Genetic Counseling And Testing For Alzheimer Disease

Discuss the risk of inheriting a mutation from a parent affected with autosomal dominant AD is 50%. In the absence of identifying a mutation in apparent autosomal dominant families, risk to offspring could be as high as 50% but may be less.

Testing for genes associated with early-onset autosomal dominant AD should be offered in the following situations:

○ A symptomatic individual with EOAD in the setting of a family history of dementia or in the setting of an unknown family history (e.g., adoption).

○ Autosomal dominant family history of dementia with one or more cases of EOAD.

○ A relative with a mutation consistent with EOAD (currently PSEN1/2 or APP).

Discuss the likelihood of identifying a mutation in PSEN1, PSEN2, or APP, noting that current experience indicates that this likelihood decreases with lower proportions of affected family members and/or older ages of onset.

Ideally, an affected family member should be tested first. If no affected family member is available for testing and an asymptomatic individual remains interested in testing despite counseling about the low likelihood of an informative result (a positive result for a pathogenic mutation), he/she should be counseled according to the recommended protocol. If the affected relative, or their next of kin, is uninterested in pursuing tested, the option of DNA banking should be discussed.

Inform them why their family history is consistent with familial or sporadic AD.

Discuss that both sporadic and familial cases can be due to a genetic susceptibility. Risk estimates are only available for first-degree relatives of an affected individual in sporadic or familial cases.

Genetic testing for susceptibility loci (e.g., APOE) is not clinically recommended due to limited clinical utility and poor predictive value. If a patient wishes to pursue testing despite genetic counseling and recommendations to the contrary, testing may be considered at the clinician's discretion. Testing performed should follow the HD genetic testing guidelines, with emphasis on genetic counseling with a qualified clinician. As such, DTC genetic testing is not advised.

Motives and considerations for pursuing genetic testing should be explored. This counseling should be an exploration of personal experiences, value and beliefs, and personal and family needs. Genetic testing should be discussed within the context of adapting to familial risk and when clients feel compelled to learn a more refined estimate of their risks to enhance their quality of life. As part of this, it is helpful to lead the individual through the scenario of receiving a positive test result and a negative test result, having them assess the ways these results would positively or adversely impact their psyche, life plans, and relationships.

○ Symptomatic patients: Because genetic testing of a symptomatic individual is typically requested by a relative concerned about his risk, the counselor must remain alert to any potential conflicts of interest, such as lack of interest of the symptomatic patient or of other at-risk family members. If the symptomatic patient gives any inclination of being averse to testing, it is not recommended. Instead, DNA banking should be explored.

Genetic testing: In the event testing is chosen, the following is recommended:

○ Asymptomatic patients should receive a neurologic examination to assess for signs of dementia and to establish a baseline.

○ Assess patient's and any accompanying family member's psychological state of mind. In the case of presymptomatic testing, a consultation with a psychologist/psychiatrist may be recommended for the patient as part of the HD testing approach.

If the patient seems to suffer from, or is potentially at risk for significant psychological/psychiatric problems, consider a psychotherapy referral before testing.

If the psychological assessment suggests testing is not in the person's current best interest (e.g., untreated depression or recent death), these reservations should be shared openly, and an agreement should be made to revisit testing once the underlying condition and/or stressors have diminished. A referral for psychotherapy may also be appropriate.

○ Assess and review the psychosocial impact of testing on the patient and his/her family.

Reinforce results cannot be “taken back” (although an individual can decide not to learn his or her test results after having the test performed.)

○ Discuss testing logistics, associated costs, and possible outcomes.

For EOAD genes, determine best approach to testing for patient (i.e., stepwise testing beginning with PSEN1 as the most likely gene or ordering a panel).

Discuss where results will be kept (e.g., medical record).

Determine who will accompany the patient to the result session for support.

Discuss possible test outcomes (positive, negative, or variant of uncertain significance). If testing for APOE, consider whether you will report other disease risk implications. If so, these should be included in the discussion of test outcomes with the patient. Also, it should be reiterated that APOE is a susceptibility gene and is not a predictive test. Thus, individuals with no copies of the ε4 allele still face a 2–4-fold increased lifetime risk of developing AD if they have a first-degree relative with AD.

○ Assist the patient and participating family members with informed decision making regarding whom, if anyone, they plan to share the results with and how. Inform about the importance of discretion when discussing genetic testing and results.

○ Discuss the potential impact of genetic test results on insurance, and the benefits and limitations of existing state and federal genetic discrimination legislation.

○ Obtain informed consent for all genetic testing for AD.

○ After results disclosure, revisit the individual's plans regarding with whom and how the results will be shared.

○ Arrange for a follow-up plan to “check in” with the patient and, if relevant, participating family member, and determine whether another genetic counseling session would be beneficial to the patient and/or the patient's partner/family members/friends.

Discuss the availability and status of AD research and/or DNA banking.