Liu Longjian, Gracely Edward J, Zhao Xiaopeng, Gliebus Gediminas P, May Nathalie S, Volpe Stella L, Shi Jingyi, DiMaria-Ghalili Rose Ann, Eisen Howard J
Department of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, Philadelphia, PA, United States.
Department of Family, Community & Preventive Medicine, College of Medicine, Drexel University, Philadelphia, PA, United States.
Front Aging Neurosci. 2024 Apr 2;16:1361772. doi: 10.3389/fnagi.2024.1361772. eCollection 2024.
There is a scarcity of data stemming from large-scale epidemiological longitudinal studies focusing on potentially preventable and controllable risk factors for Alzheimer's disease (AD) and AD-related dementia (ADRD). This study aimed to examine the effect of multiple metabolic factors and cardiovascular disorders on the risk of cognitive decline and AD/ADRD.
We analyzed a cohort of 6,440 participants aged 45-84 years at baseline. Multiple metabolic and cardiovascular disorder factors included the five components of the metabolic syndrome [waist circumference, high blood pressure (HBP), elevated glucose and triglyceride (TG) concentrations, and reduced high-density lipoprotein cholesterol (HDL-C) concentrations], C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), factor VIII, D-dimer, and homocysteine concentrations, carotid intimal-medial thickness (CIMT), and urine albumin-to-creatinine ratio (ACR). Cognitive decline was defined using the Cognitive Abilities Screening Instrument (CASI) score, and AD/ADRD cases were classified using clinical diagnoses.
Over an average follow-up period of 13 years, HBP and elevated glucose, CRP, homocysteine, IL-6, and ACR concentrations were significantly associated with the risk of mortality in the individuals with incident AD/ADRD or cognitive decline. Elevated D-dimer and homocysteine concentrations, as well as elevated ACR were significantly associated with incident AD/ADRD. Elevated homocysteine and ACR were significantly associated with cognitive decline. A dose-response association was observed, indicating that an increased number of exposures to multiple risk factors corresponded to a higher risk of mortality in individuals with cognitive decline or with AD/ADRD.
Findings from our study reaffirm the significance of preventable and controllable factors, including HBP, hyperglycemia, elevated CRP, D-dimer, and homocysteine concentrations, as well as, ACR, as potential risk factors for cognitive decline and AD/ADRD.
针对阿尔茨海默病（AD）及AD相关痴呆（ADRD）的潜在可预防和可控风险因素，大规模流行病学纵向研究的数据较为匮乏。本研究旨在探讨多种代谢因素和心血管疾病对认知功能下降及AD/ADRD风险的影响。
我们分析了一组基线年龄在45 - 84岁的6440名参与者。多种代谢和心血管疾病因素包括代谢综合征的五个组分[腰围、高血压（HBP）、血糖和甘油三酯（TG）浓度升高、高密度脂蛋白胆固醇（HDL - C）浓度降低]、C反应蛋白（CRP）、纤维蛋白原、白细胞介素 - 6（IL - 6）、凝血因子VIII、D - 二聚体和同型半胱氨酸浓度、颈动脉内膜中层厚度（CIMT）以及尿白蛋白与肌酐比值（ACR）。使用认知能力筛查工具（CASI）评分定义认知功能下降，并通过临床诊断对AD/ADRD病例进行分类。
在平均13年的随访期内，HBP、血糖升高、CRP、同型半胱氨酸、IL - 6和ACR浓度与新发AD/ADRD或认知功能下降个体的死亡风险显著相关。D - 二聚体和同型半胱氨酸浓度升高以及ACR升高与新发AD/ADRD显著相关。同型半胱氨酸和ACR升高与认知功能下降显著相关。观察到剂量反应关系，表明暴露于多种风险因素的次数增加与认知功能下降或患有AD/ADRD个体的死亡风险更高相对应。
我们的研究结果再次证实了可预防和可控因素的重要性，包括HBP、高血糖、CRP、D - 二聚体和同型半胱氨酸浓度升高以及ACR，它们是认知功能下降和AD/ADRD的潜在风险因素。
