Association of Multi-Domain Factors with Cognition in the UK Biobank Study.

BACKGROUND: Dementia is a multifactorial syndrome attributable to a combination of vascular risk factors, lifestyle factors and neurodegeneration. However, little is known about the relative contribution of all these factors and their combined effects on cognition among the older population. OBJECTIVE: To examine the association of four domains of risk factors (sociodemographic, vascular risk factors, neuroimaging markers, lifestyle and psychosocial factors) with cognition in older adults. DESIGN: A cross-sectional study. SETTING: Data was obtained from a large-scale population-based study, UK Biobank study, at the first imaging visit assessment. PARTICIPANTS: Participants are citizen or permanent residents of UK, aged 60 years old and above. MEASURES: Cognitive function was assessed using the general cognitive ability score (g-factor score) derived from principal components analysis estimates of six cognitive tests. Associations with cognition were examined using multivariable linear regression for each domain and in combination. RESULTS: The study included 19,773 participants (mean age 68.5 ± 5.3 years SD, 9,726 (49%) male). Participants with lower cognitive scores (poorer cognition) were older, female, non-whites individuals, less educated and more socially deprived than participants with better cognitive scores. Participants with lower cognitive scores also tended to have higher vascular risk factors, lower brain volumes and more adverse lifestyle behaviours. The multivariable analysis found associations between adverse lifestyle and psychosocial factors with poorer cognition, i.e., being obese by measure of body fat percentage, having diabetes, higher white matter hyperintensity volume, increased sedentary screen time watching TV, being socially isolated and having depression were independently associated with poorer cognition. While larger hippocampal volume, having optimal sleep duration, adherence to a heathy diet, current and former alcohol drinking, increased wine consumption and sedentary screen time using a computer were associated with better cognition. CONCLUSION: A combination of adverse lifestyle and psychosocial factors were independently associated with poorer cognition in older adults. Findings in this study can potentially support public health communications to promote cognitive function and independence among older adults. This research has been conducted using the UK Biobank Resource under Application Number 71022.

Effects of co-trimoxazole, erythromycin, amoxycillin, tetracycline and chloroquine on sperm function in vitro.

This in-vitro study was designed to investigate the effects of commonly prescribed antibiotics on sperm movement characteristics, viability and the ability of spermatozoa to undergo the acrosome reaction. Spermatozoa were obtained by swim-up from normozoospermic semen and cultured for 24 h with increasing concentrations of co-trimoxazole, erythromycin, amoxycillin, tetracycline and chloroquine. Tetracycline at concentrations as low as 2.5 microg/ml led to a significant dose-dependent inhibition in percent rapid-moving spermatozoa, mean path velocity (VAP), straight-line velocity (VSL) and curvilinear velocity (VCL), but at 50 microg/ml tetracycline all spermatozoa were static. Erythromycin had significant effects on rapid movement, VAP, VSL and VCL only at concentrations >100 microg/ml. In contrast, percent rapid-moving spermatozoa was significantly enhanced at low concentrations of chloroquine (5 microg/ml), but significantly inhibited by higher concentrations. Co-trimoxazole did not adversely affect percent rapid-moving spermatozoa below 500 microg/ml, at which concentration movement was decreased by 34%. The mean lateral head displacement (ALH) was significantly enhanced by 5 microg/ml co-trimoxazole and reduced at 1 mg/ml erythromycin. The effects of these drugs were mostly irreversible. Amoxycillin had no effect on sperm movement characteristics over the dose range used, though it inhibited viability at high doses. Viability was significantly reduced at concentrations of all drugs which affect rapid sperm movement; these concentrations of drugs did not appear to affect the ability of spermatozoa to undergo the acrosome reaction. The results from this study, when combined with known effects on spermatogenesis, should facilitate the choice of drugs for the treatment of both genitourinary and unrelated infections in men who are attempting to conceive.

A bridge to intracytoplasmic sperm injection--high insemination concentrations benefit patients who have a reduced chance of fertilization with standard in-vitro fertilization.

This study was carried out to determine whether high insemination concentrations (HIC) could improve fertilization and pregnancy rates in patients who had either previously demonstrated poor fertilization rates in vitro using standard protocols (Group 1) or in whom a reduced chance of fertilization was indicated at semen assessment prior to in-vitro fertilization (IVF) (Groups 2 and 3). Forty nine patients were recruited for the study. Standard IVF was carried out in 1 ml volumes using 10(5) spermatozoa/ml. HIC treatment involved co-culture of spermatozoa and oocytes in microdroplets with insemination concentrations increased 10-50 fold higher than standard IVF. Fertilization and pregnancy rates were compared between standard IVF and HIC in individual patients either in consecutive cycles (Group 1) or using sibling oocytes in the same cycle (Group 2). Group 3 patients were treated with HIC for their first treatment cycle. HIC significantly improved the fertilization rate compared with standard IVF for Groups 1 (59.7 +/- 10.7 versus 19.6 +/- 5.4% respectively) and 2 (54.9 +/- 8.5 versus 34.0 +/- 8.5% respectively). HIC increased the pregnancy rate from 0% with standard IVF to 20% per embryo transfer in Group 1 patients. A single pregnancy derived from the transfer of HIC and IVF embryos occurred in Group 2. The fertilization rate (47.2 +/- 7.6%) and pregnancy rate (31.3% per embryo transfer) for Group 3 patients was higher than predicted. There was no increase in the rate of polyploidy with HIC. Provided there are sufficient numbers of motile spermatozoa, HIC may be offered as an initial form of treatment, thus permitting referral of only the poorest responders for intracytoplasmic sperm injection (ICSI).

Serum is more effective than albumin in promoting human embryo development and implantation.

OBJECTIVE: To compare the effects of serum with those of Albuminar-5 (Armour Pharmaceutical Co., Eastbourne, Sussex, United Kingdom) as medium supplements to Earl's balanced salt solution (EBSS) for IVF and subsequent embryo development. DESIGN: A retrospective study. Gametes and embryos from 318 patients were cultured in the presence of serum (group 1). Gametes and embryos from 130 patients were cultured in the presence of Albuminar-5 (group 2). Embryos obtained from IVF were replaced into the uterus within 48 hours after insemination. Surplus bipronucleate embryos were cultured up to 14 days with either serum or Albuminar-5. SETTING: Two tertiary referral fertility clinics; university teaching hospital. PATIENTS: Four hundred forty-eight patients with a wide spectrum of causes of subfertility, ranging in age from 24 to 43 years. MAIN OUTCOME MEASURES: Fertilization rate, pregnancy rate (PR), implantation rate, and surplus embryo development in vitro. RESULTS: The PR for group 1 patients was higher than that of group 2 (27.0% versus 15.4%, respectively). Although fertilization rates were identical in the two groups, cumulative embryo scores and implantation rates were significantly higher in group 1. There was no difference between the groups in age distribution, types of ovarian stimulation, numbers of patients with day 1 or day 2 transfers, or luteal phase support. Of 31 embryos cultured with serum, 54.8% reached the fully expanded blastocyst stage and 25.8% hatched. Of 19 embryos cultured with Albuminar-5, only 5.3% reached the fully expanded blastocyst stage and none hatched. CONCLUSIONS: The results suggest that, under certain conditions, serum supplementation yields better results than protein supplementation alone. The latter may be suitable only in conjunction with additional components.