Disclosure of Genetic Risk Factors for Alzheimer’s Disease to Cognitively Healthy Individuals—From Current Practice towards a Personalised Medicine Scenario

Abstract

Alzheimer’s disease (AD) is a genetically complex disorder. In addition to the relatively small number of pathogenic variants causing autosomal dominant AD, many others have been associated with the much more common sporadic form. The E4 allele of the Apolipoprotein E (APOE) is the first discovered genetic risk factor for AD. In addition, more than 70 genetic risk loci contributing to AD have been identified. Current guidelines do not recommend AD susceptibility genetic testing in cognitively healthy adults because the implications for clinical care are limited. However, secondary prevention clinical trials of disease-modifying therapies enrol individuals based on genetic criteria, and participants are often informed of APOE testing results. Moreover, the availability of direct-to-consumer genetic testing allows individuals to learn their own AD genetic risk profile without medical supervision. A number of research protocols for AD susceptibility genetic testing have been proposed. In Italy, disclosure processes and protocols beyond those developed for inherited dementia have not been established yet. We reviewed the literature on the current practice and clinical issues related to disclosing AD genetic risk to cognitively healthy individuals and provide suggestions that may help to develop specific guidelines at the national level.

Impact of sharing Alzheimer's disease biomarkers with individuals without dementia: A systematic review and meta‐analysis of empirical data

“…However, similar to pre-symptomatic testing for pathogenic mutations of AD, 71,72 for some a high likelihood and more caregiving experience may deter them from wanting to be confronted with their disposition for an incurable and fatal disease.…”

“…An explanation for these contradictory findings could be that persons with substantial concerns about their cognitive health may be a self‐selected target population for biomarker assessment in pursuit of insight and control of their future. However, similar to pre‐symptomatic testing for pathogenic mutations of AD, 71,72 for some a high likelihood and more caregiving experience may deter them from wanting to be confronted with their disposition for an incurable and fatal disease.…”

Interest in genetic susceptibility testing and disclosure of AD dementia risk in cognitively normal adults: a survey study

“…Previous participant registries have successfully used (remote) APOE genotyping as screening to recruit participants [ 21 , 22 ] and provided frameworks for scalable genetic counselling and (telephonic) disclosure within a research context [ 29 , 63 ]. However, more research is needed to align APOE-genetic disclosure protocols within a research setting for cognitively normal adults without first degree relatives with dementia [ 64 ]. Currently, evidence about safe disclosure to cognitively normal research volunteers is emerging [ 23 , 64 ].…”

“…However, more research is needed to align APOE-genetic disclosure protocols within a research setting for cognitively normal adults without first degree relatives with dementia [ 64 ]. Currently, evidence about safe disclosure to cognitively normal research volunteers is emerging [ 23 , 64 ]. Our study provides additional evidence of the generally positive attitudes of cognitively normal adults towards genetic screening for research purposes, and underscores the high interest in disclosure.…”

The Return of Biomarker Results in Research: Balancing Complexity, Precision, and Ethical Responsibility

“…There is an important distinction between a cohort-based risk profile and an individual's risk profile. As most research on risk applies to a group, not to an individual, indicators should be viewed in the context of personalized dementia risk profiles that account for a multiplicity of interdependent factors including age, race, ethnicity, concurrent pathologies, and social and structural determinants of health [8,10]. Widespread lack of ethnic, racial, and socioeconomic diversity in clinical trials adds to further uncertainty about the precision of dementia risk and is compounded by scant knowledge of the impact of disclosure on underserved individuals, their family members, and communities [6,8].…”