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Neuropathologic evaluations quantified microglial burden in the hippocampus, amyloid beta (A\u03b2), tau tangles, and limbic age\u2010related transactive response DNA\u2010binding protein 43 (TDP\u201043) encephalopathy neuropathologic changes (LATE\u2010NC), and other common brain pathologies. Mixed\u2010effect and linear regression models examined the association of microglia with a decline in global and domain\u2010specific cognitive measures, and separately with brain pathologies. Path analyses estimated direct and indirect effects of microglia on global cognition.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULT<\/jats:title><jats:p>Hippocampal microglia were associated with a faster decline in global cognition, specifically in episodic memory, semantic memory, and perceptual speed. Tau tangles and LATE\u2010NC were independently associated with microglia. Other pathologies, including A\u03b2, were not related. Regional hippocampal burden of tau tangles and TDP\u201043 accounted for half of the association of microglia with cognitive decline.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>Microglia inflammation in the hippocampus contributes to cognitive decline. 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