Low LDL Levels Linked to Parkinson's Risk

CHAPEL HILL, NC, Dec. 20 -- Low levels of LDL cholesterol appear to confer a greater risk of Parkinson's disease, suggesting that it's possible to have too little of a bad thing, according to researchers here.

Looking at cholesterol levels in patients with Parkinson's versus controls, Xuemei Huang, M.D., Ph.D., of the University of North Carolina, and colleagues, found that an LDL concentration that is ideal from a cardiovascular viewpoint was associated with a 3.5-fold increased risk for Parkinson's.

Paradoxically, statins, which act primarily by lowering LDL, appeared to have a protective effect, the authors reported online in Movement Disorders.

"Our data provide preliminary evidence that low LDL cholesterol may be associated with higher occurrence of Parkinson's disease, and/or that statin use may lower PD occurrence, either of which finding warrants further investigation," the investigators wrote.

The authors noted that while the apolipoprotein E-2 (APOE 2) allele is apparently protective against Alzheimer's disease, it appears to be associated with increased risk for sporadic Parkinson's and is consistently associated with lower plasma LDL concentrations.

"If my hypothesis was correct," Dr. Huang said, "lower LDL-C, something that is linked to healthy hearts, would be associated with a higher occurrence of Parkinson's. We found that lower LDL concentrations were indeed associated with a higher occurrence of Parkinson's disease."

She and her colleagues tested the hypothesis with a case-control study using fasting lipid profiles from 124 consecutive patients with Parkinson's disease seen at a movement disorders clinic, and 112 unmatched controls (spouses of clinic patients) who were free of Parkinson's disease at the time of enrollment.

The authors calculated multivariate odds ratios using unconditional logistic regressions, with adjustments for age, gender, smoking status, and use of statins or other cholesterol-lowering agents.

They found that an "optimal" plasma LDL concentration -- in the range of 93-114 mg/dL -- was associated with the highest risk for Parkinson's, with an odds ratio of 3.5 (95% confidence interval 1.6-8.1) compared with an LDL level > 139 mg/dL.

Similarly, participants with an LDL from 115 to 138 mg/dL had a more than two-fold risk for Parkinson's (odds ratio 2.2, 95% CI , 0.9 -5.1), and those with the lowest LDL levels -- < 93 mg/dL -- had an odds ratio of 2.6 (95% CI., 1.1-5.9).

"Interestingly, use of either cholesterol-lowering drugs, or statins alone, was related to lower Parkinson's disease occurrence," the authors wrote.

After adjusting for age, gender, and smoking status, the multivariate odds ratio for the use of any cholesterol-lowering agent was 0.36 (95% CI, 0.19-0.68).

They found similar results when they looked separately at statins. The odds ratio for statin use with further adjustment for LDL concentrations was 0.37 (95% CI, 0.19-0.72) and without adjustment was 0.41 (95% CI, 0.22- 0.79).

Their findings raise two fundamental questions, Dr. Huang said.

"One is whether lower cholesterol predates the onset of Parkinson's. Number two, what is the role of statins in that? In other words, does taking cholesterol-lowering drugs somehow protect against Parkinson's? We need to address these questions," she said.

"The study was retrospective in nature, and we could not make a causal inference between LDL-C and/or statin use and risk of Parkinson's disease," the authors pointed out. "Further, the study had a relatively small sample size, and thus limited statistical power."