Morrison Laura, Dyer Adam H, Dolphin Helena, Batten Isabella, Reddy Conor, Widdowson Matthew, Woods Conor P, Gibney James, Bourke Nollaig M, Kennelly Sean P
Tallaght Institute for Memory and Cognition, Tallaght University Hospital, Dublin, Ireland.
Discipline of Medical Gerontology, School of Medicine, Trinity College Dublin, Ireland.
Brain Behav Immun Health. 2024 Sep 16;41:100862. doi: 10.1016/j.bbih.2024.100862. eCollection 2024 Nov.
Midlife cardiovascular risk factors such as Type 2 Diabetes (T2DM) and obesity are associated with the later development of cognitive impairment and dementia. Systemic inflammation is postulated as a crucial mechanism, yet there are few studies examining this at the earliest stages prior to overt cognitive impairment. To assess this, we recruited a cohort of middle-aged cognitively-unimpaired individuals with and without uncomplicated T2DM. Comprehensive neuropsychological assessment was performed at baseline and at 4-year follow-up. Ten serum chemokines and cytokines (Eotaxin, MCP-1, MIP-1β, CXCL10, IL-6, IL-10, IL12p70, IL-17A, IFN-γ and TNF-α) were measured at both baseline and follow-up using high-sensitivity assays. Overall, 136 participants were recruited including 90 with uncomplicated midlife T2DM (age 52.6 ± 8.3; 47% female) and 46 without (age 52.9 ± 8.03; 61% female). Cognitive trajectories were stable over time and did not differ with T2DM. Yet on cross-sectional analyses at both baseline and follow-up, greater circulating IL-17A was consistently associated with poorer performance on tests of executive function/attention (β: 0.21; -0.40, -0.02, p = 0.03 at baseline; β: 0.26; -0.46, -0.05, p = 0.02 at follow-up). Associations persisted on covariate adjustment and did not differ by T2DM status. In summary, we provide evidence that greater circulating IL-17A levels were associated with poorer executive function in midlife, independent of T2DM. Long-term follow-up of this and other cohorts will further elucidate the earliest stages in the relationship between systemic inflammation and cognitive decline to provide further mechanistic insights and potentially identify those at greatest risk for later cognitive decline.
中年心血管危险因素，如2型糖尿病（T2DM）和肥胖，与后期认知障碍和痴呆的发生有关。全身炎症被认为是一个关键机制，但在明显认知障碍出现之前的最早阶段，很少有研究对此进行考察。为了评估这一点，我们招募了一组中年认知未受损的个体，其中一些患有未并发的T2DM，另一些没有。在基线和4年随访时进行了全面的神经心理学评估。使用高灵敏度检测法在基线和随访时测量了10种血清趋化因子和细胞因子（嗜酸性粒细胞趋化因子、单核细胞趋化蛋白-1、巨噬细胞炎性蛋白-1β、CXCL10、白细胞介素-6、白细胞介素-10、白细胞介素12p70、白细胞介素-17A、干扰素-γ和肿瘤坏死因子-α）。总体而言，共招募了136名参与者，其中包括90名患有未并发中年T2DM的个体（年龄52.6±8.3；47%为女性）和46名未患T2DM的个体（年龄52.9±8.03；61%为女性）。认知轨迹随时间稳定，且与T2DM无关。然而，在基线和随访时的横断面分析中，循环中白细胞介素-17A水平较高始终与执行功能/注意力测试中的较差表现相关（基线时β：0.21；-0.40，-0.02，p=0.03；随访时β：0.26；-0.46，-0.05，p=0.02）。在进行协变量调整后，这种关联仍然存在，且不因T2DM状态而异。总之，我们提供的证据表明，循环中白细胞介素-17A水平较高与中年时较差的执行功能相关，与T2DM无关。对该队列和其他队列的长期随访将进一步阐明全身炎症与认知衰退之间关系的最早阶段，以提供进一步的机制见解，并有可能识别出后期认知衰退风险最大的人群。
