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

Cognitive Change Clinical Trial

— WalCog  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04075448
• Other study ID #: RDG-005
• Status: Completed
• Phase: N/A
• Start date: November 8, 2019
• Est. completion date: October 30, 2020

Study information

• Verified date: August 2021
• Source: University of Reading
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: October 30, 2020
• Est. primary completion date: October 30, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 30 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain Derived Neurotrophic Factor Level
• Cognitive Change
• Inflammation
• Inflammatory Response
• Mood
• Satiety

Intervention

Other:
• Control
100 grams breakfast cereal
• 50 g Walnut
50 grams walnuts mixed with 50 gram breakfast cereal.

Locations

Country	Name	City	State
United Kingdom	University of Reading	Reading	Berkshire

Sponsors (3)

Lead Sponsor	Collaborator
University of Reading	California Walnut Commission, Tufts University

Country where clinical trial is conducted

United Kingdom, 

References & Publications (17)

Bell L, Lamport DJ, Butler LT, Williams CM. A Review of the Cognitive Effects Observed in Humans Following Acute Supplementation with Flavonoids, and Their Associated Mechanisms of Action. Nutrients. 2015 Dec 9;7(12):10290-306. doi: 10.3390/nu7125538. Review. — View Citation

Carey AN, Fisher DR, Joseph JA, Shukitt-Hale B. The ability of walnut extract and fatty acids to protect against the deleterious effects of oxidative stress and inflammation in hippocampal cells. Nutr Neurosci. 2013 Jan;16(1):13-20. doi: 10.1179/1476830512Y.0000000023. Epub 2012 Dec 4. — View Citation

Fisher DR, Poulose SM, Bielinski DF, Shukitt-Hale B. Serum metabolites from walnut-fed aged rats attenuate stress-induced neurotoxicity in BV-2 microglial cells. Nutr Neurosci. 2017 Feb;20(2):103-109. doi: 10.1179/1476830514Y.0000000150. Epub 2016 Mar 2. — View Citation

Flint A, Raben A, Blundell JE, Astrup A. Reproducibility, power and validity of visual analogue scales in assessment of appetite sensations in single test meal studies. Int J Obes Relat Metab Disord. 2000 Jan;24(1):38-48. — View Citation

Gómez-Pinilla F. Brain foods: the effects of nutrients on brain function. Nat Rev Neurosci. 2008 Jul;9(7):568-78. doi: 10.1038/nrn2421. Review. — View Citation

Haider S, Batool Z, Tabassum S, Perveen T, Saleem S, Naqvi F, Javed H, Haleem DJ. Effects of walnuts (Juglans regia) on learning and memory functions. Plant Foods Hum Nutr. 2011 Nov;66(4):335-40. doi: 10.1007/s11130-011-0260-2. — View Citation

Martínez-Lapiscina EH, Clavero P, Toledo E, Estruch R, Salas-Salvadó J, San Julián B, Sanchez-Tainta A, Ros E, Valls-Pedret C, Martinez-Gonzalez MÁ. Mediterranean diet improves cognition: the PREDIMED-NAVARRA randomised trial. J Neurol Neurosurg Psychiatry. 2013 Dec;84(12):1318-25. doi: 10.1136/jnnp-2012-304792. Epub 2013 May 13. — View Citation

Miller MG, Thangthaeng N, Poulose SM, Shukitt-Hale B. Role of fruits, nuts, and vegetables in maintaining cognitive health. Exp Gerontol. 2017 Aug;94:24-28. doi: 10.1016/j.exger.2016.12.014. Epub 2016 Dec 21. — View Citation

Nooyens AC, Bueno-de-Mesquita HB, van Boxtel MP, van Gelder BM, Verhagen H, Verschuren WM. Fruit and vegetable intake and cognitive decline in middle-aged men and women: the Doetinchem Cohort Study. Br J Nutr. 2011 Sep;106(5):752-61. doi: 10.1017/S0007114511001024. Epub 2011 Apr 11. — View Citation

O'Brien J, Okereke O, Devore E, Rosner B, Breteler M, Grodstein F. Long-term intake of nuts in relation to cognitive function in older women. J Nutr Health Aging. 2014 May;18(5):496-502. doi: 10.1007/s12603-014-0014-6. — View Citation

Pérez-Cano FJ, Castell M. Flavonoids, Inflammation and Immune System. Nutrients. 2016 Oct 21;8(10). pii: E659. — View Citation

Poulose SM, Bielinski DF, Shukitt-Hale B. Walnut diet reduces accumulation of polyubiquitinated proteins and inflammation in the brain of aged rats. J Nutr Biochem. 2013 May;24(5):912-9. doi: 10.1016/j.jnutbio.2012.06.009. Epub 2012 Aug 20. — View Citation

Pribis P, Bailey RN, Russell AA, Kilsby MA, Hernandez M, Craig WJ, Grajales T, Shavlik DJ, Sabatè J. Effects of walnut consumption on cognitive performance in young adults. Br J Nutr. 2012 May;107(9):1393-401. doi: 10.1017/S0007114511004302. Epub 2011 Sep 19. — View Citation

Ros E, Hu FB. Consumption of plant seeds and cardiovascular health: epidemiological and clinical trial evidence. Circulation. 2013 Jul 30;128(5):553-65. doi: 10.1161/CIRCULATIONAHA.112.001119. Review. — View Citation

Sánchez-Villegas A, Galbete C, Martinez-González MA, Martinez JA, Razquin C, Salas-Salvadó J, Estruch R, Buil-Cosiales P, Martí A. The effect of the Mediterranean diet on plasma brain-derived neurotrophic factor (BDNF) levels: the PREDIMED-NAVARRA randomized trial. Nutr Neurosci. 2011 Sep;14(5):195-201. doi: 10.1179/1476830511Y.0000000011. — View Citation

Valls-Pedret C, Sala-Vila A, Serra-Mir M, Corella D, de la Torre R, Martínez-González MÁ, Martínez-Lapiscina EH, Fitó M, Pérez-Heras A, Salas-Salvadó J, Estruch R, Ros E. Mediterranean Diet and Age-Related Cognitive Decline: A Randomized Clinical Trial. JAMA Intern Med. 2015 Jul;175(7):1094-1103. doi: 10.1001/jamainternmed.2015.1668. Erratum in: JAMA Intern Med. 2018 Dec 1;178(12):1731-1732. — View Citation

Willis LM, Shukitt-Hale B, Cheng V, Joseph JA. Dose-dependent effects of walnuts on motor and cognitive function in aged rats. Br J Nutr. 2009 Apr;101(8):1140-4. doi: 10.1017/S0007114508059369. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Delayed Recall	AVLT - Recall of a previously presented list of words following a 25 minute delay.	2 hours following intervention.
Primary	Delayed Recall	AVLT - Recall of a previously presented list of words following a 25 minute delay.	4 hours following intervention.
Primary	Delayed Recall	AVLT - Recall of a previously presented list of words following a 25 minute delay.	6 hours following intervention.
Primary	Word Recognition	AVLT - Visual Recognition of a previously presented list of words following a 25 minute delay.	2 hours following intervention.
Primary	Word Recognition	AVLT - Visual Recognition of a previously presented list of words following a 25 minute delay.	4 hours following intervention.
Primary	Word Recognition	AVLT - Visual Recognition of a previously presented list of words following a 25 minute delay.	6 hours following intervention.
Primary	Response interference accuracy	Accuracy performance on the Modified Attention Network Task	2 hours following intervention.
Primary	Response interference accuracy	Accuracy performance on the Modified Attention Network Task	4 hours following intervention.
Primary	Response interference accuracy	Accuracy performance on the Modified Attention Network Task	6 hours following intervention.
Primary	Response interference reaction time	Reaction time performance on the Modified Attention Network Task	2 hours following intervention
Primary	Response interference reaction time	Reaction time performance on the Modified Attention Network Task	4 hours following intervention
Primary	Response interference reaction time	Reaction time performance on the Modified Attention Network Task	6 hours following intervention
Primary	Switching Task Accuracy	Accuracy performance on the switching task	2 hours following intervention
Primary	Switching Task Accuracy	Accuracy performance on the switching task	4 hours following intervention
Primary	Switching Task Accuracy	Accuracy performance on the switching task	6 hours following intervention
Primary	Switching Task reaction time	Reaction time performance on the switching task	2 hours following intervention
Primary	Switching Task reaction time	Reaction time performance on the switching task	4 hours following intervention
Primary	Switching Task reaction time	Reaction time performance on the switching task	6 hours following intervention
Primary	N2	Change in ERP measure of N2 latency and amplitude	2 hours following intervention
Primary	N2	Change in ERP measure of N2 latency and amplitude	4 hours following intervention
Primary	N2	Change in ERP measure of N2 latency and amplitude	6 hours following intervention
Primary	P3	Change in ERP measure of P3 latency and amplitude	2 hours following intervention
Primary	P3	Change in ERP measure of P3 latency and amplitude	4 hours following intervention
Primary	P3	Change in ERP measure of P3 latency and amplitude	6 hours following intervention
Primary	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
Primary	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
Primary	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
Primary	BDNF	Change in blood serum levels of BDNF	2 hours following intervention
Primary	BDNF	Change in blood serum levels of BDNF	4 hours following intervention
Primary	BDNF	Change in blood serum levels of BDNF	6 hours following intervention
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	EEG Spectral Analysis.	Changes in Power for Alpha, Beta, Gamma, Delta, and Theta bands during performance of each cognitive task.	2 hours following intervention.
Secondary	EEG Spectral Analysis.	Changes in Power for Alpha, Beta, Gamma, Delta, and Theta bands during performance of each cognitive task.	4 hours following intervention.
Secondary	EEG Spectral Analysis.	Changes in Power for Alpha, Beta, Gamma, Delta, and Theta bands during performance of each cognitive task.	6 hours following intervention.
Secondary	Immediate Recall	AVLT - Immediate recall following first presentation of the word list	2 hours following intervention
Secondary	Immediate Recall	AVLT - Immediate recall following first presentation of the word list	4 hours following intervention
Secondary	Immediate Recall	AVLT - Immediate recall following first presentation of the word list	6 hours following intervention
Secondary	Word Learning	AVLT - Area under the curve for first five word list recalls.	2 hours following intervention
Secondary	Word Learning	AVLT - Area under the curve for first five word list recalls.	4 hours following intervention
Secondary	Word Learning	AVLT - Area under the curve for first five word list recalls.	6 hours following intervention
Secondary	Total Recall	AVLT - Sum of first 5 word list recalls.	2 hours following intervention.
Secondary	Total Recall	AVLT - Sum of first 5 word list recalls.	4 hours following intervention.
Secondary	Total Recall	AVLT - Sum of first 5 word list recalls.	6 hours following intervention.
Secondary	Final Acquisition	AVLT - Immediate recall following final presentation of the word list	2 hours following intervention
Secondary	Final Acquisition	AVLT - Immediate recall following final presentation of the word list	4 hours following intervention
Secondary	Final Acquisition	AVLT - Immediate recall following final presentation of the word list	6 hours following intervention
Secondary	Interference List Recall	AVLT - Immediate recall of second (interference) list.	2 hours following intervention.
Secondary	Interference List Recall	AVLT - Immediate recall of second (interference) list.	4 hours following intervention.
Secondary	Interference List Recall	AVLT - Immediate recall of second (interference) list.	6 hours following intervention.