Efficacy of Mealtime Interventions for Malnutrition and Oral Intake in Persons With Dementia: A Systematic Review.

Malnutrition and weight loss are highly prevalent in persons with Alzheimer's disease and related dementias. Oral intake is an important interventional target for addressing these nutritional consequences. However, the efficacy of interventions remains poorly understood as prior syntheses have failed to examine the impact of intervention approaches on malnutrition and hypothesized mechanisms of action in persons with dementia. This review aimed to determine the efficacy of mealtime interventions to improve oral intake and nutritional outcomes in persons with dementia. Four databases yielded 1712 studies, resulting in 32 studies that met inclusion criteria. Studies included education, environmental modifications, feeding, oral supplementation, and other pharmacologic/ecopsychological interventions. While the majority of studies reported statistically significant improvements in at least 1 nutritional outcome, study design and outcome measures were heterogenous with many lacking adequate statistical power or blinding. Collectively, we found moderate evidence to suggest the efficacy of oral supplementation, and preliminary evidence to suggest that feeding interventions, education, and environmental modifications may confer improvements. Findings clarify the state of existing evidence regarding various interventional strategies for improving malnutrition in persons with dementia. While some approaches are promising, adequately powered and rigorously designed multidimensional intervention trials are needed to inform clinical decision-making in real-world contexts.

B Vitamins and Fatty Acids: What Do They Share with Small Vessel Disease-Related Dementia?

Many studies have been written on vitamin supplementation, fatty acid, and dementia, but results are still under debate, and no definite conclusion has yet been drawn. Nevertheless, a significant amount of lab evidence confirms that vitamins of the B group are tightly related to gene control for endothelium protection, act as antioxidants, play a co-enzymatic role in the most critical biochemical reactions inside the brain, and cooperate with many other elements, such as choline, for the synthesis of polyunsaturated phosphatidylcholine, through S-adenosyl-methionine (SAM) methyl donation. B-vitamins have anti-inflammatory properties and act in protective roles against neurodegenerative mechanisms, for example, through modulation of the glutamate currents and a reduction of the calcium currents. In addition, they also have extraordinary antioxidant properties. However, laboratory data are far from clinical practice. Many studies have tried to apply these results in everyday clinical activity, but results have been discouraging and far from a possible resolution of the associated mysteries, like those represented by Alzheimer's disease (AD) or small vessel disease dementia. Above all, two significant problems emerge from the research: No consensus exists on general diagnostic criteria-MCI or AD? Which diagnostic criteria should be applied for small vessel disease-related dementia? In addition, no general schema exists for determining a possible correct time of implementation to have effective results. Here we present an up-to-date review of the literature on such topics, shedding some light on the possible interaction of vitamins and phosphatidylcholine, and their role in brain metabolism and catabolism. Further studies should take into account all of these questions, with well-designed and world-homogeneous trials.

Dietary interventions in mild cognitive impairment and dementia.

Dietary intervention is an enticing approach in the fight against cognitive impairment. Nutritional supplements and dietetic counseling are relatively easy and benign interventions, but research has not yet yielded irrefutable evidence as to their clinical utility. Heterogeneity in the results of available clinical studies, as well as methodological and practical issues, does not allow replication and generalization of findings. The paper at hand reviews only randomized clinical trials of single nutrients, multi-nutrient formulations and dietary counseling in mild cognitive impairment and dementia of the Alzheimer's type focusing on both cognitive and functional outcomes. Thus far, folate, vitamin E, Ω-3 fatty acids, and certain multi-nutrient formulations have shown some preliminary promising results; larger, well-designed trials are needed to confirm these findings before nutritional elements can be incorporated in recommended clinical guidelines.

Adherence to multidomain interventions for dementia prevention: Data from the FINGER and MAPT trials.

INTRODUCTION: Multidomain interventions, targeting multiple risk factors simultaneously, could be effective dementia prevention strategies, but may be burdensome and not universally acceptable. METHODS: We studied adherence rates and predictors in the Finnish Geriatric Intervevntion Study to Prevent Cognitive Impairment and Disability and Multidomain Alzheimer Preventive Trial prevention trials, for all intervention components (separately and simultaneously). Finnish Geriatric Intervevntion Study to Prevent Cognitive Impairment and Disability participants received a 2-year multidomain lifestyle intervention (physical training, cognitive training, nutritional counseling, and cardiovascular monitoring). Multidomain Alzheimer Preventive Trial participants received a 3-year multidomain lifestyle intervention (cognitive training, physical activity counseling, and nutritional counseling) with either an omega-3 supplement or placebo. RESULTS: Adherence decreased with increasing intervention complexity and intensity: it was highest for cardiovascular monitoring, nutritional counseling, and the omega-3 supplement, and lowest for unsupervised computer-based cognitive training. The most consistent baseline predictors of adherence were smoking and depressive symptoms. DISCUSSION: Reducing participant burden, while ensuring that technological tools are suitable for older individuals, maintaining face-to-face contacts, and taking into account participant characteristics may increase adherence in future trials.

Effect of monosodium L-glutamate (umami substance) on cognitive function in people with dementia.

BACKGROUND/OBJECTIVES: This study assessed the effect of continuous ingestion of monosodium L-glutamate (MSG) on cognitive function and dietary score in dementia patients. SUBJECTS/METHODS: This was a single-blind, placebo-controlled trial involving 159 subjects with dementia residing in a hospital or nursing home. We assigned the subjects to a group that ingested MSG thrice daily (0.9 g/dose) (MSG group; n = 79) or a group that ingested NaCl thrice daily (0.26 g/dose) (Control group; n = 80). This study consisted of a 12-week intake period, followed by a 4-week follow-up period without the ingestion of MSG or NaCl. We performed physical examination, cognitive symptom tests (the Touch Panel-type Dementia Assessment Scale (TDAS) and Gottfries-Bråne-Steen Scale (GBSS)), palatability and behaviour questionnaires, and blood tests before and after the intervention and after the follow-up period. RESULTS: There were no significant differences in the TDAS and GBSS total scores between the groups before and after the intervention. However, regarding the TDAS sub-items, "the accuracy of the order of a process" did not deteriorate in the MSG group compared with that observed in the Control group (p < 0.05). At the follow-up assessment, the TDAS total scores in the MSG group showed significant improvement compared with those reported in the Control group (p < 0.05). Furthermore, there was a correlation of changes from pre-intervention to post-intervention between the TDAS and enjoyment of the meal (r = -0.299, p = 0.049). CONCLUSIONS: Our results suggest that continued ingestion of MSG has an effect on cognitive function. Furthermore, the patients with improved questionnaires about palatability survey showed greater improvement in cognitive function.

Supplements, nutrition, and alternative therapies for the treatment of traumatic brain injury.

Studies using traditional treatment strategies for mild traumatic brain injury (TBI) have produced limited clinical success. Interest in treatment for mild TBI is at an all time high due to its association with the development of chronic traumatic encephalopathy and other neurodegenerative diseases, yet therapeutic options remain limited. Traditional pharmaceutical interventions have failed to transition to the clinic for the treatment of mild TBI. As such, many pre-clinical studies are now implementing non-pharmaceutical therapies for TBI. These studies have demonstrated promise, particularly those that modulate secondary injury cascades activated after injury. Because no TBI therapy has been discovered for mild injury, researchers now look to pharmaceutical supplementation in an attempt to foster success in human clinical trials. Non-traditional therapies, such as acupuncture and even music therapy are being considered to combat the neuropsychiatric symptoms of TBI. In this review, we highlight alternative approaches that have been studied in clinical and pre-clinical studies of TBI, and other related forms of neural injury. The purpose of this review is to stimulate further investigation into novel and innovative approaches that can be used to treat the mechanisms and symptoms of mild TBI.

[Analysis of the Cochrane Review: Omega-3 Fatty Acids for the Treatment of Dementia. Cochrane Database Syst Rev. 2016;4:CD009002.] / Análise da Revisão Cochrane: Suplementação Alimentar com Ácidos Gordos Ómega-3 no Tratamento da Demência. Cochrane Database Syst Rev. 2016;4:CD009002.

Dietary supplementation with omega-3 polyunsaturated fatty acids from fish and plant sources is commonly prescribed as a non-farmacological alternative to improve brain functions and slow down the progression of dementia. This use is mostly based on findings of preclinical studies which established the role of omega-3 polyunsaturated fatty acids in the development and integrity of the brain, as well as epidemiological research that found evidence of malnutrition in patients with dementia. This Cochrane systematic review included three randomized, placebo-controlled trials at low risk of bias, in which omega-3 polyunsaturated fatty acids were administered to people with mild to moderate Alzheimer's disease in the form of supplements. Of the main results of this systematic review we highlight the lack of convincing evidence for the efficacy of omega-3 polyunsaturated fatty acids supplementation in the treatment of patients with Alzheimer's disease, as well as the low frequency of reported adverse events, with a comparable overall frequency between omega-3 polyunsaturated fatty acids and the placebo groups. The effects on other populations with dementia remain unclear. This paper aims to summarize and discuss the main results and conclusions of this systematic review, as well as its implications for the daily clinical practice.

A suplementação alimentar com ácidos gordos poli-insaturados ómega-3, de origem animal e vegetal, é comummente prescrita como alternativa não farmacológica no tratamento da demência, com o objetivo de atrasar a sua progressão e melhorar a função cognitiva dos doentes. Esta utilização deriva em grande medida de estudos pré-clínicos, que estabeleceram o papel dos ácidos gordos poliinsaturados ómega-3 no desenvolvimento e manutenção da integridade do sistema nervoso central, e de estudos epidemiológicos, que demonstraram a ocorrência de estados de malnutrição em doentes com demência. Nesta revisão sistemática Cochrane, os autores incluíram três ensaios clínicos aleatorizados controlados por placebo, com baixo risco de vieses, nos quais doentes com doença de Alzheimer ligeira a moderada foram tratados com ácidos gordos poli-insaturados ómega-3, através de suplementos alimentares. Dos principais resultados desta RS destacam-se a ausência de evidência de um efeito benéfico do tratamento com suplementação com ácidos gordos poli-insaturados ómega-3 sobre a função cognitiva de doentes com doença de Alzheimer e a baixa taxa de efeitos adversos reportados, esta última comparável à dos grupos tratados com placebo. Não existem dados sobre outros tipos de demência. Neste artigo sumarizam-se e discutem-se os principais resultados e conclusões desta revisão sistemática, bem como as suas implicações para a prática clínica diária.

Dietary Polyphenols as Potential Remedy for Dementia.

With increasing life expectancy as a result of better quality of life and improved health care, the incidence of aging related diseases and disorders is heading toward epidemic proportions. Dementia, a spectrum of neurological diseases associated with aging, is an increasingly prevalent disease. No cure exists yet for dementia; however, there are many potential candidates for treatment of dementia that merit more exploration. Polyphenols, which constitute one such class of compounds, are dietary agents that are globally found in commonly consumed food. Many processes that are associated with the pathophysiology of dementia can be modulated by polyphenols. Polyphenolic compounds can alleviate oxidative stress by acting as direct scavengers of free radicals and clearing superoxide and hydroxyl radicals and by increasing the level of antioxidant enzymes such as glutathione peroxidase. They also chelate metal ions to prevent free radical formation. Polyphenols can also combat inflammation by affecting transcription factors such as NF-κB. Some polyphenols may have the potential to inhibit excitotoxicity by regulating intracellular calcium ion concentration, inhibiting glutamate receptors and increasing glutamate reuptake at the synapse. The cognitive decline in dementia due to decreased availability of acetylcholine can also be countered by polyphenols that inhibit acetyl-cholinesterase activity. Taken together, these findings suggest that increasing the consumption of polyphenol rich food may alleviate the effects of dementia. Moreover, their effects on controlling multiple mechanisms that are associated with dementia may also prevent or slow down the onset and progress of this devastating disease.

Effects of different fatty acids composition of phosphatidylcholine on brain function of dementia mice induced by scopolamine.

BACKGROUND: Phosphatidylcholine (PC), the major source of dietary choline, has been demonstrated to improve the capability of learning and memory in rodent and the amelioration of long-chain n-3 polyunsaturated fatty acids (PUFA) on anti-aging and anti-oxidation is widely known as well. In this study, three kinds of PC were chose to demonstrate the role of different fatty acids composition on glycerol backbone in improving the brain function of mice induced by scopolamine which was used to impair cholinergic system and cause oxidative stress. METHODS: Male BALB/c mice were randomly divided into 5 groups: model (M) group, control (Con) group, egg yolk lecithin (EL) group, squid PC (SQ-PC) group and sea cucumber PC (SC-PC) group. The intraperitoneal injection of scopolamine hydrobromide (5 mg/kg) was carried out on the 8(th) of group feeding and sustained daily until the end of test. Morris water maze test was used to evaluate the improvement of cognitive decline and the activity of acetylcholinesterase (AchE), superoxide dismutase (SOD) and monoamine oxidase (MAO) and malondialdehyde (MDA) content in brain were measured to assess the physiological changes. RESULTS: In behavior test, the latency of PC groups was significantly reduced, while number of crossing the platform and time in target quadrant were increased in comparison with M group and the improvements of SQ-PC and SC-PC were better than that of EL (P < 0.05). Similar trend was observed in physiological changes. The AchE activity was effectively decreased and the SOD activity increased in hippocampus, cortex and white matter when comparing PC groups with M group. SQ-PC, SC-PC and EL respectively showed 22.82, 28.80 and 11.81 % decrease in MDA level in brain compared with M group. The MAO activity in white matter of SQ-PC, SC-PC and EL group separately depressed 33.05, 33.64 and 19.73 % in comparison with M group. No significance between SQ-PC and SC-PC was found in these indicators except the SOD activity in hippocampus and white matter. SQ-PC group had a higher SOD activity in hippocampus (103.68U/mg · prot.) and lower in white matter (120.57 U/mg · prot.) than SC-PC group (95.53 U/mg · prot. in hippocampus, 134.49 U/mg · prot. in white matter). PC rich in n-3 PUFA acted more ameliorative effects than that barely contained on the indicators above. CONCLUSIONS: Different fatty acids composition of PC all could diminish the cognitive decline and biological damage and protect the brain. EPA and DHA partly enhaced to the advantageous effects.

Calcium supplementation and risk of dementia in women with cerebrovascular disease.

OBJECTIVE: To determine whether calcium supplementation is associated with the development of dementia in women after a 5-year follow-up. METHODS: This was a longitudinal population-based study. The sample was derived from the Prospective Population Study of Women and H70 Birth Cohort Study in Gothenburg, Sweden, and included 700 dementia-free women aged 70-92 years. At baseline in 2000-2001, and at follow-up in 2005-2006, the women underwent comprehensive neuropsychiatric and somatic examinations. A CT scan was performed in 447 participants at baseline. Information on the use and dosage of calcium supplements was collected. Dementia was diagnosed according to DSM-III-R criteria. RESULTS: Women treated with calcium supplements (n = 98) were at a higher risk of developing dementia (odds ratio [OR] 2.10, 95% confidence interval [CI] 1.01-4.37, p = 0.046) and the subtype stroke-related dementia (vascular dementia and mixed dementia) (OR 4.40, 95% CI 1.54-12.61, p = 0.006) than women not given supplementation (n = 602). In stratified analyses, calcium supplementation was associated with the development of dementia in groups with a history of stroke (OR 6.77, 95% CI 1.36-33.75, p = 0.020) or presence of white matter lesions (OR 2.99, 95% CI 1.28-6.96, p = 0.011), but not in groups without these conditions. CONCLUSIONS: Calcium supplementation may increase the risk of developing dementia in elderly women with cerebrovascular disease. Because our sample was relatively small and the study was observational, these findings need to be confirmed.

Nutrición y deterioro cognitivo / Nutrition and cognitive impairment

La demencia, estrechamente ligada a factores predisponentes ambientales como la dieta, supone un problema de salud pública de magnitud creciente: actualmente más de 35 millones de pacientes presentan demencia tipo Alzheimer, y se espera que se superen los 135 millones en 2050. Si conseguimos retrasar el desarrollo de la demencia 5 años, reduciremos su prevalencia en un 50%. Los pacientes con demencia alteran su dieta y se han reportado déficits, entre otros, de ácido fólico, vitaminas B12, B6 , C, E, A, D, K, betacarotenos y omega tres, que deben ser resueltos con una dieta adecuada y, en según qué casos, con aportes extra. Pero para reducir o al menos retrasar la prevalencia debemos preconizar la prevención mediante una dieta adecuada desde el inicio de la vida, idea reforzada por el hecho de que los factores de riesgo cardiovascular se relacionen de forma directa con el desarrollo de demencia. Disponemos de abundante bibliografía que, aunque con límites, nos permite hacer recomendaciones nutricionales para prevenir el deterioro cognitivo. Se han conseguido mejores resultados cuando se han estudiado dietas completas que cuando se han considerado nutrientes específicos. De especial interés es la dieta mediterránea, que garantiza un aporte elevado de vegetales, frutas, frutos secos, legumbres, cereales, pescado y aceite de oliva, y moderado de carne, productos lácteos y alcohol, y en la que nos centraremos en este artículo (AU)

Dementia, closely linked to environmental predisposing factors such as diet, is a public health problem of increasing magnitude: currently there are more than 35 million patients with Alzheimer´s disease, and is expected to exceed 135 million by 2050. If we can delay the development of dementia 5 years will reduce its prevalence by 50%. Patients with dementia modify their diet, and it has been reported in them deficits, among others, of folic acid, vitamin B12, B6 , C, E, A, D, K, beta carotene and omega 3 fatty acids, that must be resolved with proper diet and with extra contributions if needed in some cases. But to reduce, or at least delay, the prevalence of dementia we advocate prevention through proper diet from the beginning of life, an idea that is reinforced given that cardiovascular risk factors are related directly to the development of dementia. A lot of literature are available that, although with limits, allows us to make nutritional recommendations for preventing cognitive impairment. Better results are achieved when complete diets have been studied and considered over specific nutrients separately. Particularly, the Mediterranean diet has great interest in this disease, since it ensures a high intake of vegetables, fruits, nuts, legumes, cereals, fish and olive oil, and moderate intake of meat, dairy products and alcohol. We will focus more on this article in this type of diet (AU)

ESPEN guidelines on nutrition in dementia

BACKGROUND: Older people suffering from dementia are at increased risk of malnutrition due to various nutritional problems, and the question arises which interventions are effective in maintaining adequate nutritional intake and nutritional status in the course of the disease. It is of further interest whether supplementation of energy and/or specific nutrients is able to prevent further cognitive decline or even correct cognitive impairment, and in which situations artificial nutritional support is justified. OBJECTIVE: It is the purpose of these guidelines to cover these issues with evidence-based recommendations. METHODS: The guidelines were developed by an international multidisciplinary working group in accordance with officially accepted standards. The GRADE system was used for assigning strength of evidence. Recommendations were discussed, submitted to Delphi rounds and accepted in an online survey among ESPEN members. RESULTS: 26 recommendations for nutritional care of older persons with dementia are given. In every person with dementia, screening for malnutrition and close monitoring of body weight are recommended. In all stages of the disease, oral nutrition may be supported by provision of adequate, attractive food in a pleasant environment, by adequate nursing support and elimination of potential causes of malnutrition. Supplementation of single nutrients is not recommended unless there is a sign of deficiency. Oral nutritional supplements are recommended to improve nutritional status but not to correct cognitive impairment or prevent cognitive decline. Artificial nutrition is suggested in patients with mild or moderate dementia for a limited period of time to overcome a crisis situation with markedly insufficient oral intake, if low nutritional intake is predominantly caused by a potentially reversible condition, but not in patients with severe dementia or in the terminal phase of life. CONCLUSION: Nutritional care and support should be an integral part of dementia management. In all stages of the disease, the decision for or against nutritional interventions should be made on an individual basis after carefully balancing expected benefit and potential burden, taking the (assumed) patient will and general prognosis into account.(AU)

ESPEN guidelines on nutrition in dementia.

BACKGROUND: Older people suffering from dementia are at increased risk of malnutrition due to various nutritional problems, and the question arises which interventions are effective in maintaining adequate nutritional intake and nutritional status in the course of the disease. It is of further interest whether supplementation of energy and/or specific nutrients is able to prevent further cognitive decline or even correct cognitive impairment, and in which situations artificial nutritional support is justified. OBJECTIVE: It is the purpose of these guidelines to cover these issues with evidence-based recommendations. METHODS: The guidelines were developed by an international multidisciplinary working group in accordance with officially accepted standards. The GRADE system was used for assigning strength of evidence. Recommendations were discussed, submitted to Delphi rounds and accepted in an online survey among ESPEN members. RESULTS: 26 recommendations for nutritional care of older persons with dementia are given. In every person with dementia, screening for malnutrition and close monitoring of body weight are recommended. In all stages of the disease, oral nutrition may be supported by provision of adequate, attractive food in a pleasant environment, by adequate nursing support and elimination of potential causes of malnutrition. Supplementation of single nutrients is not recommended unless there is a sign of deficiency. Oral nutritional supplements are recommended to improve nutritional status but not to correct cognitive impairment or prevent cognitive decline. Artificial nutrition is suggested in patients with mild or moderate dementia for a limited period of time to overcome a crisis situation with markedly insufficient oral intake, if low nutritional intake is predominantly caused by a potentially reversible condition, but not in patients with severe dementia or in the terminal phase of life. CONCLUSION: Nutritional care and support should be an integral part of dementia management. In all stages of the disease, the decision for or against nutritional interventions should be made on an individual basis after carefully balancing expected benefit and potential burden, taking the (assumed) patient will and general prognosis into account.

Effect of eicosapentaenoic acid and docosahexaenoic acid supplementations to control cognitive decline in dementia and Alzheimer’s disease: a systematic review / Efecto de la suplementación del ácido eicosapentaenoico y ácido docosahexaenoico para controlar el deterioro cognitivo en la demencia y enfermedad de alzheimer: una revisión sistemática

Introduction: there is a lack of consensus on the benefits of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementations on cognition in dementia and/or Alzheimer’s disease (AD) elderly. Objective: this study presents a systematic review of the results of randomized clinical trials about this topic. The adopted search criteria were randomized clinical trials involving elderly over 65 years of age with no limit to the year of publication of the study. Results: we identified 139 articles, and from the eligible ones a reverse search was conducted. The quality of the trials was assessed using the Jadad scale. Of the four selected studies, three were related to mild to moderate AD elderly, of both genders. Mini Mental State Examination, Alzheimer’s Disease Assessment Scale Cognitive, and Clinical Dementia Rate were the main tests used to assess cognitive performance. Conclusion: EPA and/or DHA supplementations did not affect scores obtained on the cognitive tests. However, supplementation with EPA and/or DHA improved verbal fluency and attention in patients who had only very mild dementia or AD or presented APOEε4 negative genotype. In case of advanced AD elderly patients, EPA and/or DHA supplementations did not reduce cognitive decline rates (AU)

Introducción: no existe consenso sobre los beneficios de la suplementación con ácido eicosapentaenoico (EPA) y ácido docosahexaenoico (DHA) sobre la cognición de las personas mayores con demencia y/o Alzheimer. Objetivo: esta revisión sistemática muestra los resultados de ensayos clínicos randomizados al respecto. Métodos: se realizó una búsqueda de ensayos clínicos randomizados llevados a cabo en personas mayores de 65 años, sin estabelecer límites en cuanto al año de publicación. Resultados: se identificaron 139 artículos y a partir de los artículos candidatos se llevó a cabo una búsqueda inversa. La calidad de los ensayos clínicos aleatorios se evaluó mediante la escala de Jadad. De los cuatro estudios seleccionados, tres valoraban ancianos, con diagnóstico de enfermedad de Alzheimer de leve a moderada, en ambos sexos. Mini Examen del Estado Mental, Enfermedad de Alzheimer, Escala de Evaluación Cognitiva y Tasa Clí- nica de Demencia fueron los principales test utilizados para estudiar el rendimiento cognitivo. Conclusión: la suplementación de EPA y/o DHA no afectó las puntuaciones en las pruebas cognitivas. Sin embargo, la suplementación con EPA y/o DHA mejoró la cognición en los dominios de fluidez y de atención verbales en pacientes que únicamente presentaban demencia leve o enfermedad de Alzheimer o el genotipo APOEε4 negativo. En los pacientes ancianos con enfermedad de Alzheimer avanzada, la suplementación con EPA y/o DHA no redujo las tasas de deterioro cognitivo (AU)

Plant-based nutraceutical interventions against cognitive impairment and dementia: meta-analytic evidence of efficacy of a standardized Gingko biloba extract.

Among nutraceuticals and nutritional bioactive compounds, the standardized Ginkgo biloba extract EGb 761 is the most extensively clinically tested herbal-based substance for cognitive impairment, dementia, and Alzheimer's disease (AD). In the last three years, notwithstanding negative meta-analytic findings and the discouraging results of preventive trials against AD, some randomized controlled trials focusing particularly on dementia, AD, and mild cognitive impairment (MCI) subgroups with neuropsychiatric symptoms (NPS) and some recent meta-analyses have suggested a renowned role for EGb 761 for cognitive impairment and dementia. Meta-analytic findings suggested overall benefits of EGb 761 for stabilizing or slowing decline in cognition of subjects with cognitive impairment and dementia. The safety and tolerability of EGb 761 appeared to be excellent at different doses. Subgroup analyses showed that these clinical benefits of EGb 761 were mainly associated with the 240 mg/day dose, and also confirmed in the AD subgroup. More importantly, one of these meta-analyses showed clinical benefits in cognition, behavior, functional status, and global clinical change of EGb 761 at a dose of 240 mg/day in the treatment of patients with dementia, AD, and MCI with NPS. The inclusion of the recent randomized controlled trials focusing on dementia, AD, and MCI subgroups with NPS may partly explain the conflicting results of these recent meta-analyses and previous pooled findings.

Virgin olive oil supplementation and long-term cognition: the PREDIMED-NAVARRA randomized, trial.

OBJECTIVE: To assess the effect on cognition of a controlled intervention testing Mediterranean diets (MedDiet). DESIGN: Randomized trial after 6.5 years of nutritional intervention. SETTING: Eight primary care centers affiliated to the University of Navarra. PARTICIPANTS: A random subsample of 285 participants (95 randomly allocated to each of 3 groups) of the PREDIMED-NAVARRA trial. All of them were at high vascular risk (44.8% men, 74.1±5.7 years at cognitive evaluation). INTERVENTIONS: Nutritional intervention comparing two MedDiets (supplemented with extra-virgin olive oil [EVOO] or mixed nuts) versus a low-fat control diet. Participants received intensive education to increase adherence to the intended intervention. Participants allocated to the MedDiet groups received EVOO (1 l/week) or 30 g/day of mixed nuts. Dietary habits were evaluated using a validated 137-item food frequency questionnaire (FFQ). Additionally, adherence to MedDiet was appraised using a 14-item questionnaire both at baseline and yearly thereafter. MEASUREMENTS: Cognitive performance as a main outcome and cognitive status (normal, mild cognitive impairment [MCI] or dementia) as a secondary outcome were evaluated by two neurologists blinded to group assignment after 6.5 years of nutritional intervention. RESULTS: Better post-trial cognitive performance versus control in all cognitive domains and significantly better performance across fluency and memory tasks were observed for participants allocated to the MedDiet+EVOO group. 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, this group also showed lower MCI (OR=0.34 95% CI: 0.12-0.97) compared with control group. Participants assigned to MedDiet+Nuts group did not differ from controls. CONCLUSION: A long-term intervention with an EVOO-rich MedDiet resulted in a better cognitive function in comparison with a control diet. However, non-significant differences were found for most cognitive domains. Participants allocated to an EVOO-rich MedDiet had less MCI than controls.