Cardiovascular disease that accumulates in the brains of older adults may influence the development of parkinsonism, according to new research released Wednesday, which found that adults taking statins have a reduced risk of developing these motor symptoms.
Parkinsonism describes neurological conditions including tremors, slowed movement, and stiffness; up to 50% of older adults are affected, and a far smaller percentage receive a diagnosis of Parkinson disease (PD)—about 5% of the general population, according to the researchers writing in Neurology.
The investigators, from Rush University Medical Center in Chicago, Illinois, examined participants from 3 cohorts of older adults living at home or in congregate settings and their use of statins, which are used to prevent stroke by reducing cerebrovascular atherosclerosis, to see if usage is linked with a lower risk of incident parkinsonism and whether this association is mediated via the effects of statins on brain atherosclerosis.
The participants in the 3 groups were enrolled in 1 of 3 ongoing clinical pathological studies at Rush Alzheimer’s Disease Center.
The primary analysis included 2841 individuals with a mean (SD) age of 76.3 (7.4) years; 75% were women. A little more than a third—936 individuals—were taking statins.
Participants were followed for a mean of 5.6 (4.9) years, meeting each year with researchers, who checked the statins they were taking and to test for signs of parkinsonism, which they defined as 2 or more of the following symptoms: tremor, stiffness, parkinsonian gait, and bradykinesia. During the study, 50% (n = 1432) of participants developed parkinsonism.
After controlling for age, sex, and vascular risks, like smoking and diabetes, individuals on statins (n = 936) had a 16% lower risk of developing parkinsonism 6 years later compared with those not using the drugs (HR, 0.84; 95% CI, 0.74-0.96; P = .008).
Researchers also performed a postmortem analysis on the brains of the 1044 participants who died during follow-up; the mean age at death was 89.2 (6.7) years.
In the postmortem analysis, the researchers were looking for atherosclerosis of the large vessels of the Circle of Willis; previous studies have indicated that severe atherosclerosis in this region of the brain is linked with rapid, progressive parkinsonism, faster cognitive decline, and more severe white matter hyperintensities.
Using statins before death was linked with 37% lower odds of atherosclerosis (odds ratio, 0.63; 95% CI, 0.50-0.79; P <.001) compared with those not using statins.
The study also included data on the type of statins individuals were taking; about 79% of those on statin therapy were taking moderate- or high-intensity statins. Those on higher-intensity statins had a 7% lower risk of developing parkinsonism compared with those on low-intensity statins.
The investigators also conducted a mediation analysis, with statins as the cause, moderate to severe atherosclerosis as the mediator, and parkinsonism as the effect. Less severe cerebral atherosclerosis partially mediates the link between statins and parkinsonism before death, confirming their hypothypothesis, they said.
“These findings highlight the role of cerebrovascular pathologies in late-life parkinsonism and suggest a potential role for statins in decreasing its magnitude,” the authors wrote.
The authors cautioned that larger clinical trials testing a statin intervention would need to be conducted before any other recommendations can be made.
However, one of the authors called the results "exciting."
“Our results suggest people using statins may have a lower risk of parkinsonism and that may be partly caused by the protective effect statins may have on arteries in the brain,” study author Shahram Oveisgharan, MD, said in a statement. “Our results are exciting, because movement problems in older adults that come under the umbrella of parkinsonism are common, often debilitating, and generally untreatable.”
He added that “statins could be a therapeutic option in the future to help reduce the effects of parkinsonism in the general population of older adults, not just people with high cholesterol or who are at risk for stroke.
The study, funded by the National Institutes of Health, had a few limitations. One is that parkinsonism evaluations were not performed by movement disorder specialists, so cases of PD may have been missed, although the authors said even if that happened, results were unlikely to change.
In addition, even though 1 of the 3 groups consisted of Black participants in the Chicago area, the majority of individuals were White and so the research should be conducted in population-based studies. Also, the work was conducted in a group of older Americans, largely older than 80 years, and the authors suggested that future studies examine a younger segment of older adults.
Oveisgharan S, Yu L, Barnes LL, et al. Association of statins with cerebral atherosclerosis and incident parkinsonism in older adults. Neurology. Published online March 23, 2022. doi:10.1212/WNL.0000000000200182