Criteria for validation and selection of cognitive tests for investigating the effects of foods and nutrients.

This review is an output of the International Life Sciences Institute (ILSI) Europe Marker Initiative, which aims to identify evidence-based criteria for selecting adequate measures of nutrient effects on health through comprehensive literature review. Experts in cognitive and nutrition sciences examined the applicability of these proposed criteria to the field of cognition with respect to the various cognitive domains usually assessed to reflect brain or neurological function. This review covers cognitive domains important in the assessment of neuronal integrity and function, commonly used tests and their state of validation, and the application of the measures to studies of nutrition and nutritional intervention trials. The aim is to identify domain-specific cognitive tests that are sensitive to nutrient interventions and from which guidance can be provided to aid the application of selection criteria for choosing the most suitable tests for proposed nutritional intervention studies using cognitive outcomes. The material in this review serves as a background and guidance document for nutritionists, neuropsychologists, psychiatrists, and neurologists interested in assessing mental health in terms of cognitive test performance and for scientists intending to test the effects of food or food components on cognitive function.

Brain imaging and human nutrition: which measures to use in intervention studies?

The present review describes brain imaging technologies that can be used to assess the effects of nutritional interventions in human subjects. Specifically, we summarise the biological relevance of their outcome measures, practical use and feasibility, and recommended use in short- and long-term nutritional studies. The brain imaging technologies described consist of MRI, including diffusion tensor imaging, magnetic resonance spectroscopy and functional MRI, as well as electroencephalography/magnetoencephalography, near-IR spectroscopy, positron emission tomography and single-photon emission computerised tomography. In nutritional interventions and across the lifespan, brain imaging can detect macro- and microstructural, functional, electrophysiological and metabolic changes linked to broader functional outcomes, such as cognition. Imaging markers can be considered as specific for one or several brain processes and as surrogate instrumental endpoints that may provide sensitive measures of short- and long-term effects. For the majority of imaging measures, little information is available regarding their correlation with functional endpoints in healthy subjects; therefore, imaging markers generally cannot replace clinical endpoints that reflect the overall capacity of the brain to behaviourally respond to specific situations and stimuli. The principal added value of brain imaging measures for human nutritional intervention studies is their ability to provide unique in vivo information on the working mechanism of an intervention in hypothesis-driven research. Selection of brain imaging techniques and target markers within a given technique should mainly depend on the hypothesis regarding the mechanism of action of the intervention, level (structural, metabolic or functional) and anticipated timescale of the intervention's effects, target population, availability and costs of the techniques.

Relationship between carbohydrate-deficient transferrin, gamma-glutamyl transferase, and mean corpuscular volume levels and alcohol-related brain volume decreases in male drinkers.

OBJECTIVE: We investigated the association between mean corpuscular volume (MCV), carbohydrate-deficient transferrin (CDT), and gamma-glutamyl transferase (GGT) levels and gray and white brain matter in male drinkers to find out which if any of these biomarkers of alcohol consumption is indicative for alcohol-related differences in brain volume. METHOD: Plasma levels of CDT, GGT, and MCV and magnetic resonance imaging-determined brain gray and white matter volumes were assessed in 55 male drinkers. Current alcohol intake and lifetime alcohol intake were determined by self-report measures. The relationship between MCV, CDT, and GGT and brain volumes was explored using multiple linear regression analyses. RESULTS: There was a significant negative relationship between plasma GGT and MCV levels and gray matter volumes. Middle-aged male drinkers with highly elevated GGT and MCV levels (twice the standard deviation above the mean) have 4-12% less parietal and occipital gray matter than males with average GGT and MCV levels. There was no association between CDT levels and brain gray or white matter. CONCLUSIONS: Elevated GGT and MCV levels may be indicative of alcohol-related gray-matter decline in male drinkers. The link with GGT may reflect that elevated GGT levels are a sign of increased oxidative stress. The link with MCV levels may reflect a decreased oxygen transport to the brain.

Assessing the effects of caffeine and theanine on the maintenance of vigilance during a sustained attention task.

Caffeine and L-theanine, both naturally occurring in tea, affect the ability to make rapid phasic deployments of attention to locations in space as reflected in behavioural performance and alpha-band oscillatory brain activity (8-14 Hz). However, surprisingly little is known about how these compounds affect an aspect of attention that has been more popularly associated with tea, namely vigilant attention: the ability to maintain focus on monotonous tasks over protracted time-periods. Twenty-seven participants performed the Sustained Attention to Response Task (SART) over a two-hour session on each of four days, on which they were administered caffeine (50 mg), theanine (100 mg), the combination, or placebo in a double-blind, randomized, cross-over fashion. Concurrently, we recorded oscillatory brain activity through high-density electroencephalography (EEG). We asked whether either compound alone, or both in combination, would affect performance of the task in terms of reduced error rates over time, and whether changes in alpha-band activity would show a relationship to such changes in performance. When treated with placebo, participants showed a rise in error rates, a pattern that is commonly observed with increasing time-on-task, whereas after caffeine and theanine ingestion, error rates were significantly reduced. The combined treatment did not confer any additional benefits over either compound alone, suggesting that the individual compounds may confer maximal benefits at the dosages employed. Alpha-band oscillatory activity was significantly reduced on ingestion of caffeine, particularly in the first hour. This effect was not changed by addition of theanine in the combined treatment. Theanine alone did not affect alpha-band activity.

Relationships between tea and other beverage consumption to work performance and mood.

The aim of this research was to examine relationships between tea, coffee and other beverage consumption and associates of work performance and mood among individuals in relatively stressful and cognitively demanding work-place settings. Using a naturalistic, cross-sectional study design, 95 professional and academic staff logged their beverage intake and completed self-reports of associates of work performance (fatigue/exhaustion, mindfulness, work engagement), subjective work performance, mood, work-related strain and recovery four times daily during ten working days. Data were analysed using multilevel modelling in keeping with the hierarchical structure of the data. Tea consumption was associated with increased perceived work performance and reduced tiredness, especially when consumed without milk or sugar. Consumption of non-caffeinated beverages was associated with increased relaxation and recovery from work. In contrast, tea and other caffeinated beverages were found to enhance the negative effects of evening recovery and morning mood on mindfulness during the day. The findings suggest that beverage intake may have a role in optimising work-related psychological states and performance.

Age-related differences in brain electrical activity during extended continuous face recognition in younger children, older children and adults.

To examine the development of recognition memory in primary-school children, 36 healthy younger children (8-9 years old) and 36 healthy older children (11-12 years old) participated in an ERP study with an extended continuous face recognition task (Study 1). Each face of a series of 30 faces was shown randomly six times interspersed with distracter faces. The children were required to make old vs. new decisions. Older children responded faster than younger children, but younger children exhibited a steeper decrease in latencies across the five repetitions. Older children exhibited better accuracy for new faces, but there were no age differences in recognition accuracy for repeated faces. For the N2, N400 and late positive complex (LPC), we analyzed the old/new effects (repetition 1 vs. new presentation) and the extended repetition effects (repetitions 1 through 5). Compared to older children, younger children exhibited larger frontocentral N2 and N400 old/new effects. For extended face repetitions, negativity of the N2 and N400 decreased in a linear fashion in both age groups. For the LPC, an ERP component thought to reflect recollection, no significant old/new or extended repetition effects were found. Employing the same face recognition paradigm in 20 adults (Study 2), we found a significant N400 old/new effect at lateral frontal sites and a significant LPC repetition effect at parietal sites, with LPC amplitudes increasing linearly with the number of repetitions. This study clearly demonstrates differential developmental courses for the N400 and LPC pertaining to recognition memory for faces. It is concluded that face recognition in children is mediated by early and probably more automatic than conscious recognition processes. In adults, the LPC extended repetition effect indicates that adult face recognition memory is related to a conscious and graded recollection process rather than to an automatic recognition process.

L-theanine and caffeine improve task switching but not intersensory attention or subjective alertness.

Tea ingredients L-theanine and caffeine have repeatedly been shown to deliver unique cognitive benefits when consumed in combination. The current randomized, placebo-controlled, double-blind, cross-over study compared a combination of L-theanine (97 mg) and caffeine (40 mg) to a placebo on two attention tasks and a self-report questionnaire before, and 10 and 60 min after consumption. The combination of L-theanine and caffeine significantly improved attention on a switch task as compared to the placebo, while subjective alertness and intersensory attention were not improved significantly. The results support previous evidence that L-theanine and caffeine in combination can improve attention.

Age-related differences in brain activity during extended continuous word recognition in children.

To examine the development of verbal recognition memory in primary-school children, 36 healthy younger children (8-9 years old) and 36 healthy older children (11-12 years old) participated in an ERP study with an extended continuous recognition task. Each word of a series of 30 words was shown randomly for six times interspersed with distracter words. The children were required to make old versus new decisions. The data analyses focused on old/new effects (repetition 1 vs. new word) and multiple repetition effects (repetitions 1 through 5) for the N1, P2, N400, and the late positive complex (LPC, 500-800 ms after stimulus onset). Younger children exhibited a strong P2 multiple repetition effect across left lateral regions, with P2 amplitudes increasing linearly with the number of word repetitions. Compared to younger children, older children exhibited a much stronger N400 old/new effect across parietal regions. Old/new and repetition effects for N1 and LPC were similar in both age groups. Correlational analysis showed that in older children, larger N400 old/new effects on the continuous recognition task were moderately associated with better verbal learning on an auditory verbal learning task. In both age groups, the gain in recognition accuracy over multiple repetitions correlated with the LPC repetition effect. The age differences in P2 repetition effects and N400 old/new effects suggest that in younger children whole-word orthographic representations are dependent on the strength of the memory trace and that lexical-semantic representations develop with age. The LPC results suggest that recollection plays a substantial role in recognition memory of both younger and older children.

The influence of carbohydrate on cognitive performance: a critical evaluation from the perspective of glycaemic load.

Links between nutrition and cognition are widely acknowledged. Within the context of short-term cognitive performance, carbohydrate has been the dietary component most commonly investigated. The majority of studies investigating the influence of carbohydrate on cognitive performance have employed oral glucose drink interventions followed by measures of performance on cognitive tests. More recently, studies have investigated the effect of different carbohydrates on cognitive performance rather than just pure glucose drinks. To date, studies have not been evaluated based on a standardised measure of glycaemic response, such as glycaemic load. The present review provides a critical evaluation of eight studies that have explored the relationships between food carbohydrate and cognitive performance and allow glycaemic load to be used as a basis for comparison. The key finding is that these provide insufficient evidence to support a consistent effect of glycaemic load on short-term cognitive performance. Future studies should employ consistent test methodologies and describe food interventions in more detail to facilitate meaningful comparisons and interpretations of results.

Effects of food energy on cognitive performance: no support from event-related potentials (yet?).

Several reviews of behavioural studies have concluded that some foods may have beneficial effects on cognitive performance. The present review summarises findings from studies using event-related potentials to investigate the food effects on brain activity underlying cognition. Despite initial positive indications from observational studies, subsequent studies with a within-subject design have not consistently confirmed these effects. This could be due to several factors, e.g. the use of attention tests (in contrast to memory tests employed in behavioural studies) and the lack of a control condition in some instances. Future studies could benefit from measuring cognitive performance with more difficult tests that tap into cognitive domains other than attention, using an appropriately controlled cross-over design, and a more systematic variation and complete description and characterisation of the food intervention.

The combined effects of L-theanine and caffeine on cognitive performance and mood.

The aim of this study was to compare 50 mg caffeine, with and without 100 mg L-theanine, on cognition and mood in healthy volunteers. The effects of these treatments on word recognition, rapid visual information processing, critical flicker fusion threshold, attention switching and mood were compared to placebo in 27 participants. Performance was measured at baseline and again 60 min and 90 min after each treatment (separated by a 7-day washout). Caffeine improved subjective alertness at 60 min and accuracy on the attention-switching task at 90 min. The L-theanine and caffeine combination improved both speed and accuracy of performance of the attention-switching task at 60 min, and reduced susceptibility to distracting information in the memory task at both 60 min and 90 min. These results replicate previous evidence which suggests that L-theanine and caffeine in combination are beneficial for improving performance on cognitively demanding tasks.

Effects of chronic drinking on verb generation: an event related potential study.

In alcohol dependent individuals, abnormalities in brain functioning have been revealed using event-related potential (ERP) methods. In the present study, we investigated whether in non-alcohol dependent drinkers functioning of the brain is also compromised as a function of recent and lifetime drinking history (LDH). An ERP verb generation task consisting of two conditions (generating verbs describing the use of visually presented nouns versus reading nouns aloud) was used; subtracting ERPs in the latter condition from those in the former should reveal the sequence of brain processes involved in verb generation. Four groups were included, consisting of individuals drinking either lightly, moderately, heavily, or excessively (overall mean age 46.6 years). Participants were sober at the time of testing. Although the excessive group had the highest per cent retrieval errors, there was no continuous relationship between this score and amount of alcohol consumption. However, number of glasses per week affected differential ERPs associated with verb generation both at short (120-220 ms, mid-frontal sites) and at longer latencies (from 700 ms on),left-temporal and right-frontal electrode sites (T7, F6). It is concluded that moderate, heavy, and excessive drinkers, compared to light drinkers, show abnormal brain potentials associated with verb generation over frontal and temporal areas. Moderate to excessive drinking alters some but not all brain processes involved in verb generation. In particular the frontal and temporal brain areas appear to be vulnerable for the effects of chronic lifetime drinking.

Consumption of a mid-morning snack improves memory but not attention in school children.

Muthayya, S., T. Thomas, K. Srinivasan, K. Rao, A. V. Kurpad, J.-W. Van Klinken, G. Owen and E.A. de Bruin: Consumption of a mid-morning snack improves memory but not attention in school children. Physiol Behav 00(0) 000-000, 2006.--This study aimed to determine whether consumption of a mid-morning snack with appropriate energy compensation through a smaller breakfast or lunch, resulted in improved cognitive performance of 7-9 year old children with a low and high socioeconomic status (LSES and HSES, n=35 and 34 respectively). The children were each randomly assigned to three iso-caloric dietary interventions: control (standard breakfast, no snack and standard lunch), intervention A (small breakfast, snack, and standard lunch) and intervention B (standard breakfast, snack, and small lunch), using a cross-over design. The children were tested on three different days, each one week apart. Computerised tests of cognitive performance, consisting of memory, sustained attention and psychomotor speed, were performed during four sessions, i.e., prior to breakfast, after breakfast, after a mid-morning snack and after lunch. Having a mid-morning snack resulted in a smaller decline in immediate and delayed memory in LSES but not in HSES children. Having a snack did not influence sustained attention and psychomotor speed in either LSES or HSES children. This study shows that a more evenly distributed energy intake throughout the morning by consuming a mid-morning snack improves memory performance in school-age LSES children even when the total amount of energy consumed during the morning is not altered.

Moderate-to-heavy alcohol intake is associated with differences in synchronization of brain activity during rest and mental rehearsal.

In alcohol-dependent individuals, synchronization of brain activity is different from that in non-alcohol-dependent individuals as reflected by EEG differences at alpha and beta frequencies (8-30 Hz). These EEG differences may not only be related to long-term alcohol intake but also to genetic factors that are associated with alcohol dependence. Thus, it is not known what the pure effect of long-term alcohol intake on synchronization of brain activity is. Therefore, we investigated whether EEG synchronization differs between light (0.5-6 drinks per week), moderate (7-20 drinks per week), and heavy (21-53 drinks per week) drinkers. All participants (49 males and 47 females) were free of a personal and family history of alcohol dependence. Eyes-closed EEG was recorded at rest and during mental rehearsal of pictures. EEG synchronization was determined by computing Synchronization Likelihood for six frequency bands (0.5-4 Hz, 4-8 Hz, 8-12 Hz, 12-20 Hz, 20-30 Hz, 30-45 Hz). Both male and female heavy drinkers displayed a loss of lateralization in alpha (8-12 Hz) and slow-beta (12-20 Hz) synchronization. In addition, moderately and heavily drinking males had lower fast-beta (20-30 Hz) synchronization than lightly drinking males. It is concluded that both male and female drinkers who drink 21 alcoholic drinks per week or more have impaired synchronization of brain activity during rest and mental rehearsal at alpha and beta frequencies as compared to individuals who drink less. As individuals with a personal or family history of alcohol dependence were excluded, the confounding effects of genetic factors related to alcohol dependence on synchronization of brain activity were minimized.

Effects of chronic alcohol consumption in a visual attention task and an auditory oddball task: an event-related potential study.

BACKGROUND: In alcohol-dependent individuals changes in brain functioning, as measured with Event Related Potentials (ERP) have been reported. METHODS: In the present study a visual attention and an auditory oddball task were used to investigate possible differences between light, moderate, and heavy social drinkers and excessive drinkers. It was hypothesized that with increasing alcohol intake an increasing number of ERP components elicited in the visual attention task and the auditory oddball task would show diminished amplitudes. RESULTS: No differences were found between light, moderate, and heavy social drinkers. A trend for a smaller P3 amplitude in the visual attention task was found when comparing the alcohol-dependent participants with the light social drinkers. It is argued that this difference might be an effect of alcohol dependence and/or a reflection of possible unknown or undetected family history of alcohol-related disturbances. CONCLUSIONS: In the current study, even at rather large amounts of regular alcohol intake, no evidence was found for any toxic effect of social alcohol use neither in a visual attention task nor in an auditory oddball task.

Health risks of chronic moderate and heavy alcohol consumption: how much is too much?

This article presents the proceedings of a symposium held at the meeting of the International Society for Biomedical Research on Alcoholism (ISBRA) in Mannheim, Germany, in October 2004. Most of what we know about the deleterious effects of alcohol in vivo has been gleaned from studies in sober alcoholics recruited from substance abuse treatment programs. Little is known about effects of chronic drinking in the moderate or heavy range encountered in a much larger fraction of modern society. Extrapolation of information on the adverse effects of chronic drinking on organ function from clinical samples to social drinkers in the general population has to be met with great skepticism, as it may lead to wrong conclusions about the chronic effects of alcohol in social drinkers. Several recent studies suggest that moderate alcohol consumption has certain beneficial health effects, whereas heavy social alcohol consumption has recently been associated with organ abnormalities and cognitive deficits. These social drinking effects have attracted great public interest; reports of benefits of moderate drinking have also inspired inappropriate publications by the media, including misleading advertisements by the alcohol producing and distributing industry. Although adverse effects of moderate to heavy drinking on heart, liver, and cancer development have attracted attention by clinicians and researchers for some time, its compromising effects on brain and cognition have only recently been studied. This symposium brought together researchers from different disciplines, who reviewed and presented new data on consequences of social drinking in the areas of clinical neuropsychology and behavior (Drs. Nixon and Meyerhoff), neurophysiology (Dr. Nixon, Ms. De Bruin), neuroimaging (Ms. de Bruin, Dr. Meyerhoff), hepatic disease (Dr. Bode), and cancer (Dr. Seitz). The symposium aimed to clarify both the potential health benefits of moderate alcohol consumption and risks of moderate and heavy drinking on proper organ function and to provide insights and new data to practicing physicians and public health authorities for education on problem drinking.

Focal brain matter differences associated with lifetime alcohol intake and visual attention in male but not in female non-alcohol-dependent drinkers.

The purpose of this study was to investigate whether current or lifetime alcohol intake is related to focal gray and white matter in healthy non-alcohol-dependent drinkers, and, if so, whether these densities are related to functional brain activity associated with visual attention. Voxel-based morphometric analyses of gray- and white-matter densities, and event-related potentials in response to a visual-attention task were determined in 47 male drinkers (current alcohol intake 20 drinks per week, lifetime alcohol intake 240 kg) and 44 female drinkers (current alcohol intake 15 drinks per week, lifetime alcohol intake 170 kg). All participants had a negative personal and family history of alcohol dependence to reduce possible confounding by genetic factors related to alcohol dependence. In males, mean lifetime alcohol intake was negatively associated with gray-matter density and positively associated with white-matter density in the right frontal gyrus (BA 6) and the right parietal region (BA 40). Right frontal (but not right parietal) gray and white matter in males correlated with the P3 amplitude of the event-related potentials elicited in a visual-attention task. In females, mean lifetime alcohol intake was not associated with gray- or white-matter density. Current alcohol intake was unrelated to gray or white matter in both males and females. In conclusion, lifetime alcohol intake is associated with focal gray-matter decreases and white-matter increases in the right frontal and right parietal brain regions in non-alcohol-dependent males, but not in females. These alcohol-related differences in focal brain matter in males are associated with differences in brain function related to visual attention. As the confounding effects of genetic factors were reduced, the present results may selectively relate to the effects of alcohol intake on focal brain matter.

Associations between alcohol intake and brain volumes in male and female moderate drinkers.

BACKGROUND: Alcohol-dependent individuals have brain volume loss. Possibly, moderate drinkers who are not alcohol dependent have similar but less prominent brain damage. The authors investigated whether current or lifetime alcohol intake is related to volumes of total brain, cerebellum, ventricles, peripheral cerebrospinal fluid, and cerebral gray and white matter in moderate drinkers. METHODS: The relation between current or lifetime alcohol intake and brain volumes of 47 male moderate drinkers (current alcohol intake 20 drinks per week, lifetime alcohol intake 240 kg) and 44 female moderate drinkers (current alcohol intake 15 drinks per week, lifetime alcohol intake 170 kg), all without a personal or family history of alcohol dependence, was determined using high-resolution magnetic resonance images, corrected for intracranial volume, age, and sex. RESULTS: In males, mean lifetime alcohol intake was positively associated with cerebral white matter volume, particularly in the frontal region. In females, mean lifetime alcohol intake was not associated with brain volumes. Current alcohol intake was unrelated to brain volumes in either males or females. CONCLUSIONS: Neither current nor lifetime alcohol intake is associated with decreases in brain volumes in male or female moderate drinkers. Because all participants had a negative personal and family history of alcohol dependence, the current results relatively purely concern the effects of moderate alcohol intake on brain volumes.

Chronic effects of social drinking in a card-sorting task: an event related potential study.

OBJECTIVE: The Wisconsin Card Sorting Task (WCST) is one of the most widely used neuropsychological tests of frontal lobe function, which is thought to be affected by regular alcohol use. The present study used a computer-adapted version of the WCST to assess the effects of chronic alcohol consumption on the brain. METHODS: Participants (N=59) sorted cards according to an initially unknown sorting rule, which referred to shape, number, or color. The correctness of the chosen sorting rule was indicated by a feedback stimulus. This correct sorting rule had to be followed for a number of stimuli, and when it changed participants had to find out which rule had to be followed next. A distinction was made between early (correct sorting rule is unknown) and late trials (correct sorting rule is known and applied). To measure brain activity related during the task event related potentials (ERPs) were recorded to the target and feedback stimulus in light (N=14), moderate (N=16) and heavy (N=19) social drinkers and excessive alcohol users (N=10). RESULTS: No differences in number of series completed or the reaction time in each trial, were found between the four groups. In contrast, a mid-frontal N1 component in reaction to the feedback stimuli did reveal differences between the four groups. In the light and moderate drinkers, on early feedback trials the N1 was larger relative to late feedback trials, but this effect was absent in the heavy social drinkers and excessive drinkers. CONCLUSIONS: The reduced N1 effect with increasing alcohol intake could reflect abnormal allocation of attention or impaired conflict monitoring, possibly based on activity in the anterior cingulate cortex. SIGNIFICANCE: Heavy social drinking and excessive drinking leads to changes in the mid-frontal N1 during feedback trials of the WCST.

Abnormal EEG synchronisation in heavily drinking students.

OBJECTIVE: In alcoholics, grey and white brain matter is damaged. In addition, functional brain connectivity as measured by EEG coherence is abnormal. We investigated whether heavily drinking students, although drinking for a shorter period than alcoholics, already show differences in functional connectivity compared to light-drinking controls. METHODS: EEG was recorded in 11 light and 11 heavy male student drinkers during eyes closed, and eyes closed plus mental rehearsal of pictures. Functional connectivity was assessed with the Synchronisation Likelihood method. RESULTS: Heavily drinking students had more synchronisation in the theta (4-8 Hz) and gamma (30-45 Hz) band than lightly drinking students during eyes closed, both with and without a mental-rehearsal task. CONCLUSIONS: Heavy student drinkers have increases in EEG synchronisation that are indicative of changes in hippocampal-neocortical connectivity. SIGNIFICANCE: Heavy student drinkers show differences in functional connectivity as compared to their lightly drinking counterparts, even though they have a relatively short drinking history.