Neuroprotective effects of statins may not be related to total and low-density lipoprotein cholesterol lowering

George, Sabu; Dhond, Abhay J.; Alderson, Skip M; Ezekowitz, Michael D.

doi:10.1016/s0002-9149(02)02841-2

Cited by 11 publications

(6 citation statements)

References 36 publications

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“…Another interesting finding is the much higher percentage of use of cholesterol‐lowering agents (primarily statins) in the control versus PD subjects (PD men 20.3% vs. control men 38.0%; PD women 12.7% vs. control women 30.6%). Some statins have been hypothesized to be protective against neurodegenerative diseases,26, 27 although recent clinical trial data on Alzheimer's disease are less supportive 28–30. Examining the protective effects of statins was not the primary aim of our study, but testing this hypothesis as it relates to PD (and elucidation of potential mechanisms) is of clinical importance.…”

Section: Discussionmentioning

confidence: 96%

Lower low‐density lipoprotein cholesterol levels are associated with Parkinson's disease

et al. 2006

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The apolipoprotein E (APOE) ε2 allele has been associated with both Parkinson's disease (PD) and lower low density lipoprotein cholesterol (LDL-C). The study is to test the hypothesis that lower LDL-C may be associated with PD. This case-control study used fasting lipid profiles obtained from 124 PD cases and 110 controls, the PD cases recruited from consecutive cases presenting at our tertiary Movement Disorder Clinic, and controls recruited from the spouse populations of the same clinic. Multivariate odds ratios (OR) and 95% confidence intervals (CI) were calculated from unconditional logistic regressions, adjusting for age, gender, smoking status, and use of cholesterollowering agents. Lower LDL-C concentrations were associated with a higher prevalence of PD. Compared with participants with the highest LDL-C (≥139 mg/dL), the OR was 2.2 (95% CI 0.9-5.1) for participants with LDL-C of 115-138, 3.5 (95% CI 1.6-8.1) for LDL-C of 93-114, and 2.6 (95% CI 1.1 -5.9) for LDL-C ≤ 92. Interestingly, use of cholesterol lowering drugs or just statins was related to lower PD prevalence. Our data provide preliminary evidence that low LDL-C may be associated with higher occurrence of PD, and/or that statin use may lower PD occurrence; either of which findings warrant further investigations. KeywordsParkinson's disease; LDL cholesterol; apolipoprotein E; statin; case control study Parkinson's disease (PD) is an age-related progressive neurodegenerative disorder affecting 1-2% of the population over the age of 60 years. The lifetime risk for PD is higher in men than in women. 1 Although a few PD cases are due to several known genetic mutations, the disorder is largely idiopathic, and likely involves interactions of the genome and the environment 2 .The role of apolipoprotein (APOE) in Alzheimer's disease (AD), another age-related neurodegenerative disease, has been elucidated in the past decade. It is generally believed that the ε4 allele is a major susceptibility gene, whereas the ε2 allele is protective for AD and possibly other neurological disorders see review 3 . A recent systematic review, however, Previous epidemiological evidence on dietary fats/cholesterol and PD risk has not been consistent. 10;11 Further, these studies are not directly relevant to the potential role of cholesterol in PD etiology, as non-dietary factors may play more important roles in regulating serum lipid levels. For example, the APOE ε4 allele has been associated with higher low density lipid cholesterol (LDL-C), whereas the ε2 allele has been consistently associated with lower plasma LDL-C. 12;13 Interestingly, there has been one published abstract reporting lower plasma cholesterol concentrations in PD patients than in controls. 14 Further, Musanti et al. 15 reported dramatically lower cholesterol biosynthesis in PD patients than in controls, although there has been no subsequent follow up on this association. The above evidence, coupled with the association between ε2 and PD, led us to test hypothesis that lower serum LDL-C may be ass...

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Section: Discussionmentioning

confidence: 96%

Lower low‐density lipoprotein cholesterol levels are associated with Parkinson's disease

et al. 2006

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“…Alternative underlying causal mechanisms linking statins to a reduced risk of POCD may include antithrombotic and anti-inflammatory effects, as well as beneficial effects on endothelial function 60. Statins further reduce beta amyloid levels—a hallmark of Alzheimer’s disease—and have been linked to a lower severity of Alzheimer’s disease pathology in observational studies 12.…”

Section: Discussionmentioning

confidence: 99%

Associations of dyslipidaemia and lipid-lowering treatment with risk of postoperative cognitive dysfunction: a systematic review and meta-analysis

Feinkohl

Winterer

Pischon

2018

J Epidemiol Community Health

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“…On average, statins can lower LDL cholesterol by 1.8 mmol/l (70 mg/dl), which translates into a 60% decrease in the number of ischemic heart diseases events and a 17% reduced risk of stroke after long‐term treatment (Wald et al 2003). Aside their lipid‐lowering properties (Endo et al 1976), pleiotropic effects of statins (George et al 2002) may exert neuroprotection as it has been extensively pointed out in the last two decades by using animal stroke models. On the top of these properties, statins increase the expression of the nitric oxide synthase (NOS), specifically its endothelial isoform (eNOS), which improves endothelial function and increases cerebral perfusion in the ischemic penumbra (Endres & Laufs 2004, Yamada et al 2000, Endres et al 1998).…”

Section: Pre‐ or Post‐treatment With Different Type Of Statin In Animentioning

confidence: 99%

Evidence for the efficacy of statins in animal stroke models: a meta‐analysis

García-Bonilla

Campos

Giralt

et al. 2012

Journal of Neurochemistry

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J. Neurochem. (2012) 122, 233–243. Abstract Protective effects of statins have been well documented for stroke therapy. Here, we used a systematic review and meta‐analysis to assess these evidences. We identified 190 studies using statin treatment in stroke animal models by electronic searching. From those, only studies describing ischemic occlusive stroke and reporting data on infarct volume and/or neurological outcome were included in the analysis (41 publications, 1882 animals). The global estimate effect was assessed by Weighted Mean Difference meta‐analysis. Statins reduced infarct volume by 25.12% (20.66%–29.58%, P < 0.001) and consistently, induced an improvement on neurological outcome (20.36% (14.17%–26.56%), P < 0.001). Stratified analysis showed that simvastatin had the greatest effect on infarct volume reduction (38.18%) and neurological improvement (22.94%), whereas bigger infarct reduction was observed giving the statin as a pre‐treatment (33.5%) compared with post‐treatment (16.02%). The use of pentobarbital sodium, the timing of statin administration, the statement of conflict of interest and the type of statin studied were found to be independent factors in the meta‐regression, indicating their influence on the results of studies examining statin treatment. In conclusion, this meta‐analysis provides further evidences of the efficacy of statins, supporting their potential use for human stroke therapy.

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Neuroprotective effects of statins may not be related to total and low-density lipoprotein cholesterol lowering

Cited by 11 publications

References 36 publications

Lower low‐density lipoprotein cholesterol levels are associated with Parkinson's disease

Lower low‐density lipoprotein cholesterol levels are associated with Parkinson's disease

Associations of dyslipidaemia and lipid-lowering treatment with risk of postoperative cognitive dysfunction: a systematic review and meta-analysis

Evidence for the efficacy of statins in animal stroke models: a meta‐analysis

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