ABSTRACT
Background: Age-related cognitive decline is accelerated by vascular risk factors for cerebral small vessel disease. However, the association of vascular risk factors with cerebral small vessel disease contributing to the sex differences in cognitive decline remains unclear. Objectives: The purpose of this study was to evaluate sex differences in cognitive decline and the association between vascular risk factors and cognitive decline by sex. Methods: We used data from the UK Biobank (>55 years of age; n = 19,067) to assess cognitive tests (executive function, processing speed, and memory) while adjusting for baseline measurements to examine how vascular risk factors affect cognition. A univariate regression analysis was used to assess sex differences at the first time point (2014). A repeated measure analysis with a mixed effect model was used to determine cognitive decline (between 2014 and 2019). Any significant interaction between vascular risk factors and sex was investigated. Results: Females had lower scores in all 3 domains at the first cognitive tests (2014). We found a significant sex-by-time interaction over a 5-year period in matrix pattern completion (P = 0.03). After adjusting for vascular risk factors, this interaction was reduced (P = 0.08). High low-density lipoprotein, low education, and high blood pressure had a greater effect on the rate of cognitive decline in the executive function for females compared to males for the sex∗vascular risk factor interaction (P < 0.05). Conclusions: The rate of cognitive decline did not differ significantly between males and females. However, the impact of several vascular risk factors on cognitive decline was greater in females than in males.
ABSTRACT
BACKGROUND: T helper 17 (Th17) cells produce IL-17A cytokine and can exacerbate autoimmune diseases and asthma. The ß2 adrenergic receptor is a g protein-coupled receptor that induces cAMP second messenger pathways. We tested the hypothesis that terbutaline, a ß2-adrenergic receptor-specific agonist, promotes IL-17 secretion by memory Th17 cells in a cAMP and PKA-dependent manner. METHODS: Venous peripheral blood mononuclear cells (PBMC) from healthy human participants were activated with anti-CD3 and anti-CD28 antibodies. Secreted IL-17A was measured by enzyme linked immunosorbent assay, intracellular IL-17A, and RORγ were measured using flow cytometry, and RORC by qPCR. Memory CD3+CD4+CD45RA-CD45RO+ T cells were obtained by immunomagnetic negative selection and activated with tri-antibody complex CD3/CD28/CD2. Secreted IL-17A, intracellular IL-17A, RORC were measured, and phosphorylated-serine133-CREB was measured by western blotting memory Th cells. RESULTS: Terbutaline increased IL-17A (p < 0.001), IL-17A+ cells (p < 0.05), and RORC in activated PBMC and memory Th cells. The PKA inhibitors H89 (p < 0.001) and Rp-cAMP (p < 0.01) abrogated the effects of terbutaline on IL-17A secretion in PBMC and memory T cells. Rolipram increased IL-17A (p < 0.01) to a similar extent as terbutaline. P-Ser133-CREB was increased by terbutaline (p < 0.05) in memory T cells. CONCLUSION: Terbutaline augments memory Th17 cells in lymphocytes from healthy participants. This could exacerbate autoimmune diseases or asthma, in cases where Th17 cells are considered to be pro-inflammatory.