A. Tibben

Caregiver Burden, Health-Related Quality of Life and Coping in Dementia Caregivers: A Comparison of Frontotemporal Dementia and Alzheimer’s Disease

Frontotemporal dementia (FTD) is the second most prevalent dementia after Alzheimer’s disease (AD). We compared 29 FTD and 90 AD caregivers with respect to burden, health-related quality of life (HQoL) and coping. FTD caregivers were more burdened than AD caregivers, and caregivers of patients who were demented for shorter duration had lower HQoL. We furthermore compared the 29 FTD caregivers with 34 caregivers of institutionalized FTD patients to understand their specific caregiver issues. Caregivers of FTD patients institutionalized after shorter dementia duration were most burdened and affected in their HQoL. Overall, passive coping strategies were associated with increased burden and decreased HQoL. We recommend that FTD caregivers be offered more support than AD caregivers. Furthermore, we suggest that interventions target passive coping strategies.

Recommendations for the predictive genetic test in Huntington's disease

MacLeod R, Tibben A, Frontali M, Evers-Kiebooms G, Jones A, Martinez-Descales A, Roos RA and Editorial Committee and Working Group ‘Genetic Testing Counselling’ of the European Huntington Disease Network. Recommendations for the predictive genetic test in Huntington’s disease Clin Genet 2013: 83: 221–231.

Predicting adaptation to presymptomatic DNA testing for late onset disorders: who will experience distress? Rotterdam Leiden Genetics Workgroup.

The first comparative study on predicting post-test distress (conceptualised by intrusion and avoidance, measured with the Impact of Event Scale) after presymptomatic genetic testing for Huntingtons disease (HD, n=25), cancer syndromes (familial adenomatous polyposis (FAP, n=23)), and hereditary breast and ovarian cancer (HBOC, n=10) is reported. The variables with the highest predictive potential of post-test distress are presented. Participants who were depressed before the test were more distressed after testing, but we found that those who were anxious before the test were less distressed, that is, had less intrusive thoughts post-test. Other factors associated with a higher level of post-test intrusion were gender (being a woman), having children, and pre-test intrusion. Religion and being at risk for HBOC were associated with less post-test intrusion. Participants who showed avoidance behaviour before the test and those who had many people available for support showed more avoidance behaviour post-test. The test result did not additionally contribute to post-test distress. The prima facie simple notion that the test result, as such, determines the distress experienced seems to be a misrepresentation of the complex reality.

Preparing for presymptomatic DNA testing for early onset Alzheimer's disease/cerebral haemorrhage and hereditary Pick disease.

The acceptability of presymptomatic testing in 21 people at 50% risk for the APP-692 mutation causing presenile Alzheimers disease or cerebral haemorrhage resulting from cerebral amyloid angiopathy (FAD-CH), and in 43 people at 50% risk for hereditary Pick disease (HPD) was assessed. Neither group differed in demographic variables. Thirty-nine people (64%) in the whole group would request presymptomatic testing if it were clinically available, although two-thirds did not yet feel ready to take it. The most important reasons in the HPD and FAD-CH group for taking the test were: to further basic research (42% and 47%, respectively), informing children (47% and 50%, respectively), future planning (29% and 47%, respectively), and relieving uncertainty (46% and 27%, respectively). The most commonly cited effect of an unfavourable test result concerned increasing problems for spouses (75% and 76%, respectively) and children (61% and 57%, respectively). Most respondents denied that an unfavourable result would have adverse effects on personal mood or relationship. One-third of all respondents favoured prenatal testing where one of the parents had an increased risk for HPD or FAD-CH. Participants would encourage their offspring to have the test before starting a relationship (35%) and before family planning (44%). Thirty-seven percent of the respondents would encourage their children to opt for prenatal diagnosis. People at risk for HPD were significantly more preoccupied with the occurrence of potential symptoms in themselves, compared with those at risk for FAD-CH, reflecting the devastating impact that disinhibition in the affected patient has on the family. Our findings underline the need for adequate counselling and the availability of professional and community resources to deal with the impact of test results in subjects and their relatives.

Reproductive options for prospective parents in families with Huntington's disease: clinical, psychological and ethical reflections

BACKGROUND Huntingtons disease (HD) is an autosomal dominant neurodegenerative late onset disorder. This review of reproductive options aims to increase reproductive confidence and to prevent suffering in relation to family planning around HD and possibly other late onset neurodegenerative disorders. METHODS Selected relevant literature and own views and experiences as clinical geneticists, psychologists and ethicists have been used. RESULTS Possible options, with emphasis on prenatal diagnosis (PD) and preimplantation genetic diagnosis (PGD) to prevent the transmission of HD to the next generation, are described and discussed. They are formally presented in a decision tree, taking into account the presence or absence of a fully penetrant allele (FPA), a reduced penetrant allele (RPA) or an intermediate allele (IA). A table compares invasive and non-invasive PD and PGD. From a psychological perspective, the complex process of counselling and decision-making regarding reproductive options is discussed. Special attention is paid to the decision to avoid the transmission of the mutation and to the confrontation and coping of a mutation-free child growing up with a parent developing disease symptoms. From an ethical point of view, reflections on both PD and PGD are brought forward taking into account the difference between FPA, RPA and IA, direct testing or exclusion testing and taking into account the welfare of the child in the context of medically assisted reproduction. CONCLUSION Recommendations and suggestions for good clinical practice in the reproductive care for HD families are formulated.

Frontotemporal Dementia: Change of Familial Caregiver Burden and Partner Relation in a Dutch Cohort of 63 Patients

Background/Aims: The current study examined the change of caregiver burden and the development of the quality of the partner relation in frontotemporal dementia (FTD). Methods: During a 2-year period, deterioration, behavioural problems, caregiver burden, general psychopathology, quality of life, social support, coping strategies and relationship quality were inspected in 63 FTD caregiver-care recipient dyads. Results: After 2 years patients reached maximum dementia severity with stable Neuropsychiatric Inventory levels. Contrary to expectations, caregiver burden decreased and psychological well-being remained stable. Coping style and social support changed unfavourably. Relationship closeness and getting along were preserved, whereas communication and sharing viewpoint on life were dramatically reduced. Conclusions: FTD caregivers need support in coping with the increasingly hopeless situation of their patients. Future research methods into caregiver burden should address response shift as a means for psychological adjustment.

Decision-making on preimplantation genetic diagnosis and prenatal diagnosis: a challenge for couples with hereditary breast and ovarian cancer

STUDY QUESTION How do couples with a BRCA1/2 mutation decide on preimplantation genetic diagnosis (PGD) and prenatal diagnosis (PND) for hereditary breast and ovarian cancer syndrome (HBOC)? SUMMARY ANSWER BRCA couples primarily classify PGD and/or PND as reproductive options based on the perceived severity of HBOC and moral considerations, and consequently weigh the few important advantages of PGD against numerous smaller disadvantages. WHAT IS KNOWN ALREADY Awareness of PGD is generally low among persons at high risk for hereditary cancers. Most persons with HBOC are in favour of offering PGD for BRCA1/2 mutations, although only a minority would consider this option for themselves. Studies exploring the motivations for using or refraining from PGD among well-informed BRCA carriers of reproductive age are lacking. We studied the reproductive decision-making process by interviewing a group of well-informed, reproductive aged couples carrying a BRCA1/2 mutation, regarding their decisional motives and considerations. STUDY DESIGN, SIZE, DURATION This exploratory, qualitative study investigated the motives and considerations taken into account by couples with a BRCA1/2 mutation and who have received extensive counselling on PGD and PND and have made a well-informed decision regarding this option. Eighteen couples took part in focus group and dyadic interviews between January and September 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS Semi-structured focus groups were conducted containing two to four couples, assembled based on the reproductive method the couple had chosen: PGD (n = 6 couples) or conception without testing (n = 8 couples). Couples who had chosen PND for BRCA (n = 4) were interviewed dyadically. Two of the women, of whom one had chosen PND and the other had chosen no testing, had a history of breast cancer. MAIN RESULTS AND THE ROLE OF CHANCE None of the couples who opted for PGD or conception without testing found the use of PND, with possible pregnancy termination, acceptable. PND users chose this method because of decisive, mainly practical reasons (natural conception, high chance of favourable outcome). Motives and considerations regarding PGD largely overlapped between PGD users, PND users and non-users, all mentioning some significant advantages (e.g. protecting the child and family from the mutation) and many smaller disadvantages (e.g. the necessity of in vitro fertilization (IVF), low chance of pregnancy by IVF/PGD). For female carriers, the safety of hormonal stimulation and the time required for PGD before undergoing preventive surgeries were important factors in the decision. Non-users expressed doubts about the moral justness of their decision afterwards and emphasized the impact the decision still had on their lives. LIMITATIONS, REASON FOR CAUTION The interviewed couples were at different stages in their chosen trajectory, up to 3 years after completion. This may have led to recall bias of original motives and considerations. Couples who did not actively seek information about PGD were excluded. Therefore the results may not be readily generalizable to all BRCA couples. WIDER IMPLICATIONS OF THE FINDINGS The perceived severity of HBOC and, for female carriers, the safety of hormonal stimulation and the time frames for PGD planning before preventive surgeries are essential items BRCA couples consider in reproductive decision-making. The emotional impact of this decision should not be underestimated; especially non-users may experience feelings of doubt or guilt up to several years afterwards. PGD counselling with tailored information addressing these items and decisional support in order to guarantee well-informed decision-making is needed. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by the Dutch breast cancer foundation Stichting Pink Ribbon, grant number 2010.PS11.C74. None of the authors have competing interests to declare. TRIAL REGISTRATION NUMBER Not applicable.

Methodology in longitudinal studies on psychological effects of predictive DNA testing: a review

In the last two decades predictive testing programs have become available for various hereditary diseases, often accompanied by follow-up studies on the psychological effects of test outcomes. The aim of this systematic literature review is to describe and evaluate the statistical methods that were used in these follow-up studies. A literature search revealed 40 longitudinal quantitative studies that met the selection criteria for the review. Fifteen studies (38%) applied adequate statistical methods. The majority, 25 studies, applied less suitable statistical techniques. Nine studies (23%) did not report on dropout rate, and 18 studies provided no characteristics of the dropouts. Thirteen out of 22 studies that should have provided data on missing values, actually reported on the missing values. It is concluded that many studies could have yielded more and better results if more appropriate methodology had been used.

Sense of competence in a Dutch sample of informal caregivers of frontotemporal dementia patients.

Objective: The sense of competence (SC) of informal caregivers of frontotemporal dementia (FTD) patients is important for their task but has rarely been assessed. Here, the relationship between caregiver burden and SC and the differential value of SC in understanding caregiver suffering were studied. Methods: At 24 months of follow-up patient behavioural problems, dementia severity, caregiver SC, burden, psychological complaints and quality of life were inspected cross-sectionally in 46 caregiver/care recipient dyads. Results: SC was unrelated to dementia severity and patient behavioural problems. Principal component analysis of SC revealed 3 dimensions: ‘emotions’, ‘attributions’ and ‘sacrifice’. Sacrificing one’s personal life to caregiving was associated with more psychological complaints and a worse physical and mental quality of life, as found in structural equation modelling. Conclusions: Caregiver suffering comprised an unbalance between self-care and caring for the FTD patient. FTD caregivers may benefit from psycho-education on self-care and methods to create time for their personal needs.

Evaluation of exclusion prenatal and exclusion preimplantation genetic diagnosis for Huntington's disease in the Netherlands

van Rij MC, de Die‐Smulders CEM, Bijlsma EK, de Wert GMWR, Geraedts JP, Roos RAC, Tibben A. Evaluation of exclusion prenatal and exclusion preimplantation genetic diagnosis for Huntingtons disease in the Netherlands.