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相关，但其生物学机制尚未明确。血浆同型半胱氨酸（HOcy）升高是心血管疾病、痴呆、认知障碍及全因死亡的明确危险因素，但目前对于血浆HOcy、氰钴胺素（B12）及叶酸（FO）水平在衰弱发生发展中的潜在作用尚不清楚。本研究的首要目标是在社区居住老年人群队列中，探讨衰弱与血浆HOcy、叶酸（FO）及B12水平之间的潜在关联；次要目标是在本研究符合入组标准（即拥有完整随访数据集）的875名个体中，评估上述代谢因素对衰弱6年发病风险的影响。本研究的数据来源于纵向研究InveCe.Ab的三轮调查（2012年为本研究的基线随访、2014年及2018年），该研究纳入了1935至1939年出生的非衰弱男性及女性受试者，并对其进行了多维度评估。本研究采用基于缺陷累积的衰弱指数（FI）对衰弱状态进行评估。各随访时间点的HOcy浓度均与FI呈显著正相关，而B12及FO水平则无此关联。血浆HOcy浓度可独立于年龄、性别及教育水平预测衰弱的6年累积发病风险，而B12及FO水平与衰弱发病风险无显著关联。血浆HOcy处于最高五分位组的受试者，其无衰弱生存时间较其他组缩短5个月（风险比HR=1.487；95%置信区间CI：1.063–2.078），且该结果不受年龄、性别及教育水平的影响。上述研究结果表明，血浆HOcy水平升高是老年人群衰弱发生的危险因素。