Cognitive Impairment Abstracts 4 – Omega-3

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omega-3 fatty acids and domain-specific cognitive aging: secondary analyses of data from WHISCA.
            (Ammann et al., 2013) Download
OBJECTIVE: To test the hypothesis that higher levels of red blood cell (RBC) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have a protective association with domain-specific cognitive function in women aged 65 years and older. METHODS: A total of 2,157 women with normal cognition enrolled in a clinical trial of postmenopausal hormone therapy were followed with annual cognitive testing for a median of 5.9 years. In this retrospective cohort study, we assessed the relationship between prerandomization RBC DHA + EPA levels and a) cognitive measures at baseline, and b) cognitive change over time. Endpoints were composite cognitive function and performance in 7 cognitive domains: fine motor speed, verbal memory, visual memory, spatial ability, verbal knowledge, verbal fluency, and working memory. RESULTS: After adjustment for demographic, clinical, and behavioral characteristics, no significant (p < 0.01) cross-sectional cognitive differences were found between women in the high and low DHA + EPA tertiles at the time of the first annual cognitive battery. In addition, no significant (p < 0.01) differences were found between the high and low DHA + EPA tertiles in the rate of cognitive change over time. CONCLUSIONS: We did not find an association between RBC DHA + EPA levels and age-associated cognitive decline in a cohort of older, dementia-free women.

Effect of long-term omega 3 polyunsaturated fatty acid supplementation with or without multidomain intervention on cognitive function in elderly adults with memory complaints (MAPT): a randomised, placebo-controlled trial.
            (Andrieu et al., 2017) Download
BACKGROUND:  No large trials have been done to investigate the efficacy of an intervention combining a specific compound and several lifestyle interventions compared with placebo for the prevention of cognitive decline. We tested the effect of omega 3 polyunsaturated fatty acid supplementation and a multidomain intervention (physical activity, cognitive training, and nutritional advice), alone or in combination, compared with placebo, on cognitive decline. METHODS:  The Multidomain Alzheimer Preventive Trial was a 3-year, multicentre, randomised, placebo-controlled superiority trial with four parallel groups at 13 memory centres in France and Monaco. Participants were non-demented, aged 70 years or older, and community-dwelling, and had either relayed a spontaneous memory complaint to their physician, limitations in one instrumental activity of daily living, or slow gait speed. They were randomly assigned (1:1:1:1) to either the multidomain intervention (43 group sessions integrating cognitive training, physical activity, and nutrition, and three preventive consultations) plus omega 3 polyunsaturated fatty acids (ie, two capsules a day providing a total daily dose of 800 mg docosahexaenoic acid and 225 mg eicosapentaenoic acid), the multidomain intervention plus placebo, omega 3 polyunsaturated fatty acids alone, or placebo alone. A computer-generated randomisation procedure was used to stratify patients by centre. All participants and study staff were blinded to polyunsaturated fatty acid or placebo assignment, but were unblinded to the multidomain intervention component. Assessment of cognitive outcomes was done by independent neuropsychologists blinded to group assignment. The primary outcome was change from baseline to 36 months on a composite Z score combining four cognitive tests (free and total recall of the Free and Cued Selective Reminding test, ten Mini-Mental State Examination orientation items, Digit Symbol Substitution Test, and Category Naming Test) in the modified intention-to-treat population. The trial was registered with ClinicalTrials.gov (NCT00672685). FINDINGS:  1680 participants were enrolled and randomly allocated between May 30, 2008, and Feb 24, 2011. In the modified intention-to-treat population (n=1525), there were no significant differences in 3-year cognitive decline between any of the three intervention groups and the placebo group. Between-group differences compared with placebo were 0·093 (95% CI 0·001 to 0·184; adjusted p=0·142) for the combined intervention group, 0·079 (-0·012 to 0·170; 0·179) for the multidomain intervention plus placebo group, and 0·011 (-0·081 to 0·103; 0·812) for the omega 3 polyunsaturated fatty acids group. 146 (36%) participants in the multidomain plus polyunsaturated fatty acids group, 142 (34%) in the multidomain plus placebo group, 134 (33%) in the polyunsaturated fatty acids group, and 133 (32%) in the placebo group had at least one serious emerging adverse event. Four treatment-related deaths were recorded (two in the multidomain plus placebo group and two in the placebo group). The interventions did not raise any safety concerns and there were no differences between groups in serious or other adverse events. INTERPRETATION:  The multidomain intervention and polyunsaturated fatty acids, either alone or in combination, had no significant effects on cognitive decline over 3 years in elderly people with memory complaints. An effective multidomain intervention strategy to prevent or delay cognitive impairment and the target population remain to be determined, particularly in real-world settings. FUNDING:  French Ministry of Health, Pierre Fabre Research Institute, Gerontopole, Exhonit Therapeutics, Avid Radiopharmaceuticals.


 

Omega-3 supplementation improves cognition and modifies brain activation in young adults.
            (Bauer et al., 2014) Download
OBJECTIVE:  The current study aimed to investigate the effects of eicosapentaenoic acid (EPA)-rich and docosahexaenoic acid (DHA)-rich supplementations on cognitive performance and functional brain activation. DESIGN:  A double-blind, counterbalanced, crossover design, with a 30-day washout period between two supplementation periods (EPA-rich and DHA-rich) was employed. Functional magnetic resonance imaging scans were obtained during performance of Stroop and Spatial Working Memory tasks prior to supplementation and after each 30-day supplementation period. RESULTS:  Both supplementations resulted in reduced ratio of arachidonic acid to EPA levels. Following the EPA-rich supplementation, there was a reduction in functional activation in the left anterior cingulate cortex and an increase in activation in the right precentral gyrus coupled with a reduction in reaction times on the colour-word Stroop task. By contrast, the DHA-rich supplementation led to a significant increase in functional activation in the right precentral gyrus during the Stroop and Spatial Working Memory tasks, but there was no change in behavioural performance. CONCLUSIONS:  By extending the theory of neural efficiency to the within-subject neurocognitive effects of supplementation, we concluded that following the EPA-rich supplementation, participants' brains worked 'less hard' and achieved a better cognitive performance than prior to supplementation. Conversely, the increase in functional activation and lack of improvement in time or accuracy of cognitive performance following DHA-rich supplementation may indicate that DHA-rich supplementation is less effective than EPA-rich supplementation in enhancing neurocognitive functioning after a 30-day supplementation period in the same group of individuals.

The n-3 Polyunsaturated Fatty Acids Supplementation Improved the Cognitive Function in the Chinese Elderly with Mild Cognitive Impairment: A Double-Blind Randomized Controlled Trial.
            (Bo et al., 2017) Download
OBJECTIVE:  Intake of n-3 polyunsaturated fatty acids (n-3 PUFAs) may protect against mild cognitive impairment (MCI). However, there is still a lack of the n-3 PUFAs intervention in the elderly with MCI in China. The aim of the present study was to investigate the effect of n-3 PUFA supplementation on cognitive function in the Chinese elderly with MCI. METHODS:  Eighty six MCI individuals aged 60 years or older were randomly assigned to receive either n-3 PUFAs (480 mg DHA and 720 mg EPA per day, n = 44) or placebo (olive oil, n = 42) capsules. The changes of cognitive functions were assessed using Basic Cognitive Aptitude Tests (BCAT). RESULTS:  The mean age of participants was 71 years old, and 59% of the participants were men. n-3 PUFA supplementation was associated with improved total BCAT scores, perceptual speed, space imagery efficiency, and working memory (p < 0.01), but not with mental arithmetic efficiency or recognition memory (p > 0.05). Subgroup analysis by sex showed that n-3 PUFAs significantly improved perceptual speed (p = 0.001), space imagery efficiency (p = 0.013), working memory (p = 0.018), and total BCAT scores (p = 0.000) in males. However, in females, the significant beneficial effects can only be observed in perceptual speed (p = 0.027), space imagery efficiency (p = 0.006), and total BCAT scores (p = 0.015)-not working memory (p = 0.113). CONCLUSION:  n-3 PUFAs can improve cognitive function in people with MCI. Further studies with different fish oil dosages, longer intervention periods, and larger sample sizes should be investigated before definite recommendations can be made.

Fish Oil Supplementation Increases Event-Related Posterior Cingulate Activation in Older Adults with Subjective Memory Impairment.
            (Boespflug et al., 2016) Download
OBJECTIVES:  To determine the effects of long-chain omega-3 (LCn-3) fatty acids found in fish oil, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on cortical blood oxygen level-dependent (BOLD) activity during a working memory task in older adults with subjective memory impairment. DESIGN:  Randomized, double-blind, placebo-controlled study. SETTING:  Academic medical center. PARTICIPANTS:  Healthy older adults (62-80 years) with subjective memory impairment, but not meeting criteria for mild cognitive impairment or dementia. INTERVENTION:  Fish oil (EPA+DHA: 2.4 g/d, n=11) or placebo (corn oil, n=10) for 24 weeks. MEASUREMENTS:  Cortical BOLD response patterns during performance of a sequential letter n-back working memory task were determined at baseline and week 24 by functional magnetic resonance imaging (fMRI). RESULTS:  At 24 weeks erythrocyte membrane EPA+DHA composition increased significantly from baseline in participants receiving fish oil (+31%, p ≤ 0.0001) but not placebo (-17%, p=0.06). Multivariate modeling of fMRI data identified a significant interaction among treatment, visit, and memory loading in the right cingulate (BA 23/24), and in the right sensorimotor area (BA 3/4). In the fish oil group, BOLD increases at 24 weeks were observed in the right posterior cingulate and left superior frontal regions during memory loading. A region-of-interest analysis indicated that the baseline to endpoint change in posterior cingulate cortex BOLD activity signal was significantly greater in the fish oil group compared with the placebo group during the 1-back (p=0.0003) and 2-back (p=0.0005) conditions. Among all participants, the change in erythrocyte EPA+DHA during the intervention was associated with performance in the 2-back working memory task (p = 0.01), and with cingulate BOLD signal during the 1-back (p = 0.005) with a trend during the 2-back (p = 0.09). Further, cingulate BOLD activity was related to performance in the 2-back condition. CONCLUSION:  Dietary fish oil supplementation increases red blood cell omega-3 content, working memory performance, and BOLD signal in the posterior cingulate cortex during greater working memory load in older adults with subjective memory impairment suggesting enhanced neuronal response to working memory challenge.

 

Effect of Omega-3 Fatty Acids, Lutein/Zeaxanthin, or Other Nutrient Supplementation on Cognitive Function: The AREDS2 Randomized Clinical Trial.
            (Chew et al., 2015) Download
IMPORTANCE:  Observational data have suggested that high dietary intake of saturated fat and low intake of vegetables may be associated with increased risk of Alzheimer disease. OBJECTIVE:  To test the effects of oral supplementation with nutrients on cognitive function. DESIGN, SETTING, AND PARTICIPANTS:  In a double-masked randomized clinical trial (the Age-Related Eye Disease Study 2 [AREDS2]), retinal specialists in 82 US academic and community medical centers enrolled and observed participants who were at risk for developing late age-related macular degeneration (AMD) from October 2006 to December 2012. In addition to annual eye examinations, several validated cognitive function tests were administered via telephone by trained personnel at baseline and every 2 years during the 5-year study. INTERVENTIONS:  Long-chain polyunsaturated fatty acids (LCPUFAs) (1 g) and/or lutein (10 mg)/zeaxanthin (2 mg) vs placebo were tested in a factorial design. All participants were also given varying combinations of vitamins C, E, beta carotene, and zinc. MAIN OUTCOMES AND MEASURES:  The main outcome was the yearly change in composite scores determined from a battery of cognitive function tests from baseline. The analyses, which were adjusted for baseline age, sex, race, history of hypertension, education, cognitive score, and depression score, evaluated the differences in the composite score between the treated vs untreated groups. The composite score provided an overall score for the battery, ranging from -22 to 17, with higher scores representing better function. RESULTS:  A total of 89% (3741/4203) of AREDS2 participants consented to the ancillary cognitive function study and 93.6% (3501/3741) underwent cognitive function testing. The mean (SD) age of the participants was 72.7 (7.7) years and 57.5% were women. There were no statistically significant differences in change of scores for participants randomized to receive supplements vs those who were not. The yearly change in the composite cognitive function score was -0.19 (99% CI, -0.25 to -0.13) for participants randomized to receive LCPUFAs vs -0.18 (99% CI, -0.24 to -0.12) for those randomized to no LCPUFAs (difference in yearly change, -0.03 [99% CI, -0.20 to 0.13]; P = .63). Similarly, the yearly change in the composite cognitive function score was -0.18 (99% CI, -0.24 to -0.11) for participants randomized to receive lutein/zeaxanthin vs -0.19 (99% CI, -0.25 to -0.13) for those randomized to not receive lutein/zeaxanthin (difference in yearly change, 0.03 [99% CI, -0.14 to 0.19]; P = .66). Analyses were also conducted to assess for potential interactions between LCPUFAs and lutein/zeaxanthin and none were found to be significant. CONCLUSIONS AND RELEVANCE:  Among older persons with AMD, oral supplementation with LCPUFAs or lutein/zeaxanthin had no statistically significant effect on cognitive function. TRIAL REGISTRATION:  clinicaltrials.gov Identifier: NCT00345176.

 

Cognitive performance in older adults is inversely associated with fish consumption but not erythrocyte membrane n-3 fatty acids.
            (Danthiir et al., 2014) Download
Higher n-3 (omega-3) polyunsaturated fatty acids (PUFAs) and fish intake may help maintain cognitive function in older age. However, evidence is inconsistent; few studies have examined the relation in cognitively healthy individuals across numerous cognitive domains, and none to our knowledge have considered lifetime fish intake. We examined associations between multiple domains of cognition and erythrocyte membrane n-3 PUFA proportions and historical and contemporary fish intake in 390 normal older adults, analyzing baseline data from the Older People, Omega-3, and Cognitive Health trial. We measured n-3 PUFA in erythrocyte membranes, and we assessed historical and contemporary fish intake by food-frequency questionnaires. We assessed cognitive performance on reasoning, working memory, short-term memory, retrieval fluency, perceptual speed, simple/choice reaction time, speed of memory-scanning, reasoning speed, inhibition, and psychomotor speed. Cognitive outcomes for each construct were factor scores from confirmatory factor analysis. Multiple linear regression models controlled for a number of potential confounding factors, including age, education, sex, apolipoprotein E-epsilon 4 allele, physical activity, smoking, alcohol intake, socioeconomic variables, and other health-related variables. Higher erythrocyte membrane eicosapaentonoic acid proportions predicted slower perceptual and reasoning speed in females, which was attenuated once current fish intake was controlled. No other associations were present between n-3 PUFA proportions and cognitive performance. Higher current fish consumption predicted worse performance on several cognitive speed constructs. Greater fish consumption in childhood predicted slower perceptual speed and simple/choice reaction time. We found no evidence to support the hypothesis that higher proportions of long-chain n-3 fatty acids or fish intake benefits cognitive performance in normal older adults.

Seven-Year Follow-up of Children Born to Women in a Randomized Trial of Prenatal DHA Supplementation.
            (Gould et al., 2017) Download
The sale of prenatal supplements with docosahexaenoic acid (DHA) continues to increase, despite little evidence of benefit to offspring neurodevelopment.1 We randomized pregnant women to receive 800 mg of DHA daily or a placebo during the last half of pregnancy and found no group differences in cognitive, language, and motor development at 18 months of age, although secondary analyses revealed less cognitive delay but lower language scores in the DHA group.2 At 4 years of age there was no benefit of DHA supplementation in general intelligence, language, and executive functioning, and a possible negative effect on parent-rated behavior and executive functioning.3 This follow-up was designed to evaluate the effect of prenatal DHA on intelligence quotient (IQ) at 7 years, the earliest age at which adult performance can be indicated.

DHA Supplementation Alone or in Combination with Other Nutrients Does not Modulate Cerebral Hemodynamics or Cognitive Function in Healthy Older Adults.
            (Jackson et al., 2016) Download
A number of recent trials have demonstrated positive effects of dietary supplementation with the omega-3 polyunsaturated fatty acids (n-3 PUFAs), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on measures of cognitive function in healthy young and older adults. One potential mechanism by which EPA, and DHA in particular, may exert these effects is via modulation of cerebral hemodynamics. In order to investigate the effects of DHA alone or provided as one component of a multinutrient supplement (also including Gingko biloba, phosphatidylserine and vitamins B₉ and B₁₂) on measures of cerebral hemodynamics and cognitive function, 86 healthy older adults aged 50-70 years who reported subjective memory deficits were recruited to take part in a six month daily dietary supplementation trial. Relative changes in the concentration of oxygenated hemoglobin and deoxygenated hemoglobin were assessed using Near Infrared Spectroscopy (NIRS) during the performance of cognitive tasks prior to and following the intervention period. Performance on the cognitive tasks was also assessed. No effect of either active treatment was found for any of the NIRS measures or on the cognitive performance tasks, although the study was limited by a number of factors. Further work should continue to evaluate more holistic approaches to cognitive aging.

Brain atrophy in cognitively impaired elderly: the importance of long-chain ω-3 fatty acids and B vitamin status in a randomized controlled trial.
            (Jernerén et al., 2015) Download
BACKGROUND:  Increased brain atrophy rates are common in older people with cognitive impairment, particularly in those who eventually convert to Alzheimer disease. Plasma concentrations of omega-3 (ω-3) fatty acids and homocysteine are associated with the development of brain atrophy and dementia. OBJECTIVE:  We investigated whether plasma ω-3 fatty acid concentrations (eicosapentaenoic acid and docosahexaenoic acid) modify the treatment effect of homocysteine-lowering B vitamins on brain atrophy rates in a placebo-controlled trial (VITACOG). DESIGN:  This retrospective analysis included 168 elderly people (≥70 y) with mild cognitive impairment, randomly assigned either to placebo (n = 83) or to daily high-dose B vitamin supplementation (folic acid, 0.8 mg; vitamin B-6, 20 mg; vitamin B-12, 0.5 mg) (n = 85). The subjects underwent cranial magnetic resonance imaging scans at baseline and 2 y later. The effect of the intervention was analyzed according to tertiles of baseline ω-3 fatty acid concentrations. RESULTS:  There was a significant interaction (P = 0.024) between B vitamin treatment and plasma combined ω-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) on brain atrophy rates. In subjects with high baseline ω-3 fatty acids (>590 μmol/L), B vitamin treatment slowed the mean atrophy rate by 40.0% compared with placebo (P = 0.023). B vitamin treatment had no significant effect on the rate of atrophy among subjects with low baseline ω-3 fatty acids (<390 μmol/L). High baseline ω-3 fatty acids were associated with a slower rate of brain atrophy in the B vitamin group but not in the placebo group. CONCLUSIONS:  The beneficial effect of B vitamin treatment on brain atrophy was observed only in subjects with high plasma ω-3 fatty acids. It is also suggested that the beneficial effect of ω-3 fatty acids on brain atrophy may be confined to subjects with good B vitamin status. The results highlight the importance of identifying subgroups likely to benefit in clinical trials. This trial was registered at www.controlled-trials.com as ISRCTN94410159.

Impact of Omega-3 Fatty Acid Supplementation on Memory Functions in Healthy Older Adults.
            (Külzow et al., 2016) Download
As the process of Alzheimer's disease (AD) begins years before disease onset, searching for prevention strategies is of major medical and economic importance. Nutritional supplementation with long-chain polyunsaturated omega-3 fatty acids (LC-n3-FA) may exert beneficial effects on brain structure and function. However, experimental evidence in older adults without clinical dementia is inconsistent, possibly due to low sensitivity of previously employed test batteries for detecting subtle improvements in cognition in healthy individuals. Here we used LOCATO, recently described as a robust and sensitive tool for assessing object-location memory (OLM) in older adults, to evaluate the impact of LC-n3-FA supplementation on learning and memory formation. In a double-blind placebo-controlled proof-of-concept study, 44 (20 female) cognitively healthy individuals aged 50-75 years received either LC-n3-FA (2,200 mg/day, n = 22) or placebo (n = 22) for 26 weeks. Before and after intervention, memory performance in the OLM-task (primary) was tested. As secondary outcome parameters, performance in Rey Auditory Verbal Learning Test (AVLT), dietary habits, omega-3-index, and other blood-derived parameters were assessed. Omega-3 index increased significantly in the LC-n3-FA group compared with the placebo group. Moreover, recall of object locations was significantly better after LC-n3-FA supplementation compared with placebo. Performance in the AVLT was not significantly affected by LC-n3-FA. This double-blind placebo-controlled proof-of-concept study provides further experimental evidence that LC-n3-FA exert positive effects on memory functions in healthy older adults. Our findings suggest novel strategies to maintain cognitive functions into old age.


 

Omega-3 fatty acids moderate effects of physical activity on cognitive function.
            (Leckie et al., 2014) Download
Greater amounts of physical activity (PA) and omega-3 fatty acids have both been independently associated with better cognitive performance. Because of the overlapping biological effects of omega-3 fatty acids and PA, fatty acid intake may modify the effects of PA on neurocognitive function. The present study tested this hypothesis by examining whether the ratio of serum omega-6 to omega-3 fatty acid levels would moderate the association between PA and executive and memory functions in 344 participants (Mean age=44.42 years, SD=6.72). The Paffenbarger Physical Activity Questionnaire (PPAQ), serum fatty acid levels, and performance on a standard neuropsychological battery were acquired on all subjects. A principal component analysis reduced the number of cognitive outcomes to three factors: n-back working memory, Trail Making test, and Logical Memory. We found a significant interaction between PA and the ratio of omega-6 to omega-3 fatty acid serum levels on Trail Making performance and n-back performance, such that higher amounts of omega-3 levels offset the deleterious effects of lower amounts of PA. These effects remained significant in a subsample (n=299) controlling for overall dietary fat consumption. There were no significant additive or multiplicative benefits of higher amounts of both omega-3 and PA on cognitive performance. Our results demonstrate that a diet high in omega-3 fatty acids might mitigate the effect of lower levels of PA on cognitive performance. This study illuminates the importance of understanding dietary and PA factors in tandem when exploring their effects on neurocognitive health.

Effect of low dose omega-3 poly unsaturated fatty acids on cognitive status among older people: a double-blind randomized placebo-controlled study.
            (Mahmoudi et al., 2014) Download
BACKGROUND: Cognitive impairment is a prevalent health problem in older people and its global prevalence tends to increase parallel to the extended life expectancy in world. The beneficial effect of omega-3 PUFAs on cognitive impairment has been demonstrated in some experimental and cohort studies. In this study we aimed to assess the effect of low dose docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) supplementation on cognitive status in the elderly. METHODS: In a double-blind, randomized placebo-controlled study, 199 individuals aged >/=65 years with normal or mild to moderate cognition impairment were assigned to receive either 180 mg of DHA plus 120 mg of EPA or placebo for 180 days. Cognitive status was assessed using Mini-Mental State Examination (MMSE) and Abbreviated Mental Test (AMT) score. RESULTS: MMSE and AMT scores were not different at the time of allocation [18.84 (5.37), 18.55 (5.12), (P = 0.70) and 4.81 (2.79) and 4.64 (2.77), (P = 0.67) respectively] and over 6 months between the omega-3 PUFA- and placebo- treated groups [18.57 (5.21), 18.39 (5.10), (P = 0.80) and 4.64 (2.77) and 4.48 (2.69) and (P = 0.67)]. The participants were categorized based on MMSE score into normal cognition, mild and moderate cognitive impairment. After multivariate adjustment, there was no significant difference among categorized groups regarding the omega-3 PUFA effect except in normal cognition group, that amount of decline in AMT in omega-3 poly unsaturated fatty acids (PUFAs) was less than placebo group. CONCLUSIONS: It seems that prescription of low dose omega-3 PUFAs for 6 months had no significant beneficial effects on improvement of cognition or prevention of cognitive decline in older people.

Omega-3 Fatty Acids, Depressive Symptoms, and Cognitive Performance in Patients With Coronary Artery Disease: Analyses From a Randomized, Double-Blind, Placebo-Controlled Trial.
            (Mazereeuw et al., 2016) Download
This trial investigated the efficacy of omega-3 polyunsaturated fatty acid (n-3 PUFA) treatment for improving depressive symptoms and cognitive performance in patients with coronary artery disease (CAD) participating in cardiac rehabilitation. Patients with CAD aged 45 to 80 years were randomized to receive either 1.9-g/d n-3 PUFA treatment or placebo for 12 weeks. Depressive symptoms were measured using the Hamilton Depression Rating Scale (HAM-D, primary outcome) and the Beck Depression Inventory II (BDI-II). Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria were used to identify a depressive episode at baseline. Cognitive performance was measured using a standardized battery for vascular cognitive impairment. In 92 patients (age, 61.7 ± 8.7 y; 76% male, 40% depressed; HAM-D, 6.9 ± 5.9; BDI-II, 12.3 ± 10.9; n = 45 n-3 PUFA, n = 47 placebo), depression decreased (HAM-D, F3,91 = 2.71 and P = 0.049; BDI-II, F3,91 = 6.24 and P < 0.01), and cognitive performance improved (attention/processing speed, F1,91 = 5.57, P = 0.02; executive function, F1,91 = 14.64, P < 0.01; visuospatial memory, F1,91 = 4.01, P = 0.04) over cardiac rehabilitation. Omega-3 PUFA treatment increased plasma eicosapentaenoic acid (F1,29 = 33.29, P < 0.01) and docosahexaenoic acid (F1,29 = 15.29, P < 0.01) concentrations but did not reduce HAM-D (F3,91 = 1.59, P = 0.20) or BDI-II (F3,91 = 0.46, P = 0.50) scores compared with placebo. Treatment did not improve cognitive performance; however, n-3 PUFAs significantly increased verbal memory compared with placebo in a subgroup of nondepressed patients (F1,54 = 4.16, P = 0.04). This trial suggests that n-3 PUFAs do not improve depressive and associated cognitive symptoms in those with CAD. The possible benefits of n-3 PUFAs for verbal memory may warrant investigation in well-powered studies.


 

Low blood long chain omega-3 fatty acids in UK children are associated with poor cognitive performance and behavior: a cross-sectional analysis from the DOLAB study.
            (Montgomery et al., 2013) Download
BACKGROUND: Omega-3 long-chain polyunsaturated fatty acids (LC-PUFA), especially DHA (docosahexaenonic acid) are essential for brain development and physical health. Low blood Omega-3 LC-PUFA have been reported in children with ADHD and related behavior/learning difficulties, as have benefits from dietary supplementation. Little is known, however, about blood fatty acid status in the general child population. We therefore investigated this in relation to age-standardized measures of behavior and cognition in a representative sample of children from mainstream schools. PARTICIPANTS: 493 schoolchildren aged 7-9 years from mainstream Oxfordshire schools, selected for below average reading performance in national assessments at age seven. METHOD: Whole blood fatty acids were obtained via fingerstick samples. Reading and working memory were assessed using the British Ability Scales (II). Behaviour (ADHD-type symptoms) was rated using the revised Conners' rating scales (long parent and teacher versions). Associations were examined and adjusted for relevant demographic variables. RESULTS: DHA and eicosapentaenoic acid (EPA), accounted for only 1.9% and 0.55% respectively of total blood fatty acids, with DHA showing more individual variation. Controlling for sex and socio-economic status, lower DHA concentrations were associated with poorer reading ability (std. OLS coeff. = 0.09, p = <.042) and working memory performance (0.14, p = <.001). Lower DHA was also associated with higher levels of parent rated oppositional behavior and emotional lability (-0.175, p = <.0001 and -0.178, p = <.0001). CONCLUSIONS: In these healthy UK children with below average reading ability, concentrations of DHA and other Omega-3 LC-PUFA were low relative to adult cardiovascular health recommendations, and directly related to measures of cognition and behavior. These findings require confirmation, but suggest that the benefits from dietary supplementation with Omega-3 LC-PUFA found for ADHD, Dyspraxia, Dyslexia, and related conditions might extend to the general school population.

Omega-3 Fatty Acid Status Enhances the Prevention of Cognitive Decline by B Vitamins in Mild Cognitive Impairment.
            (Oulhaj et al., 2016) Download
A randomized trial (VITACOG) in people with mild cognitive impairment (MCI) found that B vitamin treatment to lower homocysteine slowed the rate of cognitive and clinical decline. We have used data from this trial to see whether baseline omega-3 fatty acid status interacts with the effects of B vitamin treatment. 266 participants with MCI aged ≥70 years were randomized to B vitamins (folic acid, vitamins B6 and B12) or placebo for 2 years. Baseline cognitive test performance, clinical dementia rating (CDR) scale, and plasma concentrations of total homocysteine, total docosahexaenoic and eicosapentaenoic acids (omega-3 fatty acids) were measured. Final scores for verbal delayed recall, global cognition, and CDR sum-of-boxes were better in the B vitamin-treated group according to increasing baseline concentrations of omega-3 fatty acids, whereas scores in the placebo group were similar across these concentrations. Among those with good omega-3 status, 33% of those on B vitamin treatment had global CDR scores >0 compared with 59% among those on placebo. For all three outcome measures, higher concentrations of docosahexaenoic acid alone significantly enhanced the cognitive effects of B vitamins, while eicosapentaenoic acid appeared less effective. When omega-3 fatty acid concentrations are low, B vitamin treatment has no effect on cognitive decline in MCI, but when omega-3 levels are in the upper normal range, B vitamins interact to slow cognitive decline. A clinical trial of B vitamins combined with omega-3 fatty acids is needed to see whether it is possible to slow the conversion from MCI to AD.

Diet-induced changes in iron and n-3 fatty acid status and associations with cognitive performance in 8-11-year-old Danish children: secondary analyses of the Optimal Well-Being, Development and Health for Danish Children through a Healthy New Nordic Diet School Meal Study.
            (Sørensen et al., 2015) Download
Fe and n-3 long-chain PUFA (n-3 LCPUFA) have both been associated with cognition, but evidence remains inconclusive in well-nourished school-aged children. In the Optimal Well-Being, Development and Health for Danish Children through a Healthy New Nordic Diet (OPUS) School Meal Study, the 3-month intervention increased reading performance, inattention, impulsivity and dietary intake of fish and Fe. This study investigated whether the intervention influenced n-3 LCPUFA and Fe status and, if so, explored how these changes correlated with the changes in cognitive performance. The study was a cluster-randomised cross-over trial comparing school meals with packed lunch (control). At baseline and after each treatment, we measured serum ferritin, whole-blood n-3 LCPUFA and Hb, and performance in reading, mathematics and d2-test of attention. Data were analysed using mixed models (n 726) and principal component analysis of test performances (n 644), which showed two main patterns: 'school performance' and 'reading comprehension'. The latter indicated that children with good reading comprehension were also more inattentive and impulsive (i.e. higher d2-test error%). The intervention improved 'school performance' (P=0·015), 'reading comprehension' (P=0·043) and EPA+DHA status 0·21 (95% CI 0·15, 0·27) w/w % (P<0·001), but it did not affect serum ferritin or Hb. At baseline, having small Fe stores was associated with poorer 'school performance' in girls, but with better 'reading comprehension' in both boys and girls. Both baseline EPA+DHA status and the intervention-induced increase in EPA+DHA status was positively associated with 'school performance', suggesting that n-3 LCPUFA could potentially explain approximately 20 % of the intervention effect. These exploratory associations indicate that increased fish intake might explain some of the increase in reading performance and inattention in the study.

A High Omega-3 Fatty Acid Multinutrient Supplement Benefits Cognition and Mobility in Older Women: A Randomized, Double-blind, Placebo-controlled Pilot Study.
            (Strike et al., 2016) Download
BACKGROUND:  Mobility is a key determinant of frailty in older persons, and a variety of dietary factors, such as the omega-3 fatty acid docosahexaenoic acid (DHA), are positively associated with decreased frailty and improved mobility and cognition in older persons. METHODS:  The effects of a multinutrient supplement on mobility and cognition were assessed in postmenopausal women (60-84 years). Participants received either Efalex Active 50+ (1g DHA, 160 mg eicosapentaenoic acid, 240 mg Ginkgo biloba, 60 mg phosphatidylserine, 20mg d-α tocopherol, 1mg folic acid, and 20 µg vitamin B12 per day; N = 15) or placebo (N = 12) for 6 months. Mobility was assessed by VICON 9 motion capture camera system synchronized with Kistler force plates, cognitive performance by computerized cognitive function tests, and blood fatty acid levels by pin-prick analysis. RESULTS:  Significant effects of treatment were seen in two of the four cognitive tests, with shorter mean latencies in a motor screening task (p < .05) and more words remembered (p < .03), and one of the three primary mobility measures with improved habitual walking speed (p < .05). Compared with the placebo group, supplementation also resulted in significantly higher blood DHA levels (p < .02). CONCLUSIONS:  In this pilot study, multinutrient supplementation improved cognition and mobility in able older females at clinically relevant levels, suggesting a potential role in reducing the decline to frailty.

Low Doses of Long-chain Polyunsaturated Fatty Acids Affect Cognitive Function in Elderly Japanese Men: A Randomized Controlled Trial.
            (Tokuda et al., 2015) Download
Several studies have reported that the supplementation of long-chain polyunsaturated fatty acids (LCPUFA), such as docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (ARA) improve cognitive function in the elderly. However, the doses used in these studies were higher than general dietary LCPUFA intake levels. This randomized, double-blind, placebo-controlled trial evaluated the effects of low doses of LCPUFA supplementation corresponding to general dietary intake on cognitive function in non-demented elderly Japanese participants. Japanese men aged 55-64 years were enrolled and randomly allocated to the placebo or LCPUFA group. Participants received 4 weeks of supplementation with LCPUFA-containing oil (DHA, 300 mg/day; EPA, 100 mg/day; and ARA, 120 mg/day) or purified olive oil as placebo. Event-related potential P300, reflecting cognitive processes, was measured before and after supplementation. A total of 113 participants completed the supplementation period, and the per-protocol analysis included 69 participants. Changes in P300 latency were significantly different between the placebo group (+13.6 msec) and the LCPUFA group (-1.8 msec) after supplementation. Significant increases in DHA (+0.9%) and ARA (+0.6%) contents in plasma phospholipids were observed in the LCPUFA group; no changes were observed in the placebo group. Dietary DHA, EPA, and ARA intake were in the normal range for Japan participants and remained unchanged during the study. These results suggest that low doses of LCPUFA supplementation have the potential to improve cognitive function in elderly Japanese men.

 


References

Ammann, EM, et al. (2013), ‘omega-3 fatty acids and domain-specific cognitive aging: secondary analyses of data from WHISCA.’, Neurology, 81 (17), 1484-91. PubMed: 24068783
Andrieu, S, et al. (2017), ‘Effect of long-term omega 3 polyunsaturated fatty acid supplementation with or without multidomain intervention on cognitive function in elderly adults with memory complaints (MAPT): a randomised, placebo-controlled trial.’, Lancet Neurol, 16 (5), 377-89. PubMed: 28359749
Bauer, I, et al. (2014), ‘Omega-3 supplementation improves cognition and modifies brain activation in young adults.’, Hum Psychopharmacol, 29 (2), 133-44. PubMed: 24470182
Bo, Y, et al. (2017), ‘The n-3 Polyunsaturated Fatty Acids Supplementation Improved the Cognitive Function in the Chinese Elderly with Mild Cognitive Impairment: A Double-Blind Randomized Controlled Trial.’, Nutrients, 9 (1), PubMed: 28075381
Boespflug, EL, et al. (2016), ‘Fish Oil Supplementation Increases Event-Related Posterior Cingulate Activation in Older Adults with Subjective Memory Impairment.’, J Nutr Health Aging, 20 (2), 161-69. PubMed: 26812512
Chew, EY, et al. (2015), ‘Effect of Omega-3 Fatty Acids, Lutein/Zeaxanthin, or Other Nutrient Supplementation on Cognitive Function: The AREDS2 Randomized Clinical Trial.’, JAMA, 314 (8), 791-801. PubMed: 26305649
Danthiir, V, et al. (2014), ‘Cognitive performance in older adults is inversely associated with fish consumption but not erythrocyte membrane n-3 fatty acids.’, J Nutr, 144 (3), 311-20. PubMed: 24353345
Gould, JF, et al. (2017), ‘Seven-Year Follow-up of Children Born to Women in a Randomized Trial of Prenatal DHA Supplementation.’, JAMA, 317 (11), 1173-75. PubMed: 28324081
Jackson, PA, et al. (2016), ‘DHA Supplementation Alone or in Combination with Other Nutrients Does not Modulate Cerebral Hemodynamics or Cognitive Function in Healthy Older Adults.’, Nutrients, 8 (2), 86. PubMed: 26867200
Jernerén, F, et al. (2015), ‘Brain atrophy in cognitively impaired elderly: the importance of long-chain ω-3 fatty acids and B vitamin status in a randomized controlled trial.’, Am J Clin Nutr, 102 (1), 215-21. PubMed: 25877495
Külzow, N, et al. (2016), ‘Impact of Omega-3 Fatty Acid Supplementation on Memory Functions in Healthy Older Adults.’, J Alzheimers Dis, 51 (3), 713-25. PubMed: 26890759
Leckie, RL, et al. (2014), ‘Omega-3 fatty acids moderate effects of physical activity on cognitive function.’, Neuropsychologia, 59C 103-11. PubMed: 24813150
Mahmoudi, MJ, et al. (2014), ‘Effect of low dose omega-3 poly unsaturated fatty acids on cognitive status among older people: a double-blind randomized placebo-controlled study.’, J Diabetes Metab Disord, 13 (1), 34. PubMed: 24507770
Mazereeuw, G, et al. (2016), ‘Omega-3 Fatty Acids, Depressive Symptoms, and Cognitive Performance in Patients With Coronary Artery Disease: Analyses From a Randomized, Double-Blind, Placebo-Controlled Trial.’, J Clin Psychopharmacol, 36 (5), 436-44. PubMed: 27529771
Montgomery, P, et al. (2013), ‘Low blood long chain omega-3 fatty acids in UK children are associated with poor cognitive performance and behavior: a cross-sectional analysis from the DOLAB study.’, PLoS One, 8 (6), e66697. PubMed: 23826114
Oulhaj, A, et al. (2016), ‘Omega-3 Fatty Acid Status Enhances the Prevention of Cognitive Decline by B Vitamins in Mild Cognitive Impairment.’, J Alzheimers Dis, 50 (2), 547-57. PubMed: 26757190
Sørensen, LB, et al. (2015), ‘Diet-induced changes in iron and n-3 fatty acid status and associations with cognitive performance in 8-11-year-old Danish children: secondary analyses of the Optimal Well-Being, Development and Health for Danish Children through a Healthy New Nordic Diet School Meal Study.’, Br J Nutr, 114 (10), 1623-37. PubMed: 26359192
Strike, SC, et al. (2016), ‘A High Omega-3 Fatty Acid Multinutrient Supplement Benefits Cognition and Mobility in Older Women: A Randomized, Double-blind, Placebo-controlled Pilot Study.’, J Gerontol A Biol Sci Med Sci, 71 (2), 236-42. PubMed: 26265727
Tokuda, H, et al. (2015), ‘Low Doses of Long-chain Polyunsaturated Fatty Acids Affect Cognitive Function in Elderly Japanese Men: A Randomized Controlled Trial.’, J Oleo Sci, 64 (6), 633-44. PubMed: 25891115