title: The impact of the availability of prevention studies on the desire to undergo predictive testing in persons at risk for autosomal dominant Alzheimer's disease.
abstract: Persons at risk for autosomal dominant neurodegenerative diseases provide the opportunity to efficiently test preventive interventions. Only a minority of such persons, however, choose to undergo revealing genetic testing, presenting a challenge to enrollment. Thirty-four preclinical Latinos (n = 26) and non-Latinos at risk for familial Alzheimer's disease (FAD) unaware of their genetic status were administered a questionnaire exploring their interest in undergoing revealing genetic testing at baseline and in the context of eligibility for four prevention trials of increasing invasiveness. Forty-four percent of subjects expressed a baseline interest in undergoing revealing testing which increased to 85% in order to be eligible for a study of an oral drug "felt to be very safe." If there were a 50% chance of receiving placebo, this number dropped to 62% (p = 0.02). Among those not interested in a study involving a 50% chance of receiving placebo, a range of 5% to 40% chance of receiving placebo was given as acceptable. For more invasive studies, living in the United States (as opposed to Mexico) positively influenced the likelihood of participating. Our data suggest that clinical trial designs in which persons must confront their genetic status prior to enrollment are feasible. Study designs to minimize the likelihood of being placed on placebo or provide the eventual administration of the drug through open-label extensions should be considered.
authors.affiliation: Genetic Counseling Program, Cal State University Northridge, CA, USA.
authors.forename: Megan
authors.initials: M
authors.lastname: Hooper
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Grill
authors.forename: Yaneth
authors.initials: Y
authors.lastname: Rodriguez-Agudelo
authors.forename: Luis D
authors.initials: LD
authors.lastname: Medina
authors.forename: Michelle
authors.initials: M
authors.lastname: Fox
authors.forename: Ana Isabel
authors.initials: AI
authors.lastname: Alvarez-Retuerto
authors.forename: David
authors.initials: D
authors.lastname: Wharton
authors.forename: Jenny
authors.initials: J
authors.lastname: Brook
authors.forename: John M
authors.initials: JM
authors.lastname: Ringman
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000208:ethnology / Q000235:genetics* / Q000517:prevention & control*; D016564:Amyloid beta-Protein Precursor; D002986:Clinical Trials as Topic / Q000379:methods*; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D008297:Male; D017058:Mexican Americans; D008875:Middle Aged; D011237:Predictive Value of Tests; D053764:Presenilin-1; D053766:Presenilin-2; D035842:Research Subjects / Q000523:psychology*; D014481:United States; D044465:White People
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2
keywords: AD; Alzheimer disease; FAD; FTD; Genetic; HD; Huntington disease; Pre-symptomatic; Prevention; Testing; Trials; early-onset familial Alzheimer's disease; frontotemporal dementia