Statins – Dementia and Aging

Some very interesting papers have been published recently citing benefit of statin use with REDUCED dementia and possible SLOWING  of human aging.

From the 2013 European Society of Cardiology (ESC) Congress on September 5th 2013 were two interesting studies linking Statin use to reduced dementia  (European Society of Cardiology Congress 2013. Abstracts #1609, P4077) were presented. Of critical importance the two new studies may somewhat allay concerns about cognitive dysfunction being a possible adverse effect of statins. 

The studies, both from Taiwan suggested that statin drugs may instead be linked to lower rates of dementia in older people. The first study of 58,000 patients showed a dose-related inverse relationship between statin use and new-onset non-vascular dementia. The second report, in 5221 patients with atrial fibrillation, found a lower incidence of dementia in patients taking statins compared with those not taking statins. 

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Seth S. Martin, MD, Johns Hopkins Hospital, Baltimore, Maryland, who is conducting a systematic review of the literature on statins and cognition/dementia, said these current results fit in well with existing studies. The work strengthens existing literature that is compatible with a protective effect of statins on dementia. Overall, statins appear to be good for the brain.

For the study, Lin and colleagues examined whether statin use was associated with new diagnoses of dementia in a random sample of 1 million people covered by Taiwan’s National Health Insurance. From this they identified 57,669 individuals older than age 65 years who had no history of dementia in 1997 and 1998. Of these, 15,200 were taking statins. Propensity scoring was used to match these patients with controls not taking statins. Patients receiving statins were divided into tertiles according to dose. 

The researchers identified 5516 new diagnoses of dementia (excluding vascular dementia) during the 4.5 years of follow-up. Results showed an inverse relationship between statin use and dementia, with the risk for dementia decreasing with increasing statin dose. This trend remained in different age, sex, and cardiovascular risk subgroups. The adjusted risks for dementia were significantly inversely associated with increased total or daily equivalent statin dosage,” Dr. Lin said. “Patients who received the highest doses of statins had a 3-fold decrease in the risk of developing dementia. High-potency statins such as atorvastatin and rosuvastatin showed a significant inverse association with developing dementia in a dose-response manner. Higher doses of high-potency statins gave the strongest protective effects against dementia.”

All the statins except lovastatin (a weak statin) were associated with a decreased risk for new-onset dementia when taken at higher daily doses. Dr. Lin suggested lovastatin may have shown different results because it has less cholesterol-lowering effect than other statins.

Statins Halved Dementia Risk in AF Patients

The second study, by a group led by Min-Tsun Liao, also from National Taiwan University Hospital, Hsin-Chu, included 5221 patients with atrial fibrillation, which is known to be a predisposing factor for dementia. Of these, 1652 were taking statins.

During a 6-year follow-up, 2.1% of the patients taking statins developed dementia compared with 3.5% of the nonstatin group, a statistically significant difference (P = .002). Cox regression analysis showed an odds ratio of 0.565 for statin use and the risk for new-onset dementia. Other factors that were associated with a reduced risk for dementia included male sex and lower CHADS2 score. History of myocardial infarction, peripheral artery disease, coronary artery disease, chronic kidney disease, and valvular heart disease were not associated with new-onset dementia.

New research in The FASEB Journal suggests that statins protect against DNA shortening by telomerase activation and promote healthy aging free of age-related diseases like heart disease, diabetes and cancer.

Boccardi V, et al.  “A new pleiotropic effect of statins in elderly: modulation of telomerase activity.” FASEB J., September 2013; 27:3879-3885.

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The journal of the federation of American Societies for Experimental Biology  (FASEB Journal) is one of the world’s most cited biology journals. It is a preferred venue for the latest research reports and reviews of epigenetics, iRNA mechanics, histone acetylation, nitric oxide signaling, eicosanoid biochemistry, angiogenesis, tumor suppressor genes, apoptosis, cytoskeletal function, and human stem cell research. The journal publishes  peer-reviewed, multidisciplinary original research articles, as well as editorials, reviews, and news of the life sciences .

Not only do statins extend lives by lowering atherogenic lipoprotein levels and reducing the risks of cardiovascular disease, new research in the September 2013 issue of The FASEB Journal suggests that they may extend lifespans as well. Specifically, statins may reduce the rate at which telomeres shorten, a key factor in the natural aging process. This opens the door for using statins, or derivatives of statins, as an anti-aging therapy.

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Telomeres are the end caps of chromosomes, protecting the DNA complexes from deterioration during cell division. Telomere shortening is considered a marker of cellular aging, and prematurely shortened telomeres have been linked to increased risk of cancers, heart disease, dementia and death.

By telomerase activation, statins may represent a new molecular switch able to slow down senescent cells in our tissues and be able to lead healthy lifespan extension.  This group of workers from the Department of Internal Medicine, Surgical, Neurological Metabolic Disease and Geriatric Medicine at Second University of Naples in Naples, Italy studied two groups of subjects. The first group was under chronic statin therapy, and the second group (control), did not use statins. When researchers measured telomerase activity in both groups, those undergoing statin treatment had higher telomerase activity in their white blood cells, which was associated with lower telomeres shortening along with aging as compared to the control group. This strongly highlights the role of telomerase activation in preventing the excessive accumulation of short telomeres.

Comment:

This data is interesting and certainly warrants more research.

Cardiologydoc

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