Low Levels of Selenoprotein P Are Associated With Cognitive Impairment in Patients Hospitalized for Heart Failure

Abstract

Selenoprotein P (SELENOP) is a transporter for selenium and has been shown to protect selenium-status maintenance in the brain against deficiency and to support neuronal development, neurogenesis and neurocognitive function. Selenium deficiency has previously been associated with cognitive impairment in various populations, but no studies have been carried out in subjects with heart failure (HF). To explore whether SELENOP deficiency in subjects with acute HF is associated with cognitive impairment. Plasma SELENOP, as measured by an immunoassay analysis, is a well-validated marker of plasma selenium status and has the benefit of providing information on the bioavailable fraction of selenium to preferentially supplied cells equipped with receptors for SELENOP uptake. SELENOP was measured in 320 subjects hospitalized for HF. Of the subjects, 187 also underwent 4 cognitive tests assessing global cognitive function: Montreal Cognitive Assessment (MoCA); information processing (Symbol Digit Modalities Test [SDMT]); visual attention and task switching (Trailmaking Test A [TMT-A]); and executive speed (A Quick Test of Cognitive Speed [AQT] form and color). Appropriate cutoffs were used for each cognitive test to define cognitive impairment. Cross-sectional associations between SELENOP concentrations and cognitive impairment, as defined by each cognitive test, were explored using multivariable logistic models. Further, multivariable logistic models exploring associations between selenium deficiency, defined as the lowest quartile of SELENOP levels, and cognitive impairment, defined by each cognitive test, were carried out. The 187 participants had a mean age of 73 (± 11.9) years; 31% were female and had a mean body mass index of 28.1 (± 5.6) kg/m2. Each 1 standard deviation increment in SELENOP concentrations was associated with lower odds of cognitive impairment, defined as a MoCA cut-off score < 23 (odds ratio [OR] 0.60; 95% CI 0.40-0.91; P = 0.017). Further, SELENOP concentrations in the lowest quartile (≤ 2.3 mg/L) were associated with cognitive impairment as measured by MoCA (OR 3.10; 95% CI 1.38-6.97; P = 0.006), SDMT (OR 2.26; 95% CI 1.10-4.67; P = 0.027) and TMT-A (OR 3.40; 95% CI 1.47-7.88; P = 0.004) but not by AQT form and color. In subjects admitted for HF, higher SELENOP concentrations were associated with better performance on the MoCA test, reflecting global cognition, and SELENOP deficiency was associated with cognitive impairment as defined by 3 cognitive tests.