ADSA Foundation Scholar Award: New frontiers in calf and heifer nutrition-From conception to puberty.

Dairy calf nutrition is traditionally one of the most overlooked aspects of dairy management, despite its large effect on the efficiency and profitability of dairy operations. Unfortunately, among all animals on the dairy farm, calves suffer from the highest rates of morbidity and mortality. These challenges have catalyzed calf nutrition research over the past decade to mitigate high incidences of disease and death, and improve animal health, growth, welfare, and industry sustainability. However, major knowledge gaps remain in several crucial stages of development. The purpose of this review is to summarize the key concepts of nutritional physiology and programming from conception to puberty and their subsequent effects on development of the calf, and ultimately, future performance. During fetal development, developmental plasticity is highest. At this time, maternal energy and protein consumption can influence fetal development, likely playing a critical role in calf and heifer development and, importantly, future production. After birth, the calf's first meal of colostrum is crucial for the transfer of immunoglobulin to support calf health and survival. However, colostrum also contains numerous bioactive proteins, lipids, and carbohydrates that may play key roles in calf growth and health. Extending the delivery of these bioactive compounds to the calf through a gradual transition from colostrum to milk (i.e., extended colostrum or transition milk feeding) may confer benefits in the first days and weeks of life to prepare the calf for the preweaning period. Similarly, optimal nutrition during the preweaning period is vital. Preweaning calves are highly susceptible to health challenges, and improved calf growth and health can positively influence future milk production. Throughout the world, the majority of dairy calves rely on milk replacer to supply adequate nutrition. Recent research has started to re-evaluate traditional formulations of milk replacers, which can differ significantly in composition compared with whole milk. Transitioning from a milk-based diet to solid feed is critical in the development of mature ruminants. Delaying weaning age and providing long and gradual step-down protocols have become common to avoid production and health challenges. Yet, determining how to appropriately balance the amount of energy and protein supplied in both liquid and solid feeds based on preweaning milk allowances, and further acknowledging their interactions, shows great promise in improving growth and health during weaning. After weaning and during the onset of puberty, heifers are traditionally offered high-forage diets. However, recent work suggests that an early switch to a high-forage diet will depress intake and development during the time when solid feed efficiency is greatest. It has become increasingly clear that there are great opportunities to advance our knowledge of calf nutrition; yet, a more concentrated and rigorous approach to research that encompasses the long-term consequences of nutritional regimens at each stage of life is required to ensure the sustainability and efficiency of the global dairy industry.

Longitudinal assessment revealed the shifts in rumen and colon mucosal-attached microbiota of dairy calves during weaning transition.

The objectives of this study were to investigate the shifts in rumen and colon mucosa-associated microbiota in dairy calves fed a high milk replacer feeding rate before and after weaning and to determine whether such shifts are associated with tissue physiological measures. Longitudinal biopsy was performed to collect rumen and colon mucosal tissues of 4 ruminally cannulated Holstein dairy bull calves (weaned at 6 wk of age) at the end of wk 5 (before weaning), 7 (weaning adaptation) and 12 (after weaning), and were used to assess mucosa-associated microbiota and their changes using amplicon sequencing. Both rumen and colon mucosa-associated bacterial communities shifted during the weaning process, as evidenced by their clear separation among 3 different weaning periods and increased α diversity (Shannon and Chao1 indices) during weaning transition. Among the 3 dominant bacterial phyla identified (relative abundance >1.0%), the relative abundance of Proteobacteria and Bacteroidetes decreased in the rumen mucosa, whereas the relative abundance of Firmicutes increased in both rumen and colon mucosa during weaning transition. In the rumen mucosa, Campylobacter (0.6-22.1%) gradually became prevalent during weaning transition, whereas Succinivibrio (6.2-10.3%) and Prevotella 1 (4.7-10.5%) were dominant regardless of weaning transition. In the colon mucosa, Bacteroides (12.8-25.4%) was dominant during weaning transition, although its relative abundance decreased after weaning. In the meantime, relative abundance of uncultured Lachnospiraceae increased from 2.2% to 25.7% during this period. In addition, genera Pyramidobacter (in the rumen mucosa) and Lachnoclostridium (in the colon mucosa) were positively correlated with rumen papilla surface area and colon mucosal thickness, respectively. Moreover, genera Ruminococcaceae UCG-005 and Sharpea in the rumen mucosa were positively correlated with the molar proportion of propionate and butyrate, respectively. Overall, our findings revealed that rumen and colon mucosa-associated bacterial communities altered in response to the weaning transition, and some bacterial taxa in these communities may have positive effects on rumen and colon mucosa development during this period.

Preweaning to postweaning rumen papillae structural growth, ruminal fermentation characteristics, and acute-phase proteins in calves.

This study evaluated pre- to postweaning ruminal structural development, fermentation characteristics, and acute-phase protein levels in calves with a high milk replacer (MR) feeding rate prior to weaning. Six ruminally cannulated Holstein bull calves were fed MR (150 g/L) at 15% of body weight (BW) in 2 equal volumes daily. Volumes were adjusted weekly based on BW. Calves were weaned using a 1-step weaning method, with MR decreased by 50% at the end of wk 5 and full weaning at the end of wk 6. Calf starter, chopped straw, and water were offered ad libitum. Intake was recorded daily, and BW was recorded weekly. From wk 5 to 12, ruminal pH was continuously measured using a ruminal pH bolus. Ruminal fluid was collected weekly from wk 5 to 12 for measurement of short-chain fatty acid concentrations and quantification of total bacteria and protozoa. Rumen papillae were obtained at wk 5, 6, 7, 8, and 12 for histological analysis. Serum amyloid A and lipopolysaccharide-binding protein were measured weekly. Data were analyzed using GLIMMIX procedure of SAS (SAS Institute Inc., Cary, NC), with week as a fixed effect and calf as a random effect. During the weaning step-down, starter intake was 3-fold higher and continued to increase until wk 12. Body weight increased from birth to wk 12; however, BW did not change during wk 6, 7, and 8, possibly due to low metabolizable energy intake caused by the weaning strategy. Preweaning ruminal pH was below 5.8 for approximately 936.3 ± 125.99 min/d, implying ruminal acidosis. Furthermore, ruminal pH below 5.8 reached a peak at wk 8 with 1,203.9 ± 227.65 min/d below pH 5.8 and slowly decreased to 388.1 ± 189.82 min/d below pH 5.8 at wk 12. Papillae surface area, length, and width increased during wk 12 compared with wk 5. Corneum thickness increased by week, whereas spinosum/basale thickness only increased during wk 8 compared with wk 5. The acute-phase protein concentration was highest at wk 1 and then decreased and remained constant until wk 12. In conclusion, even before step-down weaning, calves experienced ruminal acidosis despite low starter intake. Further, the observed prolonged ruminal pH depression suggests that dietary rumen adaptation after weaning can take several weeks in calves with a high MR feeding rate preweaning. The prolonged depressed ruminal pH did not affect acute-phase proteins and this finding, along with the other results, suggests that rumen epithelium barrier integrity is not compromised during weaning.

Oligosaccharide concentrations in colostrum, transition milk, and mature milk of primi- and multiparous Holstein cows during the first week of lactation.

The objective of this study was to characterize the oligosaccharide (OS) profile of colostrum and transition milk from primiparous (Pp, n = 10) and multiparous (Mp, n = 10) Holstein cows. The experiment was conducted on a commercial dairy farm, where cows were assigned to the study at calving. Colostrum (milking 1) was collected at 5.3 ± 0.7 h after parturition, followed by collection of milkings 2 through 6, milkings 8, 10, 12, and 14 at 0500 and 1600 h each day. Samples were analyzed for OS concentrations using liquid chromatography-mass spectrometry and for IgG and milk components. Concentration of IgG was highest in colostrum and milking 2. Colostral IgG concentration was less in Pp cows than in Mp cows (82.1 ± 3.1 vs. 106.1 ± 16.2 mg/mL). Colostrum and milkings 2 and 3 had 3'-sialyllactose and 6'-sialyllactose concentrations greater than those of mature milk (milkings 8+). For colostrum and milking 2, 6'-sialyllactosamine concentrations were higher than all other milkings, while disialyllactose was only higher in colostrum. In addition, 3'-sialyllactose was the most abundant OS in colostrum and milkings 2 and 3 compared with all other OS. A parity difference was observed for 6'-sialyllactosamine, with Mp having a higher concentration over the first 7 d in milk than Pp (46.4 ± 8.7 vs. 16.9 ± 3.2 µg/mL). Similar results were observed between milkings for OS yields. Parity differences were detected for 3'-sialyllactose, 6'-sialyllactose, and 6'-sialyllactosamine yield, with Mp yield being greater than Pp over the first 7 d in milk. These findings demonstrate that colostrum and transition milk contain elevated concentrations of certain OS compared with mature milk and suggest further research should be conducted regarding the potential benefits of OS in colostrum and transition milk when fed to newborn calves.

Effect of amount of milk replacer fed and the processing of corn in starter on growth performance, nutrient digestibility, and rumen and fecal fibrolytic bacteria of dairy calves.

The aim of this study was to evaluate effects of milk replacer (MR) feeding rate and processing of corn in calf starter (CS) on growth performance, nutrient digestibility, and rumen and fecal fibrolytic bacteria in dairy calves. Holstein male calves (n = 48, 2-3 d of age) were randomly assigned to 1 of 4 treatments with a 2 × 2 factorial arrangement of MR level of 0.749 kg of MR/d (LO) or up to 1.498 kg of MR/d (HI); and whole corn or flaked corn in textured CS. Calves were weaned by reducing MR offered by 50% during wk 6. Intakes of MR and CS were recorded daily, whereas body weight (BW) was measured weekly. Rumen fluid and fecal matter were collected at wk 5 and 8 to quantify fibrolytic bacteria and nutrient digestibility. Data were analyzed as a completely randomized design using mixed model ANOVA. Repeated measures were used as appropriate. Calves fed HI had greater average daily gain than calves fed LO at wk 2, 3, 4, and 5, yet at wk 7 calves fed HI had lower average daily gain compared with calves fed LO. Starter intake was greater for calves fed LO compared with HI at wk 4, 5, 6, and 7. During wk 5 and 8, calves fed LO had increased ADF and NDF digestibility compared with calves fed HI. During wk 5, dry matter and organic matter digestibility were lower for LO-fed calves compared with HI-fed calves, but during wk 8 the opposite was observed, with HI-fed calves having lower dry matter and organic matter digestibility than LO-fed calves. At wk 5, Clostridium cluster IV and Butyrivibrio fibrisolvens proportions in rumen fluid tended to be higher and Clostridium cluster IV, Fecalibacterium sp., and Prevotella sp. proportions in fecal matter were higher in calves fed LO compared with HI. From wk 8 to 16, dry matter intake was unaffected by treatment; however, energy efficiency was greater in calves fed LO, causing LO calves to have higher BW gain during this period. Greater starter digestibility was observed for calves fed LO versus HI in concert with increased fibrolytic bacteria proportions (wk 5) in fecal and rumen samples, which resulted in greater postweaning BW gain and similar BW and frame measurements by 16 wk of age. Overall the results show that rate of MR feeding has a larger effect than the processing of corn in CS on performance, fiber digestibility, and rumen and fecal fibrolytic bacterial communities.

Technical note: The development of a methodology for ruminal and colon tissue biopsying of young Holstein dairy calves.

The objectives of this study were to develop a methodology for biopsying the rumen and colon of young dairy calves and to collect suitable quality tissue samples for microscopic and gene expression analysis. Six Holstein dairy bull calves (45.0 ± 1.5 kg birth weight) were ruminally cannulated during the second week of life and weaned at the end of wk 6. Ruminal and colon tissue samples were collected at the end of wk 5, 6, 7, 8, and 12. Calves were not sedated but were restrained in a chute for sampling. The endoscope (100 cm length, 9.8 mm diameter) was introduced through the rumen cannula to harvest ruminal tissue. Endoscopic biopsies of the rumen with endoscopic biopsy forceps were unsuccessful 85% of the time because they were unable to shear the ruminal tissue. Thereafter, an Allis clamp was used to retrieve the blind sac through the rumen cannula to perform direct tissue biopsying with surgical scissors. To biopsy the colon, the lubricated distal tip of an endoscope was slowly inserted into the calf's anus. A total of 6 colon tissue samples (12.6 ± 0.74 mg) were collected per calf per time point from the distal colon 30 to 40 cm from the calf's anus using endoscopic biopsy forceps, which were inserted through the instrument channel. A new forcep was used between sites and calves. Between calves, the outside of the endoscope was washed with 4% chlorohexidine and rinsed with water and the instrument channel was washed with distilled water and 70% ethanol. Colon and ruminal samples were processed for histological measurements, and RNA was isolated and sequenced. High-quality RNA (RNA integrity number 8.8 ± 0.08) was collected from samples, and light and electron microscopy was performed on samples. In conclusion, endoscopic biopsying can be used for tissue harvest in the colon of young calves. However, it was found that collecting ruminal tissue by retracting the rumen from the cannula and taking samples with surgical scissors was more successful than an endoscopic biopsy. This method allows for tissue collection of the same animal throughout time, which can help the research community investigate the effect of weaning regimens, feed rations, and age on the structure and function of the gastrointestinal tract.

The effect of tube versus bottle feeding colostrum on immunoglobulin G absorption, abomasal emptying, and plasma hormone concentrations in newborn calves.

The objective of this study was to determine if feeding colostrum to newborn calves through an esophageal tube, compared with a nipple bottle, would delay abomasal emptying, which would in turn decrease passive transfer of IgG and plasma glucose, insulin, and glucagon-like peptide (GLP) 1 and GLP-2 concentrations. Twenty newborn Holstein bull calves were fed 3 L of colostrum replacer (200 g of IgG) through either an esophageal tube or nipple bottle at 2 h after birth followed by feeding pooled whole milk every 12 h after birth. Acetaminophen was mixed into the colostrum meal as a marker for abomasal emptying. A jugular catheter was inserted 1 h after birth and blood was sampled frequently to analyze serum for IgG and acetaminophen and plasma for glucose, insulin, GLP-1, and GLP-2. Feeding method did not affect abomasal emptying, and as a result no treatment effect was present on serum IgG concentrations. Maximum concentration of serum IgG was 24.4 ± 0.40 mg/mL (± standard error), which was reached at 14.6 ± 1.88 h after the colostrum meal for both groups. Apparent efficiency of absorption at maximum concentration of IgG was 52.9%, indicating high efficiency of passive transfer of IgG for both treatments. Tube feeding increased glucose and insulin area under the curve before the first milk meal, most likely due to the decreased time to consume the colostrum meal. In addition, tube-fed calves consumed 0.5 ± 0.13 L more milk in their first milk meal than bottle-fed calves. No treatment effect on plasma concentrations of GLP-1 or GLP-2 was present, but both hormones increased after colostrum feeding. These findings confirm that there is no effect on absorption of IgG from colostrum when feeding good-quality colostrum at a volume of 3 L through either an esophageal tube or nipple bottle.

WITHDRAWN: Dehydroepiandrosterone (DHEA) supplementation for cognitive function.

BACKGROUND: In view of the theoretical rationale for beneficial effects of DHEA and DHEAS on cognitive function in ageing and dementia, we have undertaken a thorough investigation of well-conducted studies in this area. This will provide a basis for confirmation of any effect of DHEA/S administration in humans in properly controlled trials. The review will also provide a scientific basis for effective dosage, acceptable route and duration of administration, and side effect profiles. This review is especially pertinent at this time as DHEA is currently being sold in large quantities in health food stores, particularly in the USA. In some cases the recommended dose is different for men and women (50mg/day for men and 25mg/day for women) and the basis for this recommendation needs to be explored. OBJECTIVES: To establish whether administration of DHEA, or its sulphate, DHEAS, improves cognitive function or reduces the rate of decline of cognitive function in normal older adults or in individuals with dementia. SEARCH STRATEGY: Relevant electronic databases, journals, personal communications and conference abstracts were searched for randomised controlled trials investigating the effects of DHEA/S on cognition in older adults. SELECTION CRITERIA: All relevant randomised controlled trials of DHEA/S were considered for inclusion in the review. DATA COLLECTION AND ANALYSIS: Data for the specified outcomes were independently extracted by two reviewers (FAH & JvN) and cross-checked. Any discrepancies were discussed and resolved. No data pooling was undertaken owing to the lack of availability of the relevant statistics. MAIN RESULTS: There are four included studies, three cognition in normal older people, and Barnhart 1999 in perimenopausal women with decreased well-being. There were no studies in dementia. There were a few significant findings. Wolf 1997 found significant improvement following DHEA compared with placebo in both immediate recall (MD 0.8, 95% CI 0.16, 1.44) and delayed recall (MD 0.9, 95% CI 0.09, 1.71) of a visual memory test in women, estimated in a crossover trial after 2 weeks of treatment with each of DHEA and placebo. However there was no significant improvement in men, nor a significant effect on a verbal memory test. There was also no significant effect on four other cognitive tests. Wolf 1998 (2) found that placebo group performance deteriorated significantly on a test of selective attention following a psychosocial stressor (p<0.05), while deterioration was not evident in the DHEA group (p=0.85) after two weeks of treatment. However, when compared to placebo, DHEA produced a significant impairment on a visual memory test (p<0.01) following the stressor. No significant effect was found on a third cognitive task. Effects were not found on tasks when administered in the absence of a stressor. Barnhart 1999 employed three cognitive measures and found no significant effect of DHEA compared with placebo at 3 months. Findings to date suggest that DHEA replacement seems to be well tolerated with an absence of significant side-effects. AUTHORS' CONCLUSIONS: The data offer no support at present for an improvement in memory or other aspects of cognitive function following DHEA treatment in normal older people. In view of the growing public enthusiasm for DHEA supplementation, particularly in the USA, and the possibility that any neuroprotective effect of DHEA/S may only be evident in the long term, there is a need to undertake high quality trials in which the duration of DHEA treatment is longer than one year, and the number of participants is large enough to detect effects if they exist.Recently, trials of DHEA supplementation in Alzheimer's Disease (USA), post-menopausal women (USA), normal older men (UK), and a one-year trial in normal older men and women (France) have been completed. As soon as the results are available these studies will be included in the review.

Dehydroepiandrosterone (DHEA) supplementation for cognitive function in healthy elderly people.

BACKGROUND: In view of the theoretical possibility of beneficial effects of DHEA or DHEAS in retarding age-associated deterioration in cognitive function, we have reviewed studies in this area. OBJECTIVES: To establish whether administration of DHEA, or its sulphate, DHEAS, improves cognitive function or reduces the rate of decline of cognitive function in normal older adults. SEARCH STRATEGY: Trials were identified from a last updated search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 10 October 2005 using the terms dhea*, prasterone, dehydroepiandrosterone*. In addition MEDLINE, EMBASE, PsycINFO and CINAHL were searched to find trials with volunteers who had no or minor memory complaints. Relevant journals, personal communications and conference abstracts were searched for randomized controlled trials investigating the effects of DHEA/S on cognition in older adults. SELECTION CRITERIA: All randomized placebo-controlled trials enrolling people aged over 50 without dementia and to whom DHEA/S in any dosage was administered for more than one day were considered for inclusion in the review. DATA COLLECTION AND ANALYSIS: Data for the specified outcomes were independently extracted by two reviewers (JGE and RM) and cross-checked. Any discrepancies were discussed and resolved. No data pooling was undertaken owing to the lack of availability of the relevant statistics. MAIN RESULTS: Only three studies provided results from adequate parallel-group data. Barnhart 1999 enrolled perimenopausal women with complaints of decreased well-being and, using three cognitive measures, found no significant effect of DHEA compared with placebo at 3 months. Wolf 1998b enrolled 75 healthy volunteers (37 women and 38 men aged 59-81) in a study of the effect of DHEA supplements on cognitive impairment induced by stress; after two weeks of treatment, placebo group performance deteriorated significantly on a test of selective attention following a psychosocial stressor (p<0.05), while deterioration was not evident in the DHEA group (p=0.85). However, when compared with placebo, DHEA was associated with a significant impairment on a visual memory recall test (p<0.01) following the stressor. No significant effects were found on a third cognitive task. Effects were not found on tasks when administered in the absence of a stressor. van Niekerk 2001 found no effect on cognitive function in 46 men aged 62-76 from three months of DHEA supplementation. DHEA supplements were well tolerated and without significant adverse effects apart from the reduced performance in the visual memory recall test observed in one trial. AUTHORS' CONCLUSIONS: What little evidence there is from controlled trials does not support a beneficial effect of DHEA supplementation on cognitive function of non demented middle-aged or elderly people. There is no consistent evidence from the controlled trials that DHEA produces any adverse effects. In view of growing public enthusiasm for DHEA supplementation, particularly in the USA, and the theoretical possibility of long-term neuroprotective effects of DHEA/S, there is a need for further high quality trials in which the duration of DHEA treatment is longer than one year, and the number of participants is large enough to provide adequate statistical power.

Salivary cortisol and DHEA: association with measures of cognition and well-being in normal older men, and effects of three months of DHEA supplementation.

Dehydroepiandrosterone (DHEA) is a steroid that shows a marked age-related decline in humans. Previous research suggests potential for DHEA replacement in old age to enhance cognition and well-being. We conducted a clinical trial to test these hypotheses in a non-clinical sample of 46 men aged 62-76. Participants received either 50 mg DHEA daily for 13 weeks, followed by placebo for 13 weeks, or the reverse, in a randomised double-blind cross-over trial design. Levels of salivary cortisol and DHEA were measured at 0800 h and 2000 h prior to each assessment session. Cognition was assessed with tests of speed, attention and episodic memory. Well-being was measured with questionnaires of mood and perceived health. Mood questionnaires were completed at the assessment session as well as concurrently with saliva sampling.A correlational analysis of baseline behavioural data with hormonal data, controlling for age, revealed that higher morning DHEA was associated with lower confusion (r=-0.33; P=0.04), while higher evening DHEA was associated with lower anxiety (r=-0.35; P=0.03) and lower current negative mood in the morning (r=-0.37; P=0.03). Conversely, higher morning cortisol and a morning cortisol/DHEA ratio were associated with higher anxiety (r=0.35; P=0.03), (r=0.46; P=0.004), general mood disturbance (r=0.32; P=0.046), (r=0.32; P=0.04) and higher current negative mood in the evening (r=0.37; P=0.03), (r=0.38; P=0.03). A higher morning cortisol/DHEA ratio was also associated with higher confusion (r=0.39; P=0.01) and lower visuo-spatial memory performance (r=-0.39; P=0.01). Unexpectedly, higher evening cortisol was associated with faster choice reaction time (r=-0.33; P=0.04). These findings are consistent with an impairing effect of high cortisol on episodic memory and mood in older men, which may be attenuated by DHEA. When treatment effects were analysed, no significant effects of DHEA were observed on any of the trial outcomes, providing no support for benefits of DHEA supplementation for cognition or well-being in normal older men in the shorter-term.

Dehydroepiandrosterone (DHEA) supplementation for cognitive function .

BACKGROUND: In view of the theoretical rationale for beneficial effects of DHEA and DHEAS on cognitive function in ageing and dementia, we have undertaken a thorough investigation of well-conducted studies in this area. This will provide a basis for confirmation of any effect of DHEA/S administration in humans in properly controlled trials. The review will also provide a scientific basis for effective dosage, acceptable route and duration of administration, and side effect profiles. This review is especially pertinent at this time as DHEA is currently being sold in large quantities in health food stores, particularly in the USA. In some cases the recommended dose is different for men and women (50mg/day for men and 25mg/day for women) and the basis for this recommendation needs to be explored. OBJECTIVES: To establish whether administration of DHEA, or its sulphate, DHEAS, improves cognitive function or reduces the rate of decline of cognitive function in normal older adults or in individuals with dementia. SEARCH STRATEGY: Relevant electronic databases, journals, personal communications and conference abstracts were searched for randomised controlled trials investigating the effects of DHEA/S on cognition in older adults. SELECTION CRITERIA: All relevant randomised controlled trials of DHEA/S were considered for inclusion in the review. DATA COLLECTION AND ANALYSIS: Data for the specified outcomes were independently extracted by two reviewers (FAH & JvN) and cross-checked. Any discrepancies were discussed and resolved. No data pooling was undertaken owing to the lack of availability of the relevant statistics. MAIN RESULTS: There are four included studies, three cognition in normal older people, and Barnhart 1999 in perimenopausal women with decreased well-being. There were no studies in dementia. There were a few significant findings. Wolf 1997 found significant improvement following DHEA compared with placebo in both immediate recall (MD 0.8, 95% CI 0.16, 1.44) and delayed recall (MD 0.9, 95% CI 0.09, 1.71) of a visual memory test in women, estimated in a crossover trial after 2 weeks of treatment with each of DHEA and placebo. However there was no significant improvement in men, nor a significant effect on a verbal memory test. There was also no significant effect on four other cognitive tests. Wolf 1998 (2) found that placebo group performance deteriorated significantly on a test of selective attention following a psychosocial stressor (p<0.05), while deterioration was not evident in the DHEA group (p=0.85) after two weeks of treatment. However, when compared to placebo, DHEA produced a significant impairment on a visual memory test (p<0.01) following the stressor. No significant effect was found on a third cognitive task. Effects were not found on tasks when administered in the absence of a stressor. Barnhart 1999 employed three cognitive measures and found no significant effect of DHEA compared with placebo at 3 months. Findings to date suggest that DHEA replacement seems to be well tolerated with an absence of significant side-effects. REVIEWER'S CONCLUSIONS: The data offer no support at present for an improvement in memory or other aspects of cognitive function following DHEA treatment in normal older people. In view of the growing public enthusiasm for DHEA supplementation, particularly in the USA, and the possibility that any neuroprotective effect of DHEA/S may only be evident in the long term, there is a need to undertake high quality trials in which the duration of DHEA treatment is longer than one year, and the number of participants is large enough to detect effects if they exist. Recently, trials of DHEA supplementation in Alzheimer's Disease (USA), post-menopausal women (USA), normal older men (UK), and a one-year trial in normal older men and women (France) have been completed. As soon as the results are available these studies will be included in the review.

Dehydroepiandrosterone (DHEA) supplementation for cognition and well-being.

BACKGROUND: In view of the theoretical rationale for beneficial effects of DHEA and DHEAS in aging and dementia, we believe it is timely to undertake a thorough investigation of well-conducted studies in this area. This will provide a basis for confirmation of any effect of DHEA/S administration in humans, in large-scale and properly controlled trials, which would evaluate effective dosage, acceptable route and duration of administration and side effect profiles. This is especially pertinent at this time as DHEA is currently being sold in large quantities in health food stores, particularly in the USA. In some cases the recommended dose is different for men and women (50mg/day for men and 25mg/day for women) and the basis for this recommendation needs to be explored. OBJECTIVES: To establish whether administration of DHEA, or its sulphate, DHEAS, improves psychological well-being and/or improves cognitive function or reduces the rate of decline of cognitive function in older adults or in individuals with dementia. SEARCH STRATEGY: All available electronic databases, hand searched journals, personal communications and conference abstracts were searched for randomised controlled trials of DHEA in well-being and cognition. The total yield from searching was 415 and the detailed breakdown is given in the body of this review. SELECTION CRITERIA: All relevant randomised controlled trials of DHEA or DHEAS were considered for inclusion in the review. Studies where groups are matched, rather than randomised, were also considered. DATA COLLECTION AND ANALYSIS: Data for the specified outcomes were independently extracted by two reviewers (FAH & JvN) and cross-checked. Any discrepancies were discussed and resolved. Where possible and appropriate, data were pooled and the mean differences estimated. MAIN RESULTS: The published DHEA trials fall into 2 categories: 1. four German studies in which DHEA was administered for a period of two weeks or less; 2. a USA study in which DHEA was administered for three months. Well-being was assessed in both sets of studies and a significant improvement was reported in the longer duration USA study, while no effect was reported in the shorter duration studies. The USA study used an open-ended questionnaire for self-assessment of well-being and stated that 67% of men and 82% of women reported enhanced well-being on DHEA compared with placebo. There was no significant change on an analogue measure of libido. The German studies assessed mood and well-being with a number of standardised scales and reported no significant effects of DHEA on any of them. Only the German studies examined performance on cognitive tests, i.e. memory, verbal fluency, speed of processing, etc. They reported no significant benefit of DHEA. REVIEWER'S CONCLUSIONS: The data at present offer limited support for improvement in a sense of well-being following DHEA treatment. This effect was reported only in the longer-term study which used a crude measure of well-being. The data offer no support at present for an improvement in memory or other aspects of cognitive function following DHEA treatment, although cognitive function was only measured in the short-duration trials. In view of the growing public enthusiasm for DHEA supplementation, particularly in the USA, it is clear that high-quality trials need to be undertaken in older adults, in which (a) the duration of DHEA treatment is in excess of two weeks, (b) the number of participants is large enough to detect effects if they exist, and (c) the outcome measures include validated scales for assessment of mood and well-being, and objective tests of cognitive function. Recently, studies of DHEA supplementation in clinical depression and Alzheimer's Disease have been completed in the USA. As soon as the results are available these studies will be reviewed. Currently, two trials (in France and the USA) in normal elderly are in progress.

Self-schemas in social phobia and panic disorder.

A modified Stroop color-naming task was used to investigate whether social phobia and panic disorder are associated with a hypervigilance to social and physical threat-related cues, respectively, as predicted by Beck's cognitive theory of anxiety disorders. Color-naming latencies of 13 individuals with social phobia and 15 with panic disorder for words representing social and physical threats, respectively, were compared to matched neutral control words. The results did not support the hypothesis that the self-schemas of individuals with panic disorder are hypersensitive to information association with physical threat and that persons with social phobia are overly concerned with social threat.