Effects of testosterone on cognition in young adult male rhesus monkeys

The relationships between testosterone (T) and cognitive function remain unclear. In men, associations between endogenous T levels and cognitive performance have not consistently been found and the effects of T treatment on cognition remain ambiguous: several studies have reported beneficial effects of T administration on cognitive function, but recent data indicate no effect or even detrimental effects of T. Studies in nonhuman primates may help resolve these discrepancies.We conducted the first study examining the activational effects of T on cognition in adult male nonhuman primates. Six young adult male rhesus monkeys (5-6 years old) were tested for 16 weeks on a battery of 4 memory tasks (1) when intact at baseline (winter); (2) when hypogonadal with add-back of T or placebo in a double blind cross-over design and (3) when intact following wash-out (summer phase). The cognitive tasks consisted of the Delayed Non-Matching-To-Sample (DNMS) with mixed delays, the spatial-Delayed Recognition Span Test (spatial-DRST) and the Delayed Response (DR) task. Following a 4-week baseline period, monkeys were treated with a gonadotropin releasing hormone (GnRH) agonist (Depot Lupron, 200 μg/kg) before being randomly assigned to one of 2 treatment groups: Lupron + testosterone enanthate (TE, 20 mg/kg) or Lupron + oil vehicle. In each treatment group, monkeys received Lupron + TE, or Lupron + oil, for 4 weeks before crossing over to the alternate treatment for an additional 4 weeks. After a 2 months wash-out period, monkeys were retested on the battery of tasks for an additional 4 weeks.T levels did not vary significantly between the winter and summer months of testing, indicating a lack of seasonal effect in these monkeys housed indoors. TE treatment yielded supraphysiological T levels decreasing progressively over 4 weeks. This treatment was associated with impaired recognition memory at the 600 s delay of the DNMS, suggesting compromised medial temporal lobe function, but had no effect on DR or spatial-DRST. Further studies are needed to determine whether T may enhance memory in aged male monkeys.     

Impairments in acquisition and reversals of two-choice discriminations by aged rhesus monkeys

The ability to learn and perform reversals of two object, two patterns, and one spatial discrimination was examined in eight aged (28–34 years), and four adult (8–13 years) behaviorally naive monkeys. As a group, the aged monkeys demonstrated significant difficulties in learning and reversing some of the visual discrimination problems, but had no difficulty learning or reversing the spatial discrimination. Additional analyses revealed that an impairment in learning an object discrimination by the aged monkeys was characterized by a prolonged period of chance performance, and the impairments in performing visual discrimination reversals was related to difficulties in two distinct stages of reversal learning. Despite age-related differences, there was considerable variability in performance among the aged monkeys. These experiments provide the first evidence of significant impairments in learning and reversing visual discriminations by aged monkeys that have not had prior exposure to complex behavioral tasks.     

Optimal dose and type of exercise to improve cognitive function in older adults: A systematic review and bayesian model-based network meta-analysis of RCTs

ObjectiveTo examine the dose-response relationship between overall and specific types of exercise with cognitive function in older adults.DesignSystematic Review and Bayesian Model-Based Network Meta-Analysis.Data sourcesSystematic search of MEDLINE, Web of Science, Scopus, PsycINFO and SPORTDiscus.Eligibility criteria for selecting studiesRandomized controlled trials of exercise interventions in participants aged 50 years or over, and that reported on at least one global cognition outcome.ResultsThe search returned 1998 records, of which 44 studies (4793 participants; 102 different effect sizes) were included in this review with meta-analysis. There was a non-linear, dose-response association between overall exercise and cognition. We found no minimal threshold for the beneficial effect of exercise on cognition. The estimated minimal exercise dose associated with clinically relevant changes in cognition was 724 METs-min per week, and doses beyond 1200 METs-min per week provided less clear benefits. We also found that the dose-response association was exercise type dependent, and our results show that clinically important effects may occur at lower doses for many types of exercise. Our findings also highlighted the superior effects of resistance exercises over other modalities.ConclusionsIf provided with the most potent modalities, older adults can get clinical meaningful benefits with lower doses than the WHO guidelines. Findings support the WHO recommendations to emphasise resistance training as a critical component of interventions for older adults.     

Sex steroids to maintain cognitive function in women after the menopause: A meta-analyses of treatment trials

It is still debated whether estrogen treatment after the menopause could result in improved cognitive function in women. This debate is based on many animal and cell culture data showing that estrogens can positively affect the aging brain. Observational data also show a halved risk of dementia in women who took estrogens around the age of menopause. However, large treatment trials have shown negative effects of long-term treatment with estrogens in older women. The present meta-analyses included 36 randomised treatment trials and tested various hypotheses which have been developed to attempt to explain discrepant data. Results indicated that, contrary to expectations, age of women and duration of time elapsed when treatment was initiated since menopause (‘window of opportunity’ hypothesis) did not significantly affect treatment outcome, nor did it matter whether women were symptomatic or not. It was not clear whether bilateral oophorectomy affected the outcome, as this effect was based on only a few studies from the same group and some observational studies show negative effects on cognition in surgical menopausal women treated with hormones for more than 10 years. Duration of treatment overall significantly affected outcome. More negative effects were seen in longer studies, where positive effects were mainly seen in short term studies (<4 months). Treatment with combined estrogens and progestagens also negatively affected the outcome. Whether women with symptoms should be treated for a couple of months or using other (intermittent) modes of treatment and whether this could have long-term positive consequences remains to be investigated.