Disclosing genetic risk of Alzheimer’s disease to cognitively impaired patients and visit companions: Findings from the REVEAL Study

doi:10.1016/j.pec.2016.12.005

Patient Education and Counseling

Volume 100, Issue 5, May 2017, Pages 927-935

https://doi.org/10.1016/j.pec.2016.12.005 Get rights and content

Highlights

•
Alzheimer’s disease risk discussion for cognitively impaired patients was examined.
•
These disclosures (APOE genotype included or not) display a psychosocial orientation.
•
Risk disclosures are less patient-centered when genetic findings are included.
•
Visit companions were more participatory when patients were ε4-positive.

Abstract

Objective

To describe the impact of genetic information on Alzheimer’s disease (AD) risk communication to patients with mild cognitive impairment (MCI) and their visit companions.

Methods

Participants of the fourth REVEAL Study trial were randomized to receive AD risk assessments with or without genotype results. We coded 79 audio recorded risk disclosure sessions with the Roter Interaction Analysis System. Multilevel analyses explored differences in communication when disclosed risks were based on age and MCI diagnosis alone or in addition to APOE genotype status.

Results

The addition of genotype results diminished the patient-centered nature of the sessions (p < 0.001). When ε4 positive relative to ε4 negative results were disclosed, visit companions were more verbally active (p < 0.05), disclosed more medical information (p < 0.05), were more positive verbally and non-verbally (p < 0.05) and were more proactive in setting the visit agenda (p < 0.05).

Conclusions

Delivery of complex genetic risk information reduces the patient-centeredness of disclosure sessions. Visit companions are more actively engaged in session communication when patients are at increased genetic risk for AD.

Practice implications

AD risk discussions can be improved by supporting the positive role of visit companions and addressing the challenges inherent in the delivery of complex genetic information in a patient-centered manner.

Introduction

Prevention and early detection of Alzheimer’s disease (AD) is a national priority with research initiatives increasingly targeting individuals who have mild cognitive impairment (MCI) [1], [2]. Despite this trend, few studies have described how clinicians disclose AD risk to cognitively impaired individuals. Understanding complex and unfamiliar concepts associated with genomic risk is difficult for many patients, including older, less literate and more medically complex adults and especially patients with cognitive deficits [3], [4], [5], [6]. The few studies that have specifically examined the interaction between clinicians and patients with cognitive impairment have found low levels of verbal engagement. One such study analyzed visit recordings in which a dementia diagnosis was delivered to family accompanied patients already suffering from mild dementia. That study found that the disclosure sessions were characterized by frequent checks for understanding and expression of approval and agreement by clinicians, but low levels of emotionally explicit communication directed to patients or their family members [7]. Another study of informed consent encounters for dementia research found that the more cognitively impaired patients asked fewer questions, initiated little discussion, and were more likely to express passive agreement with clinician statements than patients with less impairment [8].

The current study was designed to understand how the communication dynamics of AD risk disclosure to patients with MCI and their visit companions changed when APOE genotyping results were included. In light of prior studies that have described AD genotype discussions as complex and biomedically and technically focused [9], we hypothesized that the genotype discussions would be less patient-centered and have a more didactic teaching style, characterized by greater provision of basic biomedical information and less psychosocial, emotional and facilitative talk compared to AD risk discussions that omitted genotype discussions. We also hypothesized that the delivery of results indicating an increased risk of AD (i.e., presence of the APOE ε4 allele) would trigger more active engagement by a visit companion, considering the serious implications of positive results for blood relatives in terms of their own AD vulnerability and implications for caretaker responsibilities.

Section snippets

Study design, subjects and setting

Analyses were based on a sample of audio-recorded AD risk disclosure sessions collected as part of the fourth independent trial of the REVEAL Study, a randomized clinical trial designed to compare the impact of AD risk communication, conveyed with and without genotype results, to patients with MCI diagnoses and their visit companions. The protocol for patient recruitment and risk disclosure were adapted from prior REVEAL Study trials [10], [11], [12] to target patients with amnestic diagnoses

Sample characteristics

A full description of sample characteristics, stratified by genotype disclosure group, is presented in Table 2. Three genetic counselors participated in this study, representing three study sites (Boston, Philadelphia, and Ann Arbor); all the counselors were female Caucasians aged 26, 34, and 48. The number of patients seen by each genetic counselor was 4, 35, and 40.

The 79 patients comprising our study sample averaged 76 years of age, with the majority of patients being male (56%) and

Discussion

Our study results are consistent with our two study hypotheses; disclosure discussions that included genotype results were 30% less patient-centered than discussions that did not include genetic information, and visit companions were more verbally active and engaged in session dialogue when patients received ε4 positive test results.

Overall, the psychosocially oriented, patient-centered communication pattern identified in our study is consistent with previous findings of dementia diagnosis

Conflicts of interest

The authors report no conflicts of interest.

Acknowledgements:

This work was supported by NIH grants HG002213, HG006500, HD077671, AG013846, RR000533, RR010284, and TR001102. Additional members of the REVEAL Study Group are Deborah Blacker, Massachusetts General Hospital/Harvard Medical School and Harvard School of Public Health, Boston, Massachusetts; Melissa Butson, Case Western Reserve University, Cleveland, Ohio; Clara Chen, Boston University School of Public Health, Boston, Massachusetts; Robert Cook-Deegan, Sanford School of Public Policy, Durham,

References (24)

R.A. Sperling
Toward defining the preclinical stages of Alzheimer's disease: recommendations from the national institute on aging-Alzheimer's association workgroups on diagnostic guidelines for Alzheimer's disease
Alzheimers Dement.
(2011)
J.L. Wolff et al.
Family presence in routine medical visits: a meta-analytical review
Soc. Sci. Med.
(2011)
J.T. Heshka
A systematic review of perceived risks: psychological and behavioral impacts of genetic testing
Genet. Med.
(2008)
B. Lerner
Distinct communication patterns during genetic counseling for late-onset Alzheimer's risk assessment
Patient Educ. Couns.
(2014)
R.C. Green
A randomized noninferiority trial of condensed protocols for genetic risk disclosure of Alzheimer's disease
Alzheimers Dement.
(2015)
D. Roter et al.
The Roter interaction analysis system (RIAS): utility and flexibility for analysis of medical interactions
Patient Educ. Couns.
(2002)
N. Mead et al.
Patient-centredness: a conceptual framework and review of the empirical literature
Soc. Sci. Med.
(2000)
M.F. Folstein et al.
Mini-mental state: A practical method for grading the cognitive state of patients for the clinician
J. Psychiatr. Res.
(1975)
K.L. Schmidt et al.
Verbal communication among Alzheimer's disease patients: their caregivers, and primary care physicians during primary care office visits
Patient Educ. Couns.
(2009)
R.A. Sperling et al.
Testing the right target and right drug at the right stage
Sci. Transl. Med.
(2011)

L.M. Chen et al.

Primary care visit duration and quality: does good care take longer?

Arch. Intern. Med.

(2009)

J.S. Roberts et al.

Using Alzheimer's disease as a model for genetic risk disclosure: implications for personal genomics

Clin. Genet.

(2011)

Cited by (18)

Longitudinal Analysis of the Retina and Choroid in Cognitively Normal Individuals at Higher Genetic Risk of Alzheimer Disease
2022, Ophthalmology Retina
To assess the baseline differences and longitudinal rate of change in retinal and choroidal imaging parameters between apolipoprotein ε4 (APOE ε4) carriers and noncarriers with normal cognition.
Prospective study.
Four hundred thirteen eyes of 218 individuals with normal cognition aged ≥ 55 years with known APOE status (98 APOE ε4 carriers and 120 noncarriers). The exclusion criteria included diabetes mellitus, uncontrolled hypertension, glaucoma, and vitreoretinal or neurodegenerative disease.
OCT and OCT angiography (OCTA) were performed at baseline and 2 years (Zeiss Cirrus HD-OCT 5000 with AngioPlex; Zeiss Meditec). The groups were compared using sex- and age-adjusted generalized estimating equations.
OCT parameters: retinal nerve fiber layer thickness, macular ganglion cell-inner plexiform layer thickness, central subfield thickness (CST), and choroidal vascularity index. OCT angiography parameters: foveal avascular zone area, perfusion density (PD), vessel density, peripapillary capillary PD (CPD), and capillary flux index (CFI). The rate of change per year was calculated.
At the baseline, the APOE ε4 carriers had lower CST (P = 0.018), PD in the 6-mm ETDRS circle (P = 0.049), and temporal CFI (P = 0.047). Seventy-one APOE ε4 carriers and 78 noncarriers returned at 2 years; at follow-up, the 6-mm ETDRS circle (P = 0.05) and outer ring (P = 0.049) showed lower PD in the APOE ε4 carriers, with no differences in the rates of change between the groups (all P > 0.05).
There was exploratory evidence of differences in the CST, PD, and peripapillary CFI between the APOE ε4 carriers and noncarriers with normal cognition. Larger and longer-term studies may help further elucidate the potential prognostic value of these findings.
Diagnostic and Prognostic Laboratory Testing for Alzheimer Disease
2020, Clinics in Laboratory Medicine
Citation Excerpt :
Genetic testing for risk genes, such as the ε4 allele of the apolipoprotein E gene, while routinely done for research purposes, currently is not recommended by the American Academy of Neurology because it has little bearing on diagnosis, prognosis, or treatment decisions.17 Several research studies have disclosed ε4 allele status and have found that disclosure of such results in increased anxiety and apprehension regarding the possibility of impending AD but otherwise appears to have no negative influences on quality of life and/or lifestyle decisions.31,32 A general lack of education of both the general population as well as health care professionals that might seek out such testing, however, limits the ability of such testing to truly inform decisions, such as those under consideration for individuals and families potentially at risk for autosomal dominant AD.
Modeling Alzheimer's disease with human iPS cells: advancements, lessons, and applications
2019, Neurobiology of Disease
Citation Excerpt :
Increased understanding of the genetic components that determine AD risk also necessitate policymaking decisions about screening and genetic counseling of patients. A series of clinical studies, part of the REVEAL trial, has been conducted to investigate the psychological and behavioral impact of genetic screening results (Guan et al., 2017). Isolation of patient cell lines harboring some of the mutations discussed above has also opened the door to iPSC-based studies that show great promise for increasing our understanding of AD at a molecular level and enabling the development of therapeutics.
One in three people will develop Alzheimer’s disease (AD) or another dementia and, despite intense research efforts, treatment options remain inadequate. Understanding the mechanisms of AD pathogenesis remains our principal hurdle to developing effective therapeutics to tackle this looming medical crisis. In light of recent discoveries from whole-genome sequencing and technical advances in humanized models, studying disease risk genes with induced human neural cells presents unprecedented advantages. Here, we first review the current knowledge of the proposed mechanisms underlying AD and focus on modern genetic insights to inform future studies. To highlight the utility of human pluripotent stem cell-based innovations, we then present an update on efforts in recapitulating the pathophysiology by induced neuronal, non-neuronal and a collection of brain cell types, departing from the neuron-centric convention. Lastly, we examine the translational potentials of such approaches, and provide our perspectives on the promise they offer to deepen our understanding of AD pathogenesis and to accelerate the development of intervention strategies for patients and risk carriers.
Learning About a Heightened Genetic Risk for Dementia: Anticipated Stigma is Greater than Experienced Stigma
2024, SSRN
Research Participants' Perspectives on Precision Diagnostics for Alzheimer's Disease
2024, Journal of Alzheimer's Disease
The Return of Biomarker Results in Research: Balancing Complexity, Precision, and Ethical Responsibility
2024, Journal of Alzheimer's Disease

View all citing articles on Scopus

View full text

Genetic Testing and CounselingDisclosing genetic risk of Alzheimer’s disease to cognitively impaired patients and visit companions: Findings from the REVEAL Study

Highlights

Abstract

Objective

Methods

Results

Conclusions

Practice implications

Introduction

Section snippets

Study design, subjects and setting

Sample characteristics

Discussion

Conflicts of interest

Acknowledgements:

Alzheimers Dement.

Soc. Sci. Med.

Genet. Med.

Patient Educ. Couns.

Alzheimers Dement.

Patient Educ. Couns.

Soc. Sci. Med.

J. Psychiatr. Res.

Patient Educ. Couns.

Testing the right target and right drug at the right stage

Sci. Transl. Med.

Primary care visit duration and quality: does good care take longer?

Arch. Intern. Med.

Using Alzheimer's disease as a model for genetic risk disclosure: implications for personal genomics

Clin. Genet.

Genetic Testing and Counseling
Disclosing genetic risk of Alzheimer’s disease to cognitively impaired patients and visit companions: Findings from the REVEAL Study