Archive

Research Area: Cognitive Health

The Walnuts and Healthy Aging Study (WAHA): Protocol for a nutritional intervention trial with walnuts on brain aging.

Rajaram, S., C. Valls-Pedret, M. Cofán, J. Sabaté, M. Serra-Mir, A.M. Pérez-Heras, A. Arechiga, R.P. Casaroli-Marano, S. Alforja, A. Sala-Vila, M. Doménech, I. Roth, T.M. Freitas-Simoes, C. Calvo, A. López-Illamola, E. Haddad, E. Bitok, N. Kazzi, L. Huey, J. Fan, E. Ros, 2017. The Walnuts and Healthy Aging Study (WAHA): Protocol for a nutritional intervention trial with walnuts on brain aging.Front. Aging Neurosci. 2017 Jan 10;8:333.

Introduction: An unwanted consequence of population aging is the growing number of elderly at risk of neurodegenerative disorders, including dementia and macular degeneration. As nutritional and behavioral changes can delay disease progression, we designed the Walnuts and Healthy Aging (WAHA) study, a two-center, randomized, 2-year clinical trial conducted in free-living, cognitively healthy elderly men and women. Our interest in exploring the role of walnuts in maintaining cognitive and retinal health is based on extensive evidence supporting their cardio-protective and vascular health effects, which are linked to bioactive components such as n-3 fatty acids and polyphenols. Methods: The primary aim of WAHA is to examine the effects of ingesting walnuts daily for 2 years on cognitive function and retinal health, assessed with a battery of neuropsychological tests and optical coherence tomography, respectively. All participants followed their habitual diet, adding walnuts at 15% of energy (~30-60 g/d) (walnut group) or abstaining from walnuts (control group). Secondary outcomes include changes in adiposity, blood pressure, and serum and urinary biomarkers in all participants and brain magnetic resonance imaging in a subset. Results: From May 2012 to May 2014, 708 participants (mean age 69 years, 68% women) were randomized. The study ended in May 2016 with a 90% retention rate. Discussion: The results of WAHA might provide high-level evidence of the benefit of regular walnut consumption in delaying the onset of age-related cognitive impairment and retinal pathology. The findings should translate into public health policy and sound recommendations to the general population.

Effects of walnut consumption on mood in young adults-a randomized controlled trial.

Pribis, P., 2016. Effects of walnut consumption on mood in young adults-a randomized controlled trial. Nutrients.  8(11), 668; doi:10.3390/nu8110668.

Abstract: Walnuts contain a number of potentially neuroprotective compounds like vitamin E, folate, melatonin, several antioxidative polyphenols and significant amounts of ω-3 fatty acids. The present study sought to determine the effect of walnuts on mood in healthy volunteers. Sixty-four college students were randomly assigned to two treatment sequences in a crossover fashion: walnut-placebo or placebo-walnut. At baseline mood was assessed using Profiles of Mood States (POMS). Data was collected again after eight weeks of intervention. After six-weeks of washout, the intervention groups followed the diets in reverse order. Data was collected once more at the end of the eight-week intervention period. No significant changes in mood were observed in the analyses with both genders combined and in females. However, we have observed a significant medium effect size improvement in the Total Mood Disturbance score (-27.49%, p = 0.043, Cohen’s d = 0.708) in males. In non-depressed healthy young males, walnuts seem to have the ability to improve mood.

A cross sectional study of the association between walnut consumption and cognitive function among adult us populations represented in NHANES.

Arab, L., A. Ang, 2015. A cross sectional study of the association between walnut consumption and cognitive function among adult us populations represented in NHANES. J Nutr Health Aging. 19(3):284-290.

Objective: To examine the association between walnut consumption and measures of cognitive function in the US population. Design: Nationally representative cross-sectional study using 24-hour dietary recalls of intakes to assess walnut and other nut consumption as compared to the group reporting no nut consumption. Setting: 1988–1994 and 1999–2002 rounds of the National Health and Nutrition Examination Survey (NHANES). Population Representative weighted sample of US adults 20 to 90 years of age. Main Outcome Measure: The Neurobehavioral Evaluation System 2 (NES2), consisting of simple reaction time (SRTT), symbol digit substitution (SDST), the single digit learning (SDLT), Story Recall (SRT) and digit-symbol substitution (DSST) tests. Results: Adults 20–59 years old reporting walnut consumption of an average of 10.3 g/d required 16.4ms less time to respond on the SRTT, P=0.03, and 0.39s less for the SDST, P=0.01. SDLT scores were also significantly lower by 2.38s (P=0.05). Similar results were obtained when tertiles of walnut consumption were examined in trend analyses. Significantly better outcomes were noted in all cognitive test scores among those with higher walnut consumption (P < 0.01). Among adults 60 years and older, walnut consumers averaged 13.1 g/d, scored 7.1 percentile points higher, P=0.03 on the SRT and 7.3 percentile points higher on the DSST, P=0.05. Here also trend analyses indicate significant improvements in all cognitive test scores (P < 0.01) except for SRTT (P = 0.06) in the fully adjusted models. Conclusion: These significant, positive associations between walnut consumption and cognitive functions among all adults, regardless of age, gender or ethnicity suggest that daily walnut intake may be a simple beneficial dietary behavior.

 

Dietary supplementation of walnuts improves memory deficits and learning skills in transgenic mouse model of Alzheimer’s Disease.

Muthaiyah, B., Essa, M.M., Lee, M., Chauhan, V., Kaur, K., Chauhan, A., 2014. Dietary supplementation of walnuts improves memory deficits and learning skills in transgenic mouse model of Alzheimer’s Disease. J Alzheimers Dis. 42(4):1397-405.

Previous in vitro studies have shown that walnut extract can inhibit amyloid-β (Aβ) fibrillization, can solubilize its fibrils, and has a protective effect against Aβ-induced oxidative stress and cellular death. In this study, we analyzed the effect of dietary supplementation with walnuts on learning skills, memory, anxiety, locomotor activity, and motor coordination in the Tg2576 transgenic (tg) mouse model of AD (AD-tg). From the age of 4 months, the experimental groups of AD-tg mice were fed custom-mixed diets containing 6% walnuts (T6) or 9% walnuts (T9), i.e., equivalent to 1 or 1.5 oz, respectively, of walnuts per day in humans. The control groups, i.e., AD-tg and wild-type mice, were fed a diet without walnuts (T0, Wt). These experimental and control mice were examined at the ages of 13-14 months by Morris water maze (for spatial memory and learning ability), T maze (for position discrimination learning ability), rotarod (for psychomotor coordination), and elevated plus maze (for anxiety-related behavior). AD-tg mice on the control diet (T0) showed memory deficit, anxiety-related behavior, and severe impairment in spatial learning ability, position discrimination learning ability, and motor coordination compared to the Wt mice on the same diet. The AD-tg mice receiving the diets with 6% or 9% walnuts (T6 and T9) showed a significant improvement in memory, learning ability, anxiety, and motor development compared to the AD-tg mice on the control diet (T0). There was no statistically significant difference in behavioral performance between the T6/T9 mice on walnuts-enriched diets and the Wt group on the control diet. These findings suggest that dietary supplementation with walnuts may have a beneficial effect in reducing the risk, delaying the onset, or slowing the progression of, or preventing AD.

 

Serum metabolites from walnut-fed aged rats attenuate stress-induced neurotoxicity in BV-2 microglial cells.

Fisher, D.R., Poulose, S.M., Bielinski, D.F., Shukitt-Hale, B., 2014. Serum metabolites from walnut-fed aged rats attenuate stress-induced neurotoxicity in BV-2 microglial cells. Nutr Neurosci. Aug 25. [Epub ahead of print]

The shift in equilibrium towards excess reactive oxygen or nitrogen species production from innate antioxidant defenses in brain is a critical factor in the declining neural function and cognitive deficit accompanying age. Previous studies from our laboratory have reported that walnuts, rich in polyphenols, antioxidants, and omega fatty acids such as alpha-linolenic acid and linoleic acid, improve the age-associated declines in cognition and neural function in rats. Possible mechanisms of action of these effects include enhancing protective signaling, altering membrane microstructures, decreasing inflammation, and preventing accumulation of polyubiquitinated protein aggregates in critical regions of the brain. In the current study, we investigated whether the serum collected from aged animals fed with walnut diets (0, 6, and 9%, w/w) would enhance protection on stressed BV-2 microglia in vitro. In the growth medium, fetal bovine serum was substituted with the serum collected from 22-month-old rats fed per protocol for 12 weeks. Walnut diet serum (6 and 9%) significantly attenuated lipopolysaccharide-induced nitrite release compared to untreated control cells and those treated with serum from rats fed 0% walnut diets. The results also indicated a significant reduction in pro-inflammatory tumor necrosis factor-alpha, cyclooxygenase-2, and inducible nitric oxide synthase. These results suggest antioxidant and anti-inflammatory protection or enhancement of membrane-associated functions in brain cells by walnut serum metabolites.

Mediterranean diet improves cognition: the PREDIMED-NAVARRA randomized trial.

Martínez-Lapiscina, E.H., P. Clavero, E. Toledo, R. Estruch, J. Salas-Salvadó, B. San Julián, A. Sanchez-Tainta, E. Ros, C. Valls-Pedret, M.Á. Martinez-Gonzalez, 2013. Mediterranean diet improves cognition: the PREDIMED-NAVARRA randomized trial. J Neurol Neurosurg Psychiatry. doi:10.1136/jnnp-2012-304792.

Objective: Previous observational studies reported beneficial effects of the Mediterranean diet (MedDiet) on cognitive function, but results were inconsistent. We assessed the effect on cognition of a nutritional intervention using MedDiets in comparison with a low-fat control diet. Methods: We assessed 522 participants at high vascular risk (44.6% men, age 74.6 ± 5.7 years at cognitive evaluation) enrolled in a multicentre, randomised, primary prevention trial (PREDIMED), after a nutritional intervention comparing two MedDiets (supplemented with either extra-virgin olive oil (EVOO) or mixed nuts) versus a low-fat control diet. Global cognitive performance was examined by Mini-Mental State Examination (MMSE) and Clock Drawing Test (CDT) after 6.5 years of nutritional intervention. Researchers who assessed the outcome were blinded to group assignment. We used general linear models to control for potential confounding. Results: After adjustment for sex, age, education, Apolipoprotein E genotype, family history of cognitive impairment/dementia, smoking, physical activity, body mass index, hypertension, dyslipidaemia, diabetes, alcohol and total energy intake, participants allocated to the MedDiet+EVOO showed higher mean MMSE and CDT scores with significant differences versus control (adjusted differences: +0.62 95% CI +0.18 to +1.05, p=0.005 for MMSE, and +0.51 95% CI +0.20 to +0.82, p=0.001 for CDT). The adjusted means of MMSE and CDT scores were also higher for participants allocated to the MedDiet+Nuts versus control (adjusted differences: +0.57 (95% CI +0.11 to +1.03), p=0.015 for MMSE and +0.33 (95% CI +0.003 to +0.67), p=0.048 for CDT). These results did not differ after controlling for incident depression. Conclusions: An intervention with MedDiets enhanced with either EVOO or nuts appears to improve cognition compared with a low-fat diet.

Polyphenol-rich foods in the Mediterranean diet are associated with better cognitive function in elderly subjects at high cardiovascular risk.

Valls-Pedret, C., R.M. Lamuela-Raventos, R.M., A. Medina-Remon, M. Quintana, D. Corella, X. Pinto, M.A. Martınez-Gonzalez, R. Estruch, E. Ros, 2012. Polyphenol-rich foods in the Mediterranean diet are associated with better cognitive function in elderly subjects at high cardiovascular risk. Journal of Alzheimer’s Disease. 29:773–782.

Brain oxidative processes play a major role in age-related cognitive decline, thus consumption of antioxidant-rich foods might help preserve cognition. Our aim was to assess whether consumption of antioxidant-rich foods in the Mediterranean diet relates to cognitive function in the elderly. In asymptomatic subjects at high cardiovascular risk (n = 447; 52% women; age 55–80 y) enrolled in the PREDIMED study, a primary prevention dietary-intervention trial, we assessed food intake and cardiovascular risk profile, determined apolipoprotein E genotype, and used neuropsychological tests to evaluate cognitive function. We also measured urinary polyphenols as an objective biomarker of intake. Associations between energy-adjusted food consumption, urinary polyphenols, and cognitive scores were assessed by multiple linear regression models adjusted for potential confounders. Consumption of some foods was independently related to better cognitive function. The specific associations [regression coefficients (95% confidence intervals)] were: total olive oil with immediate verbal memory [0.755 (0.151–1.358)]; virgin olive oil and coffee with delayed verbal memory [0.163 (0.010–0.316) and 0.294 (0.055–0.534), respectively];walnuts with working memory [1.191 (0.061–2.322)]; and wine with Mini-Mental State Examination scores [0.252 (0.006–0.496)]. Urinary polyphenols were associated with better scores in immediate verbal memory [1.208 (0.236–2.180)]. Increased consumption of antioxidant-rich foods in general and of polyphenols in particular is associated with better cognitive performance in elderly subjects at high cardiovascular risk. The results reinforce the notion that Mediterranean diet components might counteract age-related cognitive decline.

Effects of walnut consumption on cognitive performance in young adults.

Pribis P., R.N. Bailey, A.A. Russell, M.A. Kilsby, M. Hernandez, W.J. Craig, T. Grajales, D.J. Shavlik, J. Sabatè, 2011. Effects of walnut consumption on cognitive performance in young adults. Br J Nutr. 107(9):1393-1401.

Walnuts contain a number of potentially neuroprotective compounds like vitamin E, folate, melatonin, several antioxidative polyphenols and significant amounts of n-3 α-linolenic fatty acid. The present study sought to determine the effect of walnuts on verbal and non-verbal reasoning, memory and mood. A total of sixty-four college students were randomly assigned to two treatment sequences in a crossover fashion: walnuts-placebo or placebo-walnuts. Baseline data were collected for non-verbal reasoning, verbal reasoning, memory and mood states. Data were collected again after 8 weeks of intervention. After 6 weeks of washout, the intervention groups followed the diets in reverse order. Data were collected once more at the end of the 8-week intervention period. No significant increases were detected for mood, non-verbal reasoning or memory on the walnut-supplemented diet. However, inferential verbal reasoning increased significantly by 11.2 %, indicating a medium effect size (P = 0.009; d = 0.567). In young, healthy, normal adults, walnuts do not appear to improve memory, mood or non-verbal reasoning abilities. However, walnuts may have the ability to increase inferential reasoning.

The beneficial effects of tree nuts on the aging brain.

Carey, A.N., S.M. Poulose, B. Shukitt-Hale, 2012. The beneficial effects of tree nuts on the aging brain. Nutrition and Aging. 1:55–67.

Dietary patterns may play an important role in protecting the brain from the cellular and cognitive dysfunction associated with the aging process and neurodegenerative diseases. Tree nuts are showing promise as possible dietary interventions for age-related brain dysfunction. Tree nuts are an important source of essential nutrients, like vitamin E, folate, and fiber. Tree nuts also contain a variety of components, such as phytochemicals like flavonoids, proanthocyanidins, and phenolic acids, as well as monounsaturated and omega-3 and omega-6 polyunsaturated fatty acids that have the potential to combat age-related brain dysfunction. Evidence is accumulating that suggests that tree nuts and their bioactive constituents have the potential to reduce oxidative stress and inflammation, as indicated by decreased lipid peroxidation in vivo and reduced production of the free radical nitric oxide and the pro-inflammatory cytokine tumor necrosis factor-alpha in vitro. Also, tree nut consumption might have the ability to mitigate some of the cognitive decline associated with aging. Here we review the current knowledge of how the consumption of nuts may improve brain health, specifically focusing on walnuts, almonds, pistachios, and pecans.

The effect of the Mediterranean diet on plasma brain-derived neurotrophic factor (BDNF) levels: The PREDIMED-NAVARRA randomized trial. Nutritional Neuroscience.

Sánchez-Villegas, A., C. Galbete, M.Á. Martinez-González, J.A. Martinez, C. Razquin, J. Salas-Salvadó, R. Estruch, P. Buil-Cosiales, A. Martí, 2011. The effect of the Mediterranean diet on plasma brain-derived neurotrophic factor (BDNF) levels: The PREDIMED-NAVARRA randomized trial. Nutritional Neuroscience.  14(5):195-201.

Objectives: There are no human studies assessing the effect of nutritional interventions on plasma brainderived neurotrophic factor (BDNF) concentrations. The aim of this study was to assess the role of a nutritional intervention based on a Mediterranean diet (MeDiet) on plasma BDNF levels. Methods: PREvención con Dieta MEDiterránea (PREDIMED) is a randomized clinical trial designed to assess the effect of a Mediterranean diet (MeDiet) on the primary prevention of cardiovascular disease. For this analysis, 243 participants from the Navarra centre were randomly selected. Participants were assigned to one of three dietary interventions: control (low-fat) diet, MeDiet supplemented with virgin olive oil (MeDiet + VOO), or MeDiet supplemented with nuts (MeDiet + Nuts). Plasma BDNF levels were measured after 3 years of intervention. Multivariate-adjusted means of BDNF for each intervention were compared using generalized linear models. Logistic regression models were fit to assess the association between the dietary intervention and the likelihood to have low plasma BDNF values (<13 μg/ml, 10th percentile). Analyses were repeated after stratifying the sample according to baseline prevalence of different diseases. Results: Higher but non-significant plasma BDNF levels were observed for participants assigned to both MeDiets. Participants assigned to MeDiet + Nuts showed a significant lower risk (odds ratios (OR) = 0.22; 95% confidence intervals (CI) = 0.05–0.90) of low plasma BDNF values (<13 μg/ml) as compared to the control group. Among participants with prevalent depression at baseline, significantly higher BDNF levels were found for those assigned to the MeDiet+ Nuts. Discussion: Adherence to a MeDiet was associated to an improvement in plasma BDNF concentrations in individuals with depression.