Serum high-sensitivity C-reactive protein and dementia in a community-dwelling Japanese older population (JPSC-AD)
Authors: Tachibana Ayumi , Iga Jun-ichi , Ozaki Tomoki , Yoshida Taku , Yoshino Yuta , Shimizu Hideaki , Mori Takaaki , Furuta Yoshihiko , Shibata Mao , Ohara Tomoyuki , Hata Jun , Taki Yasuyuki , Mikami Tatsuya , Maeda Tetsuya , Ono Kenjiro , Mimura Masaru , Nakashima Kenji , Takebayashi Minoru , Ninomiya Toshiharu , Ueno Shu-ichi ,   the JPSC-AD study group, Honda Takanori , Akiyama Masato , Nakaji Shigeyuki , Murashita Koichi , Sawada Kaori , Yokoyama Shintaro , Ishizuka Naoki , Akasaka Hiroshi , Terayama Yasuo , Yonezawa Hisashi , Takahashi Junko , Noguchi-Shinohara Moeko , Iwasa Kazuo , Yuki-Nozaki Sohshi , Yamada Masahito , Bun Shogyoku , Niimura Hidehito , Shikimoto Ryo , Kida Hisashi , Fukada Yasuyo , Kowa Hisanori , Nakano Toshiya , Wada Kenji , Kishi Masafumi , Ishikawa Tomohisa , Yuki Seiji , Fukuhara Ryuji , Koyama Asuka , Hashimoto Mamoru , Ikeda Manabu , Kokubo Yoshihiro , Uchida Kazuhiro , Esaki Midori , Tatewaki Yasuko , Thyreau Benjamin , Yonemoto Koji , Yoshida Hisako , Muto Kaori , Inoue Yusuke , Ri Izen , Momozawa Yukihide , Terao Chikashi , Kubo Michiaki , Kiyohara Yutaka 
Published: March 2024

In recent years, the association between neuroinflammatory markers and dementia, especially Alzheimer’s disease (AD), has attracted much attention. However, the evidence for the relationship between serum-hs-CRP and dementia including AD are inconsistent. Therefore, the relationships of serum high-sensitivity CRP (hs-CRP) with dementia including AD and with regions of interest of brain MRI were investigated. A total of 11,957 community residents aged 65 years or older were recruited in eight sites in Japan (JPSC-AD Study). After applying exclusion criteria, 10,085 participants who underwent blood tests and health-related examinations were analyzed. Then, serum hs-CRP levels were classified according to clinical cutoff values, and odds ratios for the presence of all-cause dementia and its subtypes were calculated for each serum hs-CRP level. In addition, the association between serum hs-CRP and brain volume regions of interest was also examined using analysis of covariance with data from 8614 individuals in the same cohort who underwent brain MRI. After multivariable adjustment, the odds ratios (ORs) for all-cause dementia were 1.04 (95% confidence interval [CI] 0.76–1.43), 1.68 (95%CI 1.08–2.61), and 1.51 (95%CI 1.08–2.11) for 1.0–1.9 mg/L, 2.0–2.9 mg/L, and ≥ 3.0 mg/L, respectively, compared to < 1.0 mg/L, and those for AD were 0.72 (95%CI 0.48–1.08), 1.76 (95%CI 1.08–2.89), and 1.61 (95%CI 1.11–2.35), for 1.0–1.9 mg/L, 2.0–2.9 mg/L, and ≥ 3.0 mg/L, respectively, compared to < 1.0 mg/L. Multivariable-adjusted ORs for all-cause dementia and for AD prevalence increased significantly with increasing serum hs-CRP levels (p for trend < 0.001 and p = 0.001, respectively). In addition, the multivariable-adjusted temporal cortex volume/estimated total intracranial volume ratio decreased significantly with increasing serum hs-CRP levels (< 1.0 mg/L 4.28%, 1.0–1.9 mg/L 4.27%, 2.0–2.9 mg/L 4.29%, ≥ 3.0 mg/L 4.21%; p for trend = 0.004). This study’s results suggest that elevated serum hs-CRP levels are associated with greater risk of presence of dementia, especially AD, and of temporal cortex atrophy in a community-dwelling Japanese older population.