Benadryl and Alzheimers
I expected the Herald story “Hay fever pills linked to Alzheimer’s risk – study” to be the usual thing, where a fishing expedition found a marginal correlation in low-quality data. It isn’t.
The first thing I noticed when I found the original article is that I know several of the researchers. On the one hand that’s a potential for bias, on the other hand, I know they are both sensible and statistically knowledgeable. The study has good quality data: the participants are all in one of the Washington HMOs, and there is complete information on what gets prescribed for them and whether they fill the prescriptions.
One of the problems with drug:disease associations is confounding by indication. As Samuel Goldwyn observed, “Any man who goes to a psychiatrist needs to have his head examined”, and more generally the fact that medicine is given to sick people tends to make it look bad. In this case, however, the common factor between the medications being studied is an undesirable side-effect for most of them, unrelated to the reason they are prescribed. In addition to reducing depression or preventing allergic reactions, these drugs also block part of the effect of the neurotransmitter acetylcholine. The association remained just as strong when recent drug use was excluded, or when antidepressant drugs were excluded, so it probably isn’t that early symptoms of Alzheimer’s lead to treatment.
The association replicates results found previously, and is quite strong, about four times the standard error (“4σ”) or twice the ‘margin of error’. It’s not ridiculously large, but is enough to be potentially important: a relative rate of about 1.5.
It’s still entirely possible that the association is due to some other factor, but the possibility of a real effect isn’t completely negligible. Fortunately, many of the medications involved are largely obsolete: modern hayfever drugs (such as fexofenadine, ‘Telfast’) don’t have anticholinergic activities, and nor do the SSRI antidepressants. The exceptions are tricyclic antidepressants used for chronic pain (where it’s probably worth the risk) and the antihistamines used as non-prescription sleep aids.
Thomas Lumley (@tslumley) is Professor of Biostatistics at the University of Auckland. His research interests include semiparametric models, survey sampling, statistical computing, foundations of statistics, and whatever methodological problems his medical collaborators come up with. He also blogs at Biased and Inefficient See all posts by Thomas Lumley »
“medicine is given to sick people” – and, often, old people – whether sick or not (yet).
9 years ago
Yes — though they did get the same results when they excluded drugs used within 12 months of diagnosis. Also, all the analyses compared users and non-users at the same age, so it can’t be an age effect.
9 years ago
Yes, just particularly unfortunate that medication contributes to an age-related problem when I suspect the aged are more likely to be medicated in the first place. So, not a confounding effect but a compounding effect, perhaps.
9 years ago
I can vouch for Group Health’s ability to track the prescriptions and clinical outcomes accurately and completely, having worked for a sister company that uses the same medical record system (and has the same Medical Group). A 30 year study is theoretically possible and could be done in California as well.
Benadryl always made me woolly headed.
Now another reason not to take it.
9 years ago