The Risk Evaluation and Education for Alzheimer's disease (REVEAL) Study is a multicenter randomized, controlled trial examining the impact of genetic susceptibility testing and disclosure on asymptomatic adult children of patients with AD. Details of the study rationale, design, and other results have been published elsewhere.6–11
Eligible participants had only 1 living or deceased affected parent who developed AD after the age of 60. The diagnosis of AD in the affected parent was determined by obtaining written documentation from medical records or a letter from the diagnosing physician. In the minority of cases where written documentation was unavailable, the diagnosis of AD was determined using a detailed interview with the participant regarding the parent's history. Individuals were excluded if they exhibited clinically significant cognitive impairment, depression, and anxiety.
Two hundred eighty-nine individuals were initially eligible for the study, dropping to 162 by the randomization phase (). At each phase before randomization (education session, blood draw to test for genotype status, neuropsychologic and psychiatric screening), participants were allowed to drop out if they did not want to receive clinical information offered in that phase. Before randomization, participants attended an education session where they were informed about the difference between deterministic and susceptibility genetic testing. The session emphasized that although the APOE ε4 allele is an important risk factor for AD, it is neither necessary nor sufficient to cause the disease. Participants were also told that there are no proven preventive measures for AD; they received a handout outlining therapies under investigation but not currently recommended for their protective effects against AD such as vitamin E, anti-inflammatory medications, hormone replacement therapies, cholesterol-lowering drugs, and mental stimulation. Participants who proceeded to randomization did not differ significantly from those who declined participation earlier in the protocol with regard to age, sex, race, income, or number of affected relatives; details of this analysis have been published elsewhere.5,6
Participants' progression through the REVEAL Study.
A blocking technique was used to generate the random allocation sequence, and the allocation was concealed from the investigators, and the participants until interventions were assigned. Participants were randomized in a 2:1 ratio to the intervention and control arms of the study, respectively, to have sufficient power to examine response to risk assessment by APOE genotype (ie, ε4+ vs. ε4−). Subjects who were randomized to the control arm received an individualized numerical risk assessment on the basis of family history and sex alone. Subjects in the intervention arm received APOE genotype disclosure and an individualized numerical risk assessment on the basis of family history, sex, and APOE genotype. In both arms, risk estimates were illustrated to participants with cumulative risk curves constructed from epidemiologic data, details of which are described in a separate paper.8
Control participants were given lifetime risk estimates through age 85 ranging between 18% and 29%, whereas intervention participants received estimates between 13% and 57%.
One year after disclosure, participants were asked 3 questions related to health behavior changes made specifically for the purpose of AD prevention. These questions focused on: (1) changes in diet, (2) changes in exercise, or (3) changes in medications and/or vitamins (participants were also allowed to describe these changes in an open-ended format). The primary outcome variable for this analysis was a composite variable gauging whether or not participants answered at least one of these questions affirmatively.
Rather than comparing controls with the disclosure group as a whole, logistic regression analyses using SAS 8.2 were used to test the preplanned dual hypotheses that participants who learned that they were ε4+ were more likely to make changes in AD-specific health behaviors than participants who learned that they were ε4− and than controls. Covariates included demographic data (age, sex, and education) and a composite comorbidity variable that was considered positive if the participant had a history of diabetes mellitus, heart disease, hypertension, hypercholesterolemia, thyroid disease, cancer, or osteoporosis (all conditions where behavioral modifications have potentially preventive effects). Post hoc analyses included a term for the numerical lifetime risk estimate that was also given to each participant as part of the disclosure protocol.