Comparison Of Striatal Dat Availability Between The Groups
DAT availability for each striatal subregion in each group is shown in and . The PD-statin group had a significantly lower DAT availability in the anterior putamen compared to the PD-statin group . Propensity score-matched subsamples revealed that the PD-statin group still had more severely decreased DAT availability in the anterior , posterior , and ventral putamina than the matched PD-statin group . Multivariate linear regression analysis revealed that statin therapy was significantly and independently associated with more severely decreased DAT availability in the anterior putamen , posterior putamen and ventral putamen after adjusting for age at symptom onset, sex, disease duration, the presence of hypertension, diabetes mellitus, cardiac disease and ischaemic stroke, smoking status, BMI, total WMHs and total cholesterol levels . The absolute value of the standardized coefficients was the highest in the posterior putamen model. We determined that the generalized variance inflation factor and GVIF1/ of each variable was < 2, indicating that multicollinearity did not occur .
Design Setting And Participants
A prospective study including 38,191 men and 90,874 women participating in two ongoing US cohorts, the Health Professional Follow-up and the Nurses Health Study. Information on regular cholesterol lowering drug use was collected in 1994 in both cohorts via questionnaire. Relative risks and 95% confidence intervals were computed using Cox proportional hazards models adjusting for age, smoking, caffeine intake, duration of hypercholesterolemia, and other covariates.
Assessment Of Potential Covariates
Dietary intakes were assessed every four years with validated semi-quantitative food frequency questionnaires in both cohorts. 11 Information on age, weight, height, smoking status, elevated cholesterol, hypertension, diabetes, coronary heart disease, and use of ibuprofen was collected through biennial questionnaires. Body mass index was calculated as weight / height 2. Duration of hypercholesterolemia was estimated by summing use across the 2-year periods encompassed by the biennial questionnaires.
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Neurocrine Biosciences Submits Supplemental Nda For Valbenazine In The Treatment Of Huntington Disease Chorea
In addition to presenting data from the phase 3 KINECT-HD study of valbenazine in the treatment of chorea associated with Huntington disease, Neurocrines chief medical officer noted that the company recently submitted an sNDA to the FDA for the therapy.
In total, 214 of the 321 AEs identified in the trial were related to simvastatin. The proportion of related AEs associated with known adverse effects increased as the dose of simvastatin increased . Additionally, the most frequently observed common AE effect across all groups was myalgia . Notably, 6 of the 171 AEs reported by participants not taking active treatment occurred following simvastatin discontinuation of at least 6 days.
The a priori repeated measures model of MDS-UPDRS part III score while not taking medication, under superiority assumptions, showed a mean between-group difference of 2.74 at 12 months and 1.17 at 24 months. This prompted a post hoc blinded futility analysis of the 12-month change in MDS-UPDRS part III score, which indicated that the simvastatin group had deteriorated, on average, by 2.74 points more than the placebo group. However, in a superiority analysis, the between-group difference of the 12-month change in MDS-UPDRS part III score was not statistically significant .
Why Was Simvastatin Tested In People With Parkinsons
Finding existing drugs that are already approved and in use for other conditions that could be beneficial for Parkinsons is an approach known as drug repurposing.
If successful, repurposing could provide new treatments for Parkinsons much more quickly and cost-effectively than creating brand new treatments from scratch. There are many existing drugs that have potential for Parkinsons.
Previous research showed that statin use may lower the risk of developing Parkinsons. Lab studies suggested statin drugs may protect brain cells from damaging processes involved in Parkinsons. Simvastatin has also shown promise for slowing the progression of multiple sclerosis.
Claire Bale, Head of Research Communications & Engagement at Parkinson’s UK, said:
“These results are disappointing but mean we can now move on to focus on other promising opportunities to find new and better treatments for Parkinsons.
There are many new clinical trials on the way to test potential new therapies that aim to slow Parkinsons or improve symptoms. People can find opportunities to take part in research through our Take Part Hub and by signing up to our Research Support Network to get the latest news and opportunities by email.
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Statins May Reduce The Risk Of Parkinsons
Older adults who take a cholesterol-lowering drug known as a statin may have a lower risk of developing Parkinsons-like movement symptoms, according to an NIA-funded observational study published in Neurology. Fatty plaques in brain blood vessels have been linked to parkinsonism, an umbrella term for conditions that cause movement symptoms associated with Parkinsons disease. The researchers found that taking a statin was associated with improved brain blood vessel health and decreased parkinsonian signs in older adults.
Parkinsons is a serious nervous system disorder that affects less than 5% of the population however, approximately 30% of adults over age 65 have parkinsonism. People with parkinsonism experience movement symptoms seen in Parkinsons, including characteristic changes in gait, slowness of movement, tremor, and muscle stiffness. These undesirable symptoms can also increase the risk of falls, disability, and dementia.
This research was supported in part by NIA grants R01AG043379, R01AG047976, R01AG056352, R01AG017917, RF1AG022018, P30AG10161, and R01AG15819.
Simvastatin Fails To Demonstrate Disease
In a planned superiority analysis, the between-group difference of the 12-month change in MDS-UPDRS part III score was not statistically significant.
Findings from a randomized, double-blind, placebo-controlled study showed that simvastatin, a statin used to treat high cholesterol and triglyceride levels, was futile as a disease-modifying therapy for patients with moderate forms of Parkinson disease .1
The prespecified primary outcome, 24-month change in Movement Disorder Society Unified Parkinson Disease Rating Scale part III score, on average, worsened by an additional 1.52 points for those on simvastatin compared with placebo. According to the study investigators, these findings provide no evidence to support a phase 3 trial.
For the trial, lead author Kara N. Stevens, PhD, MSc, statistician, Exploristics, and colleagues recruited 235 participants aged 40 to 90 years with idiopathic PD, with a modified Hoehn and Yahr stage of 3.0 or less while taking medication, and taking dopaminergic medication with wearing-off phenomenon. Patients were allocated 1:1 to either simvastatin or matched placebo through a computer-generated random sequence, stratified by Hoehn and Yahr stage.
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The Evolution Of Treatment Options For Ms
When Dr. Mowry began working with people with MS in the mid 1990s, there was one FDA-approved treatment for the disease. Today there are almost 25 FDA-approved medications for MS that can help people manage symptoms and reduce the degree of long-term disability.
The early phases of MS are caused, we think, by the immune system causing injuries in the brain and the spinal cord, says Dr. Mowry. These injuries cause neurologic symptoms, such as vision loss and trouble with coordination, in addition to damaging nerves in the brain. The latter can be visible on MRI scans.
In the early stages of MS, medications can help reduce the number of these attacks and minimize damage to multiple areas of the brain. This type of early treatment is especially important in preventing severe disability that becomes more likely as the disease progresses. As damage to the nerves in the brain accumulates over time, it can lead to progressive MSan advanced stage of MS without any currently approved treatments.
Quantitative Analyses Of 18f
Quantitative analyses of 18F-FP-CIT PET data were performed according to the methods reported in our previous study. The striatum was divided into the anterior caudate, posterior caudate, anterior putamen, posterior putamen, ventral putamen and ventral striatum. DAT availability in each striatal subregion was defined as .
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Trial Design And Setting
This is a double-blind, randomised, placebo-controlled, multi-centre, parallel group trial in patients with PD of moderate severity. There are three embedded substudies. Participants are individually randomised in a 1:1 ratio to receive either oral simvastatin or matched placebo for 24 months. A 1-month low-dose phase is followed by a 23-month high-dose phase and treatment ends with a 2-month washout period. Recruitment took place between March 2016 and March 2018, with a target of at least 198 participants progressing successfully to the high-dose phase of the study 26-month follow-up of all participants is expected to be completed by May 2020. The trial design, including scheduled follow-up assessments, is summarised in .
AST/ALT monitoring outcomes and action required 6 weeks after temporary stop of study treatment
If the participant reports jaundice or new or unusually severe nausea, malaise or lethargy, an AST/ALT level should be checked . If study treatment needs to be stopped temporarily, AST/ALT should be checked again after 6 weeks, and then action taken in accordance with .
If the participant reports new or unusually severe muscle pain, tenderness or weakness, the CK level should be checked .
AEs may also be reported to the research team outside of a participants scheduled clinic visit, either by the participant, non-study clinician or other informant by contacting the trial centre.
Longitudinal Assessment Of The Changes In Leds
The Statin×Time interaction term in the linear mixed model was statistically significant after adjusting for age at symptom onset, sex, disease duration, DAT availability in the posterior putamen, the presence of hypertension, diabetes mellitus, cardiac disease and ischaemic stroke, smoking status, BMI, total WMHs, total cholesterol level, statin, time and statin×time, indicating that the PD-statin group needs 13.194 more LED annually than the PD-statin group.
In further analyses according to statin type, the PD-statin -L × time and PD-statin -H×Time interaction terms in the linear mixed model were both statistically significant , indicating that the PD-statin -L or PD-statin -H group requires 8.36 or 28.30 more LED annually than the PD-statin group, respectively.
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Statins May Speed Symptoms Of Onset Parkinson’s Disease In Some People
Statins may cause symptoms of onset Parkinsons disease to advance more quickly in those who are susceptible to the disease, according to a new study published in Movement Disorders.
Statins may cause symptoms of onset Parkinsons disease to advance more quickly in those who are susceptible to the disease, according to a new study published in Movement Disorders.
Researchers at Penn State College of Medicine investigated previous inconsistent research that suggested the use of statins could protect against Parkinsons disease while treating high cholesterol. The inconsistent results could be because of the 2 types of statinswater-soluble statins that cannot enter the brain, and fat-soluble statins that can.
One of the reasons that may have explained these prior inconsistent results is that higher cholesterol, the main indication to use statins, has been related to lower occurrence of Parkinsons disease, Xuemei Huang, professor of neurology, said in a statement. This made it hard to know if the statin protective effect was due to the drug or preexisting cholesterol status.
The results led the researchers to conclude that statin use and higher risk of Parkinsons disease are related, and the symptoms are more apparent following the use of the statin.
We are not saying that statins cause Parkinsons disease, but rather that our study suggests that statins should not be used based on the idea that they will protect against Parkinsons, concludes Huang.
Statins Cholesterol And Parkinson Disease
- LucaMascitelli, Medical Officer, Comando Brigata alpina Julia, Udine, [email protected]
- Luca Mascitelli, Udine, Italy Mark R Goldstein, Naples, FL
Editorialists Tan and Tan commented on the study by Lee et al. who evaluated the association between discontinuation of statin use and the incidence of Parkinson disease (PD. The editorialists caution against accepting on accepting a beneficial role of statins in PD. We suggest that continued statin use might represent a proxy for high cholesterol and absence of muscle complaints.
Patients with PD have been shown to have a dramatically lower cholesterol biosynthesis than controls , and it is likely that patients at higher short risk for PD discontinue statins because of lower cholesterol levels. Furthermore, an association between a diminished PD risk and moderate physical activity in preceding years has been reported. Statin use is associated with an increased likelihood of musculoskeletal condition diagnoses and therefore individuals on statin therapy who develop muscle complaints are more likely to both discontinue the drug and reduce exercise activity.
Finally, the autoimmune response against autoantigens may be beneficial in PD prevention, and regulatory T cells can suppress this beneficial response and promote the disease. Tregs, which have been found to increase with age and statin use, may prevent the beneficial local autoimmune response and increase the risk of PD.
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Trial Results Show Statin Drug Does Not Slow Parkinson’s
Simvastatin is a drug already used to lower cholesterol, and prevent heart attacks and strokes. Initial results from a major clinical trial show it doesn’t have potential to slow the progression of Parkinson’s as previously hoped.
Initial results from the PD-STAT trial show that, in comparison with a placebo , simvastatin was futile in slowing the rate of progression of Parkinsons.
PD-STAT examined whether simvastatin, a widely-used cholesterol-lowering drug, had the potential to reduce the rate of neurodegenerative decline in people with Parkinsons.
The 2 year trial funded by The Cure Parkinsons Trust was conducted at 23 hospitals across England, with 235 participants with moderate stage Parkinsons. Participants were randomly assigned to receive either simvastatin or a placebo for 2 years, followed by a final study assessment of their Parkinsons 2 months later.
Lifestyle Changes To Improve Outcomes
Dr. Shulman and Dr. Mowry also shared how making certain lifestyle changesincluding regular exercise, a healthy diet, and plenty of quality sleepcan help people with Parkinsons and MS.
Exercise
Research shows that a combination of aerobic exercise, muscle strengthening, and stretching has the power to improve outcomes, symptoms, and mobility for people living with Parkinsons and MS.
Right now, if you were to ask what intervention has the most evidence delay the progression of Parkinsons disease, that is exercise, Dr. Shulman says. What you find is that there is a huge difference in the number of connections in the motor pathwaysa huge difference in the survival of the neurons, the nerve cells in those pathwaysand I think thats what were seeing in our patients.
Based on smaller studies, exercise also appears to be beneficial for managing some MS symptoms that dont typically respond well to medication. These symptoms include fatigue, which is one of the major symptoms of MS, as well as depression and anxiety. Exercise also reduces insulin resistance , which in turn lowers the risk of health issues like diabetes and high blood pressureboth of which have been shown to accelerate damage to the brain.
Diet
While overall research is inconclusive, one study suggests that people who eat a Mediterranean-style dietincluding fruits, vegetables, and fish and avoiding red meat and fatty foodsmay have a lower risk for developing MS.
For example:
Sleep
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Statistical Methods And Assessment Of Homogeneity
On account of the low incidence of PD, the distinctions among RR, HR, and OR could be ignored . Therefore, we combined case-control and cohort studies and calculated the summary RRs and 95% CIs. We assessed heterogeneity among studies using the Cochrane’s Q test and I2 statistics. For the Q test, a p value < 0.10 was considered to indicate significant heterogeneity, while for I2, a value of 0%25% represented insignificant heterogeneity, a value > 25% but 50% represented low heterogeneity, a value > 50% but 75% represented moderate heterogeneity, and a value > 75% represented high heterogeneity . In cases of moderate heterogeneity, summary RRs were calculated using the random-effects model , which allowed each of the studies in the meta-analysis to estimate a different effect size. We used the results of the original studies from multivariate models with the most complete adjustment for potential confounders.
Publication bias was assessed by both the Begg’s rank correlation test and the Egger’s linear regression test, with p < 0.10 indicating statistical significance. Additionally, the funnel plot was applied.
Sensitivity analyses and subgroup analyses were performed. We conducted subgroup meta-analyses by the type of study design, the study region, the variables adjusted and the quality of studies.
To examine the association between individual statin use and the risk of PD, we calculated the pooled RRs from studies providing these particular data.
Statin Use And The Risk Of Parkinson’s Disease: An Updated Meta
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Contributed equally to this work with: Shuang Bai, Yi Song
Affiliation Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
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Contributed equally to this work with: Shuang Bai, Yi Song
Affiliation Department of Ultrasound, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
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Affiliation Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
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Affiliation Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
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Affiliation Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
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* E-mail:
¶ These authors also contributed equally to this work.
Affiliation Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
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* E-mail:
¶ These authors also contributed equally to this work.
Affiliation Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
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Stopping Criteria For Discontinuation Of Trial Treatment
The defined stopping criteria for the discontinuation of trial medication are:
Abnormalities in CK or ALT/AST fulfilling stopping criteria as outlined above, OR
New severe muscular symptoms , not attributable to other cause, which in the opinion of the PI may be related to the study medication even in the absence of abnormal CK, OR
Onset of a clinical condition for which prescription of a statin is indicated.