Confusing News on Statins and Dementia

Contributed by: David Geldmacher, M.D., Medical Director of the Memory Disorders Clinic at the University of Virginia.

The news is in
The latest Cochrane Review on the role of statin drugs states that they do not lower the risk of dementia.

These findings come primarily from the results of two prospective randomized trials involving over 26,000 subjects. Neither clinical impressions nor neuropsychological tests revealed any reduced dementia risk over three to five years of treatment. The average LDL cholesterol level at study entry was about 135 mg/dl, which is within the current indication for treatment, but not by a lot.

For better or worse?
Statin treatment was also not associated with worsened cognition, but the size of these studies would prevent rare but meaningful cases of from showing up in the statistical outcomes. See here for an example of what can go wrong in statin use.

So, why is this news? Many reports, including one from the well-respected Rotterdam Study earlier this year, suggest that statins, but not other cholesterol lowering agents, have a substantial effect on lowering dementia risk.

Apples and Oranges
The Cochrane Review identifies “indication bias” as a likely contributor to the differences between prior observational studies and the randomized trials. I agree.

Since most statin prescriptions were written for much higher levels of total and LDL cholesterol when data was collected for the observational studies, the "indication" for treatment probably differed between the old studies and the new ones. The differing outcomes may therefore simply represent the result of an apples-and-oranges comparison beween the effects of statin use in people with cholesterol levels high enough to warrant prescription drug treatment and others with cholesterol levels low enough that placebo use wasn't considered dangerous.

If you’re having a sense of déjà vu about this mismatch, we’ve seen much the same story with hormone replacement therapy and dementia risk. See here for more of my thoughts on that can of worms.

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