A 1-year randomized controlled trial of a nutritional blend to improve nutritional biomarkers and prevent cognitive decline among community-dwelling older adults: The Nolan Study.

Introduction: This study aimed to test the efficacy of a nutritional blend (NB) in improving nutritional biomarkers and preventing cognitive decline among older adults. Methods: A 1-year randomized, double-blind, multicenter, placebo-controlled trial with 362 adults (58.6% female, mean 78.3 years, SD = 4.8) receiving an NB or placebo. Erythrocyte ω-3 index and homocysteine concentrations were primary outcomes. Other outcomes included Patient-Reported Outcomes Measurement Information System (PROMIS) Applied Cognition-Abilities, composite cognitive score (CCS), Cognitive Function Instrument (CFI) self-assessment and study partner, hippocampal volume (HV), and Alzheimer's disease signature cortical thickness (CT). Results: A total of 305 subjects completed the follow-up. Supplementation increased ω-3 index and decreased homocysteine, but did not affect CCS, CFI self-assessment, HV, and CT. Placebo improved and treatment did not change PROMIS at 1 month. Intervention showed a positive effect on CFI study partner. Discussion: Although improving nutritional biomarkers, this 1-year trial with a multi-nutrient novel approach was not able to show effects on cognitive outcomes among older adults.

A Decentralized Study Setup Enables to Quantify the Effect of Polymerization and Linkage of α-Glucans on Post-Prandial Glucose Response.

The complexity of the carbohydrate structure is associated with post-prandial glucose response and diverse health benefits. The aim of this study was to determine whether, thanks to the usage of minimally invasive glucose monitors, it was possible to evaluate, in a decentralized study setup, the post-prandial glycemic response (PPGR) of α-glucans differing systematically in their degree of polymerization (DP 3 vs. DP 60) and in their linkage structure (dextrin vs. dextran). Ten healthy subjects completed a double-blind, randomized, decentralized crossover trial, testing at home, in real life conditions, four self-prepared test beverages consisting of 25 g α-glucan dissolved in 300 mL water. The incremental area under the curve of the 120 min PPGR (2h-iAUC) was the highest for Dextrin DP 3 (163 ± 27 mmol/L*min), followed by Dextrin DP 60 (-25%, p = 0.208), Dextran DP 60 (-59%, p = 0.002), and non-fully caloric Resistant Dextrin (-68%, p = 0.002). These results show that a fully decentralized crossover study can be successfully used to assess the influence of both polymerization and structure of α-glucans on PPGR.

A blood-based nutritional risk index explains cognitive enhancement and decline in the multidomain Alzheimer prevention trial.

INTRODUCTION: Multinutrient approaches may produce more robust effects on brain health through interactive qualities. We hypothesized that a blood-based nutritional risk index (NRI) including three biomarkers of diet quality can explain cognitive trajectories in the multidomain Alzheimer prevention trial (MAPT) over 3-years. METHODS: The NRI included erythrocyte n-3 polyunsaturated fatty acids (n-3 PUFA 22:6n-3 and 20:5n-3), serum 25-hydroxyvitamin D, and plasma homocysteine. The NRI scores reflect the number of nutritional risk factors (0-3). The primary outcome in MAPT was a cognitive composite Z score within each participant that was fit with linear mixed-effects models. RESULTS: Eighty percent had at lease one nutritional risk factor for cognitive decline (NRI ≥1: 573 of 712). Participants presenting without nutritional risk factors (NRI=0) exhibited cognitive enhancement (ß = 0.03 standard units [SU]/y), whereas each NRI point increase corresponded to an incremental acceleration in rates of cognitive decline (NRI-1: ß = -0.04 SU/y, P = .03; NRI-2: ß = -0.08 SU/y, P < .0001; and NRI-3: ß = -0.11 SU/y, P = .0008). DISCUSSION: Identifying and addressing these well-established nutritional risk factors may reduce age-related cognitive decline in older adults; an observation that warrants further study.

The Impact of Epicatechin on Human Cognition: The Role of Cerebral Blood Flow.

Epicatechin is a monomeric flavanol found in food sources such as tea, apples, berries and cocoa. A number of large-scale epidemiological studies have demonstrated an association between the consumption of these foods and cognitive function, as well as improved blood flow. The aim of this review is to summarise the evidence from intervention studies to clarify the effect of epicatechin on cognition and to consider the role of increased cerebral blood flow as a mechanism for any effects. The effects of epicatechin as consumed in cocoa are, therefore, reviewed here as this represents the only dietary source where it is purported to be the major active component. Our main findings are that a) the positive modulation of tasks that involve memory, executive function and processing speed in older adults; b) the cognitive benefits are more often shown in studies containing more than 50 mg epicatechin/day; and c) all studies with a duration of 28 days or longer in populations >50 years old demonstrate a cognitive improvement. However, as highlighted by this review, it is not currently possible to attribute effects solely to epicatechin without consideration of synergies. In order to overcome this issue, further studies examining the cognitive effects of epicatechin in isolation are required. The role of cerebral blood flow also requires further investigation through simultaneous measurement alongside cognitive function.

Effects of a single, oral 60 mg caffeine dose on attention in healthy adult subjects.

Caffeine induces positive effects on sustained attention, although studies assessing the acute effects of low caffeine dose (<75 mg) on sustained attention are limited and use short-term tests. Therefore, we investigated the acute effects of a 60 mg dose of caffeine on sustained attention in tests lasting up to 45 minutes using 82 low or non-caffeine-consuming healthy male ( n=41) and female ( n=41) adults aged between 40 and 60 years. Vigilance was measured using Mackworth Clock test, Rapid Visual Information Processing Test, adaptive tracking test, saccadic eye movement and attention switch test. Effects on mood and fatigue were analysed using Bond and Lader and Caffeine Research visual analogue scales, and Samn-Perelli questionnaire. Saliva sampling was performed for both compliance and caffeine pharmacokinetic analysis. Administration of a 60 mg caffeine dose resulted in a significant improvement in sustained attention compared with the placebo. Also a significantly improved peak saccadic velocity and reaction time performance was found, and decreased error rate. Significantly increased feelings of alertness, contentment and overall mood after caffeine treatment compared with placebo were observed. This study demonstrated that in healthy adult subjects oral administration of a single 60 mg caffeine dose elicited a clear enhancement of sustained attention and alertness, measured both in multiple objective performances and in subjective scales.

Effect of short-duration lipid supplementation on fat oxidation during exercise and cycling performance.

The effect of intramyocellular lipids (IMCLs) on endurance performance with high skeletal muscle glycogen availability remains unclear. Previous work has shown that a lipid-supplemented high-carbohydrate (CHO) diet increases IMCLs while permitting normal glycogen loading. The aim of this study was to assess the effect of fat supplementation on fat oxidation (Fox) and endurance performance. Twenty-two trained male cyclists performed 2 simulated time trials (TT) in a randomized crossover design. Subjects cycled at ∼53% maximal voluntary external power for 2 h and then followed 1 of 2 diets for 2.5 days: a high-CHO low-fat (HC) diet, consisting of CHO 7.4 g·kg(-1)·day(-1) and fat 0.5 g·kg(-1)·day(-1); or a high-CHO fat-supplemented (HCF) diet, which was a replication of the HC diet with ∼240 g surplus fat (30% saturation) distributed over the last 4 meals of the diet period. On trial morning, fasting blood was sampled and Fox was measured during an incremental exercise; a ∼1-h TT followed. Breath volatile compounds (VOCs) were measured at 3 time points. Mental fatigue, measured as reaction time, was evaluated during the TT. Plasma free fatty acid concentration was 50% lower after the HCF diet (p < 0.0001), and breath acetone was reduced (p < 0.05) "at rest". Fox peaked (∼0.35 g·kg(-1)) at ∼42% peak oxygen consumption, and was not influenced by diet. Performance was not significantly different between the HCF and HC diets (3369 ± 46 s vs 3398 ± 48 s; p = 0.39), nor were reaction times to the attention task and VOCs (p = NS for both). In conclusion, the short-term intake of a lipid supplement in combination with a glycogen-loading diet designed to boost intramyocellular lipids while avoiding fat adaptation did not alter substrate oxidation during exercise or 1-hour cycling performance.

Effects of drinking supplementary water at school on cognitive performance in children.

We investigated the beneficial effects of drinking supplementary water during the school day on the cognitive performance and transitory subjective states, such as fatigue or vigor, in 168 children aged between 9 and 11years who were living in a hot climate (South Italy, Sardinia). The classes were randomly divided into an intervention group, which received water supplementation, and a control group. Dehydration was determined by urine sampling and was defined as urine osmolality greater than 800mOsm/kg H(2)O (Katz, Massry, Agomn, & Toor, 1965). The change in the scores from the morning to the afternoon of hydration levels, cognitive performance and transitory subjective states were correlated. In line with a previous observational study that evaluated the hydration status of school children living in a country with a hot climate (Bar-David, Urkin, & Kozminsky, 2005), our results showed that a remarkable proportion of children were in a state of mild, voluntary dehydration at the beginning of the school day (84%). We found a significant negative correlation between dehydration and the auditory number span, which indicates a beneficial effect of drinking supplementary water at school on short-term memory. Moreover, there was a positive correlation between dehydration and performance in the verbal analogy task. The results are discussed in the light of the complexity of the neurobiological mechanisms involved in the relationship between hydration status and cognition.

Does coffee enriched with chlorogenic acids improve mood and cognition after acute administration in healthy elderly? A pilot study.

RATIONALE: Caffeine exerts positive effects on cognitive and behavioral processes, especially in sub-optimal conditions when arousal is low. Apart from caffeine, coffee contains other compounds including the phenolic compounds ferulic acid, caffeic acid, and the chlorogenic acids, which have purported antioxidant properties. The chlorogenic acids are the most abundant family of compounds found in coffee, yet their effects on cognition and mood have not been investigated. OBJECTIVES: This study aims to ascertain whether a coffee rich in chlorogenic acid modulates brain function. METHODS: The present pilot study examined the acute effects of decaffeinated coffee with regular chlorogenic acid content and decaffeinated coffee with high chlorogenic acid content on mood and cognitive processes, as measured by behavioral tasks and event-related potentials (ERPs). Performance and ERP responses to a battery of cognitive tasks were recorded at baseline and following the equivalent of three cups of coffee in a randomized, double-blind, crossover study of 39 healthy older participants. RESULTS: Compared with the decaffeinated coffee with regular chlorogenic acid and placebo, caffeinated coffee showed a robust positive effect on higher-level mood and attention processes. To a lesser extent, the decaffeinated coffee high in chlorogenic acid also improved some mood and behavioral measures, relative to regular decaffeinated coffee. CONCLUSIONS: Our pilot results suggest that non-caffeine compounds in coffee such as the chlorogenic acids may be capable of exerting some acute behavioral effects, thus warranting further investigation.

Nutrition and cognition: meeting the challenge to obtain credible and evidence-based facts.

Nutrition provides a practical and appealing approach to cognitive enhancement, including the modulation of long-term cognitive processes such as neurodevelopment and neurodegeneration. An abundance of promising nutritional influences on cognition have been identified, but many long-term effects remain to be confirmed by data from randomized controlled trials (RCTs). The current article provides a general outline of various factors that hamper the demonstration of causal long-term nutritional effects on cognition by RCTs and advocates the development of methodological solutions to enable substantiation in future RCTs.

The effect of acute tryptophan depletion on performance and the BOLD response during a Stroop task in healthy first-degree relatives of patients with unipolar depression.

Previous research has shown that low central serotonin, induced by acute tryptophan depletion (ATD), results in depressed mood and impairs cognition in healthy volunteers with a predisposition for depression. It remains unknown whether ATD affects emotional processing via mood changes or directly. In the present study we investigated the interaction between vulnerability for depression and the effect of ATD on mood, cognition and the associated brain activation. In a previous functional MRI study, we tested the effect of ATD during a combined cognitive and emotional Stroop task in healthy women without a family history of depression (FH-). In this study, we present the data of an additional group of 12 healthy women with a positive family history of unipolar depression (FH+). The effect of ATD on mood and Stroop performance was different for the FH+ group as compared with the FH- group. Scores on the depression sub-scale of the Profile of Mood States (POMS) did not correlate with performance changes, but did correlate with the anterior cingulate cortex response during Stroop interference. This study showed that a family history of unipolar depression interacts with the effect of ATD.

Food ingredients and cognitive performance.

PURPOSE OF REVIEW: To integrate recent discoveries in the cognitive neuroscience field on overall brain development, performance and energy requirements, with insight obtained on the cellular and molecular mechanisms of stimulation with food at the periphery. RECENT FINDINGS: A clear picture emerges of the brain energy demand, its changes through life and the nutritional requirements to provide an optimally functioning intellect at any time. Of particular importance is the dynamic range resulting from differences between 'poor diet' and 'optimal diet'. On the basis of a healthy brain, the question becomes: what drives transient cognitive performance, and to what extent does food-related input from the periphery modulate cognition in general? Over the last decade, vast achievements in the understanding of chemosensory signal transduction on the tongue have been made. Most molecular receptors for various taste modalities have been identified, and the logic of their coding into the brain has been largely unravelled. Moreover, an intriguing discovery has been made that most of the known taste receptors are also expressed in the gastrointestinal tract. SUMMARY: Brain energy supply and balanced diet are being unravelled on the molecular and cellular levels as prerequisites for proper cognitive development. With additional insight emerging into the fundamentals of sensory stimulation and perception, we are entering a scientific era that ultimately will link metabolic needs with food preferences, hedonics and healthy nutrition.

Caffeine improves physical and cognitive performance during exhaustive exercise.

UNLABELLED: Caffeine is thought to act as a central stimulant and to have effects on physical, cognitive, and psychomotor functioning. PURPOSE: To examine the effects of ingesting a performance bar, containing caffeine, before and during cycling exercise on physical and cognitive performance. METHODS: Twenty-four well-trained cyclists consumed the products [a performance bar containing 45 g of carbohydrate and 100 mg of caffeine (CAF), an isocaloric noncaffeine performance bar (CHO), or 300 mL of placebo beverage (BEV)] immediately before performing a 2.5-h exercise at 60% VO2max followed by a time to exhaustion trial (T2EX) at 75% VO2max. Additional products were taken after 55 and 115 min of exercise. Cognitive function measures (computerized Stroop and Rapid Visual Information Processing tests) were performed before exercise and while cycling after 70 and 140 min of exercise and again 5 min after completing the T2EX ride. RESULTS: Participants were significantly faster after CAF when compared with CHO on both the computerized complex information processing tests, particularly after 140 min and after the T2EX ride (P < 0.001). On the BEV trial, performance was significantly slower than after both other treatments (P < 0.0001). There were no speed-accuracy tradeoffs (P > 0.10). T2EX was longer after CAF consumption compared with both CHO and BEV trials (P < 0.05), and T2EX was longer after CHO than after BEV (P < 0.05). No differences were found in the ratings of perceived exertion, mean heart rate, and relative exercise intensity (% VO2max; P > 0.05). CONCLUSION: Caffeine in a performance bar can significantly improve endurance performance and complex cognitive ability during and after exercise. These effects may be salient for sports performance in which concentration plays a major role.

Sex differences in the effect of acute tryptophan depletion on declarative episodic memory: a pooled analysis of nine studies.

Acute tryptophan depletion (ATD) studies have shown that serotonin plays a role in learning and memory processes. In this study, we performed a pooled analysis of nine ATD studies in order to examine the nature of the memory-impairing effects of ATD and mediating factors, such as gender, age and vulnerability for disease in which disturbed serotonin was hypothesized to play a role. All studies that were used in this pooled analysis assessed declarative episodic memory using a verbal learning task paradigm. Immediate recall, delayed recall, and delayed recognition scores were examined. A total of 211 participants were included in the analysis. The analysis revealed that ATD impaired not only delayed recall, but also immediate recall. The ATD-induced impairments were larger in females than in males. Furthermore, ATD did not interact with any other serotonergic vulnerability and age. This suggests that the only factor that actually has the properties of a serotonergic vulnerability factor for declarative memory performance is female gender. The findings provide further support for a critical role of serotonin in declarative episodic memory.

Effects of acute tryptophan depletion on mood and facial emotion perception related brain activation and performance in healthy women with and without a family history of depression.

The present study examined the effects of acute tryptophan (Trp) depletion (ATD), a well-recognized method to lower central serotonin (5-HT) metabolism, on brain activation during a facial emotion perception task. Brain activation was measured using fMRI, and healthy female volunteers with a positive family history of unipolar depression (FH+) were compared to healthy female volunteers without such a history (FH-). Participants viewed two morphed faces and were instructed to choose between the faces based either on the intensity of the emotional expression (direct task) or the gender of the face (incidental task). In the FH+ group, depletion led to the expected lowering of mood, which partly determined the effect of depletion on performance and brain activation. A stronger mood lowering effect was associated with less accurate performance on faces expressing a negative emotion in the incidental task and a stronger right amygdala response to fearful faces in comparison to happy faces. These results were explained in terms of a mood-induced bias leading to a stronger impact of the expressed negative emotion which subsequently leads to more interference in the incidental task and a stronger amygdala response. It was concluded that the effects of ATD on mood, performance, and brain activation in a facial emotion perception task depend on family history of depression. Performance and brain activation partly depend on the effect of ATD on mood.

Driving impairment in depressed patients receiving long-term antidepressant treatment.

BACKGROUND: Depression is a common mental disorder with cognitive deficits, but little information is available on the effects of antidepressant treatment on driving performance in depressed patients. AIMS: Assessing actual driving performance and cognition of depressed patients receiving long-term antidepressant treatment. MATERIALS AND METHODS: Performance was assessed in depressed patients receiving selective serotonin reuptake inhibitor (SSRI) or serotonin and noradrenalin reuptake inhibitor (SNRI) treatment for 6-52 weeks and in matched healthy controls by means of two standardised on-the-road driving tests and laboratory tests of cognition. RESULTS: Data showed poorer driving performance as indicated by a higher standard deviation of lateral position or 'weaving motion' in medicated patients relative to controls. Time to speed adaptation and critical flicker fusion threshold were also impaired in medicated patients. The Hamilton Depression Rating Scale scores in medicated patients were significantly higher as compared to that of controls. No other significant results between the two groups were demonstrated on the variables of the driving tests and laboratory tests of cognition. CONCLUSIONS: The depressed patients receiving long-term treatment with SSRI- and SNRI-type antidepressants show impaired driving performance. This impairment in driving performance can probably be attributed to residual depressive symptoms instead of the antidepressant treatment.

The effect of acute tryptophan depletion on the BOLD response during performance monitoring and response inhibition in healthy male volunteers.

RATIONALE: Serotonin (5-HT) was implicated in both clinical and experimental studies in flexible, goal-directed behavior. However, the way in which 5-HT manipulations affect brain activation patterns underlying different subprocesses of cognitive flexibility remains largely unknown. OBJECTIVES: The aim of this study was to investigate the effect of a transient lowering of 5-HT on brain activation during performance monitoring and response inhibition. MATERIALS AND METHODS: We used acute tryptophan depletion (ATD), a well-known method to reduce central 5-HT, to investigate the effect of a transient lowering of 5-HT on the blood-oxygen-level dependent (BOLD) response in an event-related functional MRI study. Thirteen healthy male volunteers performed a modified Go/NoGo task in a counterbalanced, placebo-controlled, within-subject design. RESULTS: ATD significantly lowered plasma tryptophan but did not affect mood and cognitive performance. ATD decreased the BOLD response in the dorsomedial prefrontal cortex (BA 8) during performance monitoring. ATD did not affect the BOLD response during response inhibition. CONCLUSIONS: This study provides more evidence for the suggested role of 5-HT in performance monitoring. Because ATD studies have revealed inconsistent effects of ATD on performance and on brain activation, it was suggested that gender and personality traits are important variables to take into account for future research.

Acute tryptophan depletion reduces activation in the right hippocampus during encoding in an episodic memory task.

Acute tryptophan depletion (ATD), a well-recognized method to lower central serotonin levels, was used to examine the effects of lower central serotonin levels on memory function in healthy males. Functional Magnetic Resonance Imaging (fMRI) was used to examine changes in brain activation during the encoding and the retrieval phase of a visual verbal episodic memory task. ATD led to more positively rated words in the encoding phase and to poorer recognition of these positively rated words in the retrieval phase. Furthermore, encoding was accompanied by enhanced brain activation in occipital, middle and superior frontal, anterior and posterior cingulate and striatal areas. Retrieval attempt was accompanied by enhanced activation in the cuneus, inferior occipital gyrus and inferior and middle frontal areas. Retrieval success was accompanied by activation in an extensive network including frontal, parietal, temporal, cingulate, striatal and cerebellar areas. In the encoding phase ATD attenuated activation in the right hippocampus and ATD did not affect brain activity in the retrieval phase. These results show that serotonin is important in long term memory processes, and that serotonin acts on the encoding phase and not on the retrieval phase.

Effects of 5-HT on memory and the hippocampus: model and data.

5-Hydroxytryptamine (5-HT) transmission has been implicated in memory and in depression. Both 5-HT depletion and specific 5-HT agonists lower memory performance, while depression is also associated with memory deficits. The precise neuropharmacology and neural mechanisms underlying these effects are unknown. We used neural network simulations to elucidate the neuropharmacology and network mechanisms underlying 5-HT effects on memory. The model predicts that these effects are largely dependent on transmission over the 5-HT1A and 5-HT3 receptors, which regulate the selectivity of retrieval. It also predicts differential memory deficit profiles for 5-HT depletion and overactivation. The latter predictions were confirmed in studies with healthy and depressed participants undergoing acute tryptophan depletion or ipsipirone challenge. The results suggest that the memory impairments in depressed subjects may be related to 5-HT undertransmission, and support the notion that 5-HT1A agonists ameliorate memory deficits in depression.

General methodological considerations for the assessment of nutritional influences on human cognitive functions.

The premise that cognitive functioning can be influenced through dietary means has gained widespread interest. The assessment of cognitive functioning is a key method to scientifically substantiate such nutritional effects on cognition. The current paper provides a basic overview of the main concepts, issues and pitfalls of human cognitive research. General methods of cognitive assessment, selection of appropriate tests, factors that may mediate task performance and issues pertaining to the interpretation of the results are discussed.