Genetic counseling for early onset and familial dementia: Patient perspectives on exome sequencing

Rolf, Bradley A; Blue, Elizabeth; Bucks, Stephanie A.; Dorschner, Michael O.; Jayadev, Suman

doi:10.1002/jgc4.1379

Cited by 7 publications

(7 citation statements)

References 26 publications

(24 reference statements)

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“…The positive correlation between factor 2 and factor 3 ("Perceived Benefits of Testing") is in line with the previous validation study of Angelidou et al (2023), who also found a comparable correlation between their second ("Intention to be Screened") and third factor ("Preventive Health Behaviors"). The relationship between both constructs is underlined by other studies, as the majority of the mentioned benefits are the most convincing motivations for pursuing pre-symptomatic screening (Chao et al, 2008;Wikler et al, 2013;Rolf et al, 2021). Conversely, factor 1, "Perceived Harms of Testing", exhibits weak negative correlations with the other factors.…”

Section: Psychometric Properties 25-item Pre-adsmentioning

confidence: 87%

Attitudes toward pre-symptomatic screening for Alzheimer’s dementia in five European countries: a comparison of family members of people with Alzheimer’s dementia versus non-family members

Angelidou,

Makri,

Beyreuther

et al. 2023

Front. Genet.

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Introduction: Pre-symptomatic screening is getting more attention in healthcare as it detects the risk for developing neurodegenerative diseases like Alzheimer’s disease (AD), which is very useful for treatment or prevention. AD screening could play an important role in individuals with at least one affected first-degree relative, but also without family history. As the demand for screening is rising worldwide, it is important to consider possible cross-cultural differences in attitudes toward pre-symptomatic screening in order to tailor healthcare services to the needs of each country.Objective: This study aims to investigate the attitudes of family members and non-family members of people with dementia toward pre-symptomatic screening and explore possible differences in attitudes across five European countries (Belgium, Germany, Greece, Spain, Turkey) using translated versions of the “Perceptions regarding pRE-symptomatic Alzheimer’s Disease Screening” questionnaire (PRE-ADS).Methods: The multicultural sample (N = 650) was recruited from samples that were previously used in validation studies of the translated PRE-ADS versions. The subscale “Acceptability of Screening”, consisting of five PRE-ADS items to specifically explore willingness to undergo screening, was created. Ιnternal consistency was measured, and structural validity was determined using Confirmatory Factor Analysis (CFA). Group comparisons were performed to investigate differences in attitudes toward pre-symptomatic AD screening regarding family history and country of origin using the PRE-ADS and the “Acceptability of Screening” mean scores.Results: Construct validity was acceptable for the PRE-ADS. Both the PRE-ADS (α = 0.76) and its subscale “Acceptability of Screening” (α = 0.90) had good internal consistency. Overall, 56.9% of the total sample expressed a positive intention toward pre-symptomatic AD screening. T-tests showed significantly higher mean scores of participants with an affected family member. An international comparison revealed differences in the “Acceptability of Screening” mean score across the five European countries. No cross-cultural differences were found for the PRE-ADS mean score after adjusting for confounding variables.Conclusion: The PRE-ADS and its subscale are reliable tools for assessing pre-symptomatic AD screening attitudes. Variations in the acceptability of screening seem to be linked to family history and cultural influences. Further research with larger samples is needed to explore underlying relationships.

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Section: Psychometric Properties 25-item Pre-adsmentioning

confidence: 87%

Attitudes toward pre-symptomatic screening for Alzheimer’s dementia in five European countries: a comparison of family members of people with Alzheimer’s dementia versus non-family members

Angelidou,

Makri,

Beyreuther

et al. 2023

Front. Genet.

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“…When individuals who are suspected of carrying an AD gene have tested negative on a focused panel of established dementia genes (such as the three AD genes as well as frontotemporal dementia-associated genes [MAPT, GRN, TBK1, C9orf72] and PRNP, which causes prion disease), little appears to be gained from proceeding to expansive exome sequencing. 101,102 Therefore, although exome sequencing has been pursued on a large-scale research basis, it remains of limited use in the clinic.…”

Section: Genetic Testingmentioning

confidence: 99%

“…As discussed above, however, families with mendelian forms are rare. Once high-throughput sequencing facilitated genetic testing in well-phenotyped research cohorts, it became apparent that even in patients with an age of onset younger than 65 years, the rate of carrying a pathogenic variant in an established AD gene is low, estimated at between 1% and 6% 8,101,102 . In the author’s clinic, for individuals with a family history of early-onset AD and for those with an early onset (younger than age 55) even without a family history of AD, a discussion regarding genetic testing for APP, PSEN1 and PSEN2 is typically initiated if patients have not raised the question themselves.…”

Section: Genetic Testingmentioning

confidence: 99%

“…Once high-throughput sequencing facilitated genetic testing in well-phenotyped research cohorts, it became apparent that even in patients with an age of onset younger than 65 years, the rate of carrying a pathogenic variant in an established AD gene is low, estimated at between 1% and 6%. 8,101,102 In the author's clinic, for individuals with a family history of early-onset AD and for those with an early onset (younger than age 55) even without a family history of AD, a discussion regarding genetic testing for APP, PSEN1 and PSEN2 is typically initiated if patients have not raised the question themselves. The clinical overlap between other dementing diseases, including frontotemporal dementia, genetic prion disease, and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), warrants considering genes associated with neurodegeneration other than AD.…”

Section: Genetic Testingmentioning

confidence: 99%

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Genetics of Alzheimer Disease

Jayadev¹

2022

CONTINUUM: Lifelong Learning in Neurology

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PURPOSE OF REVIEWThis article discusses the spectrum of genetic risk in familial and sporadic forms of early- and late-onset Alzheimer disease (AD). Recent work illuminating the complex genetic architecture of AD is discussed in the context of high and low risk and what is known in different populations.RECENT FINDINGSA small proportion of AD is autosomal dominant familial AD caused by variants in PSEN1, PSEN2, or APP, although more recently described rare genetic changes can also increase risk substantially over the general population, with odds ratios estimated at 2 to 4. APOE remains the strongest genetic risk factor for late-onset AD, and understanding the biology of APOE has yielded mechanistic insights and leads for therapeutic interventions. Genome-wide studies enabled by rapidly developing technologic advances in sequencing have identified numerous risk factors that have a low impact on risk but are widely shared throughout the population and involve a repertoire of cell pathways, again shining light on potential paths to intervention. Population studies aimed at defining and stratifying genetic AD risk have been informative, although they are not yet widely applicable clinically because the studies were not performed in people with diverse ancestry and ethnicity and thus population-wide data are lacking.SUMMARYThe value of genetic information to practitioners in the clinic is distinct from information sought by researchers looking to identify novel therapeutic targets. It is possible to envision a future in which genetic stratification joins other biomarkers to facilitate therapeutic choices and inform prognosis. Genetics already has transformed our understanding of AD pathogenesis and will, no doubt, continue to reveal the complexity of brain biology in health and disease.

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“…Importantly, genetic counseling – which encompasses counseling and support in addition to the information provision that was provided in these studies – has been hypothesized to be an effective strategy to elicit meaningful behavior change to reduce the risk for common complex diseases [12]. For example, studies of providing genetic risk information in the context of genetic counseling about Alzheimer’s disease have found some evidence to suggest that it may influence diet and exercise habits for some individuals [20].…”

Section: Introductionmentioning

confidence: 99%

Behavioral Changes after Psychiatric Genetic Counseling: An Exploratory Study

Huynh¹,

Morris²,

Inglis³

et al. 2023

Public Health Genomics

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Introduction: Though it is well established that genetic information does not produce behavior changes, there are limited data regarding whether genetic counseling can facilitate change in life-style and health behaviors that can result in improved health outcomes. Methods: To explore this issue, we conducted semi-structured interviews with eight patients who had lived experience of psychiatric illness, and who had received psychiatric genetic counseling (PGC). Using interpretive description, we used a constant comparative approach to data analysis. Results: Participants talked about how, prior to PGC, they held misconceptions and/or uncertainties about the causes of and protective behaviors associated with mental illness, which caused feelings of guilt, shame, fear and hopeless. Participants reported that PGC reframed things in a way that provided them a sense of agency over illness management, allowed a greater acceptance of illness, and provided release from some of the negative emotions associated with their initial framing of their illness, which seemed to be related to the self-reported increase in engagement in illness management behaviors and consequent improved mental health outcomes. Conclusion: This exploratory study provides data to support that through addressing emotions associated with perceived cause of illness and facilitating understanding of etiology and risk-reducing strategies, PGC may lead to an increase in behaviors, which protect mental health.

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Genetic counseling for early onset and familial dementia: Patient perspectives on exome sequencing

Cited by 7 publications

References 26 publications

Attitudes toward pre-symptomatic screening for Alzheimer’s dementia in five European countries: a comparison of family members of people with Alzheimer’s dementia versus non-family members

Attitudes toward pre-symptomatic screening for Alzheimer’s dementia in five European countries: a comparison of family members of people with Alzheimer’s dementia versus non-family members

Genetics of Alzheimer Disease

Behavioral Changes after Psychiatric Genetic Counseling: An Exploratory Study

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