A large retrospective analysis of 190,308 propensity-matched participants found that long-term anti-inflammatory therapy (AIT) reduced the risk of developing major neurodegenerative diseases by 53% overall. The protective effects were consistent across Alzheimer's disease (60% reduction), Parkinson's (57% reduction), multiple sclerosis (75% reduction), and ALS (52% reduction), with benefits equally strong in both sexes. Immunomodulator drugs showed the greatest protective effect with an 81% risk reduction, while NSAIDs and corticosteroids provided more modest but significant benefits. The findings reinforce the growing understanding that chronic neuroinflammation drives multiple neurodegenerative pathways, suggesting shared inflammatory mechanisms across seemingly distinct diseases. Duration mattered critically—protection required sustained use, with benefits escalating from minimal effects under one year to 75% risk reduction after six years of treatment. This temporal relationship supports causation beyond mere correlation. However, important caveats temper enthusiasm: this retrospective observational design cannot establish definitive causation, and the study represents a preprint awaiting peer review, meaning results could change. The challenge lies in translating these population-level associations into practical prevention strategies while managing the well-known risks of chronic anti-inflammatory therapy.