The Acute Effect of a Walnut Intervention on Cognitive Performance, Brain Activation, and Serum Markers of Inflammation in Young Adults

Study Overview
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Brief Summary
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This study investigates the effect of acute walnut consumption on the cognitive behaviour, mood, brain activation, and markers of inflammation in young adults. In a within subjects design participants will receive a 50 g walnut or placebo intervention in a randomised order with a one week washout between interventions.

Detailed Description
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Participants will attend two test session days separated by a 7 day wash out period. The procedure on each day will be identical save for the intervention breakfast which will either be a walnut rich muesli containing 50g walnut and 50g mixed cereal ingredients (active intervention), or control muesli containing 100g mixed cereal ingredients (placebo intervention). The order of intervention will be randomised such that 50% of participants receive the active intervention during visit 1 and 50% during visit 2. Participants will be required to follow a low flavonoid diet for 48 hours in advance of testing and to fast (water only) for the final 12 hours of this period. The test day will be 8hrs in total starting at 0830. Cognitive Measures: There will be four cognitive task battery sessions taking place at baseline, then 2, 4, and 6 hours following intervention. The cognitive battery will last for 30 minutes and include: Auditory Verbal Learning Task (AVLT) - Participants hear and recall a list of 15 words on 8 occasions followed by a forced choice visual recognition task (10 minutes duration). Modified Attention Network Task (MANT) - Participants view different arrays of arrows displayed on a monitor and respond by indicating the direction of the arrow closest to a central fixation point (8 minutes duration). Switching Task - Participants view eight equally spaced radii of circle displayed in such a way that there are four equally spaced segments above and below a bold line. Stimulus digits selected from between 1 - 9 (excluding 5) appear in each segment in turn. Participants respond to digits above the bold line in terms of whether they are odd or even and below the bold line in terms of whether they are above or below the number 5 (10 minutes duration). PANAS-NOW - This measure of trait mood will be completed at the beginning and end of each task battery giving a total of 8 measurements across the day. Participants rate the extent to which they are experiencing 20 different emotions on a 5-point Likert scale ranging from 'very slightly' to 'very much' (1 minute duration). EEG: All participants will be tested in our dedicated lab within the Reading University Centre for Integrative Neuroscience and Neurodynamics using the Brain Products EEG system with 32 channel active electrode caps. At Baseline, 2, 4 and 6 hrs waveband PSD data will be recorded during all tasks with specific attention being paid to the theta bandwidth during the AVLT and gamma bandwidth during the executive function tasks. ERP data, anchored to each trial of the executive function tasks, will also be considered with specific attention being given to latency and strength of N1 and P3 peaks. Bloods: Participants will have bloods taken twice on each test visit with a draw being taken from each arm. The initial draw will be taken immediately prior to the baseline task battery and then immediately prior to either the 2, 4 or 6 hr session with the second draw time being randomised in such a way that 16 participants will have blood drawn at 2hrs, 16 at 4hrs, and 16 at 6hrs. Following each draw, the blood samples will be left to clot for 30-60 minutes. The serum will be separated via centrifuge and stored at at -80°C until analysis is complete. Whole blood samples will not be stored at any point during the study. Blood serum will be analysed for anti-inflammatory ability, as well as levels of BDNF, a signalling protein known to be positively related to memory function. To determine possible mechanisms of action of walnut components through which the walnut polyphenols produce their beneficial effects, microglial cells from rats will be exposed to serum from participants in both walnut and placebo conditions prior to exposure to an inflammatory challenge (LPS). Markers of inflammation will then be assessed including extracellular release of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α) as well as intracellular levels of inducible nitrous oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). We will then determine if those subjects with the most protective serum in the cell model are those with the better cognitive performance. Appetite Measures: Ratings of subjective appetite and fullness will be taken using visual analogue scales after baseline, breakfast, and each of the remaining test sessions. As a further measure of satiety, weighted food measurements will be taken before and after consumption of the standard low flavonoid/PUFA lunch (given immediately after task battery session 3 at 1330) to ascertain total food consumption.

Official Title
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The Acute Effect of a Walnut Intervention on Cognitive Performance , Brain Activation, and Serum Markers of Inflammation in Young Adults

Conditions
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Cognitive Change, Mood, Inflammatory Response, Brain Derived Neurotrophic Factor Level, Satiety

Intervention / Treatment
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* Other: Control
* Other: 50 g Walnut


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Normal or corrected hearing and vision Exclusion Criteria: Smoker. Allergic to treatment contents. Currently on medication which may interfere with the treatment Anaemic

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Participants will be assigned to both the walnut and control conditions in a randomised order.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Control - 50g Walnut<br>Control condition followed by experimental condition. | Other: Control<br>* 100 grams breakfast cereal<br>Other: 50 g Walnut<br>* 50 grams walnuts mixed with 50 gram breakfast cereal.<br>|
| Experimental: 50 g Walnut - Control<br>Experimental condition followed by control condition. | Other: Control<br>* 100 grams breakfast cereal<br>Other: 50 g Walnut<br>* 50 grams walnuts mixed with 50 gram breakfast cereal.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Delayed Recall | AVLT - Recall of a previously presented list of words following a 25 minute delay. | 2 hours following intervention. | 
| Delayed Recall | AVLT - Recall of a previously presented list of words following a 25 minute delay. | 4 hours following intervention. | 
| Delayed Recall | AVLT - Recall of a previously presented list of words following a 25 minute delay. | 6 hours following intervention. | 
| Word Recognition | AVLT - Visual Recognition of a previously presented list of words following a 25 minute delay. | 2 hours following intervention. | 
| Word Recognition | AVLT - Visual Recognition of a previously presented list of words following a 25 minute delay. | 4 hours following intervention. | 
| Word Recognition | AVLT - Visual Recognition of a previously presented list of words following a 25 minute delay. | 6 hours following intervention. | 
| Response interference accuracy | Accuracy performance on the Modified Attention Network Task | 2 hours following intervention. | 
| Response interference accuracy | Accuracy performance on the Modified Attention Network Task | 4 hours following intervention. | 
| Response interference accuracy | Accuracy performance on the Modified Attention Network Task | 6 hours following intervention. | 
| Response interference reaction time | Reaction time performance on the Modified Attention Network Task | 2 hours following intervention | 
| Response interference reaction time | Reaction time performance on the Modified Attention Network Task | 4 hours following intervention | 
| Response interference reaction time | Reaction time performance on the Modified Attention Network Task | 6 hours following intervention | 
| Switching Task Accuracy | Accuracy performance on the switching task | 2 hours following intervention | 
| Switching Task Accuracy | Accuracy performance on the switching task | 4 hours following intervention | 
| Switching Task Accuracy | Accuracy performance on the switching task | 6 hours following intervention | 
| Switching Task reaction time | Reaction time performance on the switching task | 2 hours following intervention | 
| Switching Task reaction time | Reaction time performance on the switching task | 4 hours following intervention | 
| Switching Task reaction time | Reaction time performance on the switching task | 6 hours following intervention | 
| N2 | Change in ERP measure of N2 latency and amplitude | 2 hours following intervention | 
| N2 | Change in ERP measure of N2 latency and amplitude | 4 hours following intervention | 
| N2 | Change in ERP measure of N2 latency and amplitude | 6 hours following intervention | 
| P3 | Change in ERP measure of P3 latency and amplitude | 2 hours following intervention | 
| P3 | Change in ERP measure of P3 latency and amplitude | 4 hours following intervention | 
| P3 | Change in ERP measure of P3 latency and amplitude | 6 hours following intervention | 
| Inflammatory Measure of nitrous oxide, tumor necorsis factor-alpha, inducible nitrous oxide synthase, and tumor necrosis facor-alpha. | Change in blood serum markers of inflammation | 2 hours following intervention | 
| Inflammatory Measure of nitrous oxide, tumor necorsis factor-alpha, inducible nitrous oxide synthase, and tumor necrosis facor-alpha. | Change in blood serum markers of inflammation | 4 hours following intervention | 
| Inflammatory Measure of nitrous oxide, tumor necorsis factor-alpha, inducible nitrous oxide synthase, and tumor necrosis facor-alpha. | Change in blood serum markers of inflammation | 6 hours following intervention | 
| BDNF | Change in blood serum levels of BDNF | 2 hours following intervention | 
| BDNF | Change in blood serum levels of BDNF | 4 hours following intervention | 
| BDNF | Change in blood serum levels of BDNF | 6 hours following intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual analogue measure of hunger, satiety, fullness, and prospective food consumption (Flint et al., 2000). | Satiety Measure recorded on a 100 millimetre scale. Scores closer to 0 millimetres indicate less hunger - taken as a positive outcome, less satiety - taken as a negative outcome, less fullness - taken as a negative outcome, and less desire for prospective food consumption - taken as a positive. | 2 hours following intervention. | 
| Visual analogue measure of hunger, satiety, fullness, and prospective food consumption (Flint et al., 2000). | Satiety Measure recorded on a 100 millimetre scale. Scores closer to 0 millimetres indicate less hunger - taken as a positive outcome, less satiety - taken as a negative outcome, less fullness - taken as a negative outcome, and less desire for prospective food consumption - taken as a positive. | 4 hours following intervention. | 
| Visual analogue measure of hunger, satiety, fullness, and prospective food consumption (Flint et al., 2000). | Satiety Measure recorded on a 100 millimetre scale. Scores closer to 0 millimetres indicate less hunger - taken as a positive outcome, less satiety - taken as a negative outcome, less fullness - taken as a negative outcome, and less desire for prospective food consumption - taken as a positive. | 6 hours following intervention. | 
| EEG Spectral Analysis. | Changes in Power for Alpha, Beta, Gamma, Delta, and Theta bands during performance of each cognitive task. | 2 hours following intervention. | 
| EEG Spectral Analysis. | Changes in Power for Alpha, Beta, Gamma, Delta, and Theta bands during performance of each cognitive task. | 4 hours following intervention. | 
| EEG Spectral Analysis. | Changes in Power for Alpha, Beta, Gamma, Delta, and Theta bands during performance of each cognitive task. | 6 hours following intervention. | 
| Immediate Recall | AVLT - Immediate recall following first presentation of the word list | 2 hours following intervention | 
| Immediate Recall | AVLT - Immediate recall following first presentation of the word list | 4 hours following intervention | 
| Immediate Recall | AVLT - Immediate recall following first presentation of the word list | 6 hours following intervention | 
| Word Learning | AVLT - Area under the curve for first five word list recalls. | 2 hours following intervention | 
| Word Learning | AVLT - Area under the curve for first five word list recalls. | 4 hours following intervention | 
| Word Learning | AVLT - Area under the curve for first five word list recalls. | 6 hours following intervention | 
| Total Recall | AVLT - Sum of first 5 word list recalls. | 2 hours following intervention. | 
| Total Recall | AVLT - Sum of first 5 word list recalls. | 4 hours following intervention. | 
| Total Recall | AVLT - Sum of first 5 word list recalls. | 6 hours following intervention. | 
| Final Acquisition | AVLT - Immediate recall following final presentation of the word list | 2 hours following intervention | 
| Final Acquisition | AVLT - Immediate recall following final presentation of the word list | 4 hours following intervention | 
| Final Acquisition | AVLT - Immediate recall following final presentation of the word list | 6 hours following intervention | 
| Interference List Recall | AVLT - Immediate recall of second (interference) list. | 2 hours following intervention. | 
| Interference List Recall | AVLT - Immediate recall of second (interference) list. | 4 hours following intervention. | 
| Interference List Recall | AVLT - Immediate recall of second (interference) list. | 6 hours following intervention. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Flavonoid, Omega 3 Fatty Acid