional Hazards Models; D012107:Research Design; D006113:United Kingdom
keywords: EPIDEMIOLOGY; THERAPEUTICS