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IntroductionPresent study was to investigate hs-CRP concentration, brain structural alterations, and cognitive function in the context of AD [Subjective cognitive decline (SCD), mild cognitive impairment (MCI), and AD].MethodsWe retrospectively included 313 patients (Mean age = 76.40 years, 59 SCD, 101 MCI, 153 AD) in a cross-sectional analysis and 91 patients (Mean age = 75.83 years, 12 SCD, 43 MCI, 36 AD) in a longitudinal analysis. Multivariable linear regression was conducted to investigate the relationship between hs-CRP concentration and brain structural alterations, and cognitive function, respectively.ResultsHs-CRP was positively associated with gray matter volume in the left fusiform (β = 0.16, pFDR = 0.023) and the left parahippocampal gyrus (β = 0.16, pFDR = 0.029). Post hoc analysis revealed that these associations were mainly driven by patients with MCI and AD. The interaction of diagnosis and CRP was significantly associated with annual cognitive changes (β = 0.43, p = 0.008). Among these patients with AD, lower baseline CRP was correlated with greater future cognitive decline (r = −0.41, p = 0.013).ConclusionOur study suggests that increased hs-CRP level may exert protective effect on brain structure alterations and future cognitive changes among patients already with cognitive impairment.