The effects of short-term low energy availability, achieved through diet or exercise, on cognitive function in oral contraceptive users and eumenorrheic women.

To date, no research has explored the effects of low energy availability on cognitive performance using dietary and exercise regimens relevant to athletes. Twenty female participants (10 eumenorrheic, 10 oral contraceptive [OC] users) completed three 3-day conditions: 1) controlled-balanced energy availability without exercise (BAL; 45 kcal·kg lean body mass [LBM]-1·day-1); 2) diet-induced low energy availability without exercise (DIET; 15 kcal·kg LBM-1·day-1); and 3) exercise-induced low energy availability (EX; 15 kcal·kg LBM-1·day-1, including 30 kcal·kg LBM-1·day-1 treadmill running at 70% maximal oxygen uptake). A cognitive test battery was completed before and after each 3-day condition. Mental rotation test accuracy improved in the BAL condition, but there was a decline in accuracy in the EX condition (BAL, +2.5%; EX, -1.4%; P = 0.042, d = 0.85). DIET (+1.3%) was not different to BAL or EX (P > 0.05). All other measures of cognitive performance were not affected by condition (P > 0.05) and OC use did not affect cognitive responses (P > 0.05). Accuracy in the mental rotation test was impaired when low energy availability was induced through increased exercise energy expenditure. All other aspects of cognition were unaffected by 3 days of low energy availability through diet or exercise. OC use did not mediate the effect of low energy availability on cognition. Novelty: Cognitive function was not affected by 3 days of diet-induced low energy availability. Only spatial awareness was impaired during 3 days of exercise-induced low energy availability. Reproductive hormones affected spatial awareness independent of energy availability.

Volatile organic compound markers of psychological stress in skin: a pilot study.

The forehead was studied as a possible sampling site for capturing changes in volatile organic compound (VOC) profiles associated with psychological-stress. Skin-VOCs were sampled with a polydimethylsilicone (PDMS)-coupon and the resulting VOCs were recovered and analysed with two-stage thermal desorption gas chromatography-mass spectrometry. Fifteen young adult volunteers (19 years-26 years) participated in two interventions run in a randomised crossover design. One intervention, termed 'Neutral', required the participants to listen to peaceful music, the other, termed a 'paced audio serial addition task', required the participants to undertake a series of rapid mental arithmetic calculations in a challenging environment that induced a stress response. Skin-VOC samples were taken during each intervention. The resultant data were processed with dynamic background compensation, deconvolved, and registered to a common retention index scale. The importance of freezing skin patch samplers to -80 °C was determined during the method development phase of this study. The cumulative distribution function of the GC-MS data indicates the possibility that PDMS-coupons are selective towards the lower volatility VOC components in skin. The frequency distribution of the GC-MS data was observed to be approximately log-normal, and on the basis of this study, a further two-orders of magnitude reduction in sensitivity may be required before the complete skin-VOC profile may be characterised. Multi-variate analysis involving Pareto-scaling prior to partial least squares discriminant analysis identified four VOCs with the highest probability of contributing to the variance between the two states, and the responses to these VOCs were modelled with principle components analysis (PCA). Two VOCs, benzoic acid and n-decanoic acid were upregulated (14 and 8 fold respectively) and appear to be PASAT sensitive, with areas under (AUC) their receiver operator characteristic (ROC) curves of 0.813 and 0.852 respectively. A xylene isomer and 3-carene were down regulated 75% and 97% respectively, and found to be predictive of the neutral intervention (ROC AUC values of 0.898 and 0.929 respectively). VOC profiles in skin appear to change with stress either due to increased elimination, elevated bacterial activity, or perhaps increased oxidative pathways.

Phytoestrogen consumption and risk for cognitive decline and dementia: With consideration of thyroid status and other possible mediators.

It is predicted that around 20% of the worlds population will be age 60 or above by 2050. Prevalence of cognitive decline and dementia is high in older adults and modifiable dietary factors may be able to reduce risk for these conditions. Phytoestrogens are bioactive plant chemicals found in soy, which have a similarity in structure to natural estradiol (the most abundant circulating estrogen). This structural likeness enables phytoestrogens to interact with estrogen receptors in the brain, potentially affecting cognition. However, findings in this domain are largely inconsistent, with approximately 50% of studies showing positive effects of phytoestrogens on cognition and the other half resulting in null/negative findings. This paper provides an updated review of the relationship between consumption of phytoestrogens and risk for cognitive decline and/or dementia. In particular, possible mediators were identified to explain discrepant findings and for consideration in future research. A case can be made for a link between phytoestrogen consumption, thyroid status and cognition in older age, although current findings in this area are very limited. Evidence suggests that inter-individual variants that can affect phytoestrogen bioavailability (and thus cognitive outcome) include age and ability to breakdown ingested phytoestrogens into their bioactive metabolites. Factors of the study design that must be taken into account are type of soy product, dosage, frequency of dietary intake and type of cognitive test used. Guidelines regarding optimal phytoestrogen dosage and frequency of intake are yet to be determined.

The effect of a paced auditory serial addition test (PASAT) intervention on the profile of volatile organic compounds in human breath: a pilot study.

This study sought to identify if detectable changes in human breath profiles may be observed following a psychological intervention designed to induce stress, a paced auditory serial addition test (PASAT). Breath samples were collected from 22 participants (10 male and 12 female) following a double cross-over randomized design with two experimental interventions. One intervention required participants to listen to classical music chosen to be neutral. The other intervention required participants to undertake a PASAT that induced cardiovascular responses consistent with acute stress. Both interventions also involved two sequences of cognitive function tests. Blood-pressure and heart-rate were recorded throughout each intervention and distal breath samples were collected onto Tenax® TA/Carbograph 1 thermal desorption tubes, using an adaptive breath sampler. Samples were collected before and after the PASAT. Breath samples were analysed by thermal desorption gas chromatography-mass spectrometry. Data registration using retention indexing and peak deconvolution followed by partial least-squares discriminant analysis identified six stress sensitive compounds. A principal components analysis model based on these components generated a model that predicted post-PASAT versus post-neutral intervention samples with a sensitivity of 83.3% and a selectivity of 91.6% for females, compared to 100% sensitivity and 90% selectivity for males. Of the six compounds indole, 2-hydroxy-1-phenylethanone, benzaldehyde, and 2-ethylhexan-1-ol were identified on the basis of mass spectral, retention indexing and confirmation against pure standards. 2-methylpentadecane was tentatively identified from mass spectral and retention indexing, whilst one component has yet to be assigned, although the mass spectrum is indicative of a terpene. Indole and 2-methylpentadecane concentrations increased in response to the PASAT intervention, while the other compounds reduced in their abundance in human breath, possibly as a result of ventilation effects.

Testosterone levels and cognition in elderly men: a review.

Average testosterone levels and many cognitive functions show a decline with age. There is evidence to suggest that this association is not just age related. Results from cell culture and animal studies provide convincing evidence that testosterone could have protective effects on brain function. Alzheimer's disease (AD) is characterised by brain pathology affecting cognitive function and AD prevalence increases with age. Testosterone levels are lower in AD cases compared to controls, and some studies have suggested that low free testosterone (FT) may precede AD onset. Men with AD may show accelerated endocrinological ageing, characterised by an earlier lowering of thyroid stimulating hormone, an earlier increase in sex hormone binding globulin (SHBG), a subsequent earlier decrease in FT and an earlier increase in gonadotropin levels in response to this. Positive associations have been found between testosterone levels and global cognition, memory, executive functions and spatial performance in observational studies. However, non-significant associations were also reported. It may be that an optimal level of testosterone exists at which some cognitive functions are improved. This may be modified with an older age, with a shifting of the optimal testosterone curve to maintain cognition to the left and a lower optimal level thus needed to be beneficial for the brain. Genetic factors, such as APOE and CAG polymorphisms may further interact with testosterone levels in their effects on cognition. The roles of SHBG, gonadotropins, thyroid hormones and estrogens in maintaining cognitive function and preventing dementia in men are also not completely understood and should be investigated further. Hypogonadal men do not seem to benefit from testosterone supplementation but small scale, short term intervention studies in eugonadal men with and without cognitive impairments have shown promising results. Larger randomised, controlled trials are needed to further investigate testosterone treatment in protecting against cognitive decline and/or dementia.

Modification of estrogen's association with Alzheimer's disease risk by genetic polymorphisms.

Contrasting effects of estrogen treatment on cognitive function and Alzheimer's disease (AD) risk have been reported. It may be that genetic factors modify these relations. In the present study, 696 participants from the Oxford Project to Investigate Memory and Ageing were included (355 AD cases, 341 controls). Those individuals with other types of dementia and those using hormone treatment had been excluded. Analyses controlled for body mass index, age at blood sampling, and education. Analyses of variance revealed main effects, but not an interaction, for apolipoprotein E (APOE) and Catechol-O-methyl transferase (COMT) genotypes on estradiol (E2) levels in men (p=0.003 and p=0.10, respectively), but not in women (p=0.82 and p=0.49, respectively). Men carrying the APOE ε4 allele had lower E2 levels, while those carrying the COMT Val/Val alleles had higher E2 levels compared to Met/Val (p<0.05) allele carriers. Higher estrone (E1) levels and carrying the APOE ε4 allele (but not COMT alone, or in combination with the APOE genotype) were independent risk factors for AD. Similar to earlier studies, the heterozygous COMT genotype (Met/Val) showed a synergistic effect with the APOE ε4 allele being non-significantly associated with lower cognitive function. In conclusion, the present study suggests that elevated E1 levels significantly increase AD risk in both men and women. However, interactions between APOE ε4 and genetic polymorphisms related to sex steroid metabolism and AD risk need to be further investigated.

The effects of exercise, heat, cooling and rehydration strategies on cognitive function in football players.

We investigated the cognitive effects of exercising in the heat on the field players of two football teams in a series of three matches. Different rehydration and cooling strategies were used for one of the teams during the last two games. Cognitive functions were measured before, during and immediately after each football match, as well as core temperature, body mass, plasma osmolality and glucose levels, allowing an estimate of their differential impacts on cognition. The pattern of results suggests that mild-moderate dehydration during exercise in the heat (up to 2.5%) has no clear effect on cognitive function. Instead, plasma glucose and core temperature changes appear to be the main determinants: higher glucose was related to faster and less accurate performance, whereas core temperature rises had the opposite effect. The 50% correlation between plasma glucose and core temperatures observed during exercise in the heat may help to stabilize cognitive performance via their opposing effects. The glucose-like effects of sports drinks appear to be mediated by increased plasma glucose levels, because drinks effects became non-significant when plasma glucose levels were added to the models. The cooling intervention had only a beneficial effect on complex visuo-motor speed.

Brain and cognition. Is there any case for improving cognitive function in menopausal women using estrogen treatment?

In the 1990s, estrogens were thought to protect the aging brain. Large randomized controlled studies, however, showed that estrogens did not treat dementia symptoms and even increased risk for dementia in older women. These findings contrast with earlier positive findings, including a wealth of cell culture and animal data all suggesting that estrogens could be a prophylactic treatment for dementia. Observational data had also suggested a significantly decreased risk for dementia in women who had been treated with estrogens for menopausal symptoms in midlife. This review discusses the "Critical Window", Healthy Cell Bias' and "Limited Duration" hypotheses, and forms of bias (healthy user, recall and survivor bias) and potential mediators (e.g., body mass, genetics) to attempt to explain the differences seen between the studies. On the basis of limited data, we conclude that estrogens only have limited positive effects on some tests for a number of months regardless of age. These effects were seen in recently menopausal women, but also in women with dementia, who are at least 15 years past the average age of menopause. In addition, after a longer period of time, treatment may confer risk, especially in older women. From this it would follow that longer term treatment with estrogens to maintain cognitive function is not indicated for older women. Whether there still is a case to treat surgical menopausal women with estrogens for a longer or shorter period of time remains to be tested.

Increasing testosterone levels and effects on cognitive functions in elderly men and women: a review.

Low testosterone (T) levels may predispose to Alzheimer disease (AD), but it is unclear whether this is a co-morbid effect due to cachexia, subclinical hyperthyroidism or other co-morbidity. The biological plausibility for potential protective effects of T on brain functions is substantial. In addition, higher levels of gonadotropins found in older cases with AD suggest that low levels of T are not due to brain degeneration and that the hypothalamic-pituitary-gonadal (HPG) axis is still intact. Men genetically at risk for AD were also already found to have lower levels of T. However, despite having lower levels of T, women do not show accelerated cognitive decline with age when compared to men. In addition, castration has not necessarily shown a decline in cognitive functions; some studies even found improvement of memory recall. Age may be an important factor when assessing optimal levels of T and several studies suggest that free or bioavailable T may be a better marker than total T levels when investigating associations of androgen activity with cognitive function. Small-scale T intervention trials in elderly men with and without dementia suggest that some cognitive deficits may be reversed, at least in part, by short term T supplementation. Age and prior hypogonadism may play an important role in therapy success and these factors should be investigated in more detail in future large scale randomized controlled studies. For elderly women, T treatment does not seem to have additional benefits over estrogen treatment for postmenopausal complaints and cognitive decline and may increase cardiovascular disease.

Low free testosterone is an independent risk factor for Alzheimer's disease.

The purpose of this study was to assess pituitary gonadotropins and free testosterone levels in a larger cohort of men with Alzheimer's disease (AD, n=112) and age-matched controls (n=98) from the Oxford Project to Investigate Memory and Ageing (OPTIMA). We measured gonadotropins (follicle stimulating hormone, FSH, and luteinizing hormone, LH), sex hormone binding globulin (SHBG, which determines the amount of free testosterone) and total testosterone (TT) using enzyme immunoassays. AD cases had significantly higher LH and FSH and lower free testosterone levels. LH, FSH and SHBG all increased with age, while free testosterone decreased. Low free testosterone was an independent predictor for AD. Its variance was overall explained by high SHBG, low TT, high LH, an older age and low body mass index (BMI). In controls, low thyroid stimulating hormone levels were also associated with low free testosterone. Elderly AD cases had raised levels of gonadotropins. This response may be an attempt to normalize low free testosterone levels. In non-demented participants, subclinical hyperthyroid disease (a risk factor for AD) which can result in higher SHBG levels, was associated with low free testosterone. Lowering SHBG and/or screening for subclinical thyroid disease may prevent cognitive decline and/or wasting in men at risk for AD.

The validity and reliability of 6 sets of clinical criteria to classify Alzheimer's disease and vascular dementia in cases confirmed post-mortem: added value of a decision tree approach.

Data from 204 participants from the Oxford Project to Investigate Memory and Ageing, who were diagnosed post-mortem using the histopathological criteria of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), were used to assess the validity of the clinical criteria for Alzheimer's disease (AD) of the 'National Institute of Neurological and Communicative Disorders and Stroke/the Alzheimer's Disease and Related Disorders Association' (NINCDS/ADRDA). Cases who had been diagnosed as NINCDS/ADRDA 'probable AD' in life were usually confirmed at autopsy, but half of the NINCDS/ADRDA 'negative' cases were not (low specificity). It was hypothesized that the overall clinical impression may have taken precedence over the use of the actual criteria. We therefore investigated the validity and reliability of the clinical criteria using a computerized 'dementia diagnosis system' for each of 6 sets of criteria [Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), NINCDS/ADRDA and three sets of criteria specifically for vascular dementia (VaD): NINCDS-AIREN, State of California Alzheimer's Disease Diagnostic and Treatment Centers (ADDTC), and Vascular Cognitive Impairment (VCI)] to classify a subset (n = 96) of the cases confirmed post-mortem. The use of the computerized system significantly (p = 0.01) increased the specificity (81%, similar to sensitivity) of the NINCDS/ADRDA diagnoses, which were shown to have 'moderate' inter-rater reliability. The DSM-IV criteria had good validity for AD when compared with post-mortem confirmation and showed 'substantial' inter-rater reliability. The ADDTC and VCI criteria for VaD had good specificity (88%) and sensitivity (75%), but only for one rater. The DSM-IV and NINCDS-AIREN criteria for VaD showed poor validity and inter-rater reliability. We conclude that the forced use of decision trees through a computerized system enhances the accuracy of the clinical diagnoses of dementia.