Dementia: Update for the Practitioner

The decision of whether or not to offer testing has to be weighed very carefully. A study published in 2001 in the American Journal of Medical Genetics determined that genetic testing is useful when there is an available treatment for the disease and a highly predictive test for the gene. Phenylketonuria is the model example of this; if we identify the disease early we can act to make a dramatic difference. At the opposite end of the spectrum, APOE testing has a low predictive value and there is no intervention that would stop progression of Alzheimer's disease.


	To Test or Not To Test . . .


	The decision of whether or not to offer testing is based primarily on a test's predictive value and the availability of treatment. Courtesy of Jennifer Williamson-Catania, M.S.

The situation is more complicated for Huntington's disease or early-onset Alzheimer's disease. Clearly, detecting a mutation in an individual or in a family is very predictive, but it has little medical value. In these cases, one needs to weigh the psycho-social issues for the individual or family. The publication of the 2001 study discusses the need for nondirective counseling when working with families with mutations so that individuals can weigh the risks and benefits of genetic testing for themselves.

In general, genetic testing for asymptomatic individuals is only warranted for families with autosomal-dominant early-onset Alzheimer's disease and autosomal-dominant frontotemporal dementia. Even then, the likelihood of detecting a mutation in those families is still low, especially in frontotemporal dementia, but the counseling can be valuable.

Regardless of whether a person is at risk for early-onset or late-onset, someone who is very concerned about the risk of developing these diseases, based on the fact that he or she knows there is a genetic role in these diseases, may have their concerns addressed by genetic counseling.

Another interesting study, published in the Archives of Neurology in 2001, looked at what happens when we offer genetic testing for those individuals who know there is a mutation in the family. The study looked at 251 such individuals and provided them the opportunity to have genetic counseling and testing. Only 8 percent of at-risk individuals actually pursued testing.

The clinicians expected that there would be some value in confirming a diagnosis or confirming early symptoms of the disease. Individuals who were found to have negative test results did experience relief, but, interestingly, some of them continued to have some anxiety and depression following the results. People with positive test results displayed very strong coping skills, possibly because the study was of a self-selective group of people who were emotionally well and ready to handle this kind of information. These results did have an impact on marriage and family relationships, and that corresponds with our experiences at Columbia with Huntington's disease and Alzheimer's disease. This particular study only followed participants for a year and a half to three years, so the long-term impacts of having this information, especially as people get closer to onset of the disease, are unknown.

We do genetic counseling and testing at Columbia, and we follow a strict protocol following the model we established for the Huntington's disease presymptomatic testing program. We take a multidisciplinary approach involving neurologists, psychiatrists, psychologists, genetic counseling, and social work. We want a support person to be involved if at all possible, and usually we require it.

Counseling for sporadic and late-onset Alzheimer's disease also has a value for individuals who are concerned about their risk and discussion of their family history. We discuss the reasons why someone may or may not want to have APOE testing and why we do not offer it at Columbia, even though there may be some utility of APOE testing in rare instances for symptomatic individuals. We discuss the potential for future research, and most of these people do go on to participate in our research studies. I refer individuals with late-onset history who really want to pursue genetic testing to the Reveal Study at Cornell, Boston, and Case Western Reserve, which is doing APOE testing on presymptomatic individuals.

In those cases in which we may have something to offer in terms of testing, the protocol is intense. We require pretest counseling and a meeting with a neurologist to have a baseline evaluation. We discuss the risk based on an individual's family history, the likelihood of finding a mutation, what it would mean if we find a mutation, and what it would mean if we do not find one. If there is a strong family history and we do not find a mutation, we do not know that we can reduce the risk, and we only know that we are not able to find a mutation in one of the three known genes. There may be other genes that have not yet been found that may explain the results for that family.


	Pretest Genetic Counselor Responsibilities obtain family history confirm diagnosis of affected relatives discuss risk based on family history information discuss testing options available discuss predictive value of the test discuss risks, benefits, and limitations of testing explore motives for considering testing discuss readiness for testing discuss confidentiality outline logistics of testing provide written materials and documentation if patient decides to proceed with testing, obtain informed consent.

	Pretesting genetic counseling is primarily focused on the psychosocial impacts of testing, risks, and testing options. Courtesy of Jennifer Williamson-Catania, M.S. Source of data: W. C. McKinnon et al., "Predisposition Genetic Testing for Late-Onset Disorders in Adults. A Position Paper of the National Society of Genetic Counselors," The Journal of the American Medical Association 278, no. 15 (1997): 1217–20.

In our counseling, we place heavy emphasis on the psycho-social impact of testing, especially the impact testing would have on potential discrimination and relationships. What would it mean for individuals to have this information and then have to tell their siblings that there is a mutation in the family that they are at risk of inheriting? We discuss confidentiality; we are very cautious about what it means for someone who is presymptomatic to get tested. We only provide results in person.

Our current research focuses on the genetics of late-onset disease, particularly in Caribbean Hispanic families, and at the genetics of early-onset disease. The National Institute on Aging has started a genetics initiative for Alzheimer's disease research centers to collaborate and collect families. APOE4 is the only confirmed genetic risk factor, but we think there are other genetic risk factors out there. Many of the genetic researchers working on Alzheimer's disease are studying the same families, so we need to find more families in order to be able to look for other genes associated with this disease. The purpose of this initiative is to collect families and cell lines and to collaborate in the search for genes associated with Alzheimer's disease.

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