Higher Serum Brain-derived Neurotrophic Factor Levels Research Articles

Serum brain-derived neurotrophic factor levels as a predictor for Alzheimer disease progression.

Brain-derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of Alzheimer's disease (AD), and decreased peripheral levels of this protein are associated with an increased risk of developing the disease. This study focuses on whether serum BDNF levels could be used as a predictor of AD progression. In this longitudinal observational study, we recruited cognition normal participants (N=98) and AD (N=442) from the Clinic at the Taipei Veterans General Hospital. We conducted a mini-mental status exam, a 12-item memory test, a categorical verbal fluency test, and a modified 15-item Boston naming test. A Serum BDNF level and Apolipoprotein E (APOE) allele status were measured. The AD patients were followed prospectively. Based on the difference of MMSE scores, these patients were divided into fast decliners (decline ≧ 3/year) and slow decliners (MMSE decline < 3/year). Logistic regression was conducted to examine the impact of serum BDNF levels and other factor on the likelihood of AD patients being slow decliners. Pearson's correlation was used to estimate the relationship between serum BDNF levels and the score of neuropsychological tests. In a logistic regression model containing serum BDNF levels, age, sex, APOE4 carrier status, education levels, and baseline MMSE score, higher serum BDNF levels were associated with a slower rate of cognitive decline in the AD group. Serum BDNF levels positively correlated with the results of multiple neuropsychological tests. BDNF is a protective factor against AD progression and likely plays a role in establishing a link between AD pathology and clinical manifestations.

Preliminary study on changes in BDNF in patients with depression after percutaneous coronary intervention

IntroductionDepression and coronary artery disease (CAD) are often comorbid conditions. The presence of depression significantly interferes with the recovery after CAD therapy intervention, such as percutaneous coronary intervention (PCI), one of the most common medical procedures in developed countries. Brain derived neurotrophic factor (BDNF) has a major role in angiogenesis and neuromodulation. Its levels were previously shown to be reduced in patients with depression, and latest studies indicate similar in patients with CAD. However, the correlation of BDNF levels and depression after CAD treatment is unknown.ObjectivesThe aim of this preliminary study is to assess the changes in BDNF levels in patients with depressive symptoms during a six-month period upon PCI.MethodsAntidepressant-free participants that underwent PCI with stent placement due to myocardial infarction or angina pectoris were enrolled in the study. Depressive symptoms were evaluated at baseline using the Beck’s Depression Inventory II (BDI-II) with a cut-off score ≥20 indicating moderate depression. Serum BDNF levels were measured from blood samples drawn a day after (baseline) and six-months upon a successful PCI without complications. The t-test for dependent samples was used with marked significant differences at p&lt;0,05.ResultsAltogether, 76 participants were included in the study, of which 25 finished a six-month follow-up. Participants with BDI-II≥20 at baseline had higher serum BDNF levels in the second measurement (M=23,12, SD=6,20; M=32,02, SD=12,26, respectively). No significant difference was found in serum BDNF levels in measurements between participants with and without depressive symptoms (t=0,33, p=0,74; t=-1,40, p=0,18, respectively). Statistically significant difference was found between serum BDNF in the first and second measurement in the overall sample (t=-2,28, p=0,03) and in participants with baseline moderate depressive symptoms (t=-2,46, p= 0,03), but not in those without (t=-0,59, p=0,57).ConclusionsSerum BDNF levels in participants with baseline moderate depressive symptoms increased after a six-month period upon successful PCI treatment, whereas that trend was not observed in participants without depressive symptoms. This highlights the potential synergistic role of BDNF in comorbid depression and CAD.Disclosure of InterestNone Declared

Higher Serum BDNF Levels are Associated with Lower Risk of Cognitive Decline in Older Adults :The Otassha Study

Introduction: There has been growing interest in the use of circulating levels of brain-derived neurotrophic factor (BDNF) in the blood as a biomarker in the context of patients with Alzheimer’s and other neurodegenerative diseases. Prospective data on cognitive decline in the broad older population, however, remain limited. We assessed the relationship of serum BDNF levels with short-term decline in cognitive functioning of community-dwelling older adults. Methods. Prospective study of 405 adults 65-84 years old without dementia in Tokyo, Japan. The Montreal Cognitive Assessment-Japanese version (MoCA-J) and its subscales were used. Linear regression assessed standardized differences in test score differences between baseline (2011) and follow-up (2013) visits, according to baseline serum BDNF quartiles, with adjustment for baseline demographics, disease indicators, and cognitive scores. Results: Among participants who performed on the MoCA-J at baseline (scores in bottom quartile), cognitive decline was .65 (95% CI: .08 - 1.2; p=.025) standard deviations (SD) more pronounced in those with lowest than highest BDNF levels. Decline in executive function, but not in other subdomains, was also most pronounced in those with lowest baseline serum BDNF levels (difference: .32 SD; 95%CI: .08-.55; p=.007) Conclusion: Lower serum BDNF levels were associated with greater 2-year cognitive decline in community-dwelling older Japanese adults. Decline varied among cognitive subdomains, and baseline cognition. Research seeking to evaluate the added-value of serum BDNF for screening and/or health promotion initiatives involving physical activity, which has been linked to increment in BDNF levels, is warranted.

Curiosity-Based Interventions Increase Everyday Functioning Score But Not Serum BDNF Levels in a Cohort of Healthy Older Adults.

An enriched environment is effective in stimulating learning and memory in animal models as well as in humans. Environmental enrichment increases brain-derived neurotrophic factor (BDNF) in aged rats and reduces levels of Alzheimer-related proteins in the blood, including amyloid-β (Aβ) peptides and misfolded toxic forms of tau. To address whether stimulation of curiosity, which is a form of enrichment, may provide a buffer against Alzheimer’s disease (AD), we measured levels of biomarkers associated with AD at baseline and after a 6-week intervention in older adults (>65 years of age) randomized to one of three different intervention conditions. Specifically, in this pilot study, we tested the effectiveness of a traditional, structured learning environment compared to a self-motivated learning environment designed to stimulate curiosity. There were no significant differences from baseline to post-intervention in any of the groups for Aβ42/Aβ40 ratio or t-tau (total-tau) plasma levels. Serum BDNF levels decreased significantly in the control group. Interestingly, individuals who had the lowest serum BDNF levels at baseline experienced significantly higher increases in BDNF over the course of the 6-week intervention compared to individuals with higher serum BDNF levels at baseline. As expected, older individuals had lower MoCA scores. Years of education correlated negatively with Aβ levels, suggesting a protective effect of education on levels of this toxic protein. ECog scores were negatively correlated with BDNF levels, suggesting that better performance on the ECog questionnaire was associated with higher BDNF levels. Collectively, these findings did not suggest that a 6-week cognitive training intervention focused on curiosity resulted in significant alterations in blood biomarkers but showed interesting correlations between cognitive scores and BDNF levels, further supporting the role of this trophic factor in brain health in older adults.

Evolution of BDNF serum levels during the first six months after alcohol withdrawal

Objectives Brain-Derived Neurotrophic Factor (BDNF) has been associated with alcohol dependence and appear to vary after withdrawal, although the link with the withdrawal outcome on the long term is unknown. We aimed to assess the evolution of BDNF levels during the six months following withdrawal and determine the association with the status of alcohol consumption. Methods Serum BDNF levels of alcohol-dependent patients (n = 248) and biological and clinical parameters were determined at the time of alcohol cessation (D0), 14 days (D14), 28 days (D28), and 2, 4, and 6 months after (M2, M4, M6). Results Abstinence decreased during follow-up and was 31.9% after six months. BDNF levels increased by 14 days after withdrawal and remained elevated throughout the six-month period, independently of alcohol consumption. Serum BDNF levels evolved over time (p < 0.0001), with a correlation between BDNF and GGT levels. The prescription of baclofen at the time of withdrawal was associated with higher serum BDNF levels throughout the follow-up and that of anti-inflammatory drugs with lower BDNF levels. Conclusions A link between BDNF levels, liver function, and the inflammatory state in the context of alcohol abuse and not only with alcohol dependence itself is proposed.

Elevated serum BDNF levels are associated with favorable outcome in CLL patients: Possible link to CXCR4 downregulation

Increased chemokine C-X-C receptor 4 (CXCR4) expression is related to unfavorable outcome in chronic lymphocytic leukemia (CLL). Brain-derived neurotrophic factor (BDNF) is a neuronal growth factor that has been shown previously to interact with CXCR4 in neuronal cells. Here, we studied the in vitro effect of BDNF on CXCR4 expression and chemotaxis toward stromal derived factor-1 (SDF-1) in freshly isolated CLL cells. We also explored the correlations between serum BDNF levels in CLL patients and disease characteristics and clinical course. Incubation of CLL cells with recombinant BDNF (50 ng/mL) resulted in a downregulation of CXCR4 surface expression and atenuated chemotaxis toward SDF-1. Higher serum BDNF levels were associated with a mutated immunoglobulin heavy chain variable (IGHV) gene, an early clinical stage, and a stable clinical course. Our findings suggest that increased circulating blood BDNF may be associated with a favorable effect in CLL. However, the exact mechanism of this favorable effect should be investigated further.

High-flavonoid intake induces cognitive improvements linked to changes in serum brain-derived neurotrophic factor: Two randomised, controlled trials.

BACKGROUND: Recent clinical studies have indicated the beneficial impact of dietary flavonoid intake on human cognitive performance. Although the mechanisms that mediate such improvements are currently unclear, animal and human trial data suggest that changes in neurotrophin expression, and related signalling apparatus, may be involved.OBJECTIVE: To investigate the link between changes in serum brain-derived neurotrophic factor (BDNF) and changes in human cognitive performance following flavonoid intake.METHODS: The relationship between serum levels of BDNF and age, gender, BMI, waist circumference, blood pressure and cognition at baseline, and following flavonoid intake, was investigated in two distinct randomised, controlled clinical trials. Trial 1 was conducted in men and women (aged 26–70 y; consuming an average of 3 portions of fruit and vegetables per day) and delivered high-flavonoid (>15 mg/100 g) or low-flavonoid (<5 mg/100 g) fruit and vegetables and increased intake by 2 portions every 6 weeks. The control arm was habitual diet over the same time frame. Trial 2 was conducted in an older males and female cohort (aged 62–75 y) intervening with a high-flavanol cocoa drink (494 mg total flavanols) and a low-flavanol cocoa drink (23 mg total flavanols) for 12 weeks.RESULTS: Serum BDNF levels increased linearly to the age of 65, after which BDNF levels were found to decrease markedly. All other physiological and anthropometric measurements proved to not be significantly associated with serum BDNF levels (p > 0.05), although higher levels in males compared to females almost achieved significance (p = 0.056). At baseline, higher serum BDNF levels were associated with significantly better global cognition scores, relative to individuals with lower serum levels. In addition, following intervention for 18 weeks, high-flavonoid, but not low-flavonoid, fruit and vegetable intake induced significant improvements in cognitive performance and increases in serum BDNF levels (p = <0.001). Flavanol intervention for 12 weeks also resulted in significant increases in serum BDNF (p = <0.001), and such increases were correlated with improvements in global cognitive performance.CONCLUSION: Increases in global cognition induced by high flavonoid fruit and vegetables, and cocoa flavanols were paralleled by concurrent changes in serum BDNF levels, suggesting a role for BDNF in flavonoid-induced cognitive improvements. Furthermore, we provide further data suggesting that serum BDNF levels may represent a biomarker of cognitive function.

Remission of depression following electroconvulsive therapy (ECT) is associated with higher levels of brain-derived neurotrophic factor (BDNF).

Research on the association between electroconvulsive therapy (ECT) and increased brain derived neurotrophic factor (BDNF) levels has produced conflicting result. There have been few studies which have evaluated BDNF levels in clinical contexts where there was remission following treatment. The objective of this study was to investigate whether remission of depression following ECT is associated with changes in BDNF levels. Adult inpatients in a psychiatric unit were invited to participate in this naturalistic study. Diagnoses were made using the Mini-International Neuropsychiatric Interview (MINI) and symptoms were evaluated at admission and discharge using the Hamilton Rating Scale for Depression (HDRS-17). Thirty-one patients who received a diagnosis of depression and were subjected to ECT were included retrospectively. Clinical remission was defined as a score of less than eight on the HDRS-17 at discharge. Serum BDNF levels were measured in blood samples collected at admission and discharge with a commercial kit used in accordance with the manufacturer's instructions. Subjects HDRS-17 scores improved following ECT (t = 13.29; p = 0.00). A generalized estimating equation (GEE) model revealed a remission × time interaction with BDNF levels as a dependent variable in a Wald chi-square test [Wald χ(2) = 5.98; p = 0.01]. A post hoc Bonferroni test revealed that non-remitters had lower BDNF levels at admission than remitters (p = 0.03), but there was no difference at discharge (p = 0.16). ECT remitters had higher serum BDNF levels at admission and the level did not vary during treatment. ECT non-remitters had lower serum BDNF levels at admission, but levels increased during treatment and were similar to those of ECT remitters at discharge.

Serum BDNF Levels in Relation to Illness Severity, Suicide Attempts, and Central Serotonin Activity in Patients with Major Depressive Disorder: A Pilot Study

The aim of this study was to test the hypothesis that serum levels of brain-derived neurotrophic factor (BDNF) are correlated with the loudness dependence of auditory evoked potentials (LDAEP). The question of whether there is a difference in BDNF levels between depressive patients according to their illness severity, history of suicide attempts, and central serotonin activity was also addressed. A sample of 51 patients who met the criteria for major depressive disorder following diagnosis using axis I of the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders – text revision comprised the study subjects. The patients were stratified into two subgroups based on their illness severity, history of suicide attempts, and their LDAEP values. The LDAEP was evaluated by measuring the auditory event-related potentials, and serum BDNF was measured using blood sampling before beginning medication with serotonergic agents. There was no difference in serum BDNF levels between the two patient subgroups. The subgroup with moderate-to-severe depression (n = 16) was reanalyzed after stratifying it into two subgroups according to LDAEP and BDNF values (dichotomized at the medians into low and high). The high-LDAEP subgroup had higher serum BDNF levels and total Barratt Impulsiveness Scale score than the low-LDAEP subgroup (p = 0.03 and 0.036, respectively). Serum BDNF levels were positively correlated with LDAEP and total Beck Hopelessness Scale (BHS) score (r = 0.56, p = 0.025, and r = 0.59, p = 0.016, respectively). The high-BDNF subgroup had a higher LDAEP and total BHS score than the low-BDNF subgroup (p = 0.046 and p = 0.011, respectively). This is the first study to demonstrate a relationship between the BDNF level and LDAEP in Asian depressive patients. Intriguingly, the high-BDNF subgroup (divided according to illness severity) exhibited a more severe psychopathology on some psychometric rating scales, a finding that conflicts with previous results.

High BDNF Levels May Offer Protection Against Alzheimer’s

Back to table of contents Next article Clinical & ResearchFull AccessHigh BDNF Levels May Offer Protection Against Alzheimer’sJoan Arehart-TreichelJoan Arehart-TreichelSearch for more papers by this authorPublished Online:7 Feb 2014https://doi.org/10.1176/appi.pn.2014.1a11AbstractIf BDNF is a factor that helps blocks development of Alzheimer’s and other dementias, then boosting BDNF levels might someday be a way to treat or prevent them.It appears that higher blood levels of brain-derived neurotrophic factor (BDNF) may be able to protect people against development of Alzheimer’s disease and other types of dementia, according to a study published online November 25 in JAMA Neurology.BDNF is widely expressed throughout the central nervous system, especially in the cerebral cortex and in the brain’s memory seat—the hippocampus. Moreover, researchers found a link between low blood levels of BDNF and a smaller hippocampus and poorer memory in older dementia-free adults. In light of these previous findings, Sudha Seshadri, M.D., a professor of neurology at Boston University, and colleagues conducted a study to see whether blood levels of BDNF might influence the risk for Alzheimer’s or other types of dementia.Their study included more than 2,000 individuals aged 60 or older (average age 72) in whom blood levels of BDNF were measured. Subjects were then followed for a decade to determine whether any of them developed Alzheimer’s disease or another type of dementia.A total of 117 subjects developed Alzheimer’s, while 23 developed another type of dementia. The researchers then assessed whether there were any correlations between subjects’ BDNF levels and their risk for Alzheimer’s or other types of dementia, while taking potential confounders—for example, age, gender, education, blood pressure, history of cardiovascular disease, diabetes, smoking status, and APOE-e4 status—into consideration.Such correlations did in fact appear. Each standard-deviation increment in BDNF was associated with a 33 percent lower risk for developing Alzheimer’s or another dementia. Compared with the bottom quintile, BDNF levels in the top quintile were associated with less than half the risk for Alzheimer’s or dementia. However, these links were restricted to men and women over age 80, women under age 80, and individuals with a college education or graduate degree.Thus, the researchers concluded, “Higher serum BDNF levels may protect against future occurrence of dementia and Alzheimer’s.”“This is a potentially important study from the perspective of reducing the risk of dementia,” Dilip Jeste, M.D., chair in aging at the University of California, San Diego, and immediate past APA president, told Psychiatric News. “BDNF has been previously shown to be related to lifestyle factors and interventions. One study even reported an increase in BDNF in individuals with schizophrenia who received cognitive enhancement therapy. Continued research on BDNF and related neurotrophic factors in people at risk of dementia is necessary to help develop interventions to treat and prevent cognitive deficits in older adults,” Jeste said.“This study highlights the beneficial neuroprotective effects of BDNF, especially for women, individuals with college degrees, or those who have lived past 80 years, and the possibility that serum BDNF could one day be a ‘blood test’ biomarker for the risk for developing dementia and Alzheimer’s disease,” geriatric psychiatrist Mohit Chopra, M.D., a lecturer in psychiatry at Harvard Medical School, said in an interview.This is indeed an eventuality, Seshadri agreed. Giving BDNF to older people might prevent or counter Alzheimer’s symptoms, she suggested. “We need to study the benefits and potential side effects of giving BDNF to people. Ways of doing this—such as using agonists that would cross the blood-brain barrier into the brain—are being studied. “Interestingly, lithium, long used in the treatment of bipolar disorder, has been found to increase BDNF levels in individuals with Huntington’s disease, Seshadri pointed out. So there is reason to believe that if lithium increases BDNF levels, then it might also possess some effectiveness against Alzheimer’s, she indicated. Preliminary evidence reported in the May 2012 Drugs and Aging bolsters this possibility.Finally, there is something that people can do on their own to increase their BDNF levels and possibly, as a result, lower their risk for Alzheimer’s, Seshadri and colleagues suggested in their study report. And that is to exercise, because “BDNF levels can be elevated through simple lifestyle measures such as increased physical activity.”She and her team will continue to conduct research in this domain, Seshadri said. “We plan to look at BDNF in younger individuals, average age 45, to see if it affects cognition at that age as well. And we will explore the mechanisms, genetic and otherwise, that may underlie BDNF’s impact on Alzheimer’s and dementia.”The study was funded by the National Institutes of Health. ■An abstract of “Serum Brain-Derived Neurotrophic Factor and the Risk for Dementia” is posted at http://archneur.jamanetwork.com/article.aspx?articleid=1779513. ISSUES NewArchived

Serum Brain-Derived Neurotrophic Factor and the Risk for Dementia

In animal studies, brain-derived neurotrophic factor (BDNF) has been shown to impact neuronal survival and function and improve synaptic plasticity and long-term memory. Circulating BDNF levels increase with physical activity and caloric restriction, thus BDNF may mediate some of the observed associations between lifestyle and the risk for dementia. Some prior studies showed lower circulating BDNF in persons with Alzheimer disease (AD) compared with control participants; however, it remains uncertain whether reduced levels precede dementia onset. To examine whether higher serum BDNF levels in cognitively healthy adults protect against the future risk for dementia and AD and to identify potential modifiers of this association. Framingham Study original and offspring participants were followed up from 1992 and 1998, respectively, for up to 10 years. We used Cox models to relate BDNF levels to the risk for dementia and AD and adjusted for potential confounders. We also ran sensitivity analyses stratified by sex, age, and education, as well as related BDNF genetic variants to AD risk. This community-based, prospective cohort study involved 2131 dementia-free participants aged 60 years and older (mean [SD] age, 72 [7] years; 56% women). Ten-year incidence of dementia and AD. During follow-up, 140 participants developed dementia, 117 of whom had AD. Controlling for age and sex, each standard-deviation increment in BDNF was associated with a 33% lower risk for dementia and AD (P = .006 and P = .01, respectively) and these associations persisted after additional adjustments. Compared with the bottom quintile, BDNF levels in the top quintile were associated with less than half the risk for dementia and AD (hazard ratio, 0.49; 95% CI, 0.28-0.85; P = .01; and hazard ratio, 0.46; 95% CI, 0.24-0.86; P = .02, respectively). These associations were apparent only among women, persons aged 80 years and older, and those with college degrees (hazard ratios for AD: 0.65, [95% CI, 0.50-0.85], P = .001; 0.63 [95% CI, 0.47-0.85], P = .002; and 0.27 [95% CI, 0.11-0.65], P = .003, respectively). Brain-derived neurotrophic factor genetic variants were not associated with AD risk. Higher serum BDNF levels may protect against future occurrence of dementia and AD. Our findings suggest a role for BDNF in the biology and possibly in the prevention of dementia and AD, especially in select subgroups of women and older and more highly educated persons.