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Risk of Multiple System Atrophy and the Use of Anti-Inflammatory Drugs: A Danish Register-Based Case-Control Study
Charlotte Starhof1, Anne-Mette Hejl2, Lise Korbo2
1Department of Neurology, Bispebjerg University Hospital, Copenhagen, Denmark, CSTA0096@regionh.dk.
Introduction:
Multiple system atrophy (MSA) is a rare rapidly progressive atypical Parkinson disorder presenting clinically with parkinsonism and/or a cerebellar syndrome in combination with dysautonomia. Severe neuroinflammation develops along with hallmark neuropathological changes, and as in Parkinson's disease, intake of anti-inflammatory medication has been hypothesized to be protective for development of disease. We aimed to investigate if use of non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs), low-dose aspirin, or statins were associated with a reduced risk of MSA.
Methods:
We performed a register-based case-control study in MSA (n = 155) cases and population controls (n= 7,750) matched on age, gender, and place of residency by risk-set sampling. Pharmacological exposure prior to diagnosis was assessed in 2 categories (user vs. nonuser, cumulated dose in tertiles [T1-T3]). In an unconditional logistic regression model, adjusted for age, gender, residency, and chronic obstructive pulmonary disease (COPD), we estimated ORs and 95% CIs.
Results:
Data suggested a trend towards non-aspirin NSAID use to be associated with a decreased risk of MSA (OR 0.72 [95% CI 0.49-1.06]) compared to nonusers, decreasing dose-dependently (T2 OR 0.77 [95% CI 0.43-1.38]; T3 OR 0.55 [95% CI 0.29-1.06]). However, data were based on small numbers. Use of statins and low-dose aspirin was not associated with a decreased risk of MSA. Results were lagged 5 years from index date to address reverse causation.
Conclusion:
A trend toward use of non-aspirin NSAID and an associated reduced risk of MSA was observed in this study. However, our analyses had limited statistical precision, and further studies including larger sample sizes and longer exposure periods are needed.
Insights
Non-aspirin NSAID use showed a trend toward reduced risk for Multiple System Atrophy (MSA), a rare Parkinsonian disorder. Further research with larger sample sizes is needed to confirm this association for neuroinflammation.
Area of Science:
- Neuroscience
- Pharmacology
- Epidemiology
Background:
- Multiple system atrophy (MSA) is a rare, rapidly progressive Parkinsonian disorder characterized by parkinsonism, cerebellar syndrome, and dysautonomia.
- Neuroinflammation is a key feature of MSA, similar to Parkinson's disease, prompting investigation into anti-inflammatory medications.
- Previous hypotheses suggest anti-inflammatory drug intake may be protective against neurodegenerative diseases.
Purpose of the Study:
- To investigate the association between the use of non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs), low-dose aspirin, or statins and the risk of developing MSA.
- To determine if specific pharmacological exposures correlate with a reduced risk of MSA.
- To explore potential neuroprotective effects of common anti-inflammatory and cholesterol-lowering medications in MSA.
Main Methods:
- A register-based case-control study involving 155 MSA cases and 7,750 population controls matched for age, gender, and residency.
- Pharmacological exposure (non-aspirin NSAIDs, low-dose aspirin, statins) was assessed prior to diagnosis, categorized as user vs. nonuser and by cumulative dose tertiles.
- Unconditional logistic regression models adjusted for age, gender, residency, and COPD were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).
Main Results:
- A trend suggested non-aspirin NSAID use was associated with a decreased risk of MSA (OR 0.72), with a dose-dependent effect observed (T3 OR 0.55).
- However, these findings were based on small numbers, limiting statistical precision.
- Use of statins and low-dose aspirin did not show a significant association with a reduced risk of MSA.
Conclusions:
- A trend towards reduced risk of MSA associated with non-aspirin NSAID use was observed.
- The study highlights the need for further investigation due to limited statistical power and small sample sizes.
- Larger sample sizes and longer exposure periods are required to definitively confirm or refute the potential protective role of non-aspirin NSAIDs in MSA.
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