Alzheimer's: does anyone want genetic testing?

22 July 2009

The association between different alleles of the apolipoprotein E (APOE) gene and an increased susceptibility to late-onset Alzheimer’s disease (AD) has been known for more than 10 years. The relative risk of developing AD increases around 4-fold for individual’s with a single copy of the ApoE4 variant (approximately 25% of the population), and around 12-fold for those with two copies (less than 1% of the population, see previous news). However, a test for APOE status is not useful for predicting for who will actually develop the disease.

A recent publication reports a study examining the effect of genotype disclosure of APOE status, in adults who had a parent with AD, on levels of anxiety, depression and test-related stress [Green RC et al. (2009) N Eng J Med 361(3):245-54]. This New England Journal of Medicine paper builds on earlier research conducted by the same group in the Risk Evaluation and Education for Alzheimer’s disease (REVEAL) study (see previous news).

In their previous study [Roberts JS et al. (2004) Genet Med 6(4):197-203], the group conducted a randomised control trial (RCT) examining both the uptake and impact of genetic risk susceptibility testing for AD. As part of the randomisation process, individuals were assigned to two groups, one in which APOE status was disclosed (n=111), the other without APOE disclosure (n=51). Preliminary results indicated that the vast majority of RCT participants did not experience adverse psychological effects. In their more recent paper, the data support no statistically significant differences between the two disclosure groups in terms of changes in time-related measures of anxiety, depression or test-related stress. Unsurprisingly, baseline scores for anxiety and depression were strongly associated with post-disclosure scores of these measures.

Comment: People with a family history of AD are already at a higher risk than those without. Would testing for genetic predisposition to this disease cause further anxiety, depression or any other type of distress? APOE testing is not currently recommended for asymptomatic persons, partially due to its limited clinical utility and partially due to concerns over the emotional effects of the genetic-risk assessment. This study suggests that there are no short-term psychological risks associated with APOE genotype disclosure. However, due to the short-term nature of the evaluations conducted (after 6 weeks, 6 months and 1 year), it is possible that persons in the disclosure group testing positive for the risk allele may react to this information many years later and so, as noted by the study authors, larger studies with longer periods of follow-up are required to investigate any long-term effects. The participants in this study are also quite a select group in that they are a well educated, high socioeconomic status group interested in this research with genetic counselling provided throughout the study. Individuals with low scores in the depression and anxiety tests were excluded from this study meaning that the results are not generalizable to the public. Moreover, no distinction is drawn beween heterozygotes and homozygotes for the ApoE4 variant, which given the large difference in relative risk between them, could substantially affect the phsychological impact of the result. Nonetheless, the greatest value derived from this study is the empirical data which starts to provide evidence that genetic tests (with appropriate counselling) do not cause serious psychological harm and thus should not be treated any differently to other medical tests.

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