Department of Neuropsychiatry, Neuroscience, Ehime University Graduate School of Medicine, Shitsukawa, Toon City, Ehime, 791-0295, Japan.
Department of Neuropsychiatry, Matsukaze Hospital, Shikokuchuo, Ehime, Japan.
Sci Rep. 2024 Mar 28;14(1):7374. doi: 10.1038/s41598-024-57922-1.
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.
近年来,神经炎症标志物与痴呆,尤其是阿尔茨海默病(AD)之间的关联引起了广泛关注。然而,血清 hs-CRP 与痴呆(包括 AD)之间的关系的证据并不一致。因此,本研究旨在探讨血清高敏 C 反应蛋白(hs-CRP)与痴呆(包括 AD)及脑 MRI 感兴趣区之间的关系。本研究共纳入了日本 8 个地区的 11957 名 65 岁及以上的社区居民(JPSC-AD 研究)。在应用排除标准后,对 10085 名接受血液检查和健康相关检查的参与者进行了分析。然后,根据临床截断值对血清 hs-CRP 水平进行分类,并计算每个血清 hs-CRP 水平下所有原因痴呆及其亚型的存在的比值比(OR)。此外,还使用同队列中 8614 名接受脑 MRI 检查的个体的协方差分析来检查血清 hs-CRP 与脑体积感兴趣区之间的关联。在多变量调整后,与 <1.0mg/L 相比,血清 hs-CRP 水平为 1.0-1.9mg/L、2.0-2.9mg/L 和 ≥3.0mg/L 的所有原因痴呆的 OR 分别为 1.04(95%CI 0.76-1.43)、1.68(95%CI 1.08-2.61)和 1.51(95%CI 1.08-2.11),血清 hs-CRP 水平为 1.0-1.9mg/L、2.0-2.9mg/L 和 ≥3.0mg/L 的 AD 的 OR 分别为 0.72(95%CI 0.48-1.08)、1.76(95%CI 1.08-2.89)和 1.61(95%CI 1.11-2.35)。与 <1.0mg/L 相比,血清 hs-CRP 水平为 1.0-1.9mg/L、2.0-2.9mg/L 和 ≥3.0mg/L 的所有原因痴呆和 AD 的患病率的多变量调整 OR 随着血清 hs-CRP 水平的升高而显著增加(趋势检验 p<0.001 和 p=0.001)。此外,随着血清 hs-CRP 水平的升高,多变量调整后的颞叶皮质体积/估计总颅内体积比显著降低(<1.0mg/L 4.28%、1.0-1.9mg/L 4.27%、2.0-2.9mg/L 4.29%、≥3.0mg/L 4.21%;趋势检验 p=0.004)。本研究结果表明,在日本社区居住的老年人群中,血清 hs-CRP 水平升高与痴呆(尤其是 AD)的发生风险增加以及颞叶皮质萎缩有关。