Staving Off Dementia

Dementia is high on my list of conditions I'd like to avoid, as I suspect it is for most.  The vision of ending my life totally dependent on others for even the most basic of needs is not at all attractive, but perhaps more disturbing than that is the complete loss of self those with Alzheimer's disease manifest, along with loss of self-determination.  Small wonder then that the search for effective medications roars along, as does research on better means of diagnosing the condition, predicting its course, and that Holy Grail, prevention.  How disappointing then, but still revelatory, is a study in this issue of Alzheimer's and Dementia.

The Alzheimer's Disease Anti-inflammatory Prevention Trial, abbreviated ADAPT, enrolled some 2500 elderly persons to receive either naproxen (Naprosen) or celecoxib (Celebrex) for two years or placebo. Over 90% of participants completed the trial, and 117 hardy individuals actually volunteered to undergo a spinal tap to allow biomarkers found in cerebrospinal fluid to be measured.  (!)

Here's what they found:  for folks who had a preliminary condition to full blown Alzheimer's disease (which we will now abbreviate AD) known as cognitive impairment-no dementia (surprise, surprise!  another acronym: CIND), use of naproxen or celecoxib appears to increase the risk of developing AD.  The authors note this is consistent with other prospective and observational studies which have disappointingly shown the same results.  For folks who had no evidence of CIND or AD, however, the nonsteroidal anti-inflammatory drugs (NSAIDs) seemed to have a protective effect, but only after two to three years of treatment.  As I quip to Rick in this week's podcast, I'm hoping that one benefit of the NSAIDs I regularly use for cycling related aches and pains will keep AD at bay. 

What is so interesting about this study is the fact that once again, a theme we've seen emerging for some time in all kinds of conditions, from cancers of all types to diabetes to dementia, disease is a moving target.  Medicalese for this is 'natural history,' simply defined as the steps or stages a condition passes through as time goes on.  It's increasingly evident that just as in life itself, what works at one stage not only doesn't work at another but may actually be harmful.  And while at first glance that may seem like bad news, it's actually an opportunity to develop more effective interventions than we currently have.  Additionally, such observations argue in support of basic science endeavors to understand these stages biologically, so that more effective and rational approaches can be designed.

What of those aforementioned amazing souls who underwent spinal taps to assess markers of AD in their brains? Biomarkers tended toward reduction (read that improvement) in the naproxen treated group.  My own opinion about this is it argues for better and less invasive methods of assessing impact of treatments in AD.  But should we all take naprosen to reduce our risk?  Rick and I both agree the jury is still out.  For now, we continue to beat the same drum regarding healthy lifestyles to reduce your risk of aging-related diseases.

Other topics this week include the value of ver sensitive sentinel node assessment techniques in breast cancer in JAMA, a way to improve transplanted kidney survival in NEJM, and the impact of Medicare part D in JAMA.  Until next week, y'all live well.

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