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Background: Cognitive decline is influenced by various factors including diet, cardiovascular disease, and glucose control. However, the combined effect of these risk factors on cognitive performance is yet to be fully understood. Objective: The current study aimed to explore the inter-relationship between these risk factors and cognitive performance in older adults at risk of future cognitive decline. Methods: The sample comprised 163 (Age: M = 65.23 years, SD = 6.50) participants. Food Frequency Questionnaire data was used to score diet quality and adherence to the Western Style Diet (WSD) and Prudent Style Diet (PSD). Glucose control was gauged by serum levels of glycated hemoglobin (HbA1c) and arterial stiffness was measured using carotid to femoral pulse wave velocity. Cognitive performance was assessed using two subtests of the Swinburne University Computerized Cognitive Assessment Battery (SUCCAB) and Rey’s Verbal Learning Test (RVLT). Results: Diet quality, adherence to the WSD or PSD, and glucose control were not significantly related to cognitive outcomes. However, a significant negative association was found between arterial stiffness and the spatial working memory subtest of SUCCAB (β= –0.21, p

Objective To investigate the effects of acute Panax quinquefolius (American ginseng) administration on steady state visually evoked potentials (SSVEPs) during completion of working memory and continuous performance tasks. Methods A randomised, double‐blind, placebo controlled, balanced, cross‐over trial was conducted in middle‐aged volunteers aged between 40 and 60 years. Participants were administered 200 mg P. quinquefolius and placebo on two separate testing sessions. Six‐h post‐dose participants completed spatial working memory (SWM) and continuous performance (CP) tasks while SSVEP from a diffuse task‐irrelevant 13 Hz flicker was recorded. Results During SWM retrieval, P. quinquefolius was associated with significantly reduced prefrontal SSVEP latency. There were no significant treatment effects on CP nor behavioural performance of either task. Conclusions These findings provide preliminary evidence of increased recruitment of prefrontal brain regions during working memory processing following a single acute dose of P. quinquefolius.

Docosahexaenoic acid is the main long-chain omega-3 polyunsaturated fatty acids in the brain and accounts for 30−40% of fatty acids in the grey matter of the human cortex. Although the influence of docosahexaenoic acid on memory function is widely researched, its association with brain volumes is under investigated and its association with spatial navigation is virtually unknown. This is despite the fact that spatial navigation deficits are a new cognitive fingerprint for symptomatic and asymptomatic Alzheimer’s disease. We investigated the cross-sectional relationship between docosahexaenoic acid levels and the major structural and cognitive markers of preclinical Alzheimer’s disease, namely hippocampal volume, entorhinal volume and spatial navigation ability. Fifty-three cognitively normal adults underwent volumetric magnetic resonance imaging, measurements of serum docosahexaenoic acid (DHA, including lysophosphatidylcholine DHA) and APOE ε4 genotyping. Relative regional brain volumes were calculated and linear regression models were fitted to examine DHA associations with brain volume. APOE genotype modulated serum DHA associations with entorhinal cortex volume and hippocampal volume. Linear models showed that greater serum DHA was associated with increased entorhinal cortex volume, but not hippocampal volume, in non APOΕ ε4 carriers. APOE also interacted with serum lysophosphatidylcholine DHA to predict hippocampal volume. After testing interactions between DHA and APOE on brain volume, we investigated whether DHA and APOE interact to predict spatial navigation performance on a novel virtual reality diagnostic test for Alzheimer’s disease in an independent population of APOE genotyped adults (n = 46). APOE genotype modulated DHA associations with spatial navigation performance, showing that DHA was inversely associated with path integration in APOE ε4 carriers only. This exploratory analysis suggests that interventions aiming to increase DHA blood levels to protect against cognitive decline should consider APOE ε4 carrier status. Future work should focus on replicating our initial findings and establishing whether a specific dose of supplementary DHA, at a particular time in the preclinical disease course can have a positive impact on Alzheimer’s disease progression in APOE ε4 carriers., Docosahexaenoic acid’s neuroprotective effect may be concentrated in the entorhinal cortex and hippocampus. Here, we show that docosahexaenoic acid’s association with entorhinal volume and spatial navigation ability is modulated by the APOE genotype, with non-significant or inverse associations found in APOE ε4 carriers who are genetically-at-risk of Alzheimer’s disease., Graphical Abstract Graphical Abstract

Curcumin (a flavonoid isolated from turmeric) affects several processes involved in neurocognitive aging. We have previously reported that short term (4-weeks) administration of a highly bioavailable curcumin preparation (Longvida&copy, ) improved working memory and reduced fatigue and stress reactivity in a healthy older cohort. The present trial (ACTRN12616000484448) was a partial replication study, evaluating similar effects at 4 and 12-weeks Longvida&copy, supplementation. A double-blind, placebo-controlled, parallel-groups trial was conducted. Eighty participants aged 50&ndash, 80 years (mean = 68.1, SD = 6.34) were randomised to receive Longvida&copy, (400 mg daily containing 80 mg curcumin) or a matching placebo. Assessment took place at baseline then following 4 and 12 weeks treatment. Outcome measures included cognitive performance, mood and biomarkers. Compared with placebo, curcumin was associated with several significant effects. These included better working memory performance at 12-weeks (Serial Threes, Serial Sevens and performance on a virtual Morris Water Maze), and lower fatigue scores on the Profile of Mood States (POMS) at both 4 and 12-weeks, and of tension, anger, confusion and total mood disturbance at 4-weeks only. The curcumin group had significantly elevated blood glucose. These results confirm that Longvida&copy, improves aspects of mood and working memory in a healthy older cohort. The pattern of results is consistent with improvements in hippocampal function and may hold promise for alleviating cognitive decline in some populations.

The flavonoid curcumin is believed to be responsible for the purported health benefits of turmeric. Like other flavonoids, curcumin affects several systemic and central processes involved in neurocognitive aging. We have previously shown that one month administration of a highly bioavailable curcumin extract (Longvida™) improved working memory and reduced fatigue and workload stress in an older, cognitively intact cohort(1). This study focused on the effects of the same extract, focusing on memory tasks subserved by the hippocampus, one of two areas of the adult brain believed to be capable of adult neurogenesis.Eighty healthy older participants (aged 50–80 years, mean = 68.1, ± SD 6.34) took part in this double-blind, placebo-controlled, parallel-groups trial. Volunteers were randomised to receive administration of 400 mg daily Longvida™ (containing 80 mg curcumin) or a matching placebo. Assessment took place at baseline and 4 and 12 weeks thereafter. Outcomes included two tasks evaluating memory processes relevant to hippocampal function. These were i) a human analogue of the widely used rodent Morris Water Maze - the virtual Morris Water Maze (vMWM) and ii) a Mnemonic Similarity task evaluating pattern separation. Measures of mood, cardiovascular function and other blood biomarkers were collected, and a subset of the cohort underwent neuroimaging using functional magnetic resonance imaging.Compared with placebo, there were a number of improvements in the curcumin group. The curcumin group had significantly better performance at 12 weeks on the virtual Morris Water Maze (p = .019). Curcumin was also associated with better performance on a pattern separation task (p = .025). Curcumin was also associated with number of significantly benefits to mood, including, from the Profile of Mood States (POMS), including, at 28 days only, total mood disturbance (p = .006), tension-anxiety (p = .028), confusion-bewilderment (p = .019), anger-Hostility (p = .009). There were also significant benefits to the POMS fatigue scores at both assessments (p ≤ .011). There were no group differences in biomarker levels.These results confirm that Longvida™ curcumin improves aspects of mood and working memory in a healthy older cohort. The pattern of results is consistent with improvements in hippocampal function and may hold promise for alleviating cognitive decline in populations at risk of pathological cognitive decline.

A systematic review and meta-analysis was undertaken to examine and quantify the effects of B vitamin supplementation on mood in both healthy and ‘at-risk’ populations. A systematic search identified all available randomised controlled trials (RCTs) of daily supplementation with ≥3 B group vitamins with an intervention period of at least four weeks. Random effects models for a standardized mean difference were used to test for overall effect. Heterogeneity was tested using the I2 statistic. Eighteen articles (16 trials, 2015 participants) were included, of which 12 were eligible for meta-analysis. Eleven of the 18 articles reported a positive effect for B vitamins over a placebo for overall mood or a facet of mood. Of the eight studies in ‘at-risk’ cohorts, five found a significant benefit to mood. Regarding individual facets of mood, B vitamin supplementation benefited stress (n = 958, SMD = 0.23, 95% CI = 0.02, 0.45, p = 0.03). A benefit to depressive symptoms did not reach significance (n = 568, SMD = 0.15, 95% CI = −0.01, 0.32, p = 0.07), and there was no effect on anxiety (n = 562, SMD = 0.03, 95% CI = −0.13, 0.20, p = 0.71). The review provides evidence for the benefit of B vitamin supplementation in healthy and at-risk populations for stress, but not for depressive symptoms or anxiety. B vitamin supplementation may particularly benefit populations who are at risk due to (1) poor nutrient status or (2) poor mood status.

Background: Healthy aging has been associated with reduced appetite and lower energy intake, which can lead to loss of bodyweight, undernutrition and related health problems. The causes for the decline in caloric intake are multifactorial, involving physiological and non-physiological processes. Aims: Here we examined the effect of glucose on brain function in healthy adults as well as age-related, physiological changes in brain responses associated with macronutrient intake. Methods: Using a randomized, double-blind, balanced cross-over design, younger ( n = 16, aged 21–30) and older ( n = 16, aged 55–78) adults received a drink containing glucose and a taste-matched placebo after an overnight fast. Blood glucose and hunger were assessed at baseline and 20 min post-ingestion, after which participants underwent resting state functional magnetic resonance imaging. Results: Frequency-dependent changes associated with glucose administration in slow-5 (0.01–0.027 Hz) and slow-4 (0.027–0.073 Hz) amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) of the blood oxygen level-dependent (BOLD) signal were investigated within the young healthy adults, and then extended to the older age group. Consistent with previous reports, glucose decreased amplitude in slow-5 fALFF within the left orbitofrontal cortex and insular cortex in the young adults. We observed a significant interaction in slow-5 ALFF and fALFF in the left insula, such that younger participants showed a decrease in BOLD amplitude, whereas older participants showed an increase, after glucose administration. We further observed an interaction in slow-4 ALFF in the occipital region and precuneus, with older participants showing an increase in magnitude of slow-4 ALFF and younger participants showing a decrease in the same measure. Conclusion: These age-related, frequency-dependent changes in the magnitude of the BOLD signal in the insula, a key region related to energy homeostasis following feeding, may point to a change in satiety or homeostatic signalling contributing to behavioural changes in energy intake during senescence.

Clinical diagnoses of Attention Deficit Hyperactivity Disorder (ADHD) and the use of prescription medications for its treatment have increased in recent years. Current treatments may involve the administration of amphetamine-type substances, a treatment path many parents are apprehensive to take. Therefore, alternative pharmacological treatments are required. Few nutritional or pharmacological alternatives that reduce ADHD associated symptoms (hyperactivity and inattention) have been subjected to rigorous clinical trials. Bacopa monnieri is a perennial creeping herb. CDRI 08 is a special extract of Bacopa monnieri which has been subjected to hundreds of scientific studies and has been shown in human randomized controlled trials (RCTs) to improve memory, attention, and mood. It is hypothesised that chronic administration of CDRI 08 will improve attention, concentration and behaviour in children with high levels of hyperactivity and/or inattention. This paper reports the protocol for the first 16-week, randomized, placebo-controlled, double-blind, parallel groups trial examining the efficacy and safety of CDRI 08 in male children aged 6–14 years with high levels of inattention and hyperactivity. The primary outcome variable will be the level of hyperactivity and inattention measured by the Conners’ Parent Rating Scale (CPRS). Secondary outcome variables include cognition, mood, sleep, and EEG. Trial registration: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12612000827831.

This study explored the effects of four-week multi-vitamin and mineral (MVM) supplementation on mood and neurocognitive function in healthy, young adults. Fifty-eight healthy adults, 18–40 years of age (M = 25.82 years, SD = 4.87) participated in this randomised, double-blind, placebo-controlled trial, in which mood and blood biomarkers were assessed at baseline and after four weeks of supplementation. Compared to placebo, MVM supplementation was associated with significantly lowered homocysteine and increased blood B-vitamin levels (p &lt, 0.01). MVM treatment was also associated with significantly improved mood, as measured by reduced scores on the “depression-dejection” subscale of the Profile of Mood States (p = 0.018). These findings suggest that the four weeks of MVM supplementation may have beneficial effects on mood, underpinned by elevated B-vitamins and lowered homocysteine in healthy young adults.

Introduction: Cohort studies indicate that long-chain n-3 polyunsaturated fatty acids and flavonoids may improve cognition and reduce dementia risk. The neuroprotective effects of these dietary components indicate that they are likely to be additive and potentially synergistic. Methods: The Cognitive Ageing, Nutrition and Neurogenesis trial hypothesizes that an intervention comprising long-chain n-3 polyunsaturated fatty acids (docosahexaenoic acid and eicosapentaenoic acid) and cocoa flavan-3-ols (n-3 FLAV) will mitigate the cognitive decline anticipated to naturally occur over 1 year in older adults with mild cognitive impairment or subjective memory impairment. A double-blinded, placebo-controlled parallel design is used. Two hundred fifty-nine adults (aged ≥55 years) with mild cognitive impairment or subjective memory impairment were recruited and randomized to a control or n-3 FLAV group (1.5 g docosahexaenoic acid + eicosapentaenoic acid and 500 mg n-3 FLAV daily) for 12 months. Cognitive performance was measured three times over the 1-year intervention, at 0 (baseline), 3, and 12 months. The primary end point is hippocampus-sensitive cognitive function (e.g., number of false-positives on the Picture Recognition Task of the Cognitive Drug Research test battery). Secondary outcomes include additional cognitive measures, brain atrophy and blood flow (assessed by magnetic resonance imaging), vascular function, circulating biomarkers of cardiovascular and cognitive health, gut microflora speciation and metabolism, red blood cell fatty acid status, and urine flavan-3-ol metabolites. The intervention arms were matched for sex and apolipoprotein E4 status to allow retrospective exploratory analysis of the impact of these variables on response to intervention. Results: Screening began in 2015, with all baseline visits completed in March 2017. The intervention was finished in March 2018. Discussion: Cognitive Ageing, Nutrition and Neurogenesis aims to identify an effective diet-based intervention to prevent or delay cognitive impairment in cognitively at-risk individuals, which could ultimately contribute to a reduced population burden of dementia.

Objective Cognitive benefits of multivitamins have been observed in the elderly, but fewer trials have investigated younger, healthy cohorts. This randomised, double-blind, placebo-controlled study investigated the cognitive effects of 16-week multivitamin supplementation in adults aged 20–49 years. Method A total of 138 participants aged 20–50 years were randomised and 116 completed the trial. The participants completed a computerised battery of cognitive tasks before and after 16-week supplementation with a multivitamin containing minerals and herbs or placebo. Blood measures of homocysteine, vitamin B6, B12 and folate were collected at both time points. Results In men, there was a strong trend (p = 0.01; which did not reach significance when adjusted for multiple comparisons) for the multivitamin to improve performance on the incongruent stroop task, a measure of selective attention and response inhibition. There were no cognitive benefits of multivitamin supplements in women. Multivitamin supplementation substantially increased blood levels of vitamin B6, B12 and folate in both genders and decreased homocysteine in men. In men who received the multivitamin, improved stroop congruent performance was associated with increased vitamin B6 levels. Conclusion Multivitamin supplementation may be useful for maintaining levels of B vitamins. The effects of multivitamins on speeded attention such as the stroop task in young adults warrant further investigation. Copyright © 2014 John Wiley & Sons, Ltd.

Previous research has suggested that multivitamin (MV) supplementation may be associated with beneficial effects for mood and general well-being, although treatment durations have typically been less than 90 days, samples have often been restricted to males only and acute effects have not been adequately differentiated from chronic effects. In the current study a MV supplement containing high levels of B-vitamins was administered daily to 138 healthy young adult participants between the ages of 20 and 50 years over a 16-week period. Chronic mood measures (GHQ-28, POMS, Chalder fatigue, PILL, Bond-Lader and custom visual analogue scales) were administered pre-dose at baseline, 8- and 16-weeks. Changes in Bond-Lader and VAS in response to a multi-tasking framework (MTF) were also assessed at 8- and 16-weeks. For a subset of participants, at-home mobile-phone assessments of mood were assessed on a weekly basis using Bond-Lader and VAS. No significant treatment effects were found for any chronic laboratory mood measures. In response to the MTF, a significant treatment x time interaction was found for STAI-S, with a trend towards a greater increase in stress ratings for male participants in the MV group at 16 weeks. However, this finding may have been attributable to a larger proportion of students in the male MV group. In contrast, at-home mobile-phone assessments, where assessments were conducted post-dose, revealed significantly reduced stress, physical fatigue and anxiety in the MV group in comparison to placebo across a number of time points. Further research using both acute and chronic dosing regimens are required in order to properly differentiate these effects.

This study explored the neurocognitive effects of 4 weeks daily supplementation with a multi-vitamin and -mineral combination (MVM) in healthy adults (aged 18–40 years). Using a randomized, double-blind, placebo-controlled design, participants underwent assessments of brain activity using functional Magnetic Resonance Imaging (fMRI; n = 32, 16 females) and Steady-State Visual Evoked Potential recordings (SSVEP; n = 39, 20 females) during working memory and continuous performance tasks at baseline and following 4 weeks of active MVM treatment or placebo. There were several treatment-related effects suggestive of changes in functional brain activity associated with MVM administration. SSVEP data showed latency reductions across centro-parietal regions during the encoding period of a spatial working memory task following 4 weeks of active MVM treatment. Complementary results were observed with the fMRI data, in which a subset of those completing fMRI assessment after SSVEP assessment (n = 16) demonstrated increased BOLD response during completion of the Rapid Visual Information Processing task (RVIP) within regions of interest including bilateral parietal lobes. No treatment-related changes in fMRI data were observed in those who had not first undergone SSVEP assessment, suggesting these results may be most evident under conditions of fatigue. Performance on the working memory and continuous performance tasks did not significantly differ between treatment groups at follow-up. In addition, within the fatigued fMRI sample, increased RVIP BOLD response was correlated with the change in number of target detections as part of the RVIP task. This study provides preliminary evidence of changes in functional brain activity during working memory associated with 4 weeks of daily treatment with a multi-vitamin and -mineral combination in healthy adults, using two distinct but complementary measures of functional brain activity.

In considering targeting of HIV testing, National Institute of Health and Care Excellence (NICE) guidance pinpoints men who have sex with men and Black minority ethnic (BME) communities.1–3 In particular, it has been recommended that testing be taken out to these communities to help overcome barriers to testing. Venepuncture is difficult in community settings, and point-of-care testing (POCT) is seen as a more viable alternative, but both require skill either in the procedure or delivering a result. Dried blood spot (DBS) sampling offers an alternative method to venepuncture and POCT and has …

Recent evidence suggests that dietary intake of vitamins, in particular the B-vitamins including B6, B9 and B12 may have a number of positive effects on mood and stress. Given the effects of stress on a range of biological mechanisms including the endocrine system, it could be reasonably expected that multivitamin supplementation may also affect markers of these mechanisms such as diurnal cortisol secretion. In the current double-blind placebo-controlled study 138 adults (aged 20 to 50 years) were administered a multivitamin containing B-vitamins versus placebo over a 16-week period. Salivary cortisol measurements were taken at waking, 15-min, 30-min and at bedtime, at baseline, 8-weeks and 16-weeks. Perceived Stress (PSS) was measured at baseline, 8-weeks and 16-weeks, while blood serum measures of B6, B12 and homocysteine (HCy) as well as red cell folate (B9) were also collected at these time points. A significant interaction was found between treatment group and study visit for the Cortisol Awakening Response (CAR). Compared to placebo, at 16-weeks multivitamin supplementation was found to be associated with a near-significant trend towards an increased CAR. No significant differences in PSS were found between groups, with PSS increasing in both groups across the course of the study. Red cell folate was found to be significantly correlated with the CAR response at 16-weeks while HCy levels were not found to be associated with the CAR response, although HCy significantly correlated with waking cortisol levels at 8-weeks. A possible interpretation of the elevation in CAR associated with multivitamin supplementation is that this represents an adaptive response to everyday demands in healthy participants.

Previous work has identified the positive effects of the acute administration of a multivitamin-guarana preparation during an effortful executive/working memory task. Here, we aimed to differentiate the effects of multivitamins with and without guarana and to examine the neural substrates of such effects using functional magnetic resonance imaging (fMRI). Following a double-blind, placebo-controlled, randomised, balanced crossover design, 20 participants (mean age 29 ± 5.54 years) consumed multivitamin preparations with or without guarana (Berocca® Performance and Boost, respectively) and a placebo. Thirty minutes post-treatment, they underwent neurocognitive assessment, consisting of a 10 min Cognitive Demand Battery, with mood ratings taken immediately before and after the battery. Five additional participants underwent post-treatment fMRI scanning during Rapid Visual Information Processing and Inspection Time activation tasks. The multivitamin with guarana treatment was associated with significantly enhanced Serial Threes performance and self-rated contentment. fMRI revealed that both multivitamin treatments increased activation in areas associated with working memory and attentional processing, with the effect being greater in the multivitamin with guarana condition. These data confirm the acute benefits of multivitamins with guarana on mood and cognitive performance. Furthermore, they demonstrate for the first time increased brain activation from multivitamin preparations both with and without guarana, as measured using fMRI.

Background While many randomised controlled trials have been conducted on multivitamins, to our knowledge no qualitative research exploring the subjective experience of taking a multivitamin during a clinical trial has been reported. Methods Semi-structured and open-ended written questions were incorporated into a 16-week double-blind, randomised, placebo-controlled, parallel groups trial of once-daily multivitamin administration. At the final study visit (week 16), three open-ended questions were posed to elucidate any positive, negative or unusual experiences from taking either the multivitamin or matched placebo. Qualitative thematic analysis was undertaken by researchers who were blind as to treatment condition of participants, and triangulation (independent analysis from three researchers) was employed to ensure methodological rigour. Participant’s experiences were categorised as “positive” or “negative” and a Chi Square analysis was then applied to each of the experiential themes, to compare experiences between the multivitamin and placebo groups, (subdividing the groups by gender). Usual experiences were categorised and discussed separately. Results Of the 182 participants enrolled, 116 completed the study and qualitative data were available from 114 participants. Thematic analysis revealed significant effects in favour of the multivitamin over placebo for participants experiencing increased energy levels (p=.022) and enhanced mood (p=.027). The beneficial effect on energy levels was particularly evident among female participants. A trend was found for participants reporting better sleep in the multivitamin over placebo. The multivitamin and placebo groups did not significantly differ in perceived positive or negative effects in areas relating to other aspects of mental function or physical health. No significant negative effects were revealed, although there was a non-significant trend for more people in the multivitamin group having minor digestive complaints. Conclusion This represents the first documented qualitative investigation of participants’ experience of chronic administration of a multivitamin. Results uncovered a range of subjective beneficial effects that are consistent with quantitative data from previously published randomised controlled trials examining the effects of multivitamins and B vitamin complexes on mood and well-being. Trial registration Prior to commencement this trial was registered with the Australian New Zealand Clinical Trials Registry (http://www.anzctr.org.au) ACTRN12611000092998

The study investigated hypnosis-related electroencephalographic (EEG) coherence and power spectra changes in high and low hypnotizables (Stanford Hypnotic Clinical Scale) induced by a virtual reality hypnosis (VRH) induction system. In this study, the EEG from 17 participants (Mean age = 21.35, SD = 1.58) were compared based on their hypnotizability score. The EEG recording associated with a 2-minute, eyes-closed baseline state was compared to the EEG during a hypnosis-related state. This novel induction system was able to produce EEG findings consistent with previous hypnosis literature. Interactions of significance were found with EEG beta coherence. The high susceptibility group (n = 7) showed decreased coherence, while the low susceptibility group (n = 10) demonstrated an increase in coherence between medial frontal and lateral left prefrontal sites. Methodological and efficacy issues are discussed.

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