Higher serum cholesterol and decreased Parkinson's disease risk: A statin‐free cohort study

Rozani, Violetta; Gurevich, Tanya; Giladi, Nir; El-Ad, Baruch; Tsamir, Judith; Hemo, Beatriz; Peretz, Chava

doi:10.1002/mds.27413

Cited by 87 publications

(102 citation statements)

References 39 publications

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“…Therefore, the protective effect of high cholesterol could be misinterpreted as protective because of statin use. A recent statin‐free cohort study revealed that high cholesterol reduced PD risk . This assumption could explain why many previous reports had a tendency to show an inverse association of statins with PD risk.…”

Section: Discussionmentioning

confidence: 97%

“… Huang and colleagues reported that statins and low cholesterol could increase PD risk in a prospective study. A previous study suggested that high cholesterol levels might attenuate the processes of neurodegeneration in PD via effects on peripheral organs or that low cholesterol levels could be markers of lifestyle changes influenced by nonmotor symptoms in the early stages of PD . At a molecular level, cholesterol stabilizes lysosomal membranes and prevents lysosomal permeabilization that leads to direct neural death .…”

Section: Discussionmentioning

confidence: 99%

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Association of statin use with Parkinson's disease: Dose–response relationship

2019

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Background There have been conflicting results on the association between statin use and Parkinson's disease (PD) incidence. Objectives This study investigated the association between time‐varying status of statin use and incidence of PD while considering the dose–response relationship and total cholesterol level. Methods Using the database of the Korean National Health Insurance Service from 2002 to 2015, we examined 76,043 subjects (≥60 years old) free of PD, dementia, and stroke at baseline. The dose of statin use was classified into the following four 6‐month categories (<180, 180‐365, 365‐540, and ≥540 days) for each 2‐year interval. The incidence of PD was identified by the prescription records for any anti‐PD medication with a diagnosis of PD. Results During 10 years of follow‐up, 1,427 PD cases occurred. Statin “ever use” was significantly associated with a high risk of PD incidence (adjusted hazard ratio = 1.28; 95% confidence interval = 1.12‐1.46) when compared with statin nonuse. In terms of a dose–response relationship, although a duration of statin use <365 days was associated with a higher risk of PD, the duration of statin use ≥365 days was not significantly associated with an increased risk of PD. Conclusions Statin use was associated with an elevated PD risk of PD, but long‐term and adherent statin use was not significantly associated with elevated PD risk. However, there was no evidence of benefit with any statin treatment related to PD risk. Our study suggests that there is a complex relationship among cholesterol level, statin use, and PD risk that warrants further studies. © 2019 International Parkinson and Movement Disorder Society

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Association of statin use with Parkinson's disease: Dose–response relationship

2019

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“…For example, smoking has been repeatedly shown as a protective factor for PD, but has been recently suggested to be causally related to a higher risk of ALS . Opposite result patterns have also been shown for lipids . Similar or contrasting findings between ALS and PD, when studying risk factors or disease pathways, might therefore provide improved understanding of the disease etiologies for both.…”

Section: Discussionmentioning

confidence: 99%

“…18,19 Opposite result patterns have also been shown for lipids. 18,[22][23][24]28,29 Similar or contrasting findings between ALS and PD, when studying risk factors or disease pathways, might therefore provide improved understanding of the disease etiologies for both.…”

Section: Discussionmentioning

confidence: 99%

Peripheral immune biomarkers and neurodegenerative diseases: A prospective cohort study with 20 years of follow‐up

Yazdani

Mariosa

Hammar

et al. 2019

Annals of Neurology

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Objective To assess the associations of several blood immune biomarkers with the future risks of amyotrophic lateral sclerosis and Parkinson disease in a prospective cohort study with 20 years of follow‐up. Methods The Swedish Apolipoprotein‐Related Mortality Risk study is a longitudinal cohort study including 812,073 participants with repeated blood biomarker measurements between 1985 and 1996 and a follow‐up until 2011. Using a Cox model, we first estimated hazard ratios of amyotrophic lateral sclerosis and Parkinson disease in relation to leukocytes, immunoglobulin G, haptoglobin, and uric acid. We further described the temporal changes of these biomarkers during the 20 years prior to the diagnosis of these diseases. Results A total of 585 incident cases of amyotrophic lateral sclerosis and 3,769 incident cases of Parkinson disease were identified during the follow‐up. Increasing concentrations of leukocytes, haptoglobin, and uric acid were associated with a lower risk of Parkinson disease. No statistically significant association was, however, noted between the studied biomarkers and amyotrophic lateral sclerosis. Parkinson disease patients appeared to have lower levels of leukocytes and haptoglobin between 20 and 10 years before diagnosis and lower levels of uric acid during the 20 years before diagnosis, compared to controls, although statistically significant differences were only noted during parts of the respective time intervals after multivariable adjustment. No clear differences were noted between patients with amyotrophic lateral sclerosis and controls. Interpretation If verified in studies of independent populations, our findings may suggest a different role of systemic inflammation on the risk of Parkinson disease compared to amyotrophic lateral sclerosis. ANN NEUROL 2019;86:913–926

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“…The situation is complicated further with regard to statins because the indication for their initiation (generally cardiovascular disease) is itself a risk factor for PD development, as are associated factors (such as physical inactivity and diabetes). In addition, the therapeutic effect of statins (lowering of cholesterol) also influences PD risk, with low cholesterol being associated with a higher risk of incident PD, a finding which was previously reported and is replicated in Jeong's study . The postulated mechanisms for this include alteration of lysosomal membrane stability (which is cholesterol dependent) or reducing levels of coenzyme Q10.…”

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confidence: 70%