In absence of therapies targeting symptomatic dementia, better understanding of the biology underlying a cognitive decline is warranted. Here we present the results of a meta-analysis of the impact of osteoarthritis (OA) on cognitive decline and overall mortality. Across 7 independent datasets obtained in studies of populations in the USA, EU and Australia (NBER, NSHAP, TILDA, NACC, Kaiser Permanente, GRIM BOOKS, OAI, with a total of >7 × 107 profiles), OA cohorts demonstrated higher cognitive scores, later dementia onset as well as longer lifespan and lower age-specific all-cause mortality. Moreover, generalized OA with multiple localizations is associated with more significant reduction of mortality and dementia than a singly localized OA or no arthritis. In OA patients with younger ages, all-cause mortality was disproportionally reduced as compared to that in controls, while exponential term of Gompert'z hazard function was increased, accelerating mortality accrual at later ages. Up to 8-10% of poly-osteoarthritic patients are predicted and observed to reach centenarian lifespan, while in matched non-OA population the same benchmark is reached by less than 1% of patients. These results point at a possibility of life-extending and cognition preserving impacts of OA-conditioned immune system.