Older people with low levels of high-density lipoprotein cholesterol (HDL-C) and increased variability in HDL-C levels over time may be at a higher risk of Parkinson disease (PD), according to study results published in Neurology.

This population-based cohort study used data from a database in the Korean National Health Insurance System (NHIS) and the rare intractable diseases registry. In total, study researchers included 382,391 people 65 years of age or older who underwent 3 or more health examinations conducted by the Korean NHIS from 2008 to 2013.

All participants were followed up until 2017. Investigators assessed HDL-C variability and the association between HDL-C and PD incidence.

At baseline, the mean HDL-C of the participants in the overall study cohort was 53.1 (standard deviation, ±13.0) mg/dL, while the median HDL-C variability was 7.6, as measured with variability independent of the mean (VIM). A total of 2733 out of 380,404 participants in the study developed PD during a median follow-up period of 5 years. Of the participants in the study, 62% were men.

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An increased PD incidence was associated with the lowest quartile (Q1) group of baseline HDL-C (adjusted hazard ratio [aHR], 1.20; 95% CI, 1.08-1.34) and mean HDL-C (aHR, 1.16; 95% CI, 1.04-1.30) compared with the highest quartile (Q4) population. Compared with patients in Q1, those in Q4 with a VIM of HDL-C had an increased PD risk (aHR, 1.19; 95% CI, 1.06-1.33). The highest PD incidence was observed in patients in the Q1 of baseline HDL-C and in the Q4 of HDL-C variability (aHR, 1.6; 95% CI, 1.31-1.96).

Limitations of this study included the lack of information on participants’ genetics as well as the lack of a consensus on measurements of intra-individual HDL-C variability.

Although this study suggests HDL-C variability is associated with a higher risk of PD, the study researchers wrote that additional “studies are required to elucidate the exact mechanism of this association between HDL-C variability and PD and action for HDL-C to modulate PD.”


Park JH, Lee CW, Nam MJ, et al. Association of high-density lipoprotein cholesterol variability and the risk of developing Parkinson disease. Neurology. 2021;96(10):e1391-e1401. doi:10.1212/WNL.0000000000011553