Transcranial direct current stimulation (tDCS) is a non-invasive type of brain stimulation that uses electrical currents to modulate neuronal activity. A small number of studies have investigated the ...effects of tDCS on cognition in patients with Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD), and have demonstrated variable effects. Emerging evidence suggests that tDCS is most effective when applied to active brain circuits. Aerobic exercise is known to increase cortical excitability and improve brain network connectivity. Exercise may therefore be an effective, yet previously unexplored primer for tDCS to improve cognition in MCI and mild AD.
Participants with MCI or AD will be randomized to receive 10 sessions over 2 weeks of either exercise primed tDCS, exercise primed sham tDCS, or tDCS alone in a blinded, parallel-design trial. Those randomized to an exercise intervention will receive individualized 30-min aerobic exercise prescriptions to achieve a moderate-intensity dosage, equivalent to the ventilatory anaerobic threshold determined by cardiopulmonary assessment, to sufficiently increase cortical excitability. The tDCS protocol consists of 20 min sessions at 2 mA, 5 times per week for 2 weeks applied through 35 cm
bitemporal electrodes. Our primary aim is to assess the efficacy of exercise primed tDCS for improving global cognition using the Montreal Cognitive Assessment (MoCA). Our secondary aims are to evaluate the efficacy of exercise primed tDCS for improving specific cognitive domains using various cognitive tests (n-back, Word Recall and Word Recognition Tasks from the Alzheimer's Disease Assessment Scale-Cognitive subscale) and neuropsychiatric symptoms (Neuropsychiatric Inventory). We will also explore whether exercise primed tDCS is associated with an increase in markers of neurogenesis, oxidative stress and angiogenesis, and if changes in these markers are correlated with cognitive improvement.
We describe a novel clinical trial to investigate the effects of exercise priming before tDCS in patients with MCI or mild AD. This proof-of-concept study may identify a previously unexplored, non-invasive, non-pharmacological combination intervention that improves cognitive symptoms in patients. Findings from this study may also identify potential mechanistic actions of tDCS in MCI and mild AD.
Clinicaltrials.gov, NCT03670615 . Registered on September 13, 2018.
OBJECTIVEWhile transcranial direct current stimulation (tDCS) can enhance aspects of memory in patients with mild cognitive impairment (MCI) and Alzheimer disease (AD), there has been wide ...variability in both the placement of tDCS electrodes and treatment response. This study compared the effects of bifrontal (anodal stimulation over the dorsolateral prefrontal cortices), bitemporal (anodal stimulation over the temporal cortices), and sham tDCS on cognitive performance in MCI and AD.
METHODSSeventeen patients diagnosed with MCI or mild AD received 3 sessions of anodal tDCS (bifrontal, bitemporal, 2 mA for 20 minutes; and sham) in random order. Sessions were separated by 1 week. The Alzheimerʼs Disease Assessment Scale–Cognitive Word Recognition Task, Alzheimerʼs Disease Assessment Scale–Cognitive Word Recall Task, 2-back, and Montreal Cognitive Assessment were used to assess cognition.
RESULTSThere was a significant effect of stimulation condition on 2-back accuracy (F2,28 = 5.28 P = 0.01, ηp = 0.27), with greater improvements following bitemporal tDCS compared with both bifrontal and sham stimulations. There were no significant changes on other outcome measures following any stimulation. Adverse effects from stimulation were mild and temporary.
CONCLUSIONSThese findings demonstrate that improvements in specific memory tasks can be safely achieved after a single session of bitemporal tDCS in MCI and mild AD patients.
•Randomized controlled trial design is known to influence antidepressant efficacy results•The impact of trial design on adverse events (AEs) has not previously been tested•This study found that ...inclusion of a placebo arm was associated with ~20% more AEs in antidepressant arms•Subjects may monitor themselves more carefully for AEs when they might be on a placebo•This observation has important implications for interpretation of trial tolerability findings
Antidepressant efficacy is influenced by patient expectations and, in randomized controlled trials (RCTs), the probability of receiving a placebo. It is unclear whether tolerability demonstrates a similar pattern. This study aimed to determine whether study design influences adverse event (AE) rates in antidepressant trials for subjects receiving active treatment or placebo.
RCTs comparing one antidepressant to another antidepressant, placebo, or both in major depressive disorder (MDD) (1996-2018) were retrieved from Medline and PsycINFO. Clinicaltrials.gov was searched for unpublished trials. Of 1,997 studies screened, 77 trials were included. Studies were classified as drug-drug, drug-drug-placebo, or drug-placebo based on design and overall number of subjects experiencing any AE was recorded. Subgroup meta-analysis of proportions and meta-regression techniques were used to compare AE rates across study designs in patients receiving active antidepressant treatment and placebo.
Among the actively treated, AE rates were lower in drug-drug trials (58.5%) compared to drug-drug-placebo (75.7%) and drug-placebo (76.4%) (the model reported coefficients for percent differences between AE rates of different study designs were B=17.0, p<0.001 and B=17.8, p<0.001, respectively). AE rates in patients receiving placebo were not different between study designs.
The present study is limited by the diverse range of study populations, variability in reporting of AEs, and specific antidepressants employed in the included trials.
The inclusion of a placebo arm in the study design was unexpectedly associated with higher rates of AEs among patients receiving active medication in antidepressant trials. This observation has important implications for interpretation of trial tolerability findings.
Sleep and Attention in Alzheimer's Disease Hennawy, Mirna; Sabovich, Solomon; Liu, Celina S ...
The Yale journal of biology & medicine,
03/2019, Letnik:
92, Številka:
1
Journal Article
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Individuals with Alzheimer's disease (AD) present with a wide variety of symptoms, including sleep disruption and sleep disorders. Conversely, disordered sleep has been associated with an increased ...risk of developing AD. Both conditions individually have adverse effects on attention, which can be further divided into selective, sustained, divided, and alternating attention. The neural mechanisms underpinning sleep problems in AD involve the disruption of the circadian system. This review comprehensively discusses the types of attention impairments, the relationship between AD pathology and sleep disruption, and the effect of sleep issues on attention in AD. Recommendations for future research include addressing the lack of consistency among study designs and outcomes, and the need to continue exploring the biology of sleep and attention in AD.
Transcranial direct current stimulation (tDCS) has recently been investigated as a potential nonpharmacological treatment for individuals with mild cognitive impairment (MCI) and Alzheimer's disease ...(AD). A comprehensive literature search was performed on tDCS studies published until March 2017 using MEDLINE, Embase and PsychINFO databases. 12 articles with a total of 202 MCI or AD participants were included. Although ten of the 12 studies demonstrated positive findings with tDCS, two studies reported no effect on cognition. There was a wide range of methodological approaches used and in the cognitive functions measured. The variability in treatment response may be related to the heterogeneity in stimulation parameters including the site of stimulation, and cognitive assessments used. Patient-related factors including individual psychological, biological, and physiological status at the time of stimulation may also influence treatment response. We recommend that more comparative studies using similar patient factors and study parameters are needed in order to better understand the efficacy of tDCS in MCI and AD.
This chapter explores the evidence supporting inflammation-associated depression. Data to date suggest a bidirectional relationship between inflammation and depression wherein one process can drive ...the other. A wealth of animal and clinical studies have demonstrated an association between concentrations of pro-inflammatory cytokines - specifically interleukin (IL)-1β, IL-6, and tumor necrosis factor-α - and depressive symptoms. There is also evidence that this pro-inflammatory state is accompanied by aberrant inflammation-related processes including platelet activation factor hyperactivity, oxidative and nitrosative stress, and damage to mitochondria. These complex and interrelated mechanisms can collectively contribute to negative neurobiological outcomes that may, in part, underlie the etiopathology of depression. Mounting evidence has shown a concomitant reduction in both depressive symptoms and pro-inflammatory cytokine concentrations following treatment with pharmacological anti-inflammatory interventions. Taken together, the reviewed preclinical and clinical findings may suggest the existence of a distinct inflammatory subtype of depression in which these patients exhibit unique biochemical and clinical features and may potentially experience improved clinical outcomes with inflammation-targeted pharmacotherapy.
Bipolar disorder (BD) is a disabling and chronic neuropsychiatric disorder that is typified by a complex illness presentation, episode recurrence and by its frequent association with psychiatric and ...medical comorbidities. Over the past decade, obesity has emerged as one of many comorbidities generating substantial concern in the BD population due to important prognostic implications. This comprehensive review details the bidirectional relationship between obesity and BD as evidenced by alterations in the structure and function of the central nervous system, in addition to greater depressive recurrence, cognitive dysfunction and risk of suicidality. Drawing on current research results, this article presents several putative mechanisms underlying the synergistic toxic effects and provides a framework for future treatment options for the obesity–BD comorbidity. There is a need for more large-scale prospective studies to investigate the bidirectional relationships between obesity and BD.
Cancer results from a breakdown of normal gene expression control, so the study of gene regulation is critical to cancer research. To gain insight into the transcriptional and epigenetic factors ...regulating abnormal gene expression patterns in cancers, we developed the Cistrome Cancer web resource (http://cistrome.org/CistromeCancer/). We conducted the systematic integration and modeling of over 10,000 tumor molecular profiles from The Cancer Genome Atlas (TCGA) with over 23,000 ChIP-seq and chromatin accessibility profiles from our Cistrome collection. The results include reconstruction of functional enhancer profiles, "super-enhancer" target genes, as well as predictions of active transcription factors and their target genes for each TCGA cancer type. Cistrome Cancer reveals novel insights from integrative analyses combining chromatin profiles with tumor molecular profiles and will be a useful resource to the cancer gene regulation community.
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Application of stem cell biology to breast cancer research has been limited by the lack of simple methods for identification and isolation of normal and malignant stem cells. Utilizing in vitro and ...in vivo experimental systems, we show that normal and cancer human mammary epithelial cells with increased aldehyde dehydrogenase activity (ALDH) have stem/progenitor properties. These cells contain the subpopulation of normal breast epithelium with the broadest lineage differentiation potential and greatest growth capacity in a xenotransplant model. In breast carcinomas, high ALDH activity identifies the tumorigenic cell fraction, capable of self-renewal and of generating tumors that recapitulate the heterogeneity of the parental tumor. In a series of 577 breast carcinomas, expression of ALDH1 detected by immunostaining correlated with poor prognosis. These findings offer an important new tool for the study of normal and malignant breast stem cells and facilitate the clinical application of stem cell concepts.
Heat shock factors (Hsfs) and Heat shock proteins (Hsps) belong to an essential group of molecular regulators involved in controlling cellular processes under normal and stress conditions. The role ...of Hsfs and Hsps is well known in model plant species under diverse stress conditions. While plants Hsfs are vital components of the signal transduction response to maintain cellular homeostasis, Hsps function as chaperones helping to maintain folding of damaged and newly formed proteins during stress conditions. In lettuce (Lactuca sativa), a highly consumed vegetable crop grown in the field and in hydroponic systems, the role of these gene families in response to artificial light is not well characterized.
Using a genome-wide analysis approach, we identified 32 Hsfs and 22 small heat shock proteins (LsHsps) in lettuce, some of which do not have orthologs in Arabidopsis, poplar, and rice. LsHsp60s, LsHsp90s, and LsHsp100s are highly conserved among dicot and monocot species. Surprisingly, LsHsp70s have three times more members than Arabidopsis and two times more than rice. Interestingly, the lettuce genome triplication did not contribute to the increased number of LsHsp70s genes. The large number of LsHsp70s was the result of genome tandem duplication. Chromosomal distribution analysis shows larger tandem repeats of LsHsp70s genes in Chr1, Chr7, Chr8, and Chr9. At the transcriptional level, some genes of the LsHsfs, LsHsps, LsHsp60s, and LsHsp70s families were highly responsive to UV and high intensity light stress, in contrast to LsHsp90s and LsHsp100s which did not respond to a light stimulus.
Our genome-wide analysis provides a detailed identification of Hsfs and Hsps in lettuce. Chromosomal location and syntenic region analysis together with our transcriptional analysis under different light conditions provide candidate genes for breeding programs aiming to produce lettuce varieties able to grow healthy under hydroponic systems that use artificial light.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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