Sunday, April 29, 2007

The fog of war

The New York Times front page today features an article on the cognitive side effects of chemotherapy, sometimes known as "chemobrain." (Chemotherapy fog is no longer ignored as illusion.) The reported symptoms include short-term memory loss, difficulties with concentration and multi-tasking, and word-finding problems (anomia). The symptoms sound like those typically reported in aging populations under the syndrome of "mild cognitive impairment" or MCI.

The angle that the NY Times takes with the piece is that cancer patients have been complaining about these symptoms for years, and only recently have doctors taken the concerns seriously. On the other hand, it's clear even from reading the Times piece that objective evidence for the existence of this phenomenon is mixed. It's hard to know whether a subtle word finding or working memory problem that cancer patients experience following chemotherapy is different from what they would have experienced had they not chosen chemo. (I'm guessing that you can't very readily do a true random assignment, clinical-trial style, experiment to address a question like this.)

The mechanism through which chemotherapy would directly affect cognition is an even bigger mystery. The Mayo Clinic's website suggests that some of the chemotherapy drugs may be getting across the blood-brain barrier, which keeps a lot of substances in the blood from affecting the brain directly. Alternatively, the effects could be a more indirect effect of stress or depression caused by chemo (or of the cancer diagnosis itself) or of hormone therapy, which is part of the treatment regimen for some forms of cancer. The existing studies of the chemobrain phenomenon seem to be based primarily on breast-cancer patients, who often undergo hormone therapy in addition to chemo.

A quick Pubmed search for Tim Ahles of Sloan-Kettering, one of the investigators referenced in the Times, led me to his recently published article in Nature Reviews Cancer. In that article, he and co-author Andrew Saykin suggest that genetic risk factors predispose some individuals both to cancer and to cognitive decline. In other words, this could be a classic example of the third-variable problem; the chemotherapy may not be directly causing mild cognitive impairment, but rather both the need for chemo and the MCI might both stem from a third factor (a common genetic predisposition). This isn't just getting bogged down in semantics; if the direct relationship between chemo and so-called chemobrain existed, then avoiding chemo would result in avoiding chemobrain. This would not be the case if the relationship were mediated primarily by a third-variable. Of course, the dynamics of this are much more complicated, as Ahles and Saykin discuss, and may involve a complex web of interactions between the predispositions and the suite of more direct effects of cancer, chemotherapy, and all its associated treatments and stressers.

Recommended reading:
Ahles, T. A., & Saykin, A, J. (2007). Candidate mechanisms for chemotherapy-induced cognitive changes. Nature Reviews Cancer, 7, 192-201.

2 comments:

peter said...
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edward said...
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