This study investigates the relationship between systemic inflammation and cognitive decline in Alzheimer's disease (AD). Acute and chronic systemic inflammation, characterized by the production of tumor necrosis factor α (TNF-α), were found to be associated with increased cognitive decline in a prospective cohort of 275 community-dwelling subjects with mild to severe AD. The study used cognitive assessments and blood samples to measure TNF-α levels and systemic inflammatory markers. Acute systemic inflammatory events, which occurred in about half of the subjects, were associated with a 2-fold increase in the rate of cognitive decline over a 6-month period. High baseline levels of TNF-α were linked to a 4-fold increase in cognitive decline. Subjects with low TNF-α levels throughout the study showed no cognitive decline. The findings suggest that both acute and chronic systemic inflammation, particularly high baseline TNF-α levels, are significant factors in the progression of AD.This study investigates the relationship between systemic inflammation and cognitive decline in Alzheimer's disease (AD). Acute and chronic systemic inflammation, characterized by the production of tumor necrosis factor α (TNF-α), were found to be associated with increased cognitive decline in a prospective cohort of 275 community-dwelling subjects with mild to severe AD. The study used cognitive assessments and blood samples to measure TNF-α levels and systemic inflammatory markers. Acute systemic inflammatory events, which occurred in about half of the subjects, were associated with a 2-fold increase in the rate of cognitive decline over a 6-month period. High baseline levels of TNF-α were linked to a 4-fold increase in cognitive decline. Subjects with low TNF-α levels throughout the study showed no cognitive decline. The findings suggest that both acute and chronic systemic inflammation, particularly high baseline TNF-α levels, are significant factors in the progression of AD.