Statins were tied to a lower rate of dementia among older
adults who experienced a concussion, according to an observational study
involving nearly 30,000 people.
Older adults taking a statin within 90 days of a concussion had a 13%
reduced risk of dementia over about 4 years compared with those not
taking a statin, reported Donald Redelmeier, MD, of Sunnybrook Health
Sciences Center in Toronto, and co-authors in
JAMA Neurology.
Moreover, people over age 65 who had a concussion had a 100% relative
risk of dementia: "On average, a concussion doubled a person's risk of
subsequent dementia," Redelmeier told
MedPage Today. "That was particularly true if you had a lot of risk factors."
Although
many people in the study used other drugs, "none of those medications
made any difference -- they didn't make things better, they didn't
make things worse -- with one exception: being on a statin at the time
of the concussion led to about a 10% to 15% reduction in the long-term
risk of subsequent dementia," Redelmeier said. "This was distinct to
statins; it was not found with any other lipid-lowering medication or
any other cardiovascular medication."
Traumatic brain injuries (TBI) among
military veterans and
professional athletes
have garnered much attention, but little is known about the
relationship between concussion and dementia in other populations, he
noted. "To do this type of research, you really need to identify
thousands and thousands of patients and follow them up for years and
years before you can find out anything, simply because the onset of
dementia has such a time lag," he said in a
JAMA Neurology podcast interview.
"Furthermore, you have to do all that fighting against the standard
stereotypes that are propagated in the popular media -- such as James
Bond, who gets knocked out in one scene and is cracking jokes in the
next scene, as if to imply these injuries to the brain have no lasting
damage at all," he added.
Statins
have known effects as antioxidants and may preserve brain
microcirculation and modify neuroinflammation, he noted. Smaller studies
have shown a weak signal supporting a neuroprotective benefit of
statins in concussion: "Of four randomized trials, two showed a positive
benefit, two showed no significant difference, and none showed a
detrimental problem," he said. Of 11 observational studies, five showed a
positive benefit on neurocognitive outcomes and six showed a negligible
association.
In this study, Redelmeier and colleagues identified 28,815 people
ages 66 and older from the Ontario Health Insurance Plan who had been
diagnosed with a concussion from April 1993 through April 2013. They
excluded people with a prior diagnosis of dementia or delirium, as well
as people admitted to the hospital within 2 days of concussion or who
died within 90 days. They obtained prescription information from the
Ontario Drug Benefit Program database.
In total, 61.3% of the sample was female and the median age in the
study was 76. About a quarter (7,058 people or 24.5%) had received a
statin within 90 days of the concussion and 75.5% did not.
Over a mean follow-up of 3.9 years, 4,727 people developed dementia.
People who received a statin had a 13% reduced risk of dementia compared
with people who did not receive a statin (RR 0.87, 95% CI 0.81-0.93;
P<0.001). After adjusting for baseline characteristics, statin use was tied to a 16% (95% CI 10%-22%;
P<0.001) drop in the risk of overall dementia.
This
decreased dementia risk was independent of other cardiovascular
medications. Higher statin doses were not more beneficial. Low dementia
risk was greatest among people taking rosuvastatin (Crestor).
In this study, people with concussions who received statins had an
annual incidence of 37 cases of dementia per 1,000 versus 43 cases per
1,000 in the no-statin group. By contrast, the annual incidence of
dementia in Ontario was 19 cases per 1,000 adults ages 65 and older in
the general population, Redelmeier and colleagues noted.
The researchers tested similar models in older adults in the Ontario
Health Insurance Plan who had been diagnosed with an ankle sprain
instead of concussion; the link between statin use and reduced dementia
was not seen. In another analysis, they looked at depression instead of
dementia and found insignificant results.
This study has a number of strengths, observed Rachel Whitmer, PhD, of the University of California Davis, in an
accompanying editorial.
"This was a large group of individuals followed up for up to 20 years,
enough time to accumulate a large enough group of patients with
concussions; this enabled the statistical power to test if a prescribed
medication was associated with the outcome," she wrote. Concussion was
based on diagnoses and statin exposure on filled prescriptions,
eliminating the problems of self-reported data.
"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 work to discover more about potentially protective
factors or risks for dementia after brain injury, she added.
The study has several limitations, Redelmeier and co-authors noted.
Associations may reflect confounding due to earlier indications for
statin use. The researchers could not adjust for smoking, drug
adherence, or other factors that might influence dementia risk. The
study also lacked sufficient power to determine whether statins
contributed to lower dementia risk before, during, or after a
concussion. The total number of concussions an individual sustained over
a lifetime was unknown. In addition, median follow-up in this study was
4 years; dementia trajectories often span decades of subclinical
changes.
Last Updated May 20, 2019
This study was supported by a
Canada Research Chair in Medical Decision Sciences, the Canadian
Institutes of Health Research, the Bright Focus Foundation, and the
Comprehensive Research Experience for Medical Students at the University
of Toronto.
The researchers reported no conflicts of interest. The editorialist also reported no conflicts.
Primary Source
JAMA Neurology
Secondary Source
JAMA Neurology
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