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 Egger's 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.
Meta‐analytic data suggests that blood concentrations of brain‐derived neurotrophic factor (BDNF) are increased after a single session of exercise. BDNF response to acute exercise is heterogeneous, may differ across genders, and may be influenced by exercise duration. These data provide support for the theory that one mechanism through which physical activity enhances brain health is via increasing BDNF concentrations.
Genetic evidence implicates a causal role for the complement pathway in Alzheimer's disease (AD). Since studies have shown inconsistent differences in cerebrospinal fluid (CSF) and peripheral blood ...complement protein concentrations between AD patients and healthy elderly, this study sought to summarize the clinical data. Original peer-reviewed articles measuring CSF and/or blood concentrations of complement or complement regulator protein concentrations in AD and healthy elderly control (HC) groups were included. Of 2966 records identified, means and standard deviations from 86 studies were summarized as standardized mean differences (SMD) by random effects meta-analyses. In CSF, concentrations of clusterin (N
/N
= 625/577, SMD = 0.53, Z
= 8.81, p < 0.005; I
< 0.005%) and complement component 3 (C3; N
/N
= 299/522, SMD = 0.45, Z
= 3.21, p < 0.005; I
= 68.40%) were significantly higher in AD, but differences in C1q, C-reactive protein (CRP), serum amyloid protein (SAP), and factor H concentrations were not significant. In peripheral blood, concentrations of CRP were elevated in AD (N
/N
= 3404/3332, SMD = 0.44, Z
= 3.43, p < 0.005; I
= 93.81%), but differences between groups in C3, C4, C1-inhibitor, SAP, factor H and clusterin concentrations were not significant, and inconsistent between studies. Of 64 complement pathway proteins or regulators in the quantitative synthesis, trends in C1q, factor B, C4a, and late-stage complement pathway components (e.g. C9) in blood, C4 in CSF, and the membrane attack complex in blood and CSF, might be investigated further. The results collectively support elevated complement pathway activity in AD, which was best characterized by increased CSF clusterin concentrations and less consistently by CSF C3 concentrations. Complement activity related to an AD diagnosis was not reflected consistently by the peripheral blood proteins investigated.
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.
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.
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.
Aerobic but not resistance training interventions increased resting BDNF concentrations in peripheral blood.
•Cerebral blood flow (CBF), measured using a number of neuroimaging phenotypes, is a core metric of brain health, and CBF abnormalities are associated with vascular disease.•Decreased CBF in BD ...depression and differential perfusion patterns in response to tasks were found in studies of CBF in BD across methodologies.•Studies examining CBF in BD prospectively, and as a treatment target are warranted.
Neuroimaging of cerebral blood flow (CBF) can inform our understanding of the pathophysiology of bipolar disorder (BD) as there is increasing support for the concept that BD is in part a vascular disease. Despite numerous studies examining CBF in BD, there has not yet been a review of the literature on the topic of CBF in BD.
A systematic review of the literature on CBF in BD was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Studies included measured CBF by single-photon emission computerized tomography (SPECT), positron emission tomography (PET), arterial spin labelling (ASL) or perfusion weighted imaging (PWI) in a group of BD patients.
Thirty-three studies with a total of 508 subjects with BD and 538 controls were included (n = 15 SPECT; n = 8 PET; n = 7 ASL; n = 1 PWI; n = 2 other). The majority of studies in BD depression and mania reported widespread resting hypoperfusion in cingulate gyrus, frontal, and anterior temporal regions in comparison to healthy controls (HC). Findings in euthymic BD subjects and in symptomatically heterogeneous groups were less consistent. Studies that examined CBF responses to cognitive or emotional stimuli in BD subjects have reported hypoperfusion or different regions involved in comparison to HC.
Important methodological heterogeneity between studies, and small number of subjects per study.
The most consistent findings to date are hypoperfusion in BD mood episodes, and hypoactive CBF responses to emotional or cognitive challenges. Future studies examining CBF are warranted, including prospective studies, studies examining CBF as a treatment target, and multimodal imaging studies.
Type 2 diabetes mellitus (T2DM) can result in microvascular complications such as neuropathy, retinopathy, nephropathy, and cerebral small vessel disease, and contribute to macrovascular ...complications, such as heart failure, peripheral arterial disease, and large vessel stroke. T2DM also increases the risks of depression and dementia for reasons that remain largely unclear. Perturbations in the cytochrome P450-soluble epoxide hydrolase (CYP-sEH) pathway have been implicated in each of these diabetes complications. Here we review evidence from the clinical and animal literature suggesting the involvement of the CYP-sEH pathway in T2DM complications across organ systems, and highlight possible mechanisms (e.g., inflammation, fibrosis, mitochondrial function, endoplasmic reticulum stress, the unfolded protein response and autophagy) that may be relevant to the therapeutic potential of the pathway. These mechanisms may be broadly relevant to understanding, preventing and treating microvascular complications affecting the brain and other organ systems in T2DM.
Motor learning may be enhanced when a single session of aerobic exercise is performed immediately before or after motor skill practice. Most research to date has focused on aerobically trained (AT) ...individuals, but it is unknown if aerobically untrained (AU) individuals would equally benefit. We aimed to: (a) replicate previous studies and determine the effect of rest (REST) versus exercise (EXE) on motor skill retention, and (b) explore the effect of aerobic fitness level (AU, AT), assessed by peak oxygen uptake (VO
peak), on motor skill retention after exercise. Forty-four participants (20-29 years) practiced a visuomotor tracking task (acquisition), immediately followed by 25-min of high-intensity cycling or rest. Twenty-four hours after acquisition, participants completed a motor skill retention test. REST and EXE groups significantly improved motor skill performance during acquisition F(3.17, 133.22) = 269.13, P = 0.001, but had no group differences in motor skill retention across time. AU-exercise (VO
peak = 31.6 ± 4.2 ml kg
min
) and AT-exercise (VO
peak = 51.5 ± 7.6 ml kg
min
) groups significantly improved motor skill performance during acquisition F(3.07, 61.44) = 155.95, P = 0.001, but had no group differences in motor skill retention across time. Therefore, exercise or aerobic fitness level did not modify motor skill retention.
Abstract Background Higher intake of omega-3 fatty acids (n-3 FAs) is associated with a reduced risk of Alzheimer's disease (AD) and milder forms of cognitive impairment (e.g. cognitive impairment no ...dementia CIND); however, findings from interventional trials are inconsistent. This meta-analysis examined the neuropsychological benefit of n-3 FAs in randomized double-blind placebo-controlled studies (RCTs) including healthy, CIND, or AD subjects. Methods Literature was searched using Medline, Embase, PsycInfo, Cochrane Library, Allied and Complementary Medicine Database (AMED), and Cumulative Index to Nursing and Allied Health Literature (CINAHL) up to September 2011. Treatment effects were summarized across cognitive subdomains, and effect sizes were estimated using Hedge's g and random effects modeling. Results Ten RCTs were combined quantitatively. There was no effect of n-3 FAs on composite memory (g = 0.04 95% CI: −0.06–0.14, N = 934/812, p = 0.452). When examined by domain, no overall benefit for immediate recall (0.04 −0.05–0.13, N = 934/812, p = 0.358) was detected; however, an effect in CIND subjects (0.16 0.01–0.31, N = 349/327, p = 0.034) was found. A benefit for attention and processing speed was also detected in CIND (0.30 0.02–0.57, N = 107/86, p = 0.035), but not healthy subjects. Benefits for delayed recall, recognition memory, or working memory and executive function were not observed. Treatment did not benefit AD patients as measured by the Mini-Mental State Examination (MMSE) or Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS–cog). No differences in adverse events (AE), dropout, or dropout due to AE between groups were observed. Conclusions These results suggest an effect of n-3 FAs within specific cognitive domains in CIND, but not in healthy or AD subjects.
Background. Ten percent of stroke survivors develop dementia, which increases to more than a third after recurrent stroke. Other survivors develop less severe vascular cognitive impairment. In the ...general population, depression, and diabetes interact in predicting dementia risk, and they are both prevalent in stroke. Objective. To assess the cumulative association of comorbid depressive symptoms and type 2 diabetes with cognitive outcomes among stroke survivors. Methods. Multicenter observational cohort study of people within 6 months of stroke. Depression and cognitive status were screened using the Center for Epidemiological Studies Depression (CES-D) scale and the Montreal Cognitive Assessment (MoCA), respectively. Processing speed, executive function and memory were assessed using the Trail Making Test parts A and B, and the 5 Word Delayed Free Recall task. Results. Among 342 participants (age 67.0 ± 13.5 years, 43.3% female, 46 ± 35 days poststroke), the prevalence of type 2 diabetes was 32.2% and depressive symptoms (CES-D ≥16) were found in 40.6%. Diabetes and depressive symptoms increased the risk of severe cognitive impairment (MoCA <20) with adjusted odds ratio (OR) 2.12 (95% confidence interval CI 1.20-3.74, P = .010) for 1 comorbidity and OR 3.18 (95% CI 1.26-8.02, P = .014) for both comorbidities. Associated cognitive deficits included executive function (F1, 168 = 3.43, P = .035) but not processing speed (F1, 168 = 1.86, P = .16) or memory (F1, 168 = 0.82, P = .44). Conclusions. Diabetes and depressive symptoms were associated cumulatively with poorer cognitive screening outcomes poststroke, particularly deficits in executive function. Having 1 comorbidity doubled the odds of screening for severe cognitive impairment, having both tripled the odds.
Bipolar Disorder (BD) has been conceptualized as both a cyclic and a progressive disorder. Mechanisms involved in neuroprogression in BD remain largely unknown although several non-mutually exclusive ...models have been proposed as explanatory frameworks. In the present paper, we propose that the pathophysiological changes observed in BD (e.g. brain structural alterations, cognitive deficits, oxidative stress imbalance, amyloid metabolism, immunological deregulation, immunosenescence, neurotrophic deficiencies and telomere shortening) converge on a model of accelerated aging (AA). Aging can be understood as a multidimensional process involving physical, neuropsychological, and social changes, which can be highly variable between individuals. Determinants of successful aging (e.g environmental and genetic factors), may also confer differential vulnerability to components of BD pathophysiology and contribute to the clinical presentation of BD. Herein we discuss how the understanding of aging and senescence can contribute to the search for new and promising molecular targets to explain and ameliorate neuroprogression in BD. We also present the strengths and limitations of this concept.
White matter hyperintensities (WMHs) are frequently seen on brain magnetic resonance imaging scans of older people. Usually interpreted clinically as a surrogate for cerebral small vessel disease, ...WMHs are associated with increased likelihood of cognitive impairment and dementia (including Alzheimer's disease AD). WMHs are also seen in cognitively healthy people. In this collaboration of academic, clinical, and pharmaceutical industry perspectives, we identify outstanding questions about WMHs and their relation to cognition, dementia, and AD. What molecular and cellular changes underlie WMHs? What are the neuropathological correlates of WMHs? To what extent are demyelination and inflammation present? Is it helpful to subdivide into periventricular and subcortical WMHs? What do WMHs signify in people diagnosed with AD? What are the risk factors for developing WMHs? What preventive and therapeutic strategies target WMHs? Answering these questions will improve prevention and treatment of WMHs and dementia.
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