Table_1_Homocysteine, Folic Acid, Cyanocobalamin, and Frailty in Older People: Findings From the “Invece. Ab” Study.docx

Frailty is an important age-related syndrome associated with several adverse health outcomes. Its biological basis is undefined. Raised plasma homocysteine (HOcy) is an established risk factor for cardiovascular disease, dementia, cognitive impairment, and mortality, but little is known about the possible role of plasma HOcy, cyanocobalamin (B12), and folate (FO levels in the development of frailty. Our first aim was to explore the possible association between frailty and plasma concentrations of HOcy, FO, and B12 in a cohort of community-dwelling older people. The second was to assess the influence of these metabolic factors on six-year incidence of frailty in the 875 individuals eligible for inclusion in this study (those with a full follow-up dataset). This research is based on data from three waves – 2012 (herein taken as baseline), 2014, and 2018 – of a longitudinal study (InveCe.Ab) in which non-frail men and women born between 1935 and 1939 underwent multidimensional assessments. Frailty was estimated using a deficit accumulation-based frailty index (FI). HOcy concentration was significantly positively correlated with FI at all timepoints, while B12 and FO levels were not. Plasma concentration of HOcy emerged as a predictor of six-year cumulative incidence of frailty, independent of age, sex, and education, while B12 and FO levels showed no relationship with frailty incidence. Individuals with plasma HOcy in the top quintile showed five months less frailty-free survival (HR 1.487; 95% CI: 1.063–2.078), regardless of age, sex, and education. These results demonstrate that higher HOcy is a risk factor for frailty onset in older adults.

衰弱（frailty）是一种重要的年龄相关性综合征，与多种不良健康结局密切相关，但其生物学基础尚未明确。血浆同型半胱氨酸（homocysteine, HOcy）水平升高是公认的心血管疾病、痴呆、认知功能损害及死亡的危险因素，但目前对于血浆同型半胱氨酸、氰钴胺素（维生素B12, cyanocobalamin, B12）以及叶酸（folate, FO）水平在衰弱发生发展中的潜在作用仍知之甚少。本研究的首要目标是在社区居住的老年人群队列中，探讨衰弱与血浆同型半胱氨酸、叶酸及维生素B12浓度之间的潜在关联；第二项目标则是，在本研究符合纳入标准且拥有完整随访数据集的875名个体中，评估这些代谢因素对衰弱6年发病风险的影响。本研究的数据来自一项纵向队列研究（InveCe.Ab）的三轮随访数据，分别为2012年（本研究中将其作为基线）、2014年与2018年，该研究纳入了1935至1939年出生的非衰弱男性与女性，并对其开展多维度评估。衰弱通过基于缺陷累积的衰弱指数（frailty index, FI）进行测算。各时间点的血浆同型半胱氨酸浓度均与衰弱指数呈显著正相关，而维生素B12与叶酸水平则无此关联。血浆同型半胱氨酸浓度可作为衰弱6年累积发病风险的独立预测因素，不受年龄、性别与教育水平的影响；而维生素B12与叶酸水平与衰弱发病风险并无关联。血浆同型半胱氨酸处于最高五分位组的个体，其无衰弱生存时间较其他个体缩短5个月（风险比HR=1.487；95%置信区间CI：1.063~2.078），且该关联不受年龄、性别与教育水平的干扰。上述结果表明，血浆同型半胱氨酸水平升高是老年人衰弱发病的危险因素。