Disclosing Pleiotropic Effects During Genetic Risk Assessment for Alzheimer Disease: A Randomized Trial

Area of Science:

• Genetics
• Cardiovascular Disease
• Neurology

Background:

• Genetic testing is increasingly used, prompting discussions on disclosing secondary findings, including pleiotropic information.
• Apolipoprotein E (APOE) genotype influences risk for both Alzheimer disease (AD) and coronary artery disease (CAD).

Purpose of the Study:

• To assess the safety and behavioral impact of revealing moderate associations between APOE genotype and CAD risk during APOE-based genetic risk assessments for AD.
• To evaluate psychological and behavioral responses to disclosing combined AD and CAD genetic risk information versus AD risk alone.

Main Methods:

• A randomized, multicenter equivalence clinical trial involving 257 asymptomatic adults.
• Participants received genetic risk information for AD and CAD (AD+CAD group) or AD only (AD-only group).
• Primary outcomes included anxiety (Beck Anxiety Inventory) and depression (CES-D) scores at 12 months, with secondary outcomes assessing distress and health behaviors.

Main Results:

• No significant differences in anxiety or depression scores were observed between the AD-only and AD+CAD groups at 12 months, with confidence intervals within the equivalence margin.
• Carriers of the APOE ε4 allele in the AD+CAD group reported lower distress compared to the AD-only group.
• Participants in the AD+CAD group showed increased health behavior changes, irrespective of APOE genotype.

Conclusions:

• Disclosure of pleiotropic genetic information (AD+CAD) did not elevate anxiety or depression and potentially reduced distress in at-risk individuals.
• Providing risk modification information for CAD alongside AD risk improved health behaviors.
• These findings support the potential benefits of disclosing secondary genetic findings when risk-reduction strategies are available.