Abstract
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.
Highlights
Frailty is a complex geriatric syndrome associated, with biological vulnerability to stressors and decreased physiological reserve (Clegg et al, 2013)
The participants examined for eligibility numbered 1,114; in 14 of these, the frailty index (FI) could not be calculated due to missing data, and among these, 38 had no blood sample; so, 1,062 individuals were examined at baseline for reporting descriptive data
- Individuals with plasma HOcy concentrations in the top quintile (HOcy80) had five fewer frailty-free months (HR 1.487; 95% confidence interval (CI): 1.063–2.078); this finding was independent of age, sex, and education
Summary
Frailty is a complex geriatric syndrome associated, with biological vulnerability to stressors and decreased physiological reserve (Clegg et al, 2013). Several pathophysiological factors, including dysregulation of inflammatory processes, oxidative stress, mitochondrial dysfunction, and cellular senescence, underlie the frailty syndrome (Pansarasa et al, 2019), and it is influenced by other factors, such as sociodemographic characteristics, psychological conditions, nutritional status, lack of physical activity, and comorbidities (Dent et al, 2016) It remains unclear what drives frailty, and little is known about the biological factors that contribute to the development of the syndrome (Ho et al, 2011), the latter can reasonably be thought to include raised plasma levels of HOcy. High plasma HOcy is associated with several conditions and circumstances, including older age, an unhealthy lifestyle, a poor diet, MTHFR 677C3T polymorphism, drug consumption, folate (FO) or cobalamin deficiency, diabetes, impaired renal function, and inborn errors of metabolism, such as homocystinuria (Refsum et al, 2004). Total plasma HOcy has been shown to be inversely related to the intake and plasma levels of FO and B vitamins, and HOcy level is considered to be an indirect biomarker of the metabolic action of these vitamins (Green, 2008)
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