SIB# 457- Statin Drugs Double Risk of Dementia in Select Patients
The Study: 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
Overview: This paper is a prospective, long term study of a consecutive series of patients from over 50 North American sites who were enrolled in the Alzheimer’s Disease Neuroimaging Initiative. The authors designed the study “to help clarify the relationship between statin use and subjects’ long-term cognitive trajectory.”
Key Points:
· The study looked at a total of 392 subjects with early mild cognitive impairment (eMCI) some of whom were taking statin medications and some of whom were not.
· Patients were stratified according to neuropschological status at baseline, cholesterol levels at baseline, statin use vs. non-use and also the type of statin used*.
*The authors were interested in comparing users of statins with known moderate lipophilicity (atorvastatin) vs. statins with high lipophilicity (simvastatin) to non statin users and/or users of other statin.
· 303 subjects had cholesterol levels available at baseline.
· The median cholesterol level at baseline was 206 mg/dl.
· Subjects were then divided into two groups: 1) those with cholesterol levels above the median level (103 subjects) and 2) those with cholesterol levels below the median (200 subjects).
· Patients were followed for 96 months to determine the rate of conversion to dementia and testing included parametric mapping of PET scan data to identify regions of declining cerebral metabolism within each statin group.
· Statin users with less than 96 months of use were ultimately excluded from the data set.
· Subjects in the below median cholesterol group who were taking lipophilic statins (simvastatin) showed a significant increase in the rate of conversion to dementia (24%) vs. only 10% of those patients who were not taking any statin drug.
· Additionally, the PET scan imaging studies identified areas of metabolic decline described as “highly significant” in the posterior cingulate cortex in users of this same class of lipophilic statins while no significant decline occurred either among users of other type statins or those not taking statins at all.
· For those subjects in the above median cholesterol group, there was no significant difference in the conversion rates, regardless of which type statin they were taking.
Author’s Conclusions: The authors state their findings very clearly. “Among subjects with early mild cognitive impairment and low to moderate serum cholesterol levels at baseline, lipophilic statin use was associated with more than double the risk of converting to dementia over eight years of follow-up compared with statin non-use, and with highly significant decline in metabolism of posterior cingulate cortex -- the region of the brain known to decline the most significantly in the earliest stages of Alzheimer’s disease. (emphasis ours)
Reviewer's Comments: It definitely looks like those patients with low to moderate cholesterol levels at baseline were most subject to progression of their dementia. But interestingly, the serum cholesterol levels within this “low to moderate” cholesterol group had a very wide range and did not seem to differ significantly between those who ultimately progressed to dementia during the study period and those who did not. I’m not sure exactly what to make of this other than, PERHAPS, some individuals with already marginally low levels of cholesterol are simply more susceptible to harm from lipophilic statins. As always, more study is needed but I would love to hear your thoughts on this.
Reviewer: Mark R. Payne DC
Link to Abstract: https://jnm.snmjournals.org/content/62/supplement_1/102