Statins and Dementia

Nassim Taleb, commenting on the Lindy Effect, wrote “…the only effective judge of things is time”. Since modern medicine has been around for at best 100-150 years, any medical intervention, whether a drug or procedure that has lasted for at least 3-4 decades and works well is likely to be around for a long, long time. That is why the whole “radiation causes cancer” is such a bogus argument after 128 years of the use of X-rays in medicine with not one study convincingly showing that radiation from medical imaging causes cancer.

Statins now have been in use for more than 35 years. They have conclusively been shown to improve survival. The challenges to statin use are related to the perception of side effects, mainly those related to muscle weakness, which in many instances as the N of 1 study showed are perhaps imagined or occur because of the nocebo effect.

One side effect of concern remains the issue of cognitive decline. I remember a cardiologist, a few years senior to me, many years ago decrying statins by saying that if they can reduce the fat in the blood, they can also leech away the fat from the myelin in the brain and cause premature dementia.

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Epidemiological studies have shown that the cardiovascular benefits likely outweigh the risk of cognitive decline and dementia if any. But at a personal level, I occasionally wonder…will taking statins make me lose my memory earlier or cause gradual memory loss in the years to come?.

An important study was published 3 days ago [1] by Zhou Z et al, which seems to put this fear to rest. This study looked at 18,846 people  from an aspirin trial, followed up for 4.7 years, comparing those who had received statins to those who had not, and found that there was no difference in the dementia rate and no evidence that statins accelerate cognitive decline.

Unfortunately, as keeps happening in medicine, earlier this week, saw another study [2] by Padmanabhan P and his colleagues, who looked at 303 patients with early cognitive impairment and followed them over 8 years with cognitive tests and FDG-PET scans. These patients either received statins (lipophilic or hydrophilic) or did not.  They found that those who take lipophilic statins like atorvastatin or simvastatin have double the risk (24% v/s 10%) of converting to full-blown dementia within 8 years, compared to those not on statins or those who take hydrophilic statins like rosuvastatin. The patients taking lipophilic statins also had characteristic changes on FDG- PET, in a part of the brain associated with dementia.

So, which one is correct? And does it matter? The first study looked at 18,000 odd patients over 4.7 years, while the second had 303 patients over 8 years. Smaller studies often suffer from multiple biases, the chief being that of the small patient numbers, which may lead to a replication problem. So, until another study reproduces Padmanabhan’s results, we should go with the findings from the first study with the larger numbers and more solid research.

So what is your matka here? If you need to be on statins, you must take them. They save lives. If you are worried about accelerated dementia or early cognitive decline due to statins, don’t be. If you still want to play it safe, then take or switch to a hydrophilic statin like rosuvastatin, like I do, instead of a lipophilic statin like atorvastatin or simvastatin.

Footnotes:

1. Zhen Zhou, Joanne Ryan, Michael E. Ernst et al. Effect of Statin Therapy on Cognitive Decline and Incident Dementia in Older Adults. Journal of the American College of Cardiology 2021; 77: 3145-3156.

2. Prasanna Padmanabham, Stephen Liu, Daniel Silverman. Lipophilic Statins in Subjects with Early Mild Cognitive Impairment: Associations with Conversion to Dementia and Decline in Posterior Cingulate Brain Metabolism in a Long-term Prospective Longitudinal Multi-Center Study. Journal of Nuclear Medicine May 2021, 62 (supplement 1) 102;