Genetic Testing and Self-Fulfilling Prophecies

Lineweaver et al tested 144 elderly adults for the ApoE4 gene, which is known to be a major risk factor for Alzheimers. They told half of them their test results, kept it secret from the other half, then waited. Eight months later, they asked people how they thought their memory was doing and gave everyone objective memory tests.

No one in the study population had Alzheimers yet, so everyone did okay on the memory test. But subjects who knew they had ApoE4 did significantly worse than subjects who did have ApoE4 but didn’t know it. The subjects who knew they didn’t have ApoE4 didn’t do any better on the memory test than other subjects who didn’t have ApoE4 but had not yet heard the good news, but they did give subjectively better ratings of their memory ability.

The medical community concludes from this that letting people know their genetic risks may be dangerous, and although I hate to admit it, they have a point.

Unfortunately, the study doesn’t give the methodological details I need to really understand the implications.

We know that the researchers waited eight months between giving the genetic test results and doing the memory tests. That’s good.

But was it the same researcher doing both the genes and the memory parts of the study? Was it in the same building? Did they start the memory tests by saying “Hi! I’m Dr. Lineweaver! You may remember me from such medical experiments as the one eight months ago in which you were told that you had a high risk of getting Alzheimer’s disease”?

Or did they sneakily pretend to be a separate study entirely and try to avoid mentioning the A-word throughout?

It would not surprise me if – having been primed with a reminder of their Alzheimer testing results – the subjects then performed worse on a memory test that was given immediately after in an obviously related context.

It would be much more surprising – though still not totally unbelievable – if subjects, having been told they had a high risk of Alzheimers, just went around for eight months having slightly worse memory which was reflected on everything they did including the memory test administered by the researchers.

New England Journal of Medicine compares the finding to “stereotype threat”, the phenomenon in which people can for example sometimes make women perform worse on math tests simply by telling them that it is a “test of their innate mathematical abilities” – something that women are stereotypically bad at.

The memory tests the researchers were giving are equivalent to the “innate mathematical abilities” condition in the stereotype threat research – a test clearly intended to measure how good their memory was in a very scientific way. The activities of daily living that require memory – keeping appointments, paying bills on time, et cetera – are the equivalent of the condition in stereotype threat experiments where researchers just give women a normal math test without introduction and stereotype threat is not seen.

So I see two ways in which we could get results like the ones in this study without any broader implications of ApoE4 testing harming the elderly in general.

First, being called to the same study in which the ApoE4 results were given could have primed their worries about Alzheimers and made them do especially bad on the study’s memory test compared to their usual memory.

Second, the study’s memory test could have been official-looking enough that it activated their stereotype of themselves as having innately poor memory, when, concordant with stereotype threat research, that stereotype doesn’t harm their everyday memory-requiring activities.

In either of these cases, the study would have some very limited implications, which the authors describe in an appropriately circumscribed way: “The patient’s knowledge of his or her genotype and risk of Alzheimer’s disease should be considered when evaluating cognition in the elderly.”

But this would not imply that genetic testing elderly people for ApoE4 is risky and can itself cause them to develop forgetfulness and other Alzheimer’s symptoms.

I worry that the medical community is going to miss this subtlety and start “raising awareness” of the possibility that genetic testing can cause harmful side effects, before finishing the hard task of discovering if that’s actually true.