AUTHOR=Zhang Ye , Tatewaki Yasuko , Nakase Taizen , Liu Yingxu , Tomita Naoki , Thyreau Benjamin , Zheng Haixia , Muranaka Michiho , Takano Yumi , Nagasaka Tatsuo , Taki Yasuyuki TITLE=Impact of hs-CRP concentration on brain structure alterations and cognitive trajectory in Alzheimer’s disease JOURNAL=Frontiers in Aging Neuroscience VOLUME=Volume 15 - 2023 YEAR=2023 URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2023.1227325 DOI=10.3389/fnagi.2023.1227325 ISSN=1663-4365 ABSTRACT=Present 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). We 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. Hs-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). Posthoc 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). Our 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.