Association Between Statin Use and Risk of Dementia After a Concussion

Abstract

oncussions are a common cause of brain injury occurring in more than 1 million Americans each year and disproportionately involving older adults. 1-4 The subacute consequences vary widely and include fatigue, headache, irritability, insomnia, inattention, photophobia, vertigo, and cognitive difficulties. 5-9 Most patients recover from a concussion within weeks, although some can develop lingering mood disorders or chronic neuropsychiatric disorders. 10-14 The extent of complications after a concussion is uncertain, and effective pharmacologic treatments remain elusive. 15-17 Unfortunately, many medical treatments for traumatic brain injury that showed promise in animal models have subsequently failed in human clinical trials. 18-22 Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) are a class of medications prescribed for the treatment of hyperlipidemia. 23,24 Preclinical data suggest that statin use might mitigate injury-related brain edema, oxidative stress, amyloid protein aggregation, and neuroinflammation. 25-29 The potential neuroprotective benefits from statins have also been speculated and include preserved cerebral blood flow, leading to decreased risks of Alzheimer disease, vascular dementia, and age-related cognitive decline. 30-35 Together, these findings suggest that statin use could contribute to microvascular homeostasis and immune modulation independent of systemic lipid levels. However, statins do not improve cognition for patients already diagnosed as having dementia. 36-38 IMPORTANCE Concussions are an acute injury that may lead to chronic disability, while statin use might improve neurologic recovery. OBJECTIVE To test whether statin use is associated with an increased or decreased risk of subsequent dementia after a concussion.

Dementia prevention, intervention, and care: 2020 report of the Lancet Commission

“…They suggest future RCTs as statins might mitigate injury-related brain oedema, oxidative stress, amyloid protein aggregation, and neuroinflammation. 72 …”

Risk of dementia in patients with periodontitis and related protective factors: A nationwide retrospective cohort study

“…Some studies have also shown that statins reduce periodontal inflammatory injury (Subramanian et al, 2013). In a population-based cohort study, the use of statins was associated with a reduced risk of stroke after a concussion (Redelmeier et al, 2019). It can be postulated that statins have a protective effect against stroke and therefore reduce the risk of dementia (Redelmeier et al, 2019;Subramanian et al, 2013).…”

The need for clinical judgement in the application of evidence-based medicine

“…They also do not cause hepatotoxicity, renal failure, cataracts11 or dementia 12. If anything, statins reduce the risk of dementia,12 13 as would be expected: cholesterol lowering prevents strokes, and preventing strokes is at present the best available way to prevent dementia 14 15. With the rare exception of autoimmune statin myopathy,16 probably the only valid causally related adverse effects are myopathy and a slight increase in the risk of diabetes,10 probably both due to impaired mitochondrial function resulting from depletion of ubiquinone 12…”