Adam Dinoff

The Effect of Exercise Training on Resting Concentrations of Peripheral Brain-Derived Neurotrophic Factor (BDNF): A Meta-Analysis.

Background The mechanisms through which physical activity supports healthy brain function remain to be elucidated. One hypothesis suggests that increased brain-derived neurotrophic factor (BDNF) mediates some cognitive and mood benefits. This meta-analysis sought to determine the effect of exercise training on resting concentrations of BDNF in peripheral blood. Methods MEDLINE, Embase, PsycINFO, SPORTDiscus, Rehabilitation & Sports Medicine Source, and CINAHL databases were searched for original, peer-reviewed reports of peripheral blood BDNF concentrations before and after exercise interventions ≥ 2 weeks. Risk of bias was assessed using standardized criteria. Standardized mean differences (SMDs) were generated from random effects models. Risk of publication bias was assessed using funnel plots and Egger’s test. Potential sources of heterogeneity were explored in subgroup analyses. Results In 29 studies that met inclusion criteria, resting concentrations of peripheral blood BDNF were higher after intervention (SMD = 0.39, 95% CI: 0.17–0.60, p < 0.001). Subgroup analyses suggested a significant effect in aerobic (SMD = 0.66, 95% CI: 0.33–0.99, p < 0.001) but not resistance training (SMD = 0.07, 95% CI: -0.15–0.30, p = 0.52) interventions. No significant difference in effect was observed between males and females, nor in serum vs plasma. Conclusion Aerobic but not resistance training interventions increased resting BDNF concentrations in peripheral blood.

The effect of acute exercise on blood concentrations of brain‐derived neurotrophic factor in healthy adults: a meta‐analysis

It has been hypothesized that one mechanism through which physical activity provides benefits to cognition and mood is via increasing brain‐derived neurotrophic factor (BDNF) concentrations. Some studies have reported immediate benefits to mood and various cognitive domains after a single session of exercise. This meta‐analysis sought to determine the effect of a single exercise session on concentrations of BDNF in peripheral blood, in order to evaluate the potential role of BDNF in mediating the beneficial effects of exercise on brain health. MEDLINE, Embase, PsycINFO, SPORTDiscus, Rehabilitation & Sports Medicine Source, and CINAHL databases were searched for original, peer‐reviewed reports of peripheral blood BDNF concentrations before and after acute exercise interventions. Risk of bias within studies was assessed using standardized criteria. Standardized mean differences (SMDs) were generated from random effects models. Risk of publication bias was assessed using a funnel plot and Eggers test. Potential sources of heterogeneity were explored in subgroup analyses. In 55 studies that met inclusion criteria, concentrations of peripheral blood BDNF were higher after exercise (SMD = 0.59, 95% CI: 0.46–0.72, P < 0.001). In meta‐regression analysis, greater duration of exercise was associated with greater increases in BDNF. Subgroup analyses revealed an effect in males but not in females, and a greater BDNF increase in plasma than serum. Acute exercise increased BDNF concentrations in the peripheral blood of healthy adults. This effect was influenced by exercise duration and may be different across genders.

Ceramides and depression: A systematic review

BACKGROUND Major depressive disorder is a significant contributor to global disability and mortality. The mechanisms of depression are vast and not fully understood, and as a result current treatment of depression is suboptimal. Aberrant sphingolipid metabolism has been observed in some cases of depression, specifically alterations in ceramide concentrations. The role of ceramides and other sphingolipids in depression is a novel concept. This review summarizes and evaluates the current state of evidence for a role of ceramides in depression pathophysiology and the potential for novel depression pharmacotherapies targeting ceramide metabolism. METHODS Medline, Embase, and PsycINFO databases were searched through October 2016 for English-language studies using combinations of the search terms: ceramide, depression, sphingolipid, and depressive symptoms. RESULTS Of the 489 articles screened, 14 were included in the qualitative synthesis of this review article. Pre-clinical and clinical evidence suggest that ceramide species may contribute to depression pathophysiology. In human studies, ceramides C18:0 and C20:0 are the species most strongly linked to depression. Evidence for altered ceramide metabolism in depression is present, but data for a causal role of ceramides in depression are lacking. LIMITATIONS This review was limited by potential reporting bias. Furthermore, a lack of specificity of which ceramides were altered in depression was common. CONCLUSIONS Pharmacotherapy targeting ceramide metabolism may be a novel treatment option for depression. A number of pharmacological targets exists for ceramide reduction and a number of currently approved medications inhibit ceramide production. More evidence, pre-clinical and clinical, is warranted to determine the extent and consistency of the role of ceramides in depression.

A Lipidomics Approach to Assess the Association Between Plasma Sphingolipids and Verbal Memory Performance in Coronary Artery Disease Patients Undertaking Cardiac Rehabilitation: A C18:0 Signature for Cognitive Response to Exercise

BACKGROUND Early subtle deficits in verbal memory, which may indicate early neural risk, are common in patients with coronary artery disease (CAD). While exercise can improve cognition, cognitive response to exercise is heterogeneous. Sphingolipids have been associated with the development and progression of CAD, and impairments in sphingolipid metabolism may play roles in neurodegeneration and in the neural adaptation response to exercise. OBJECTIVE In this study, change in plasma concentrations of sphingolipids was assessed in relation to change in verbal memory performance and in other cognitive domains among CAD subjects undertaking a 6-month cardiac rehabilitation (CR) program. METHODS Patients with CAD (n = 120, mean age = 64±6 y, 84% male, years of education = 16±3) underwent CR with neuropsychological assessments and blood collected at baseline, 3-, and 6-months. Z-scores based on age, gender, and education were combined for verbal memory, visuospatial memory, processing speed, executive function, and global cognition tasks to calculate cognitive domain Z-scores. Plasma sphingolipid concentrations were measured from fasting blood samples using high performance liquid chromatography coupled electrospray ionization tandem mass spectrometry (LC/MS/MS). Mixed models were used to identify sphingolipids significantly associated with performance in verbal memory and other cognitive domains, adjusting for potential confounders. RESULTS A decrease in ceramide C18:0 concentration was significantly associated with improvement in verbal memory performance (b[SE] = -0.51 [0.25], p = 0.04), visuospatial memory (b[SE] = -0.44 [0.22], p = 0.05), processing speed (b[SE] = -0.89 [0.32], p = 0.007), and global cognition (b[SE] = -1.47 [0.59], p = 0.01) over 6 months of CR. CONCLUSIONS Plasma ceramide C18:0 concentrations may be a sensitive marker of cognitive response to exercise in patients with CAD.

Plasma sphingolipids and depressive symptoms in coronary artery disease

Depression is highly prevalent in individuals with coronary artery disease (CAD) and increases the risk of future cardiac events and mortality. Sphingolipids have been implicated in the pathophysiology of both CAD and depression. This study assessed the association between plasma sphingolipid concentrations and depressive symptoms in CAD subjects.

The effect of exercise on resting concentrations of peripheral brain-derived neurotrophic factor (BDNF) in major depressive disorder: A meta-analysis

Exercise interventions have been shown to successfully improve depression in patients with major depressive disorder (MDD), but like other forms of antidepressant treatment, exercise is not effective in all patients and its mechanisms of action have not been fully elucidated. Brain-derived neurotrophic factor (BDNF), a key mediator of neurogenesis and neuronal survival, has been shown to be decreased in individuals with MDD. One potential mechanism by which exercise alleviates depression is through an increase in BDNF. In order to evaluate this hypothesis, we conducted a meta-analysis of studies that assessed the effects of a chronic (multi-week) exercise intervention on BDNF concentrations in MDD patients. MEDLINE, Embase, PsycINFO, SPORTDiscus, Rehabilitation & Sports Medicine Source, and CINAHL databases were searched for original, peer-reviewed reports of peripheral blood BDNF concentrations before and after a chronic exercise intervention in MDD patients. Standardized mean differences (SMDs) were generated from random effects models. Potential sources of heterogeneity were explored in meta-regression analyses. In six studies that met inclusion criteria, resting blood concentrations of BDNF were not significantly higher after a chronic exercise intervention (SMD = 0.43, 95% CI: -0.06-0.92, p = 0.09) in MDD patients. This meta-analysis did not find evidence that a chronic aerobic exercise intervention increases resting concentrations of BDNF in the blood of MDD patients; however, there is a lack of studies in this area making it difficult to reach a definitive conclusion. Future studies on this topic with larger sample sizes and longer durations are needed to draw more robust conclusions.

PLASMA SPHINGOLIPID RATIOS AND VERBAL MEMORY PERFORMANCE IN A CORONARY ARTERY DISEASE POPULATION AT RISK FOR VASCULAR COGNITIVE IMPAIRMENT (VCI) AND ALZHEIMER’S DISEASE

established transcranialmagnetic stimulation technique that can assess the level of cholinergic activity in the brain. However, it is not yet known whether SAI is able to distinguish the low cholinergic activity in AD patients compared to unaffected controls and detect the improvement in cholinergic function in response to treatment with ChEI such as donepezil. The objective of this study was to assess whether SAI can be used as a biomarker for increased cholinergic activity, and hence measure potential improvements in response to treatments. Methods: 14 mild-to-moderate AD patients (age 73 +/7.1 years (mean +/-SD), 7 males, MMSE 23.3 +/3.3) on 10 mg donepezil once daily and 20 unaffected control subjects (age 67 +/7.3 years), 9males, meanMMSE 29.8 +/0.5) underwent 4 SAI sessions: 2 sessions per day w4 hours apart, 13.7 +/1.31 days apart. In the AD patient group, the first TMS session of the day was performed prior to the daily dose of donepezil, and the second 3 hours post dose. Results:A mixed analysis of variance revealed no significant difference between the SAI responses between AD patients pre or post donepezil dose and unaffected control subjects (p 1⁄4 0.275). There was also no significant intra-subject difference in the SAI responses preand postdonepezil dose in AD patients (p 1⁄4 0.870). Conclusions: SAI was not able to detect a significant difference in the brain cholinergic state between patients with mild-to-moderate AD and unaffected control subjects. In addition, repeat SAI did not detect intra-subject change in the brain cholinergic state before and 3 hours after administration of donepezil in patients with mild-tomoderate AD.

THE ASSOCIATION BETWEEN ENDOTHELIAL DYSFUNCTION AND MEMORY PERFORMANCE IN PATIENTS WITH CORONARY ARTERY DISEASE UNDERTAKING CARDIAC REHABILITATION

ysis: The raw and IRT-derived HBC scores were analyzed with and without the MCI Screen using logistic regression to predict FAST stage. Results: The HBC and MCI Screen measures correlated weakly. Combining their information optimized classification of functionally normal (FAST 1, 2) vs. functionally impaired subjects (FAST 3, 4). The item difficulty and discrimination measures showed that 15 of the 16 HBC items had good psychometric validity. The raw HBC scores and IRT-derived, theta scores gave similar classification accuracies. Conclusions: The weak correlation between subjective and objective cognitive measures, and the improved classification when they are combined, indicates the subjective and objective information measure different aspects of cognitive performance. 15 of 16 HBC items have good psychometric validity. It would be helpful to understand the different aspects of cognition captured by subjective and objective assessment so that they can be more gainfully exploited.

THE ASSOCIATION BETWEEN APATHY AND EXECUTIVE FUNCTION IN CORONARY ARTERY DISEASE PATIENTS IS MODIFIED BY ENDOTHELIAL DYSFUNCTION

However, on the California Verbal Learning Test, SNAP (A-/N+) showed faster memory decline than the A-/Ngroup (p1⁄4.03), while A+/Ndid not (p1⁄4.37) (Figure 2). Conclusions: In the oldest-old, presence of both beta-amyloid and hippocampal atrophy combined confers the greatest risk for cognitive decline across domains. Isolated beta-amyloid is associated with decline on executive functions, while SNAP (isolated hippocampal atrophy) is associated with decline on verbal memory. Neither biomarker abnormality is benign in the 9 and 10 decades of life.