Alzheimer’s disease (AD) is the most common cause of all the dementing disorders 1
. With the oldest population groups rapidly growing in the United States, the number of AD patients is expected to triple in the U.S. between 2000 and 2050, from 4.5 million to 13.2 million people with AD 2
. The increase in the number of AD patients is a matter of great concern not only from an individual’s perspective, but also from an economic and pubic health point of view 3
Mutations in three genes, amyloid precursor protein (APP), presenilin 1 (PS1), and presenilin 2 (PS2), have been linked to rare early-onset forms of AD, with symptoms that usually begin in the 4th
decades. Polymorphisms in a number of other genes, in particular apolipoprotein E (APOE) and neuronal sortilin-related receptor (SORL1), are associated with the more common late-onset form of AD 4, 5
. APOE and SORL1 are susceptibility genes that are neither necessary nor sufficient to cause AD. This limitation, coupled with a general lack of treatment options for AD, has prompted several consensus statements to caution against the introduction of clinical susceptibility testing of genes in asymptomatic individuals 6-9
. At the same time, the lack of scientific data also prompted these statements to encourage research on the benefits and limitations of disclosing genetic susceptibility information. With the growing number of individuals with AD and the even greater number of older Americans at risk for AD, it is likely that genetic susceptibility testing will become an important clinical, ethical, and research issue in the near future.
The REVEAL Study (Risk Evaluation and Education for Alzheimer’s Disease) is a series of randomized clinical trials designed to evaluate the impact of risk assessment, including APOE genotype disclosure, for AD. The study protocol was developed by a multidisciplinary team of experts in the fields of AD, neurology, genetics, genetic counseling, psychology, and bioethics, many of whom had previously been involved in the consensus statements against APOE
genetic susceptibility testing. A primary aim of the REVEAL study was to determine whether AD genetic risk assessment can be provided safely and effectively to adult children and siblings of AD patients. Thus far, study results based on established outcome measures such as the Center for Epidemiologic Studies Depression Scale (CES-D), Beck Anxiety Inventory (BAI), and Impact of Event Scale (IES) have revealed that, in general, AD genetic risk assessment can be disclosed safely 10-12
In a separate but related study that collected qualitative data from select REVEAL participants approximately eighteen months after their risk assessment disclosure, there was some anecdotal
evidence to suggest that some participants did experience a certain amount of emotional distress 13
. A few participants described their genetic results as “depressing,” “frightening,” and “disappointing.” This pattern of results has previously been shown in cancer research, and underscores the possibility that certain psychological responses to genetic testing may not be fully captured by commonly used scales 14
. Because the CES-D and BAI are general measures of depression and anxiety, and because the IES was created as a measure of subject distress for any event, these instruments may not be appropriate for detecting psychological distress in a genetic testing situation 15-17
. And even though the IES has more recently been applied to assessing the psychological impact of predictive genetic testing (e.g., Huntington’s disease, and hereditary breast and ovarian cancer), AD may be sufficiently different from other health conditions to warrant a disease specific approach to measuring the psychological impact of genetic testing 18, 19
A couple of scales have been developed to assess the impact of genetic testing. One is The Multidimensional Impact of Cancer Risk Assessment (MICRA) Questionnaire 14
. It was published in 2002 as a questionnaire used to assess the impact of cancer genetic testing with BRCA 1/2 testing as a model. It is a scale that takes into account special features of genetic testing such as the impact of the results on family members and relatives. Another available instrument is the PAGIS, or the Psychological Adaptation to Genetic Information Scale, published in 2005 20
. The PAGIS is based on the conceptual framework of Skirton’s grounded theory of the client’s perspective of genetic counseling as well as on the Roy Adaptation Model 20
. The goal of the scale was to isolate the impact of genetic testing regardless of the likelihood of the gene causing the disease. The PAGIS was not developed with a specific disease in mind and it appears that to date, there are no published reports using the PAGIS.
Still, the scales described above are not disease specific to AD. Thus, the purpose of the present study was to develop a brief, self-report measure of the psychological impact of genetic susceptibility tests for AD to be used in both clinical (e.g. genetic counseling) settings as well as in research on genetic risk disclosure.