On November 3 of this year I posted on some work with a zebrafish model of tauopathy showing that a class of drug called carbonic anhydrase inhibitors could slow disease progression. Those drugs are commonly prescribed for glaucoma and other conditions. One insightful commenter has asked if it might be possible to use an existing patient database to search for a correlation between CAIs and PSP risk.

There has been one such attempt, but it included too few patients to answer this question. Earlier this year, Jay Iyer and colleagues (including me) at multiple institutions used a database of 305 patients with PSP observed over a 12-month period to look for any relationship between concomitant drug use and rate of progression on the PSP Rating Scale. It found that benzodiazepines were associated with more rapid progression. Here’s the paper. The table’s “F value,” as the caption indicates, measures the “interaction between change in PSPRS scores and time.” That’s a sophisticated version of the rate of progression.

But CAIs are too rarely prescribed to show up in that type of analysis. In fact, the statistics considered only those drugs used by at least 10% of the patients, as lower frequencies would not have produced statistically significant results.

This approach, seeking a relationship between the risk factor (medication use) and an outcome (disease severity) is only one way to approach this problem. Another is to compare people with PSP to people without it with regard to the risk factor. Another is to compare people with the risk factor to people without it with regard to the frequency of the disease. For a disease as rare as PSP and a risk factor as rare as CAIs, one would need a huge database, like those maintained by national health care systems. Unfortunately, no such analysis of PSP and CAI use has been attempted to date, but in theory, it can be done despite PSP’s misdiagnosis rate in the general population outside of dedicated movement disorder centers.