Nonsteroidal <scp>Anti‐inflammatory</scp> Use and <scp><i>LRRK2</i></scp> Parkinson's Disease Penetrance
Bibliographic record
Abstract
Abstract Background The penetrance of leucine rich repeat kinase 2 ( LRRK2 ) mutations is incomplete and may be influenced by environmental and/or other genetic factors. Nonsteroidal anti‐inflammatory drugs (NSAIDs) are known to reduce inflammation and may lower Parkinson's disease (PD) risk, but their role in LRRK2 ‐associated PD is unknown. Objectives The objective of this study is to evaluate the association of regular NSAID use and LRRK2 ‐associated PD. Methods Symptomatic ("LRRK2‐PD") and asymptomatic ("LRRK2‐non‐PD") participants with LRRK2 G2019S, R1441X, or I2020T variants (definitely pathogenic variant carriers) or G2385R or R1628P variants (risk variant carriers) from 2 international cohorts provided information on regular ibuprofen and/or aspirin use (≥2 pills/week for ≥6 months) prior to the index date (diagnosis date for PD, interview date for non‐PD). Multivariate logistic regression was used to evaluate the relationship between regular NSAID use and PD for any NSAID, separately for ibuprofen and aspirin in all carriers and separately in pathogenic and risk variant groups. Results A total of 259 LRRK2‐PD and 318 LRRK2‐non‐PD participants were enrolled. Regular NSAID use was associated with reduced odds of PD in the overall cohort (odds ratio [OR], 0.34; 95% confidence interval [CI], 0.21–0.57) and in both pathogenic and risk variant carriers (OR Pathogenic , 0.38; 95% CI, 0.21–0.67 and OR RiskVariant , 0.19; 95% CI, 0.04–0.99). Similar associations were observed for ibuprofen and aspirin separately (OR Ibuprofen , 0.19; 95% CI, 0.07–0.50 and OR Aspirin , 0.51; 95% CI, 0.28–0.91). Conclusions Regular NSAID use may be associated with reduced penetrance in LRRK2 ‐associated PD. The LRRK2 protein is involved in inflammatory pathways and appears to be modulated by regular anti‐inflammatory use. Longitudinal observational and interventional studies of NSAID exposure and LRRK2‐PD are needed to confirm this association. © 2020 International Parkinson and Movement Disorder Society
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".