Cognitive function

Effect of fish oil on arrhythmias and mortality: systematic review.

OBJECTIVE: To synthesise the literature on the effects of fish oil-docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)-on mortality and arrhythmias and to explore dose response and formulation effects. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, Embase, the Cochrane Library, PubMed, CINAHL, IPA, Web of Science, Scopus, Pascal, Allied and Complementary Medicine, Academic OneFile, ProQuest Dissertations and Theses, Evidence-Based Complementary Medicine, and LILACS. Studies reviewed Randomised controlled trials of fish oil as dietary supplements in humans. DATA EXTRACTION: The primary outcomes of interest were the arrhythmic end points of appropriate implantable cardiac defibrillator intervention and sudden cardiac death. The secondary outcomes were all cause mortality and death from cardiac causes. Subgroup analyses included the effect of formulations of EPA and DHA on death from cardiac causes and effects of fish oil in patients with coronary artery disease or myocardial infarction. DATA SYNTHESIS: 12 studies totalling 32 779 patients met the inclusion criteria. A neutral effect was reported in three studies (n=1148) for appropriate implantable cardiac defibrillator intervention (odds ratio 0.90, 95% confidence interval 0.55 to 1.46) and in six studies (n=31 111) for sudden cardiac death (0.81, 0.52 to 1.25). 11 studies (n=32 439 and n=32 519) provided data on the effects of fish oil on all cause mortality (0.92, 0.82 to 1.03) and a reduction in deaths from cardiac causes (0.80, 0.69 to 0.92). The dose-response relation for DHA and EPA on reduction in deaths from cardiac causes was not significant. CONCLUSIONS: Fish oil supplementation was associated with a significant reduction in deaths from cardiac causes but had no effect on arrhythmias or all cause mortality. Evidence to recommend an optimal formulation of EPA or DHA to reduce these outcomes is insufficient. Fish oils are a heterogeneous product, and the optimal formulations for DHA and EPA remain unclear.

BMJ. 2008 Dec 23;337:a2931

Prevention of sudden cardiac death with omega-3 fatty acids in patients with coronary heart disease: a meta-analysis of randomized controlled trials.

AIM: To systematically review trials concerning the effects of omega-3 fatty acids on sudden cardiac death (SCD), cardiac death, and all-cause mortality in coronary heart disease (CHD) patients.METHODS: PubMed, Embase, and the Cochrane database (1966-2007) were searched. We identified randomized controlled trials that compared dietary or supplementary intake of omega-3 fatty acids with control diet or placebo in CHD patients. Eligible studies had at least 6 months of follow-up data, and cited SCD as an end-point. Two reviewers independently assessed methodological quality. Meta-analysis of relative risk was carried out using the random effect model. RESULTS: Eight trials were identified, comprising 20,997 patients. In patients with prior myocardial infarction (MI), omega-3 fatty acids reduced relative risk (RR) of SCD (RR = 0.43; 95% CI: 0.20-0.91). In patients with angina, omega-3 fatty acids increased RR of SCD (RR = 1.39; 95% CI: 1.01-1.92). Overall, RR for cardiac death and all-cause mortality were 0.71 (95% CI: 0.50-1.00) and 0.77 (95% CI: 0.58-1.01), respectively. CONCLUSIONS: Dietary supplementation with omega-3 fatty acids reduces the incidence of sudden cardiac death in patients with MI, but may have adverse effects in angina patients.

Ann Med. 2009;41(4):301-10

Omega-3 dietary supplements and the risk of cardiovascular events: a systematic review.

BACKGROUND: Epidemio-logic data suggest that omega-3 fatty acids derived from fish oil reduce cardiovascular disease. The clinical benefit of dietary fish oil supplementation in preventing cardiovascular events in both high and low risk patients is unclear.OBJECTIVE: To assess whether dietary supplements of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) decrease cardiovascular events across a spectrum of patients. DATA SOURCES: MEDLINE, Embase, the Cochrane Database of Systematic Reviews, and citation review of relevant primary and review articles. STUDY SELECTION: Prospective, randomized, placebo-controlled clinical trials that evaluated clinical cardiovascular end points (cardiovascular death, sudden death, and nonfatal cardiovascular events) and all-cause mortality in patients randomized to EPA/DHA or placebo. We only included studies that used dietary supplements of EPA/DHA which were administered for at least 1 year. DATA EXTRACTION: Data were abstracted on study design, study size, type and dose of omega-3 supplement, cardiovascular events, all-cause mortality, and duration of follow-up. Studies were grouped according to the risk of cardiovascular events (high risk and moderate risk). Meta-analytic techniques were used to analyze the data. DATA SYNTHESIS: We identified 11 studies that included a total of 39,044 patients. The studies included patients after recent myocardial infarction, those with an implanted cardioverter defibrillator, and patients with heart failure, peripheral vascular disease, and hypercholesterolemia. The average dose of EPA/DHA was 1.8 +/- 1.2 g/day and the mean duration of follow-up was 2.2 +/- 1.2 years. Dietary supplementation with omega-3 fatty acids significantly reduced the risk of cardiovascular deaths (odds ratio [OR]: 0.87, 95% confidence interval [CI]: 0.79-0.95, p = 0.002), sudden cardiac death (OR: 0.87, 95% CI: 0.76-0.99, p = 0.04), all-cause mortality (OR: 0.92, 95% CI: 0.85-0.99, p = 0.02), and nonfatal cardiovascular events (OR: 0.92, 95% CI: 0.85-0.99, p = 0.02). The mortality benefit was largely due to the studies which enrolled high risk patients, while the reduction in nonfatal cardiovascular events was noted in the moderate risk patients (secondary prevention only). Meta-regression failed to demonstrate a relationship between the daily dose of omega-3 fatty acid and clinical outcome. CONCLUSIONS: Dietary supplementation with omega-3 fatty acids should be considered in the secondary prevention of cardiovascular events.

Clin Cardiol. 2009 Jul;32(7):365-72

Consumption of polyunsaturated fatty acids, fish, and nuts and risk of inflammatory disease mortality

BACKGROUND: n-3 (omega-3) Polyunsaturated fatty acids (PUFAs), fish, and nuts can regulate inflammatory processes and responses.OBJECTIVE: We investigated whether dietary intakes of PUFAs [n-3, n-6 (omega-6), and α-linolenic acid], fish, and nuts were associated with 15-y mortality attributed to noncardiovascular, noncancer inflammatory diseases. DESIGN: The analyses involved 2514 participants aged ≥49 y at baseline. Dietary data were collected by using a semiquantitative food-frequency questionnaire, and PUFA, fish, and nut intakes were calculated. Inflammatory disease mortality was confirmed from the Australian National Death Index. RESULTS: Over 15 y, 214 subjects died of inflammatory diseases. Women in the highest tertiles of total n-3 PUFA intake, compared with those in the lowest tertile of intake at baseline, had a 44% reduced risk of inflammatory

disease mortality (P for trend = 0.03). This association was not observed in men. In both men and women, each 1-SD increase in energy-adjusted intake of α-linolenic acid was inversely associated with inflammatory mortality (hazard ratio: 0.83; 95% CI: 0.71, 0.98). Subjects in the second and third tertiles of nut consumption had a 51% and 32% reduced risk of inflammatory disease mortality, respectively, compared with those in the first tertile (reference). Dietary intakes of long-chain n-3 and n-6 PUFAs and fish were not associated with inflammatory disease mortality. CONCLUSIONS: We report on a novel link between dietary intake of total n-3 PUFA and risk of inflammatory disease mortality in older women. Furthermore, our data indicate a protective role of nuts, but not fish, against inflammatory disease mortality.

Am J Clin Nutr. 2011 May;93(5):1073-9

Omega-3 fatty acid supplementation reduces one-year risk of atrial fibrillation in patients hospitalized with myocardial infarction.

PURPOSE: Current strategies for avoiding atrial fibrillation (AF) are of limited value. We aim to assess the relationship between omega-3 fatty acids (n-3 PUFA) and AF occurrence in post-myocardial infarction (MI) patients. METHODS: A population study, linking hospital discharge records, prescription databases, and vital statistics, was conducted and included all consecutive patients with MI (ICD-9: 410) in six Italian local health authorities over a 3-year period. A propensity score (PS)-based, 5-to-1, greedy 1:1 matching algorithm was used to check consistency of results. Sensitivity analysis was performed to assess the robustness of findings. RESULTS: N-3 PUFA reduced the relative risk of the hospitalization for AF [hazard ratio (HR) 0.19, 95% CI 0.07-0.51] and was associated with a further and complementary reduction in all-cause mortality (HR 0.15, 95% CI 0.05-0.46). PS-based matched analysis and sensitivity analysis confirmed the main results. CONCLUSION: n-3 PUFA reduced both all-cause mortality and incidence of 1-year AF in patients hospitalized with MI.

Eur J Clin Pharmacol. 2008 Jun;64(6):627-34

Blood eicosapentaenoic acid and docosahexaenoic acid as predictors of all-cause mortality in patients with acute myocardial infarction--data from Infarction Prognosis Study (IPS) Registry.

BACKGROUND: Although omega-3 polyunsaturated fatty acids are known to have beneficial effects on cardiovascular diseases, their prognostic value has not been studied prospectively in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: The plasma levels of phospholipids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (% of total fatty acids), were measured in 508 patients (365 males; mean age, 63 years) with AMI. Clinical and biomarker predictors of all-cause and cardiovascular mortality were identified by stepwise Cox regression model. During a mean follow-up of 16.1 months, 36 (7.1%) patients died. After controlling for confounding variables, age (hazard ratio (HR): 1.09, P<0.001), renal insufficiency (HR: 2.84, P=0.01) and EPA level (HR: 0.29, P=0.004) were identified as independent predictors of all cause-mortality. When stratified by gender, age (HR: 1.08, P=0.001) and renal insufficiency (HR: 4.49, P=0.003) were predictors of all-cause-mortality in males, whereas EPA level (HR: 0.18, P=0.009) and angiotensin-converting enzyme inhibitor use (HR: 0.24, P=0.03) were identified as predictive of all-cause-mortality in females. CONCLUSIONS: Lower plasma level of EPA, but not DHA, was an independent predictor for all-cause-mortality in patients with AMI, but this relationship was significant only in female patients.

Circ J. 2009 Dec;73(12):2250-7

A randomized clinical trial on n-3 polyunsaturated fatty acids supplementation and all-cause mortality in elderly men at high cardiovascular risk.

BACKGROUND: The benefit of n-3 polyunsaturated fatty acids (PUFA) supplementation for mortality and cardiovascular events after myocardial infarction is well documented, but the effect of n-3 PUFA in Caucasians without established cardiovascular disease is not known. Our aim was to examine the influence of supplementation with eicosapentaenoic acid and docosahexaenoic acid on all-cause mortality and cardiovascular events in elderly men at high-risk of cardiovascular disease. DESIGN: In the Diet and Omega-3 Intervention Trial, 563 Norwegian men, 64-76-year old and 72% without overt cardiovascular disease, were randomized to a 3-year 2×2 factorial designed clinical trial of diet counseling and/or 2.4 g n-3 PUFA supplementation. The n-3 PUFA arm was placebo-controlled (corn oil). METHODS: Demographic parameters and classical risk factors were obtained at baseline. Deaths and cardiovascular events were recorded through 3 years, and the effects of n-3 PUFA-intervention on these outcomes were evaluated in pooled groups of the n-3 PUFA-arm. RESULTS: There were 38 deaths and 68 cardiovascular events. The unadjusted hazard ratios of all-cause mortality and cardiovascular events were 0.57 (95% confidence interval: 0.29-1.10) and 0.86 (0.57-1.38), respectively. Adjusted for baseline age, current smoking, hypertension, body mass index and serum glucose, hazard ratios were 0.53 (0.27-1.04, P=0.063) and 0.89 (0.55-1.45, P=0.641), respectively. CONCLUSION: We observed a tendency toward reduction in all-cause mortality in the n-3 PUFA groups that, despite a low number of participants, reached borderline statistical significance. The magnitude of risk-reduction suggests that a larger trial should be considered in similar populations.

Eur J Cardiovasc Prev Rehabil. 2010 Oct;17(5):588-92

Systems biology and longevity: an emerging approach to identify innovative anti-aging targets and strategies.

Human aging and longevity are complex and multi-factorial traits that result from a combination of environmental, genetic, epigenetic and stochastic factors, each contributing to the overall phenotype. The multi-factorial process of aging acts at different levels of complexity, from molecule to cell, from organ to organ systems and finally to organism, giving rise to the dynamic “aging mosaic”. At present, an increasing amount of experimental data on genetics, genomics, proteomics and other -omics are available thanks to new high-throughput technologies but a comprehensive model for the study of human aging and longevity is still lacking. Systems biology represents a strategy to integrate and quantify the existing knowledge from different sources into predictive models, to be later tested and then implemented with new experimental data for validation and refinement in a recursive process. The ultimate goal is to compact the new acquired knowledge into a single picture, ideally able to characterize the phenotype at systemic/organism level. In this review we will briefly discuss the aging phenotype in a systems biology perspective, showing four specific examples at different levels of complexity, from a systemic process (inflammation) to a cascade-process pathways (coagulation) and from cellular organelle (proteasome) to single gene-network (PON-1), which could also represent targets for anti-aging strategies.

Curr Pharm Des. 2010;16(7):802-13

Age-related inflammation: the contribution of different organs, tissues and systems. How to face it for therapeutic approaches.

A typical feature of ageing is a chronic, low-grade inflammation characterized by a general increase in the production of pro-inflammatory cytokines and inflammatory markers (“inflamm-ageing”). This status may slowly damage one or several organs, especially when unfavorable genetic polymorphisms and epigenetic alterations are concomitant, leading to an increased risk of frailty together with the onset of age-related chronic diseases. The contribution of different tissues (adipose tissue, muscle), organs (brain, liver), immune system and ecosystems (gut microbiota) to age-related inflammation (“inflamm-ageing”) will be discussed in this review in the context of its onset/progression leading to site-restricted and systemic effects. Moreover, some of the possible strategies and therapies to counteract the different sources of molecular mediators which lead to the age-related inflammatory phenotype will be presented.

Curr Pharm Des. 2010;16(6):609-18

Fatty acids from fish: the anti-inflammatory potential of long-chain omega-3 fatty acids.

Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA) are precursors of potent lipid mediators, termed eicosanoids, which play an important role in the regulation of inflammation. Eicosanoids derived from n-6 PUFAs (e.g., arachidonic acid) have proinflammatory and immunoactive functions, whereas eicosanoids derived from n-3 PUFAs [e.g., eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] have anti-inflammatory properties, traditionally attributed to their ability to inhibit the formation of n-6 PUFA-derived eicosanoids. While the typical Western diet has a much greater ratio of n-6 PUFAs compared with n-3 PUFAs, research has shown that by increasing the ratio of n-3 to n-6 fatty acids in the diet, and consequently favoring the production of EPA in the body, or by increasing the dietary intake of EPA and DHA through consumption of fatty fish or fish-oil supplements, reductions may be achieved in the incidence of many chronic diseases that involve inflammatory processes; most notably, these include cardiovascular diseases, inflammatory bowel disease (IBD), cancer, and rheumatoid arthritis, but psychiatric and neurodegenerative illnesses are other examples.

Nutr Rev. 2010 May;68(5):280-9

The essential fatty acids omega-6 and omega-3: from their discovery to their use in therapy.

In 1929 Burr and Burr discovered the essential fatty acids omega-6 and omega-3. Since then, researchers have shown a growing interest in unsaturated essential fatty acids as they form the framework for the organism’s cell membranes, particularly the neurones in the brain, are involved in the energy-transformation process, regulate the information flows between cells. Polyunsaturated fatty acids are also precursors of ‘’hormonal’’ molecules, often with opposing effects, prostaglandins, prostacyclins, thromboxanes, leukotrienes, lipossines, resolvines, protectines that regulate immunity, platelet aggregation, inflammation, etc. They showed that raised levels of polyunsaturated fatty acids omega-3 in tissue correlate with a reduced incidence of degenerative cardiovascular disease, some mental illnesses such as depression, and neuro-degenerative diseases such as Alzheimer’s. The balance between omega-3 and omega-6 acids allows the cell membranes to develop with exactly the right flexibility and fluidity, to carry messages between neurones, that is a determining factor in physical and mental well-being and has a profound influence on all the body’s inflammatory responses. The results of a number of scientific studies suggest that omega-3 acids contribute to measuring and restricting inflammatory symptoms, whereas omega-6 acids (and saturated fats) give free range to inflammatory responses and amplify allergic reactions. Today in the Western countries, the ratio of omega-3 acids to omega-6 in the diet is weighted 1:10 in favour of omega-6 to up to 1:25 in some areas, while for proper functioning a 4:1 ratio of omega-6 acids to omega-3 acids is generally considered the optimum. In addition, the type of diet followed in the Western countries is very rich in saturated fats like butter and animal fats, but because of an excessive supply of these less noble fats, the cell membranes lose flexibility and this can affect the way they work. An appropriate supplement can be an efficient, effective and often necessary way to meet the body’s needs, enhance its daily functions and promote health and longevity.

Minerva Pediatr. 2008 Apr;60(2):219-33

Omega-3 fatty acids for major depressive disorder associated with the menopausal transition: a preliminary open trial.

OBJECTIVES: We sought to obtain preliminary data regarding the efficacy of omega-3 fatty acids for major depressive disorder associated with the menopausal transition. Secondary outcomes were assessed for vasomotor symptoms (or hot flashes). METHODS: After a single-blind placebo lead-in, participants received 8 weeks of treatment with open-label omega-3 fatty acid capsules (eicosapentaenoic acid and docosahexaenoic acid, 2 g/d). The Montgomery-Asberg Depression Rating Scale (MADRS) was the primary outcome measure. Hot flashes were monitored prospectively using daily diaries and the Hot Flash Related Daily Interference Scale. Blood samples for plasma pretreatment and posttreatment essential fatty acid assays were obtained. Because of the small sample size, data were analyzed using nonparametric techniques. RESULTS: Of 20 participants treated with omega-3 fatty acids, 19 (95%) completed the study. None discontinued because of adverse effects. The pretreatment and final mean MADRS scores were 24.2 and 10.7, respectively, reflecting a significant decrease in MADRS scores (P < 0.0001). The response rate was 70% (MADRS score decrease of ≥50%), and the remission rate was 45% (final MADRS score of ≤). Responders had significantly lower pretreatment docosahexaenoic acid levels than nonresponders did (P = 0.03). Hot flashes were present in 15 (75%) participants. Among those with hot flashes at baseline, the number of hot flashes per day improved significantly from baseline (P = 0.02) and Hot Flash Related Daily Interference Scale scores decreased significantly (P = 0.006). CONCLUSIONS: These data support further study of omega-3 fatty acids for major depressive disorder and hot flashes in women during the menopausal transition.

Menopause. 2011 Mar;18(3):279-84

Omega-3 polyunsaturated fatty acids and anxiety disorders.

Anxiety disorders are a common group of psychiatric illnesses which have significant personal, family and societal costs. Current treatments have limited efficacy in many patients highlighting a need for new therapeutic approaches to be explored. Anxiety disorders exhibit marked comorbity with mood disorders suggesting the existence of mechanistic similarities. Such a notion is supported by observations that some conventional pharmacotherapies are both effective antidepressants and anxiolytics. As such, given that omega-3 PUFA supplementation may be effective in the treatment of major depressive disorder it is reasonable to propose that they may also possess anxiolytic properties. Experimental data in support of such a hypothesis is currently lacking although reduced abundance of omega-3 PUFA have been reported in patients with anxiety, while supplementation with omega-3 PUFA appears to inhibit activation of the HPA axis and can ameliorate some of the symptoms of anxiety. Clinical investigations carried out to date have, however, involved small numbers of participants. Larger trials using a variety of omega-3 PUFA species in clinically well-defined patients with anxiety will be required to demonstrate a therapeutic role for omega-3 PUFA in these disorders. Given the excellent side effect profile of omega-3 PUFA as well as their strong theoretical rationale, such future trials appear justified.

Prostaglandins Leukot Essent Fatty Acids. 2009 Nov-Dec;81(5-6):309-12

Iodine-deficiency prophylaxis and the restriction of salt consumption - a 21st century challenge.

The World Health Organization (WHO) issued a recommendation (Technical Consultation: Paris 2006, Luxembourg 2007) that salt consumption, as a risk factor for hypertension, atherosclerosis, myocardial infarction, stroke, and select cancers, should be restricted. The European Commission looked to adhere to this recommendation by creating the High Level Group on Nutrition and Physical Activity. According to WHO recommendations, a daily allowance of 5 g NaCl (i.e., 2 g Na) for individual salt consumption should not be exceeded. At present, mean individual salt consumption in Poland totals 13.5 g, of which salt used in household constitutes 8.8 g. In some regions of Poland, this number reaches upwards of 15.0 g/person. The Position Paper on Initiatives Aimed at Decreasing Salt Consumption in Poland, developed by an expert group at the National Food and Nutrition Institute, set the course for intervention, including changing recipes for massproduced food products and large-scale catering, improving oversight by food control agencies, and continuing legislative changes. These interventions should also include education directed towards consumers, food producers, public health professionals, healthcare workers, and media representatives. The Position Paper of the Polish Hypertension Society also sets the course for promoting restricted salt consumption and controlling hypertension on a population level. However, household salt is the main carrier of iodine in the Polish model of iodine prophylaxis. Thus, any interventions also require synchronized action with the Polish Council for Control of Iodine Deficiency Disorders. Current efforts aimed at preventing iodine-deficiency look to increase consumption of other iodine-rich products (e.g., milk, mineral water) with standardized levels of iodine. Once they achieve an iodine concentration of 0.1-0.2 mg, these products can easily supplement any decrease in physiological iodine levels resulting from reduced salt consumption. Also required are wide-ranging educational campaigns which will be coordinated by the new designated WHO Collaborating Centre for Nutrition at the Chair of Endocrinology at Jagiellonian University, Collegium Medicum in Kraków.

Endokrynol Pol. 2010 Jan-Feb;61(1):135-40

Iodine deficiency.

Iodine deficiency has multiple adverse effects in humans, termed iodine deficiency disorders, due to inadequate thyroid hormone production. Globally, it is estimated that 2 billion individuals have an insufficient iodine intake, and South Asia and sub-Saharan Africa are particularly affected. However, about 50% of Europe remains mildly iodine deficient, and iodine intakes in other industrialized countries, including the United States and Australia, have fallen in recent years. Iodine deficiency during pregnancy and infancy may impair growth and neurodevelopment of the offspring and increase infant mortality. Deficiency during childhood reduces somatic growth and cognitive and motor function. Assessment methods include urinary iodine concentration, goiter, newborn TSH, and blood thyroglobulin. But assessment of iodine status in pregnancy is difficult, and it remains unclear whether iodine intakes are sufficient in this group, leading to calls for iodine supplementation during pregnancy in several industrialized countries. In most countries, the best strategy to control iodine deficiency in populations is carefully monitored universal salt iodization, one of the most cost-effective ways to contribute to economic and social development. Achieving optimal iodine intakes from iodized salt (in the range of 150-250 microg/d for adults) may minimize the amount of thyroid dysfunction in populations. Ensuring adequate iodine status during parenteral nutrition has become important, particularly in preterm infants, as the use of povidone-iodine disinfectants has declined. Introduction of iodized salt to regions of chronic iodine deficiency may transiently increase the incidence of thyroid disorders, but overall, the relatively small risks of iodine excess are far outweighed by the substantial risks of iodine deficiency.

Endocr Rev. 2009 Jun;30(4):376-408

Role of iodine, selenium and other micronutrients in thyroid function and disorders.

Micronutrients, mostly iodine and selenium, are required for thyroid hormone synthesis and function. Iodine is an essential component of thyroid hormones and its deficiency is considered as the most common cause of preventable brain damage in the world. Nowadays about 800 million people are affected by iodine deficiency disorders that include goiter, hypothyroidism, mental retardation, and a wide spectrum of other growth and developmental abnormalities. Iodine supplementation, under form of iodized salt and iodized vegetable oil, produced dramatic improvements in many areas, even though iodine deficiency is still a problem not only for developing countries. In fact, certain subpopulations like vegetarians may not reach an adequate iodine intake even in countries considered iodine-sufficient. A reduction in dietary iodine content could also be related to increased adherence to dietary recommendations to reduce salt intake for preventing hypertension. Furthermore, iodine intakes are declining in many countries where, after endemic goiter eradication, the lack of monitoring of iodine nutrition can lead to a reappearance of goiter and other iodine deficiency disorders. Three different selenium-dependent iodothyronine deiodinases (types I, II, and III) can both activate and inactivate thyroid hormones, making selenium an essential micronutrient for normal development, growth, and metabolism. Furthermore, selenium is found as selenocysteine in the catalytic center of enzymes protecting the thyroid from free radicals damage. In this way, selenium deficiency can exacerbate the effects of iodine deficiency and the same is true for vitamin A or iron deficiency. Substances introduced with food, such as thiocyanate and isoflavones or certain herbal preparations, can interfere with micronutrients and influence thyroid function. Aim of this paper is to review the role of micronutrients in thyroid function and diseases.

Endocr Metab Immune Disord Drug Targets. 2009 Sep;9(3):277-94

Projected effect of dietary salt reductions on future cardiovascular disease.

BACKGROUND: The U.S. diet is high in salt, with the majority coming from processed foods. Reducing dietary salt is a potentially important target for the improvement of public health. METHODS: We used the Coronary Heart Disease (CHD) Policy Model to quantify the benefits of potentially achievable, population-wide reductions in dietary salt of up to 3 g per day (1200 mg of sodium per day). We estimated the rates and costs of cardiovascular disease in subgroups defined by age, sex, and race; compared the effects of salt reduction with those of other interventions intended to reduce the risk of cardiovascular disease; and determined the cost-effectiveness of salt reduction as compared with the treatment of hypertension with medications. RESULTS: Reducing dietary salt by 3 g per day is projected to reduce the annual number of new cases of CHD by 60,000 to 120,000, stroke by 32,000 to 66,000, and myocardial infarction by 54,000 to 99,000 and to reduce the annual number of deaths from any cause by 44,000 to 92,000. All segments of the population would benefit, with blacks benefiting

proportionately more, women benefiting particularly from stroke reduction, older adults from reductions in CHD events, and younger adults from lower mortality rates. The cardiovascular benefits of reduced salt intake are on par with the benefits of population-wide reductions in tobacco use, obesity, and cholesterol levels. A regulatory intervention designed to achieve a reduction in salt intake of 3 g per day would save 194,000 to 392,000 quality-adjusted life-years and $10 billion to $24 billion in health care costs annually. Such an intervention would be cost-saving even if only a modest reduction of 1 g per day were achieved gradually between 2010 and 2019 and would be more cost-effective than using medications to lower blood pressure in all persons with hypertension. CONCLUSIONS: Modest reductions in dietary salt could substantially reduce cardiovascular events and medical costs and should be a public health target.

N Engl J Med. 2010 Feb 18;362(7):590-9

Urinary iodine concentration: United States National Health And Nutrition Examination Survey 2001-2002.

Urine iodine has been measured in the US population by the National Health and Nutrition Examination Survey (NHANES) since 1971. A downward trend was noted between NHANES I (320 +/- 6 microg/L in 1971-1974) and NHANES III (145 +/- 3 microg/L in 1988-1994). This report presents data from NHANES 2001-2002 that indicates that the U.S. median urine iodine (UI) level has stabilized since the initial drop between NHANES I and NHANES III. The median UI concentration in the U.S. population in NHANES 2001-2002 was found to be 167.8 microg/L (95% confidence interval [CI] 159.3-177.6). The NHANES 2001-2002 data confirm the current stability of the U.S. iodine intake and continued adequate iodine nutrition for the country.

Thyroid. 2005 Jul;15(7):692-9

Iodine deficiency in vegetarians and vegans.

Iodine content in food of plant origin is lower in comparison with that of animal origin due to a low iodine concentration in soil. Urinary iodine excretion was assessed in 15 vegans, 31 lacto- and lacto-ovovegetarians and 35 adults on a mixed diet. Iodine excretion was significantly lower in alternative nutrition groups - 172 microg/l in vegetarians and 78 microg/l in vegans compared to 216 microg/l in subjects on a mixed diet. One fourth of the vegetarians and 80% of the vegans suffer from iodine deficiency (iodine excretion value below 100 microg/l) compared to 9% in the persons on a mixed nutrition. The results show that under conditions of alternative nutrition, there is a higher prevalence of iodine deficiency, which might be a consequence of exclusive or prevailing consumption of food of plant origin, no intake of fish and other sea products, as well as reduced iodine intake in the form of sea salt.

Ann Nutr Metab. 2003;47(5):183-5

Iodine uptake and loss-can frequent strenuous exercise induce iodine deficiency?

Most of the daily dietary iodine intake (approximately 90%) will be excreted in the urine; measurement of urinary iodine excretion is thus routinely used as an index of dietary iodine intake. However, urinary excretion is not the only means of iodine loss. Subjects such as athletes or those participating in vigorous exercise can lose a considerable amount of iodine in sweat, depending on environmental factors such as temperature and humidity. In areas of lower to moderate dietary iodine intake, loss in sweat can equal that in urine. Although electrolyte loss in sweat is well-recognized and replacement strategies are adopted, there is less recognition of potential iodine loss. Crude calculations reveal that if sweat iodide losses are not replaced, dietary stores could be depleted in an athlete undergoing a regular training regime. The significance of these losses could be increased in areas where dietary iodine intake is lower in the summer months. Although there is little doubt that excessive sweating can induce a relative iodine deficiency state, there is no case as yet for iodine supplementation in those that take vigorous exercise. However, sustained iodine loss may have implications for thyroid status and possibly consequences for athletic performance.

Horm Metab Res. 2005 Sep;37(9):555-8.

Iodine: deficiency and therapeutic considerations.

Iodine deficiency is generally recognized as the most commonly preventable cause of mental retardation and the most common cause of endocrinopathy (goiter and primary hypothyroidism). Iodine deficiency becomes particularly critical in pregnancy due to the consequences for neurological damage during fetal development as well as during lactation. The safety of therapeutic doses of iodine above the established safe upper limit of 1 mg is evident in the lack of toxicity in the Japanese population that consumes 25 times the median intake of iodine consumption in the United States. Japan’s population suffers no demonstrable increased incidence of autoimmune thyroiditis or hypothyroidism. Studies using 3.0- to 6.0-mg doses to effectively treat fibrocystic breast disease may reveal an important role for iodine in maintaining normal breast tissue architecture and function. Iodine may also have important antioxidant functions in breast tissue and other tissues that concentrate iodine via the sodium iodide symporter.

Altern Med Rev. 2008 Jun;13(2):116-27

Iodine deficiency, more than cretinism and goiter.

Recent reports of the World Health Organization show iodine deficiency to be a worldwide occurring health problem. As iodine status is based on median urinary iodine excretion, even in countries regarded as iodine sufficient, a considerable part of the population may be iodine deficient. Iodine is a key element in the synthesis of thyroid hormones and as a consequence, severe iodine deficiency results in hypothyroidism, goiter, and cretinism with the well known biochemical alterations. However, it is also known that iodine deficiency may give rise to clinical symptoms of hypothyroidism without abnormality of thyroid hormone values. This led us to the hypothesis that iodine deficiency may give rise to subtle impairment of thyroid function leading to clinical syndromes resembling hypothyroidism or diseases that have been associated with the occurrence of hypothyroidism. We describe several clinical conditions possibly linked to iodine deficiency, a connection that has not been made thus far. In this paper we will focus on the relationship between iodine deficiency and obesity, attention deficit hyperactivity disorder (ADHD), psychiatric disorders, fibromyalgia, and malignancies.

Med Hypotheses. 2008 Nov;71(5):645-8

Tissue iodine content and serum-mediated 125I uptake-blocking activity in breast cancer.

In the thyroid, active transport of iodide is under control of the TSH-dependent Na+/I- symporter (NIS), whereas in the breast such control is less well understood. In this study, NIS expression was demonstrated by RT-PCR in 2 of 2 fibroadenomata and 6 of 7 breast carcinoma messenger ribonucleic acid isolates. In addition, mean total tissue iodine levels of 80.9 +/- 9.5 ng I/mg protein in 23 benign tumors (fibroadenomata) were significantly higher than those in 19 breast cancers taken from either the tumor (18.2 +/- 4.6 ng I/mg) or morphologically normal tissue taken from within the tumor-bearing breast (31.8 +/- 4.9 ng I/mg; P < 0.05 in each case). Inhibition of 125I uptake into NIS-transfected CHO cells was observed in serum from 20 of 105 (19.0%) breast carcinoma, 8 of 49 (16.3%) benign breast disease, and 27 of 86 (31.4%) Graves’ patients, but in only 1 of 33 (3.0%) age-matched female controls. IgG purified from serum of patients showing positive 125I uptake inhibition also

inhibited iodide uptake, suggesting that such inhibition was antibody mediated. 125I uptake inhibition was significantly associated with thyroid peroxidase antibody positivity (P < 0.05) in sera from breast cancer patients, but not in those with benign breast disease, once again suggesting an association between thyroid autoimmunity and breast carcinoma.

J Clin Endocrinol Metab. 2000 Mar;85(3):1245-50

Comparison of iodine contents in gastric cancer and surrounding normal tissues.

It has been suggested that iodine plays an important role in gastric cancer. Gastric cancer ranks first among the cancers in the north-eastern Anatolia region, Turkey, where iodine deficiency is common. In this study, iodine levels were determined in gastric cancer and surrounding normal tissues in 19 patients with gastric cancer. Tissue iodine levels were determined by the Foss method based on the Sandell-Kolt-hoff reaction. Tissue iodine levels were lower in gastric cancer tissue (17.8+/-3.4 ng I/mg protein, mean+/-SEM) compared with surrounding normal tissue (41.7+/-8.0 ng I/mg protein) (p<0.001). There was positive correlation between the iodine levels in gastric cancer tissue and surrounding normal tissue (r = 0.845, p<0.001). There was no significant difference in iodine levels in cancer and surrounding normal tissue between male and female subjects. The iodine deficiency in our region may be one of the factors for increased gastric cancer prevalence. Our results support the hypothesis that iodine plays an important role in gastric cancer development.

Clin Chem Lab Med. 2005;43(6):581-4

Iodine prophylaxis—the protective factor against stomach cancer in iodine deficient areas.

BACKGROUND: Poland has one of the highest death rates for stomach cancer in Europe. Moderate iodine deficiency and in consequence high goitre prevalence led to the implementation in 1996 of a very efficient mandatory model of iodine prophylaxis, based on household salt iodisation (30 +/- 10 mg KI/1 kg of salt). AIM OF THE STUDY: The aim of the study was evaluation of incidence rate of stomach cancer and its possible relation to increased iodine consumption in the years 1992-2004. METHODS: Iodine supply and effectiveness of iodine prophylaxis were evaluated on the basis of comparative analysis of goitre prevalence and ioduria in schoolchildren. To allow comparison between time periods with varying population age structures, the incidence rates of stomach cancer were standardized for age, using the “world standard population”. The direct standardization method has been applied. For each sex, the time-trend of incidence rates was shown in graphs over the years 1991-2004. RESULTS: Evident increase in iodine consumption in this period of time was proved by rise in percentage of schoolchildren (6-8 years old) with ioduria above 100 microg/l from 11.4% in 1992-1993 to 52.9.1% in 2003. It was correlated with the decrease in goitre prevalence from 18.8% to 3.2% respectively. The 24-h thyroid uptake of (131)I in investigated population fell from 45.5% in 1986 to 26.8% in 1998. In Krakow the standardized incidence ratio of stomach cancer for men decreased from 19.1 per 100,000 to 15.7 per 100,000, and for women from 8.3 per 100,000 to 5.9 per 100,000 in the years 1992-2004. A significant decline of average rate of decrease was observed in men and women (2.3% and 4.0% per year respectively). CONCLUSION: Observed association between improved iodine supply and decrease of incidence of stomach cancer could indicate the protective role against stomach cancer of iodine prophylaxis in iodine deficient areas--further studies are necessary.

Eur J Nutr. 2007 Aug;46(5):251-6

Iodide accumulation provides kelp with an inorganic antioxidant impacting atmospheric chemistry.

Brown algae of the Laminariales (kelps) are the strongest accumulators of iodine among living organisms. They represent a major pump in the global biogeochemical cycle of iodine and, in particular, the major source of iodocarbons in the coastal atmosphere. Nevertheless, the chemical state and biological significance of accumulated iodine have remained unknown to this date. Using x-ray absorption spectroscopy, we show that the accumulated form is iodide, which readily scavenges a variety of reactive oxygen species (ROS). We propose here that its biological role is that of an inorganic antioxidant, the first to be described in a living system. Upon oxidative stress, iodide is effluxed. On the thallus surface and in the apoplast, iodide detoxifies both aqueous oxidants and ozone, the latter resulting in the release of high levels of molecular iodine and the consequent formation of hygroscopic iodine oxides leading to particles, which are precursors to cloud condensation nuclei. In a complementary set of experiments using a heterologous system, iodide was found to effectively scavenge ROS in human blood cells.

Proc Natl Acad Sci U S A. 2008 May 13;105(19):6954-8

Mild cognitive impairment.

Mild cognitive impairment (MCI) is a syndrome that spans the area between normal ageing and dementia. It is classified into amnestic and non-amnestic types, both with two subtypes: single domain and multiple domains. Prevalence of MCI depends on criteria and population and can vary from 0.1 to 42% persons of older age. In contrast to dementia, cognitive deterioration is less severe and activities of daily living are preserved. Most impaired higher cognitive functions in MCI are memory, executive functions, language, visuospatial functions, attention etc. Also there are depression, apathy or psychomotor agitation, and signs of psychosis. Aetiology of MCI is multiple, mostly neurodegenerative, vascular, psychiatric, internistic, neurological, traumatic and iatrogenic. Persons with amnestic MCI are at a higher risk of converting to Alzheimer’s disease, while those with a single non-memory domain are at risk of developing frontotemporal dementia. Some MCI patients also progress to other dementia types, vascular among others. In contrast, some patients have a stationary course, some improve, while others even normalize. Every suspicion of MCI warrants a detailed clinical exploration to discover underlying aetiology, laboratory analyses, neuroimaging methods and some cases require a detailed neuropsychological assessment. At the present time there is no efficacious therapy for cognitive decline in MCI or the one that could postpone conversion to dementia. The treatment of curable causes, application of preventive measures and risk factor control are reasonable measures in the absence of specific therapy.

Srp Arh Celok Lek. 2009 Jul-Aug;137(7-8):434-9

Memory profiling in mild cognitive impairment: can we determine risk for Alzheimer’s disease?

Mild cognitive impairment (MCI) is considered a transitional stage between normal ageing and Alzheimer’s disease (AD), but not all MCI cases progress to AD and there has been limited focus on how to identify who will progress. Given claims for a characteristic kind of memory impairment in AD involving deficits in encoding and consolidation of information, we propose that ‘memory profiling’ of individuals with MCI may help identify which individuals will progress. We initially set out to establish whether the same characteristic memory profile was present prior to the onset of AD (preAD). Very few studies provided data that allowed us to examine this, but results tentatively supported an encoding/consolidation profile in preAD. A single study tested the clinically important contrast of preAD versus non-preAD MCI cases and found no difference under any condition or in memory profiles, but interpretation of the findings is limited by short duration of follow-up, ceiling effects, and task limitations in assessing more complex and qualitative aspects of memory. Although existing data lead to equivocal conclusions, we believe that memory profiling is an endeavour worth pursuing, particularly given the increasing number of people with MCI presenting for clinical assessment. We propose that tests designed specifically to measure memory processes should be sensitive to preAD and are required in prospective longitudinal designs to identify these clinically crucial MCI cases.

J Neuropsychol. 2008 Sep;2(Pt 2):361-72

Cognitive modifications associated with tobacco smoking.

INTRODUCTION: Tobacco is an important source of somatic diseases and causes high mortality. It is associated with cognitive disorders which tend to maintain addictive mechanisms. In the short term, the nicotine contained in tobacco enhances attention and memory. METHOD: To realize this review, we made a research, we made a research on Medline, Embase, PsycInfo, Google Scholar using the single or combined key-words “tobacco,” “nicotine,” “addiction,” “dependence,” “cognitive disorders,” “executive function,” “memory,” “attention,” “neuropsychological.” We selected English or French articles from 1987 to 2008 by privileging controlled studies. RESULTS: This effect can be observed in smokers (with or without withdrawal symptoms), non-smokers and in patients suffering from cognitive disorders. In the long term, tobacco accelerates dementia processes. It is associated with an increased risk of cognitive deterioration. This deterioration concerns mainly memory and processing speed. These results were reported in prospective studies. They contradict early reports, that suggested smoking could actually be protective against certain central neural system disorders. These early results relayed on case-control studies, which were certainly biased by a “healthy survival effect.” Further studies are required to evaluate nicotine’s long term effect and its potential efficacy in treating and preventing cognitive disorders or dementia.

Presse Med. 2009 Sep;38(9):1241-52

Impairment of cognitive abilities and decision making after chronic use of alcohol: the impact of multiple detoxifications.

AIMS: In the present study, the effect of previous detoxifications on prefrontal function and decision making was examined in alcohol-dependent patients. Further, we examined whether the length of abstinence affects cognitive function. METHODS: Forty-eight alcohol-dependent patients were recruited from an inpatient detoxification treatment facility and cognitive function was compared to a control group of 36 healthy controls. The patient population was then divided into a group of patients with less than two previous detoxifications (LO-detox group, n = 27) and a group of patients with two or more previous detoxifications (HI-detox group, n = 21) and cognitive function was compared. In addition, cognitive function of recently (i.e. less than 16 days; median split) and longer abstinent patients was compared. We assessed prefrontal function, memory function and intelligence. RESULTS: Alcoholics, when compared to healthy controls, performed worse with regard to the performance index Attention/Executive function. Cognitive impairment in these tasks was pronounced in recently abstinent patients. We found no significant differences between HI-detox and LO-detox patients with regard to the Attention/Executive function. However, in the IOWA gambling Task, the HI-detox group seemed to be less able to learn to choose cards from the more advantageous decks over time. CONCLUSIONS: Our results provide additional evidence for cognitive impairment of alcohol-dependent patients with regard to tasks sensitive to frontal lobe function and underline the importance of abstinence for these impairments to recover. We found only little evidence for the impairing effects of repeated withdrawal on prefrontal function and we suggest that executive function is affected earlier in dependence.

Alcohol Alcohol. 2009 Jul-Aug;44(4):372-81

Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: a randomized trial.

CONTEXT: Many observational studies have shown that physical activity reduces the risk of cognitive decline; however, evidence from randomized trials is lacking. OBJECTIVE: To determine whether physical activity reduces the rate of cognitive decline among older adults at risk. DESIGN AND SETTING: Randomized controlled trial of a 24-week physical activity intervention conducted between 2004 and 2007 in metropolitan Perth, Western Australia. Assessors of cognitive function were blinded to group membership. PARTICIPANTS: We recruited volunteers who reported memory problems but did not meet criteria for dementia. Three hundred eleven individuals aged 50 years or older were screened for eligibility, 89 were not eligible, and 52 refused to participate. A total of 170 participants were randomized and 138 participants completed the 18-month assessment. INTERVENTION: Participants were randomly allocated to an education and usual care group or to a 24-week home-based program of physical activity. MAIN OUTCOME MEASURE: Change in Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores (possible range, 0-70) over 18 months. RESULTS: In an intent-to-treat analysis, participants in the intervention group improved 0.26 points (95% confidence interval, -0.89 to 0.54) and those in the usual care group deteriorated 1.04 points (95% confidence interval, 0.32 to 1.82) on the ADAS-Cog at the end of the intervention. The absolute difference of the outcome measure between the intervention and control groups was -1.3 points (95% confidence interval,-2.38 to -0.22) at the end of the intervention. At 18 months, participants in the intervention group improved 0.73 points (95% confidence interval, -1.27 to 0.03) on the ADAS-Cog, and those in the usual care group improved 0.04 points (95% confidence interval, -0.46 to 0.88). Word list delayed recall and Clinical Dementia Rating sum of boxes improved modestly as well, whereas word list total immediate recall, digit symbol coding, verbal fluency, Beck depression score, and Medical Outcomes 36-Item Short-Form physical and mental component summaries did not change significantly. CONCLUSIONS: In this study of adults with subjective memory impairment, a 6-month program of physical activity provided a modest improvement in cognition over an 18-month follow-up period.

JAMA. 2008 Sep 3;300(9):1027-37

Preserve brain function...through physical exercise?

Over the last few years, there has been an increasing interest in the relationship between brain function and physical exercise. Preliminary evidence from observational and interventional studies in humans suggests a positive and robust effect of chronic aerobic exercise on several brain functions across the entire lifespan. Physical activity and exercise might also serve to reduce the risk of age-associated neurological disorders such as Alzheimer’s and Parkinson’s diseases. The mechanisms underlying these beneficial effects remain poorly understood. More scientific work is needed before disseminating more specific recommendations to the general population.

Rev Med Liege. 2008 May-Jun;63(5-6):293-8

Alzheimer’s disease, cerebrovascular dysfunction and the benefits of exercise: from vessels to neurons.

Exercise training promotes extensive cardiovascular changes and adaptive mechanisms in both the peripheral and cerebral vasculature, such as improved organ blood flow, induction of antioxidant pathways, and enhanced angiogenesis and vascular regeneration. Clinical studies have demonstrated a reduction of morbidity and mortality from cardiovascular disease among exercising individuals. However, evidence from recent large clinical trials also suggests a substantial reduction of dementia risk - particularly regarding Alzheimer’s disease (AD) - with regular exercise. Enhanced neurogenesis and improved synaptic plasticity have been implicated in this beneficial effect. However, recent research has revealed that vascular and specifically endothelial dysfunction is essentially involved in the disease process and profoundly aggravates underlying neurodegeneration. Moreover, vascular risk factors (VRFs) are probably determinants of incidence and course of AD. In this review, we emphasize the interconnection between AD and VRFs and the impact of cerebrovascular and endothelial dysfunction on AD pathophysiology. Furthermore, we describe the molecular mechanisms of the beneficial effects of exercise on the vasculature such as activation of the vascular nitric oxide (NO)/endothelial NO synthase (eNOS) pathway, upregulation of antioxidant enzymes, and angiogenesis. Finally, recent prospective clinical studies dealing with the effect of exercise on the risk of incident AD are briefly reviewed. We conclude that, next to upholding neuronal plasticity, regular exercise may counteract AD pathophysiology by building a vascular reserve.

Exp Gerontol. 2008 Jun;43(6):499-504

Biological mechanisms of physical activity in preventing cognitive decline.

In order to guarantee better conditions for competition, the nervous system has developed not only mechanisms controlling muscle effectors, but also retrograde systems that, starting from peripheral structures, may influence brain functions. Under such perspective, physical activity could play an important role in influencing cognitive brain functions including learning and memory. The results of epidemiological studies (cross-sectional, prospective and retrospective) support a positive relationship between cognition and physical activities. Recent meta-analysis confirmed a significant effect of exercise on cognitive functions. However, the biological mechanisms that underlie such beneficial effects are still to be completely elucidated. They include supramolecular mechanisms (e.g. neurogenesis, synaptogenesis, and angiogenesis) which, in turn, are controlled by molecular mechanisms, such as BDNF, IGF-1, hormone and second messengers.

Cell Mol Neurobiol. 2010 May;30(4):493-503

BDNF is a novel marker of cognitive function in ageing women: the DR’s EXTRA Study.

Brain-derived neurotrophic factor (BDNF) is one of the key molecules modulating brain plasticity. While low circulating levels of BDNF have been suggested to predispose to Alzheimer’s disease, very little data are available on its association with cognitive function in general population. We evaluated the association between plasma BDNF levels and cognition in a representative population sample of ageing men and women. The subjects (n=1389) were participants of the Dose-Responses to Exercise Training (DR’s EXTRA) Study and represent a random sample of Eastern Finnish people (684 men and 705 women), 57-79 years of age at baseline of the study. Plasma BDNF levels were measured by enzyme-linked immunosorbent assay (ELISA). Cognitive function was evaluated using the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) neuropsychological test battery. Women had a higher mean (+/-SEM) plasma BDNF level than men (1721+/-55vs. 1495+/-54pg/ml, P<0.001). In women, 1 SD decrease in BDNF increased the risk for a low score in Naming Test by 53% (95% CI 1.21-1.92, P<0.001), in Mini-Mental State Examination by 63% (95% CI 1.21-2.20, P=0.001), in Word List Memory by 56% (95% CI 1.08-2.26, P=0.019), in Word List Recall by 50% (95% CI 1.10-2.05, P=0.010), in Word List Saving by 49% (95% CI 1.12-1.99, P=0.007), and in Word List Recognition by 64% (95% CI 1.19-2.25, P=0.002). Data were adjusted for age, education, depression, impaired glucose metabolism, cardiovascular disease, antihypertensive medication, lipid lowering medication, use of sex hormones, smoking, alcohol consumption, storing time of plasma in the freezer and platelet count. BDNF was not associated with cognition in men. Present data suggest that plasma BDNF is a biomarker of impaired memory and general cognitive function in ageing women.

Neurobiol Learn Mem. 2008 Nov;90(4):596-603