Peter Attia: Statins, Dementia, Desmosterol

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BrianR
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Peter Attia: Statins, Dementia, Desmosterol

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Peter Attia's most recent weekly note discussion brain cholesterol, statins and desmosterol.

Does low cholesterol cause cognitive impairment? Part II
One of the most common causes of reduced desmosterol is statin therapy. Statins can cross the BBB — and while the data is conflicting — a recent study confirmed the hypothesis that lipophilic versions including simvastatin (Zocor) and atorvastatin (Lipitor) may more easily cross the BBB than hydrophilic ones including rosuvastatin (Crestor) and pravastatin (Pravachol), and therefore may inhibit cholesterol synthesis in the brain. Is low desmosterol a cause of cognitive impairment and dementia or the result of it? The short answer is we don’t know. What we do know is that cholesterol is critical to brain function and there are observational studies like the ones above (and more recent ones) suggesting low plasma desmosterol is a biomarker for MCI and AD. Unfortunately, the 2012 and 2015 papers discussed above don’t include patients on statins, which would be helpful for us to elucidate any links between statin use, desmosterol levels, and cognitive decline. It may sound cliché to hear this, but more, and better, research is needed to understand whether statins have an effect on cognition or neurological disorders like AD, in at least a subset of users.

From a clinical perspective, low desmosterol levels in patients with cognitive symptoms may serve as an indication that cholesterol synthesis is over-suppressed and the statin dose should be decreased (or stopped altogether in favor of a different drug class). We don’t like to see absolute concentrations of desmosterol below 0.8 mg/L in our patients. We also treat patients with one or two copies of the APOE e4 alleles or a family history of dementia with kid gloves and make sure they have a desmosterol level greater than 1.0 mg/L.
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