BACKGROUND: During aging, there is a progressive impairment of immune cell function that triggers the production of pro-inflammatory cytokines causing the so-called "inflammaging". Frailty represents a condition of increased vulnerability to stresses and reduced homeostatic reserve reflecting not only health status but also biological age. In older subjects without dementia, we showed that markers of inflammaging were differently associated with chronological age than with frailty. This study analysed the same markers in older people with cognitive decline and/or dementia. METHODS: The cohort consisted of 776 community-dwelling older people: 235 patients with mild cognitive impairment, 63 with Alzheimer's disease (AD), 175 with mixed dementia (MD), and 303 subjects without cognitive decline. Plasma concentrations of inflammatory cytokines and peripheral markers of neuroinflammation were analysed by next-generation ELISA. RESULTS: After adjustment for age, sex, frailty, education and Apolipoprotein E genotype, only interleukin-10, interleukin-1β, and neurofilament light chain were associated with the risk for AD and MD. Moreover, interleukin-6 showed a weak association only with AD. CONCLUSIONS: Our data showed similar associations between AD and MD, supporting the concept that late-onset dementia is a complex outcome of aging, intimately linked to the individual's health status as well as frailty.