25 results on '"Lanctôt, Krista L."'
Search Results
2. Sex differences in neuropsychiatric symptoms in Alzheimer’s disease dementia: a meta-analysis
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Eikelboom, Willem S., Pan, Michel, Ossenkoppele, Rik, Coesmans, Michiel, Gatchel, Jennifer R., Ismail, Zahinoor, Lanctôt, Krista L., Fischer, Corinne E., Mortby, Moyra E., van den Berg, Esther, and Papma, Janne M.
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- 2022
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3. Peripheral Alterations in Cytokine and Chemokine Levels After Antidepressant Drug Treatment for Major Depressive Disorder: Systematic Review and Meta-Analysis
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Köhler, Cristiano A., Freitas, Thiago H., Stubbs, Brendon, Maes, Michael, Solmi, Marco, Veronese, Nicola, de Andrade, Nayanna Q., Morris, Gerwyn, Fernandes, Brisa S., Brunoni, André R., Herrmann, Nathan, Raison, Charles L., Miller, Brian J., Lanctôt, Krista L., and Carvalho, André F.
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- 2018
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4. Endosomal-Lysosomal and Autophagy Pathway in Alzheimer's Disease: A Systematic Review and Meta-Analysis.
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Krance, Saffire H., Wu, Che-Yuan, Chan, Alison C.Y., Kwong, Stephanie, Song, Bing Xin, Xiong, Lisa Y., Ouk, Michael, Chen, Ming Hui, Zhang, Jane, Yung, Adrian, Stanley, Meagan, Herrmann, Nathan, Lanctôt, Krista L., and Swardfager, Walter
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RESEARCH ,ALZHEIMER'S disease ,LYSOSOMES ,META-analysis ,AUTOPHAGY ,RESEARCH methodology ,SYSTEMATIC reviews ,EVALUATION research ,COENZYMES ,COMPARATIVE studies ,RESEARCH funding ,CYTOPLASM ,METABOLISM - Abstract
Background: The endosomal-lysosomal and autophagy (ELA) pathway may be implicated in the progression of Alzheimer's disease (AD); however, findings thus far have been inconsistent.Objective: To systematically summarize differences in endosomal-lysosomal and autophagy proteins in the cerebrospinal fluid (CSF) of people with AD and healthy controls (HC).Methods: Studies measuring CSF concentrations of relevant proteins in the ELA pathway in AD and healthy controls were included. Standardized mean differences (SMD) with 95% confidence intervals (CI) between AD and healthy controls in CSF concentrations of relevant proteins were meta-analyzed using random-effects models.Results: Of 2,471 unique studies, 43 studies were included in the systematic review and meta-analysis. Differences in ELA protein levels in the CSF between AD and healthy controls were observed, particularly in lysosomal membrane (LAMP-1: NAD/NHC = 348/381, SMD [95% CI] = 0.599 [0.268, 0.930], I2 = 72.8%; LAMP-2: NAD/NHC = 401/510, SMD [95% CI] = 0.480 [0.134, 0.826], I2 = 78.7%) and intra-lysosomal proteins (GM2A: NAD/NHC = 390/420, SMD [95% CI] = 0.496 [0.039, 0.954], I2 = 87.7%; CTSB: NAD/NHC = 485/443, SMD [95% CI] = 0.201 [0.029, 0.374], I2 = 28.5%; CTSZ: NAD/NHC = 535/820, SMD [95% CI] = -0.160 [-0.305, -0.015], I2 = 24.0%) and in proteins involved in endocytosis (AP2B1:NAD/NHC = 171/205, SMD [95% CI] = 0.513 [0.259, 0.768], I2 = 27.4%; FLOT1: NAD/NHC = 41/45, SMD [95% CI] = -0.489 [-0.919, -0.058], I2 <0.01). LC3B, an autophagy marker, also showed a difference (NAD/NHC = 70/59, SMD [95% CI] = 0.648 [0.180, 1.116], I2 = 38.3%)), but overall there was limited evidence suggesting differences in proteins involved in endosomal function and autophagy.Conclusion: Dysregulation of proteins in the ELA pathway may play an important role in AD pathogenesis. Some proteins within this pathway may be potential biomarkers for AD. [ABSTRACT FROM AUTHOR]- Published
- 2022
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5. Psychometric Properties of Apathy Scales in Dementia: A Systematic Review.
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Mohammad, Dana, Ellis, Courtney, Rau, Allison, Rosenberg, Paul B., Mintzer, Jacobo, Ruthirakuhan, Myuri, Herrmann, Nathan, Lanctôt, Krista L., and Finger, Elizabeth
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META-analysis ,APATHY ,RESEARCH evaluation ,PSYCHOMETRICS ,DEMENTIA - Abstract
Apathy is a prevalent and problematic neuropsychiatric symptom in those with dementia that is emerging as a treatment target, necessitating accurate assessment. While many apathy scales are available, not all have been developed for use exclusively in dementia, and psychometric properties may vary across different populations. This systematic review aimed to provide an overview of the psychometric properties of apathy scales used in Alzheimer's disease (AD) and related dementias, as well as rate the methodological quality of supporting studies. In addition, for those scales identified, performance in clinical trials was reviewed. A search was conducted through Medline, Psychinfo, Embase, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. Articles that reported psychometric properties of an apathy scale in an AD or mixed dementia population were included. Of 15 articles, the methodological quality ratings of the studies ranged from adequate to excellent. Three clinical trials and two pooled analyses of clinical trials were included that used apathy scales evaluated in this review. Three scales emerged. The Neuropsychiatric Inventory apathy subscale (NPI-apathy) and the Apathy Evaluation Scale (AES) had the greatest number of studies evaluating psychometric properties and were also used in the clinical trials and have shown sensitivity to change. The Dementia Apathy Interview and Rating demonstrated excellent values of internal consistency, validity, and reliability for use in an AD population. Future research should address comparative scale performance and assess ability to distinguish subtypes of apathy. Validation may include evaluation of performance against specific imaging defined deficits. [ABSTRACT FROM AUTHOR]
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- 2018
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6. Cognitive Outcomes After Transcatheter Aortic Valve Implantation: A Metaanalysis.
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Khan, Maisha M., Herrmann, Nathan, Gallagher, Damien, Gandell, Dov, Fremes, Stephen E., Wijeysundera, Harindra C., Radhakrishnan, Sam, Sun, Yue Ran, and Lanctôt, Krista L.
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AORTIC stenosis treatment ,SURGICAL complications ,COGNITIVE testing ,INJURY risk factors ,HEART valve surgery - Abstract
Objectives: To quantitatively summarize changes in cognitive performance in individuals with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI). Design: Metaanalysis. Participants: Individuals undergoing TAVI (N = 1,065 (48.5% male) from 18 studies, average age ≥80). Measurements: The MEDLINE, EMBASE, and Cochrane Central databases were searched for original peer‐reviewed reports assessing cognitive performance using standardized cognitive tests before and after TAVI. Data were extracted for cognitive scores before TAVI; perioperatively (within 7 days after TAVI); 1, 3, and 6 months after TAVI, and 12 to 34 months after TAVI (over the long term). Standardized mean differences (SMDs) were generated using random‐effects models for changes in cognition at each time point. Metaregression analyses were conducted to assess the association between population and procedural characteristics and cognitive outcomes. Risk of bias was assessed. Results: There were no significant changes from baseline in perioperative cognitive performance (SMD = 0.05, 95% confidence interval (CI) = −0.08–0.18;
z = 0.75,P = .46), although overall cognitive performance had improved significantly 1 month after TAVI (SMD = −0.33, 95% CI = −0.50 to −0.16;z = 3.83,P < .001). There were no differences in cognitive performance 3 and 6 months after TAVI or over the long term. Cognitive outcomes were not associated with any covariates in regression analyses. Conclusion: Cognitive performance is preserved after TAVI, suggesting TAVI is not detrimental to cognition. [ABSTRACT FROM AUTHOR]- Published
- 2018
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7. Peripheral inflammatory markers in Alzheimer's disease: a systematic review and meta-analysis of 175 studies.
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Lai, Ka Sing P., Liu, Celina S., Rau, Allison, Lanctôt, Krista L., Köhler, Cristiano A., Pakosh, Maureen, Carvalho, André F., and Herrmann, Nathan
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ALZHEIMER'S disease treatment ,ENCEPHALITIS ,SYSTEMATIC reviews ,META-analysis ,PERIPHERAL neuropathy ,BIOMARKERS ,ALZHEIMER'S disease diagnosis ,ALZHEIMER'S disease ,COMPARATIVE studies ,INFLAMMATION ,NEUROPSYCHOLOGICAL tests ,RESEARCH methodology ,MEDICAL cooperation ,RESEARCH ,EVALUATION research ,DIAGNOSIS - Abstract
Objectives: Increasing evidence suggests that inflammation is involved in Alzheimer's disease (AD) pathology. This study quantitatively summarised the data on peripheral inflammatory markers in patients with AD compared with healthy controls (HC).Methods: Original reports containing measurements of peripheral inflammatory markers in AD patients and HC were included for meta-analysis. Standardised mean differences were calculated using a random effects model. Meta-regression and exploration of heterogeneity was performed using publication year, age, gender, Mini-Mental State Examination (MMSE) scores, plasma versus serum measurements and immunoassay type.Results: A total of 175 studies were combined to review 51 analytes in 13 344 AD and 12 912 HC patients. Elevated peripheral interleukin (IL)-1β, IL-2, IL-6, IL-18, interferon-γ, homocysteine, high-sensitivity C reactive protein, C-X-C motif chemokine-10, epidermal growth factor, vascular cell adhesion molecule-1, tumour necrosis factor (TNF)-α converting enzyme, soluble TNF receptors 1 and 2, α1-antichymotrypsin and decreased IL-1 receptor antagonist and leptin were found in patients with AD compared with HC. IL-6 levels were inversely correlated with mean MMSE scores.Conclusions: These findings suggest that AD is accompanied by a peripheral inflammatory response and that IL-6 may be a useful biological marker to correlate with the severity of cognitive impairment. Further studies are needed to determine the clinical utility of these markers. [ABSTRACT FROM AUTHOR]- Published
- 2017
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8. The effect of acute exercise on blood concentrations of brain-derived neurotrophic factor in healthy adults: a meta-analysis.
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Dinoff, Adam, Herrmann, Nathan, Swardfager, Walter, Lanctôt, Krista L., and Foxe, John
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PHYSICAL activity ,BRAIN-derived neurotrophic factor ,NEUROTROPHINS ,COGNITION ,META-analysis - Abstract
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. [ABSTRACT FROM AUTHOR]
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- 2017
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9. The Effect of Exercise Training on Resting Concentrations of Peripheral Brain-Derived Neurotrophic Factor (BDNF): A Meta-Analysis.
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Dinoff, Adam, Herrmann, Nathan, Swardfager, Walter, Liu, Celina S., Sherman, Chelsea, Chan, Sarah, and Lanctôt, Krista L.
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BRAIN-derived neurotrophic factor ,RESISTANCE training ,PHYSICAL activity ,BRAIN function localization ,BLOOD serum analysis - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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10. Efficacy and safety of antidepressants for treatment of depression in Alzheimer's disease: a metaanalysis.
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Thompson, Sarah, Herrmann, Nathan, Rapoport, Mark J., Lanctôt, Krista L., and Lanctôt, Krista L
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MENTAL depression ,ALZHEIMER'S patients ,ANTIDEPRESSANTS ,PSYCHIATRIC drugs ,DEMENTIA ,NEUROBEHAVIORAL disorders ,PLACEBOS ,BEHAVIORAL medicine ,MEDICAL research ,ALZHEIMER'S disease ,CLINICAL trials ,COMPARATIVE studies ,RESEARCH methodology ,MEDICAL cooperation ,META-analysis ,RESEARCH ,EVALUATION research - Abstract
Copyright of Canadian Journal of Psychiatry is the property of Sage Publications Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2007
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11. Inflammatory Markers in Mild Cognitive Impairment: A Meta-Analysis.
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Saleem, Mahwesh, Herrmann, Nathan, Swardfager, Walter, Eisen, Rebecca, and Lanctôt, Krista L.
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INFLAMMATION ,MILD cognitive impairment ,NEURODEGENERATION ,ALZHEIMER'S disease research ,DEMENTIA research ,BIOMARKERS ,COGNITION disorders ,COMPARATIVE studies ,RESEARCH methodology ,MEDICAL cooperation ,META-analysis ,RESEARCH ,EVALUATION research - Abstract
Reports of elevated inflammatory markers in mild cognitive impairment (MCI) suggest that inflammation may be a potential early marker of the neurodegenerative cascade associated with Alzheimer's disease (AD). The aim of this study was to quantitatively summarize the data on peripheral blood concentrations of inflammatory factors in patients with MCI compared to controls. Mean (±SD) blood concentrations of inflammatory factors for MCI and control subjects were extracted from original English language peer-reviewed studies for meta-analysis. Twenty-two studies measuring concentrations of cytokines, chemokines, acute phase reactant proteins, immunoglobulins, intercellular adhesion molecules, and fibrinogen were included. No significant differences in inflammatory factors studied were found between subjects with MCI and healthy controls. These findings do not support the involvement of inflammatory markers at the MCI stage of cognitive decline although significant heterogeneity was observed in some comparisons. It remains to be established whether inflammation may predict increased rate of conversion to dementia. [ABSTRACT FROM AUTHOR]
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- 2015
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12. A meta-analysis of lipid peroxidation markers in major depression.
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Mazereeuw, Graham, Herrmann, Nathan, Andreazza, Ana C., Khan, Maisha M., and Lanctôt, Krista L.
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DIAGNOSIS of mental depression ,LIPID peroxidation (Biology) ,BIOMARKERS ,ANTIDEPRESSANTS ,MALONDIALDEHYDE ,DRUG therapy ,META-analysis - Abstract
Background: Major depressive disorder (MDD) may be associated with oxidative damage to lipids, which can potentially affect mood-regulating pathways. This meta-analysis summarizes current knowledge regarding lipid peroxidation markers in clinical samples of MDD and the effects of antidepressant pharmacotherapy on those markers. Methods: MEDLINE, EMBASE, CINAHL, PsycINFO, and Cochrane Collaboration were searched for original, peer-reviewed articles measuring markers of lipid peroxidation in patients with MDD and nondepressed healthy controls up to April 2015. Standardized mean differences (SMDs) were generated from random effects models summarizing mean (± standard deviations) concentrations of selected markers. Results: Lipid peroxidation was greater in MDD than in controls (studies =17, N=857 MDD/782 control, SMD =0.83 [0.56-1.09], z=6.11, P,0.01, I2=84.0%) and was correlated with greater depressive symptom severity (B=0.05, df=8, P,0.01). Antidepressant treatment was associated with a reduction in lipid peroxidation in MDD patients (studies=5, N=222, SMD=0.71 [0.40-0.97], P,0.01; I2=42.5%). Limitations: Lipid peroxidation markers were sampled from peripheral blood, included studies comparing MDD to controls were all cross-sectional, and only five antidepressant treatment studies were eligible for inclusion. Conclusion: Increased lipid peroxidation was associated with MDD and may be normalized by antidepressants. Continued investigation of lipid peroxidation in MDD is warranted. [ABSTRACT FROM AUTHOR]
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- 2015
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13. Current and Emerging Drug Treatment Options for Alzheimer's Disease: A Systematic Review.
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Herrmann, Nathan, Chau, Sarah A., Kircanski, Ida, and Lanctôt, Krista L.
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ALKALOIDS ,ALZHEIMER'S disease ,AMANTADINE ,CHOLINESTERASE inhibitors ,MEDICAL databases ,INFORMATION storage & retrieval systems ,MEDICAL information storage & retrieval systems ,PSYCHOLOGY information storage & retrieval systems ,MEDLINE ,META-analysis ,ONLINE information services ,PROTEINS ,RESEARCH funding ,DONEPEZIL ,PHARMACODYNAMICS - Abstract
Alzheimer's disease (AD) is a progressive and ultimately fatal condition that causes debilitating memory loss and extensive deterioration of cognitive and functional abilities. Currently available treatments for AD (donepezil, rivastigmine, galantamine and memantine) are symptomatic and do not decelerate or prevent the progression of the disease. These therapies demonstrate modest, but particularly consistent, benefit for cognition, global status and functional ability. The search for disease-modifying interventions has focused largely on compounds targeting the amyloid-β pathway. To date, the treatments targeting this pathway, such as tramiprosate and semagacestat, have been unsuccessful in demonstrating efficacy in clinical stages of testing. At this point, it is likely that not only amyloid-β aggregation but other possible neuronal mechanisms--such as hyperphosphorylated tau, neuro- inflammation and other processes - play important roles in the pathophysiology of this multifactorial disorder. Development of better disease models and biomarkers is essential for the advancement of knowledge of the disease mechanisms. This systematic review critically examines the efficacy and safety data for currently approved drugs and emerging treatments in AD, as well as discussing the present and future directions of innovation in this field. [ABSTRACT FROM AUTHOR]
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- 2011
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14. Efficacy and Tolerability of Antidepressants for Treatment of Depression in Coronary Artery Disease: A Meta-Analysis.
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Dowlati, Yekta, Herrmann, Nathan, Swardfager, Walter L., Reim, Elyse K., and Lanctôt, Krista L.
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PHYSIOLOGICAL effects of antidepressants ,DRUG efficacy ,PHARMACODYNAMICS ,THERAPEUTICS ,MENTAL depression ,CORONARY heart disease treatment ,META-analysis - Abstract
Copyright of Canadian Journal of Psychiatry is the property of Sage Publications Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2010
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15. Review: Therapy for Alzheimer's disease: how effective are current treatments?
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Lanctôt, Krista L., Rajaram, Ryan D., and Herrmann, Nathan
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Available symptomatic therapies for the treatment of Alzheimer's disease (AD) have been based on known neurotransmitter dysfunctions associated with the illness. The second-generation cholinesterase inhibitors and the N-methyl D-aspartate receptor antagonist memantine have been widely prescribed and studied. Meta-analyses of these therapies were reviewed, focusing on effectiveness and tolerability. Although many of the meta-analyses demonstrate statistically significant improvements, some question if these benefits are sufficient to justify their current widespread and protracted use. This has spurred the development of new disease-modifying therapies that aim to have a greater impact on this debilitating illness. [ABSTRACT FROM PUBLISHER]
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- 2009
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16. Systematic review of the body of evidence for the use of biomarkers in the diagnosis of dementia.
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Noel-Storr, Anna H., Flicker, Leon, Ritchie, Craig W., Nguyen, Giang Huong, Gupta, Tarun, Wood, Phillip, Walton, Josephine, Desai, Meera, Solomon, Danielle Fraser, Molena, Emma, Worrall, Rosemary, Hayen, Anja, Choudhary, Prateek, Ladds, Emma, Lanctôt, Krista L., Verhey, Frans R., McCleery, Jenny M., Mead, Gillian E., Clare, Linda, and Fioravanti, Mario
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DIAGNOSIS of dementia ,ALZHEIMER'S disease diagnosis ,BIOMARKERS ,POSITRON emission tomography ,MAGNETIC resonance imaging ,META-analysis - Abstract
Abstract: Background: Although recent diagnostic criteria for Alzheimer''s disease propose the use of biomarkers, validation of these biomarkers by diagnostic test accuracy studies is a necessary first step, followed by the synthesis of the evidence from these studies in systematic reviews and meta-analyses. The quality of the resulting evidence depends on the number and size of the primary studies, their quality, and the adequacy of their reporting. This systematic review assesses the weight and quality of the evidence available from primary diagnostic test accuracy studies. Methods: A MEDLINE search was performed in August 2011 to identify all potentially relevant publications relating to the biomarkers β-amyloid, tau, positron emission tomography (
18 F-fluorodeoxyglucose or ligands for amyloid), or magnetic resonance imaging (MRI). The reporting and methodology were assessed using the Standards for Reporting of Diagnostic Accuracy and Quality Assessment of Diagnostic Accuracy Studies assessment tools, respectively. Because clinical progression to dementia is the most commonly used reference standard, this review focuses on participants with objective cognitive impairment but no dementia at baseline. Results: Of the 19,104 published references identified by the search, 142 longitudinal studies relating to the biomarkers of interest were identified, which included subjects who had objective cognitive impairment but no dementia at baseline. The highest number of studies (n = 70) and of participants (n = 4722) related to structural MRI. MRI also yielded the highest number of studies with extractable data for meta-analysis (n = 32 [46% of all structural MRI studies]), followed by cerebrospinal fluid tau (n = 24 [73%]). There were few studies on positron emission tomography ligands for amyloid having suitable data for meta-analysis (n = 4). There was considerable variation across studies in reporting outcomes, methods of blinding and selection, means of accounting for indeterminate or missing values, the interval between the test and assessments, and the determination of test thresholds. Conclusions: The body of evidence for biomarkers is not large and is variable across the different types of biomarkers. Important information is missing from many study reports, highlighting the need for standardization of methodology and reporting to improve the rigor of biomarker validation. [Copyright &y& Elsevier]- Published
- 2013
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17. The association between placebo arm inclusion and adverse event rates in antidepressant randomized controlled trials: An examination of the Nocebo Effect.
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Cheung, Christian P., Thiyagarajah, Mathura T., Abraha, Haben Y., Liu, Celina S., Lanctôt, Krista L., Kiss, Alex J., Saleem, Mahwesh, Juda, Ari, Levitt, Anthony J., Schaffer, Ayal, Cheung, Amy H., and Sinyor, Mark
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PLACEBOS , *EXPERIMENTAL design , *ANTIDEPRESSANTS , *RANDOMIZED controlled trials , *META-analysis , *SYSTEMATIC reviews , *ARM , *MENTAL depression - Abstract
Background: 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.Methods: 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.Results: 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.Limitations: 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.Conclusions: 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. [ABSTRACT FROM AUTHOR]- Published
- 2021
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18. Antidepressant-placebo differences for specific adverse events in major depressive disorder: A systematic review.
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Sinyor, Mark, Cheung, Christian P., Abraha, Haben Y., Lanctôt, Krista L., Saleem, Mahwesh, Liu, Celina S., Li, Abby, Juda, Ari, Levitt, Anthony J., Cheung, Amy H., and Schaffer, Ayal
- Subjects
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MENTAL depression , *META-analysis , *ADVERSE health care events , *PATIENT decision making , *POISSON regression , *ANTIDEPRESSANTS , *RESEARCH , *SEROTONIN uptake inhibitors , *RESEARCH methodology , *SYSTEMATIC reviews , *EVALUATION research , *MEDICAL cooperation , *PLACEBOS , *COMPARATIVE studies , *RESEARCH funding - Abstract
Background: Adverse events (AEs) are known to occur while patients are treated with placebos, part of the so-called nocebo effect. Yet evidence is limited regarding the likelihood that specific AEs occurring with antidepressant treatment are or are not due to nocebo effects.Methods: This study identified 56 placebo-controlled, randomized controlled trials (RCTs) of antidepressant monotherapy for adults with major depressive disorder that reported AE rates in sufficient detail for comparison. Poisson regression analyses compared rates of AEs according to antidepressant class weighted by study population to determine which separated from placebo. A "nocebo index" was also calculated (with 0 defined as the lowest rate and 1 or higher indicating the same or greater rate of an AE in the placebo group).Results: Numerous AEs did not differ statistically between antidepressant classes and placebo including worsening psychiatric symptoms, all forms of pain, weight gain and respiratory symptoms. Nevertheless, a number of AEs were significantly more common in antidepressants than placebos across multiple antidepressant classes. These were predominantly neurological, sexual and anticholinergic effects. Several AEs that separated statistically between antidepressants and placebos nevertheless had moderate nocebo indices (≥0.5). For example, dizziness in SSRIs separated significantly from placebo (OR 1.50, 95%CI 1.13-1.99) but had a nocebo index of 0.67.Limitations: This study relied on multiple RCTs with subtle design differences.Conclusions: This study identified several AEs that are likely the physiological result of antidepressants and many that likely represent nocebo effects. These results should inform clinical decision making and discussions with patients. [ABSTRACT FROM AUTHOR]- Published
- 2020
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19. The effect of exercise on resting concentrations of peripheral brain-derived neurotrophic factor (BDNF) in major depressive disorder: A meta-analysis.
- Author
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Dinoff, Adam, Herrmann, Nathan, Swardfager, Walter, Gallagher, Damien, and Lanctôt, Krista L.
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QUALITY of life , *MENTAL depression , *BRAIN-derived neurotrophic factor , *ANTIDEPRESSANTS , *AEROBIC exercises - Abstract
Abstract 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. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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20. Global grey matter volume in adult bipolar patients with and without lithium treatment: A meta-analysis.
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Sun, Yue Ran, Herrmann, Nathan, Scott, Christopher J.m., Black, Sandra E., Khan, Maisha M., and Lanctôt, Krista L.
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GRAY matter (Nerve tissue) , *BIPOLAR disorder in adolescence , *THERAPEUTIC use of lithium , *BRAIN physiology , *MENTAL illness treatment , *PHYSIOLOGY , *PATIENTS , *THERAPEUTICS , *ANTHROPOMETRY , *FRONTAL lobe , *MAGNETIC resonance imaging , *BIPOLAR disorder , *META-analysis , *SYSTEMATIC reviews - Abstract
Objective: The goal of this meta-analysis was to quantitatively summarize the evidence available on the differences in grey matter volume between lithium-treated and lithium-free bipolar patients.Methods: A systematic search was conducted in Cochrane Central, Embase, MEDLINE, and PsycINFO databases for original peer-reviewed journal articles that reported on global grey matter volume in lithium-medicated and lithium-free bipolar patients. Standard mean difference and Hedges' g were used to calculate effect size in a random-effects model. Risk of publication bias was assessed using Egger's test and quality of evidence was assessed using standard criteria.Results: There were 15 studies with a total of 854 patients (368 lithium-medicated, 486 lithium-free) included in the meta-analysis. Global grey matter volume was significantly larger in lithium-treated bipolar patients compared to lithium-free patients (SMD: 0.17, 95% CI: 0.01-0.33; z = 2.11, p = 0.035). Additionally, there was a difference in global grey matter volume between groups in studies that employed semi-automated segmentation methods (SMD: 0.66, 95% CI: 0.01-1.31; z = 1.99, p = 0.047), but no significant difference in studies that used fully-automated segmentation. No publication bias was detected (bias coefficient = - 0.65, p = 0.46).Limitations: Variability in imaging methods and lack of high-quality evidence limits the interpretation of the findings.Conclusions: Results suggest that lithium-treated patients have a greater global grey matter volume than those who were lithium-free. Further study of the relationship between lithium and grey matter volume may elucidate the therapeutic potential of lithium in conditions characterized by abnormal changes in brain structure. [ABSTRACT FROM AUTHOR]- Published
- 2018
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21. Zinc in Depression: A Meta-Analysis.
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Swardfager, Walter, Herrmann, Nathan, Mazereeuw, Graham, Goldberger, Kyle, Harimoto, Tetsuhiro, and Lanctôt, Krista L.
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THERAPEUTICS , *MENTAL depression , *THERAPEUTIC use of zinc , *MICRONUTRIENTS , *PATHOLOGICAL physiology , *ZINC supplements , *CELL growth , *CELL metabolism , *APOPTOSIS , *META-analysis - Abstract
Background: Zinc is an essential micronutrient with diverse biological roles in cell growth, apoptosis and metabolism, and in the regulation of endocrine, immune, and neuronal functions implicated in the pathophysiology of depression. This study sought to quantitatively summarize the clinical data comparing peripheral blood zinc concentrations between depressed and nondepressed subjects. Methods: PubMed, Cumulated Index to Nursing and Allied Health Literature, and PsycINFO were searched for original peer-reviewed studies (to June 2012) measuring zinc concentrations in serum or plasma from depressed subjects (identified by either screening or clinical criteria) and nondepressed control subjects. Mean (±SD) zinc concentrations were extracted, combined quantitatively in random-effects meta-analysis, and summarized as a weighted mean difference (WMD). Results: Seventeen studies, measuring peripheral blood zinc concentrations in 1643 depressed and 804 control subjects, were included. Zinc concentrations were approximately −1.85 µmol/L lower in depressed subjects than control subjects (95% confidence interval: [CI]: −2.51 to −1.19 µmol/L, Z 17 = 5.45, p < .00001). Heterogeneity was detected (χ2 17 = 142.81, p < .00001, I2 = 88%) and explored; in studies that quantified depressive symptoms, greater depression severity was associated with greater relative zinc deficiency (B = −1.503, t 9 = −2.82, p = .026). Effect sizes were numerically larger in studies of inpatients (WMD −2.543, 95% CI: −3.522 to −1.564, Z 9 = 5.09, p < .0001) versus community samples (WMD −.943, 95% CI: −1.563 to −.323, Z 7 = 2.98, p = .003) and in studies of higher methodological quality (WMD −2.354, 95% CI: −2.901 to −1.807, Z 7 = 8.43, p < .0001). Conclusions: Depression is associated with a lower concentration of zinc in peripheral blood. The pathophysiological relationships between zinc status and depression, and the potential benefits of zinc supplementation in depressed patients, warrant further investigation. [ABSTRACT FROM AUTHOR]
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- 2013
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22. Efficacy of non-invasive brain stimulation on global cognition and neuropsychiatric symptoms in Alzheimer's disease and mild cognitive impairment: A meta-analysis and systematic review.
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Teselink, Johannes, Bawa, Kritleen K., Koo, Grace KY, Sankhe, Krushnaa, Liu, Celina S., Rapoport, Mark, Oh, Paul, Marzolini, Susan, Gallagher, Damien, Swardfager, Walter, Herrmann, Nathan, and Lanctôt, Krista L.
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BRAIN stimulation , *TRANSCRANIAL direct current stimulation , *MILD cognitive impairment , *COGNITION , *ALZHEIMER'S disease , *TRANSCRANIAL magnetic stimulation , *META-analysis - Abstract
Non-invasive brain stimulation (NIBS) techniques have shown some promise in improving cognitive and neuropsychiatric symptoms (NPS) in people with Alzheimer's disease (AD) and its prodromal stage, mild cognitive impairment (MCI). However, data from clinical trials involving NIBS have shown inconsistent results. This meta-analysis investigated the efficacy of NIBS, specifically repetitive transcranial magnetic stimulation (rTMS), and transcranial direct current stimulation (tDCS) compared to sham stimulation on global cognition and NPS in people with AD and MCI. Multi-session randomized sham-controlled clinical trials were identified through MEDLINE, PsycINFO, and Embase until June 2021. Standardized mean difference (SMD) and 95% confidence interval (CI) between the active and sham treatments were calculated using random-effects meta-analyses. Included studies reported outcome measures for global cognition and/or NPS. Heterogeneity, from different NIBS techniques, disease populations, or tests used to assess global cognition or NPS, was measured using chi-square and I2, and investigated using subgroup analyses. Possible effects of covariates were also investigated using meta-regressions. The pooled meta-analyses included 19 studies measuring global cognition (N active =288, N sham =264), and 9 studies investigating NPS (N active =165, N sham =140). NIBS significantly improved global cognition (SMD=1.14; 95% CI=0.49,1.78; p = 0.001; I2 = 90.2%) and NPS (SMD=0.82; 95% CI=0.13, 1.50; p = 0.019; I2 = 86.1%) relative to sham stimulation in patients with AD and MCI. Subgroup analyses found these effects were restricted to rTMS but not tDCS, and to patients with AD but not MCI. Meta-regression showed that age was significantly associated with global cognition response (N studies =16, p = 0.020, I2 = 89.51%, R2 = 28.96%), with larger effects sizes in younger populations. All significant meta-analyses had large effect sizes (SMD ≥0.8), suggesting clinical utility of NIBS in the short term. There remained substantial heterogeneity across all subgroup analyses and meta-regressions (all I2 > 50%). Egger's tests showed no evidence of publication biases. rTMS improved global cognition and NPS in those with AD. Further studies in MCI and using tDCS will help to fully evaluate the specific NIBS techniques and populations most likely to benefit on global cognition and NPS measures. Additional research should investigate the long term clinical utility of NIBS in these populations. • Non-invasive brain stimulation (NIBS) is a potential therapy for Alzheimer's disease (AD) and mild cognitive impairment (MCI). • This meta-analysis showed that NIBS significantly improved global cognition and neuropsychiatric symptoms (NPS) in AD and MCI. • Repetitive Transcranial Magnetic Stimulation (rTMS) significantly improved global cognition and NPS in AD. • More research is needed in MCI population and using transcranial direct current stimulation to clarify the efficacy of NIBS. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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23. Depression in type 2 diabetes: A systematic review and meta-analysis of blood inflammatory markers.
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Nguyen, Michelle M., Perlman, George, Kim, Nakyung, Wu, Che-Yuan, Daher, Valerie, Zhou, Angela, Mathers, Emily H., Anita, Natasha Z., Lanctôt, Krista L., Herrmann, Nathan, Pakosh, Maureen, and Swardfager, Walter
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BRAIN-derived neurotrophic factor , *TYPE 2 diabetes , *MENTAL depression , *C-reactive protein - Abstract
The prevalence of depression is higher among people with type 2 diabetes (T2DM). Individually, both conditions are associated with systemic inflammation. This study aimed to summarize the clinical data comparing peripheral inflammatory markers in blood between people with T2DM, with and without comorbid depression. From 2187 records, we identified 20 original peer-reviewed articles from which blood inflammatory marker concentrations could be combined and compared between people with T2DM and comorbid depression (D) vs. no depression (ND) as standardized mean differences (SMD) in random effects meta-analysis. Concentrations of C-reactive protein (CRP; N D /N ND = 1742/15244, SMD = 0.31 95% confidence interval [0.16, 0.45], Z 16 = 4.03, p < 0.01; I2 = 84.0%) and interleukin-6 (IL-6; N D /N ND = 677/4349, SMD = 0.17 [0.04, 0.30], Z 4 = 2.58, p = 0.01; I2 = 48.1%), were higher, and concentrations of brain derived neurotrophic factor (BDNF; N D /N ND = 358/1512, SMD = −0.37 95% confidence interval [−0.64,−0.10], Z 2 = −2.68, p = 0.01; I2 = 61.2%) were lower, among those with depression. Depression in T2DM was associated with systemic inflammation and lower peripheral blood BDNF concentrations. Inconsistency between studies suggests the need to explore further population heterogeneity and pathophysiological elements. PROSPERO (CRD42020188509). • Comorbid depression in type 2 diabetes (T2DM) presents a clinical challenge. • In T2DM, depression was associated with higher interleukin-6 and C-reactive protein. • Higher C-reactive protein may reveal links with vascular comorbidity burden. • Lower brain-derived neurotrophic factor was found in depression in T2DM. [ABSTRACT FROM AUTHOR]
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- 2021
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24. A Meta-Analysis of Cytokines in Major Depression
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Dowlati, Yekta, Herrmann, Nathan, Swardfager, Walter, Liu, Helena, Sham, Lauren, Reim, Elyse K., and Lanctôt, Krista L.
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CYTOKINES , *META-analysis , *IMMUNOREGULATION , *TUMOR necrosis factors , *INFLAMMATION , *INTERLEUKINS - Abstract
Background: Major depression occurs in 4.4% to 20% of the general population. Studies suggest that major depression is accompanied by immune dysregulation and activation of the inflammatory response system (IRS). Our objective was to quantitatively summarize the data on concentrations of specific cytokines in patients diagnosed with a major depressive episode and controls. Methods: We performed a meta-analysis of studies measuring cytokine concentration in patients with major depression, with a database search of the English literature (to August 2009) and a manual search of references. Results: Twenty-four studies involving unstimulated measurements of cytokines in patients meeting DSM criteria for major depression were included in the meta-analysis; 13 for tumor necrosis factor (TNF)-α, 9 for interleukin (IL)-1β, 16 for IL-6, 5 for IL-4, 5 for IL-2, 4 for IL-8, 6 for IL-10, and 4 for interferon (IFN)-γ. There were significantly higher concentrations of TNF-α (p < .00001), weighted mean difference (WMD) (95% confidence interval) 3.97 pg/mL (2.24 to 5.71), in depressed subjects compared with control subjects (438 depressed/350 nondepressed). Also, IL-6 concentrations were significantly higher (p < .00001) in depressed subjects compared with control subjects (492 depressed/400 nondepressed) with an overall WMD of 1.78 pg/mL (1.23 to 2.33). There were no significant differences among depressed and nondepressed subjects for the other cytokines studied. Conclusions: This meta-analysis reports significantly higher concentrations of the proinflammatory cytokines TNF-α and IL-6 in depressed subjects compared with control subjects. While both positive and negative results have been reported in individual studies, this meta-analytic result strengthens evidence that depression is accompanied by activation of the IRS. [Copyright &y& Elsevier]
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- 2010
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25. Neutrophil activation in Alzheimer's disease and mild cognitive impairment: A systematic review and meta-analysis of protein markers in blood and cerebrospinal fluid.
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Wu, Che-Yuan, Bawa, Kritleen K., Ouk, Michael, Leung, Nathan, Yu, Di, Lanctôt, Krista L., Herrmann, Nathan, Pakosh, Maureen, and Swardfager, Walter
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MILD cognitive impairment , *CEREBROSPINAL fluid examination , *ALZHEIMER'S disease , *CEREBROSPINAL fluid , *BLOOD proteins , *META-analysis , *COGNITION disorders - Abstract
• Peripheral neutrophil activation is indicated in Alzheimer's disease (AD). • Peripheral blood MPO and NGAL best indicated neutrophil related changes in AD. • Blood concentrations of NGAL were also elevated in mild cognitive impairment. • Stable CSF differences in neutrophil markers between AD and controls were not seen. Inflammation is involved in the pathophysiology of Alzheimer's disease (AD), with multiple inflammatory processes implicated in its risk and progression. This review included original peer-reviewed studies measuring the cerebrospinal fluid or peripheral blood concentrations of protein markers specifically related to neutrophil activity in healthy controls (HC) and in patients with AD or mild cognitive impairment (MCI). A total of 35 studies (N HC = 3095, N AD = 2596, N MCI = 1203) were included. Random-effects meta-analyses were used to estimate between-groups standardized mean differences (SMD) and 95 % confidence intervals. In blood, concentrations of myeloperoxidase (MPO; N AD /N HC = 271/209, SMD = 0.41 [0.20, 0.62]; I2 = 15.7 %) and neutrophil gelatinase associated lipocalin (NGAL; N AD /N HC = 273/185, SMD = 0.30 [0.11, 0.49]; I2 < 0.005 %) were significantly higher in AD relative to HC. Peripheral blood concentrations of NGAL were also higher in MCI compared to HC (N MCI /N HC = 489/145, SMD = 0.39 [0.11, 0.67]; I2 = 38.6 %). None of the protein markers exhibited a significant difference between HC, MCI, or AD groups in the cerebrospinal fluid. The evidence suggests that peripheral neutrophil activation, as indicated by blood concentrations of NGAL and MPO, may be a pathological feature of cognitive impairment due to AD, evident at stages of MCI and AD dementia. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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