Donald A. Redelmeier, MD, MSHSRDonald A. Redelmeier, MD, MSHSR
Older adults who have experienced a concussion and have also received statins have a reduced risk for dementia, according to results of a large, population-based, multicenter study published in JAMA Neurology.1

Led by Donald A. Redelmeier, MD, MSHSR, of the University of Toronto in Ontario, Canada, the investigators sought to examine whether there was an association between statin use and subsequent dementia after a concussion, given that concussions are associated with increased long-term risk for dementia and statins may reduce dementia risk.

The long-term study, which began enrollment in April 1993 and completed follow-up in March 2016, included 28,815 older adults who were diagnosed with a concussion (median age, 76 years; 61.3% women), of whom 7058 received statin therapy (atorvastatin, cerivastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin) within 90 days post-concussion.

The primary outcome was a physician diagnosis of dementia, confirmed on 2 separate dates to avoid false-positive results. The investigators also conducted a secondary parallel analysis in older adults with an ankle sprain who received or didn’t receive statin therapy in order to further elucidate the potential association between statin use and subsequent dementia.

Over a mean follow-up period of 3.9 years, 4727 patients who had experienced a concussion developed dementia, with a resulting incidence of 1 case per 6 patients. Among those diagnosed with dementia, 1050 received statin therapy, with an incidence of 37 cases per 1000 patients annually. The investigators noted that this rate was twice the population norm. Among the control cohort, 3677 cases of dementia were diagnosed, with an incidence of 43 cases per 1000 patients annually.

All told, statin therapy was associated with a 13% reduced risk for dementia (95% CI, 7%-19%; P <.001) compared with patients who receiving no statin therapy (relative risk 0.87; 95% CI, 0.81-0.93; P <.001). The results remained unchanged after adjusting for patient characteristics, though the investigators noted that older age and greater health care use were both associated with increased risk.

The investigators reported that the decreased risk for dementia was specific to statins, as other lipid-lowering drugs and cardiovascular medications were not associated with reduced risk, as well as benzodiazepines, thyroid supplements, gastric acid suppressors, bronchodilators, and glaucoma eye drops.

Further analysis of statin therapy revealed that rosuvastatin was associated with the largest risk reduction, while simvastatin was associated with the smallest. No significant difference in benefit was found between high-dose and low-dose statins, or hydrophilic or lipophilic statins.

In the confirmatory secondary analysis in patients with an ankle sprain, statin use was associated with a 5% reduction in risk for dementia, demonstrating a distinct risk profile for patients with concussion who receive statin therapy.

“The findings of our study suggest a potential long-term protective association between statin use and the risk of dementia after a concussion that justifies future research,” the investigators wrote, noting several limitations to their study design that need to be explored further.

They concluded, writing that “more efforts to prevent concussions should be encouraged at all ages. Screening for past concussions might also offer new clinical insights for patients diagnosed as having dementia.”

In a related editorial,2 Rachel A. Whitmer, PhD, of the University of California, Davis, applauded the robust nature of the study’s design and population, noting that, “Population-based findings couched in well-conducted pharmacoepidemiology are important to establish, as they can suggest the therapeutic potential of classes of medication for TBI recovery.”

Whitmer emphasized the importance of identifying avenues for recovery and treatment options for traumatic brain injury in an effort to reduce its long-term effects.

“While this study cannot infer causality, it is a first step in accumulating evidence for possible future therapeutic interventions post-TBI and a call for further pharmacoepidemiologic harnessing of integrated health care systems to discover other potential protective or risk factors for dementia after brain injury.”
REFERENCES
1. Redelmeier DA, Manzoor F, Thiruchelvam D. Association between statin use and risk of dementia after a concussion [Published online May 20, 2019]. JAMA Neurol. doi:10.1001/jamaneurol.2019.1148
2. Whitmer RA. Concussions and dementia—are statins the salve in the wound? [published online May 20, 2019]. JAMA Neurol. doi:10.1001/jamaneurol.2019.0846