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Genetic neuroimaging of bipolar disorder: a systematic 2017-2020 update.
Janiri, D, Kotzalidis, GD, di Luzio, M, Giuseppin, G, Simonetti, A, Janiri, L, Sani, G
Psychiatric genetics. 2021;(2):50-64
Abstract
There is evidence of genetic polymorphism influences on brain structure and function, genetic risk in bipolar disorder (BD), and neuroimaging correlates of BD. How genetic influences related to BD could be reflected on brain changes in BD has been efficiently reviewed in a 2017 systematic review. We aimed to confirm and extend these findings through a Preferred Reporting Items for Systematic reviews and Meta-Analyses-based systematic review. Our study allowed us to conclude that there is no replicated finding in the timeframe considered. We were also unable to further confirm prior results of the BDNF gene polymorphisms to affect brain structure and function in BD. The most consistent finding is an influence of the CACNA1C rs1006737 polymorphism in brain connectivity and grey matter structure and function. There was a tendency of undersized studies to obtain positive results and large, genome-wide polygenic risk studies to find negative results in BD. The neuroimaging genetics in BD field is rapidly expanding.
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The potential role of nutritional components in improving brain function among patients with Alzheimers disease: a meta-analysis of RCT studies.
Albrahim, T
Neurosciences (Riyadh, Saudi Arabia). 2020;(1):4-17
Abstract
OBJECTIVE To find out the potential role of nutritional components in improving brain function among patients with Alzheimer`s disease (AD). METHODS The correlation between nutrition and cerebral function in cases of AD has been the focus of 19 prospective randomised controlled trials (RCTs) with a combined research sample of 2297 patients. These RCTs are subject to systematic review and meta-analysis in the current paper RESULTS Findings showed that chain-free secondary saturated fatty acids (SFA) and trans fatty acids (TFA) occurred in higher concentrations in AD patients` brains than in controls. Furthermore, neuroinflammation was caused by remodelling of the lipid membrane and AD patients` cognitive function was impacted by alterations in tyrosine, tryptophan, purine, and tocopherol pathway metabolomics. Moreover, in cases of mild-to-moderate AD, reduction in functionality was induced by administration of alpha-tocopherol for more than 12 months. Consumption of Souvenaid helps in synaptic synthesis, which enhances functional connectivity. Furthermore, consumption of the B vitamins folate, cobalamin and pyridoxine at dosages of 0.8 mg, 0.5 mg and 20 mg per day, respectively, over a period of one year resulted in lower plasma tHcy levels and brain atrophy. CONCLUSION Chain-free SFA and TFA occur in greater amounts in the brains of individuals with AD than in those without AD.
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A resting state fMRI analysis pipeline for pooling inference across diverse cohorts: an ENIGMA rs-fMRI protocol.
Adhikari, BM, Jahanshad, N, Shukla, D, Turner, J, Grotegerd, D, Dannlowski, U, Kugel, H, Engelen, J, Dietsche, B, Krug, A, et al
Brain imaging and behavior. 2019;(5):1453-1467
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Abstract
Large-scale consortium efforts such as Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) and other collaborative efforts show that combining statistical data from multiple independent studies can boost statistical power and achieve more accurate estimates of effect sizes, contributing to more reliable and reproducible research. A meta- analysis would pool effects from studies conducted in a similar manner, yet to date, no such harmonized protocol exists for resting state fMRI (rsfMRI) data. Here, we propose an initial pipeline for multi-site rsfMRI analysis to allow research groups around the world to analyze scans in a harmonized way, and to perform coordinated statistical tests. The challenge lies in the fact that resting state fMRI measurements collected by researchers over the last decade vary widely, with variable quality and differing spatial or temporal signal-to-noise ratio (tSNR). An effective harmonization must provide optimal measures for all quality data. Here we used rsfMRI data from twenty-two independent studies with approximately fifty corresponding T1-weighted and rsfMRI datasets each, to (A) review and aggregate the state of existing rsfMRI data, (B) demonstrate utility of principal component analysis (PCA)-based denoising and (C) develop a deformable ENIGMA EPI template based on the representative anatomy that incorporates spatial distortion patterns from various protocols and populations.
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Sex differences in brain responses to food stimuli: a meta-analysis on neuroimaging studies.
Yeung, AWK
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2018;(8):1110-1115
Abstract
The aims of the current study were to update the inclusion list of relevant neuroimaging studies, meta-analyse the neuroimaging data and thus synthesize a brain map showing locations with differential activations between men and women. Published studies to 2017 were retrieved and included into the analysis if they evaluated patients' brain responses to food or eating stimuli with functional magnetic resonance imaging or positron emission tomography and reported activation differences between the sexes in the form of brain coordinates based on whole-brain analysis. Eight studies that comprised a total of 231 participants fulfilled the inclusion criteria. Men had larger neural responses to food stimuli than women in the anterior and middle cingulate, which are related to emotion regulation. Meanwhile, women had larger neural responses to food stimuli than men in the parahippocampus, the thalamus and the precuneus, which are collectively relevant in the context of promotion of eating. The differential brain responses to food or eating stimuli between men and women may shed light on the neurobiology to help explain the sex differences in eating behaviour.
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Meta-analysis of synaptic pathology in Alzheimer's disease reveals selective molecular vesicular machinery vulnerability.
de Wilde, MC, Overk, CR, Sijben, JW, Masliah, E
Alzheimer's & dementia : the journal of the Alzheimer's Association. 2016;(6):633-44
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Abstract
INTRODUCTION Loss of synapses best correlates to cognitive deficits in Alzheimer's disease (AD) in which oligomeric neurotoxic species of amyloid-β appears to contribute synaptic pathology. Although a number of clinical pathologic studies have been performed with limited sample size, there are no systematic studies encompassing large samples. Therefore, we performed a meta-analysis study. METHODS We identified 417 publications reporting postmortem synapse and synaptic marker loss from AD patients. Two meta-analyses were performed using a single database of subselected publications and calculating the standard mean differences. RESULTS Meta-analysis confirmed synaptic loss in selected brain regions is an early event in AD pathogenesis. The second meta-analysis of 57 synaptic markers revealed that presynaptic makers were affected more than postsynaptic markers. DISCUSSION The present meta-analysis study showed a consistent synaptic loss across brain regions and that molecular machinery including endosomal pathways, vesicular assembly mechanisms, glutamate receptors, and axonal transport are often affected.
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Changes in cerebral metabolites in obstructive sleep apnea: a systemic review and meta-analysis.
Xia, Y, Fu, Y, Xu, H, Guan, J, Yi, H, Yin, S
Scientific reports. 2016;:28712
Abstract
Cognitive impairment is associated with changes in cerebral metabolites in patients with obstructive sleep apnea (OSA). Several studies have used magnetic resonance spectroscopy (MRS) to detect variations in cerebral metabolites; however, the results have been inconsistent. This meta-analysis summarizes the differences in cerebral metabolites between patients with OSA and controls. Two electronic databases, PubMed and Embase, were searched for articles (published before March 31, 2016) describing studies that used MRS to evaluate the cerebral metabolite changes. The overall effects were measured using the weighted mean difference with a 95% confidence interval. Subgroup analysis and sensitivity analysis were used to explore the sources of between-study heterogeneity and the stability of the results. Publication bias was also evaluated. Thirteen studies were ultimately included. In the hippocampus, the N-acetylaspartate (NAA)/creatine ratio was lower in patients with OSA. In the frontal lobe, only the NAA/choline ratio was lower in patients with OSA. Cerebral metabolites are significantly altered in the hippocampus in patients with OSA. Further clinical studies are needed to explore the underlying mechanisms between OSA and the changes in cerebral metabolites in the brain.
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Integrated genomic approaches identify major pathways and upstream regulators in late onset Alzheimer's disease.
Li, X, Long, J, He, T, Belshaw, R, Scott, J
Scientific reports. 2015;:12393
Abstract
Previous studies have evaluated gene expression in Alzheimer's disease (AD) brains to identify mechanistic processes, but have been limited by the size of the datasets studied. Here we have implemented a novel meta-analysis approach to identify differentially expressed genes (DEGs) in published datasets comprising 450 late onset AD (LOAD) brains and 212 controls. We found 3124 DEGs, many of which were highly correlated with Braak stage and cerebral atrophy. Pathway Analysis revealed the most perturbed pathways to be (a) nitric oxide and reactive oxygen species in macrophages (NOROS), (b) NFkB and (c) mitochondrial dysfunction. NOROS was also up-regulated, and mitochondrial dysfunction down-regulated, in healthy ageing subjects. Upstream regulator analysis predicted the TLR4 ligands, STAT3 and NFKBIA, for activated pathways and RICTOR for mitochondrial genes. Protein-protein interaction network analysis emphasised the role of NFKB; identified a key interaction of CLU with complement; and linked TYROBP, TREM2 and DOK3 to modulation of LPS signalling through TLR4 and to phosphatidylinositol metabolism. We suggest that NEUROD6, ZCCHC17, PPEF1 and MANBAL are potentially implicated in LOAD, with predicted links to calcium signalling and protein mannosylation. Our study demonstrates a highly injurious combination of TLR4-mediated NFKB signalling, NOROS inflammatory pathway activation, and mitochondrial dysfunction in LOAD.
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Magnetic Resonance Spectroscopy in Alzheimer's Disease: Systematic Review and Meta-Analysis.
Wang, H, Tan, L, Wang, HF, Liu, Y, Yin, RH, Wang, WY, Chang, XL, Jiang, T, Yu, JT
Journal of Alzheimer's disease : JAD. 2015;(4):1049-70
Abstract
BACKGROUND The application of non-invasive proton magnetic resonance spectroscopy (1H-MRS) could potentially identify changes in cerebral metabolites in the patients with Alzheimer's disease (AD). However, whether these metabolites can serve as biomarkers for the diagnosis of AD remains unclear. OBJECTIVE Using meta-analysis, we aimed to investigate the patterns of cerebral metabolite changes in several cerebral regions that are strongly associated with cognitive decline in AD patients. METHODS Using Hedges' g effect size, a systematic search was performed in PubMed, Cochrane Library, Ovid, Embase, and EBSCO, and 38 studies were integrated into the final meta-analysis. RESULTS According to the observational studies, N-acetyl aspartate (NAA) in AD patients was significantly reduced in the posterior cingulate (PC) (effect size (ES) =-0.924, p < 0.005) and bilateral hippocampus (left hippocampus: ES =-1.329, p < 0.005; right hippocampus: ES =-1.287, p < 0.005). NAA/Cr (creatine) ratio decreased markedly in the PC (ES =-1.052, p < 0.005). Simultaneously, significant elevated myo-inositol (mI)/Cr ratio was found not only in the PC but also in the parietal gray matter. For lack of sufficient data, we failed to elucidate the efficacy of pharmacological interventions with the metabolites changes. CONCLUSION The available data indicates that NAA, mI, and the NAA/Cr ratio might be potential biomarkers of brain dysfunction in AD subjects. Choline (Cho)/Cr and mI/NAA changes might also contribute toward the diagnostic process. Thus, large, well-designed studies correlated with cerebral metabolism are needed to better estimate the cerebral extent of alterations in brain metabolite levels in AD patients.
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Perturbed iron distribution in Alzheimer's disease serum, cerebrospinal fluid, and selected brain regions: a systematic review and meta-analysis.
Tao, Y, Wang, Y, Rogers, JT, Wang, F
Journal of Alzheimer's disease : JAD. 2014;(2):679-90
Abstract
BACKGROUND The homeostasis and physiological role of iron in Alzheimer's disease (AD) has been debated for decades. Overall, it has been difficult to reach a consensus to prove marked disease-associated changes in the iron content of the AD brain, blood, or cerebrospinal fluid (CSF). OBJECTIVES We sought to contribute to resolve this issue by quantifying the iron content in serum, CSF, and sub-regions of the AD brain. METHODS We conducted a comprehensive systematic meta-analysis and review of multiple observational studies till October 2013 that investigated the iron content in AD serum, CSF, or brain tissue. RESULTS 2,556 publications were screened. Forty-three eligible studies with 1,813 AD patients and 2,401 healthy controls were identified. Twenty-one studies investigated the serum iron in AD while seven and nineteen studies investigated the CSF iron and various brain regions iron respectively. Our meta-analysis showed that serum iron was significant lower in AD than healthy controls. CSF iron appeared not to be affected by AD although more studies are required due to the relative small number of CSF studies reported to date. We critically analyzed iron content in twelve selective brain regions by separated meta-analyses using cross-referenced statistical methods. We found that eight specific brain regions had higher iron concentrations that correlated with the clinical diagnosis of AD in a statistically validated manner. CONCLUSIONS These data provided rigorous statistical support for the model that iron homeostasis was changed in AD patients, including the finding of lower iron in their serum and evidence for iron overload in several specific brain regions.
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Folic acid supplementation use and the MTHFR C677T polymorphism in orofacial clefts etiology: An individual participant data pooled-analysis.
Butali, A, Little, J, Chevrier, C, Cordier, S, Steegers-Theunissen, R, Jugessur, A, Oladugba, B, Mossey, PA
Birth defects research. Part A, Clinical and molecular teratology. 2013;(8):509-14
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Abstract
BACKGROUND This study examines gene-environment interaction between the MTHFR C667T polymorphism and folic acid in the etiology of orofacial clefts (OFC). We used a pooled-analytical approach on four studies that used similar methods. METHODS We used logistic regression to analyze the pooled sample of 1149 isolated cases and 1161 controls. Fetal and maternal MTHFR C677T genotypes, and maternal periconceptional exposure to smoking, alcohol, vitamin containing folic acid and folic acid supplements were contrasted between the cleft types [non-syndromic clefts lip or without cleft palate (CL(P)) and non-syndromic cleft palate (CP)] and control groups. RESULTS There was a reduced risk of CL(P) with maternal folic acid use (p = 0.008; OR = 0.70, 95% CI: 0.65-0.94) and with supplements containing folic acid (p = 0.028, OR = 0.80, 95% CI: 0.65-0.94). Maternal smoking increased the risk of both CL(P) (p < 10 e-3; OR = 1.62, 95% CI: 1.35-1.95) and CP (p = 0.028; OR = 1.38, 95% CI: 1.04-1.83). No significant risk was observed with either maternal or fetal MTHFR C677T genotypes. CONCLUSION This individual participant data (IPD) meta-analysis affords greater statistical power and can help alleviate the problems associated with aggregate-level data-sharing. The result of this IPD meta-analysis is consistent with previous reports suggesting that folic acid and smoking influence OFC outcomes.