Neuroimaging biomarkers and CSF sTREM2 levels in Alzheimer's disease: a longitudinal study.

Understanding the exact pathophysiological mechanisms underlying the involvement of triggering receptor expressed on myeloid cells 2 (TREM2) related microglia activation is crucial for the development of clinical trials targeting microglia activation at different stages of Alzheimer's disease (AD). Given the contradictory findings in the literature, it is imperative to investigate the longitudinal alterations in cerebrospinal fluid (CSF) soluble TREM2 (sTREM2) levels as a marker for microglia activation, and its potential association with AD biomarkers, in order to address the current knowledge gap. In this study, we aimed to assess the longitudinal changes in CSF sTREM2 levels within the framework of the A/T/N classification system for AD biomarkers and to explore potential associations with AD pathological features, including the presence of amyloid-beta (Aß) plaques and tau aggregates. The baseline and longitudinal (any available follow-up visit) CSF sTREM2 levels and processed tau-PET and Aß-PET data of 1001 subjects were recruited from the ADNI database. The participants were classified into four groups based on the A/T/N framework: A+ /TN+ , A+ /TN- , A- /TN+ , and A- /TN- . Linear regression analyses were conducted to assess the relationship between CSF sTREM2 with cognitive performance, tau and Aß-PET adjusting for age, gender, education, and APOE ε4 status. Based on our analysis there was a significant difference in baseline and rate of change of CSF sTREM2 between ATN groups. While there was no association between baseline CSF sTREM2 and cognitive performance (ADNI-mem), we found that the rate of change of CSF sTREM2 is significantly associated with cognitive performance in the entire cohort but not the ATN groups. We found that the baseline CSF sTREM2 is significantly associated with baseline tau-PET and Aß-PET rate of change only in the A+ /TN+ group. A significant association was found between the rate of change of CSF sTREM2 and the tau- and Aß-PET rate of change only in the A+ /TN- group. Our study suggests that the TREM2-related microglia activation and their relations with AD markers and cognitive performance vary the in presence or absence of Aß and tau pathology. Furthermore, our findings revealed that a faster increase in the level of CSF sTREM2 might attenuate future Aß plaque formation and tau aggregate accumulation only in the presence of Aß pathology.

Effects of antidepressants on brain structure and function in patients with obsessive-compulsive disorder: A review of neuroimaging studies.

Obsessive-compulsive disorder (OCD) affects 2-3% of people worldwide. Although antidepressants are the standard pharmachological treatment of OCD, their effect on the brain of individuals with OCD has not yet been fully clarified. We conducted a systematic search on PubMed, Scopus, Embase, and Web of Science to explore the effects of antidepressants on neuroimaging findings in OCD. Thirteen neuroimaging investigations were included. After antidepressant treatment, structural magnetic resonance imaging studies suggested thalamic, amygdala, and pituitary volume changes in patients. In addition, the use of antidepressants was associated with alterations in diffusion tensor imaging metrics in the left striatum, the right midbrain, and the posterior thalamic radiation in the right parietal lobe. Finally, functional magnetic resonance imaging highlighted possible changes in the ventral striatum, frontal, and prefrontal cortex. The small number of included studies and sample sizes, short durations of follow-up, different antidepressants, variable regions of interest, and heterogeneous samples limit the robustness of the findings of the present review. In conclusion, our review suggests that antidepressant treatment is associated with brain changes in individuals with OCD, and these results may help to deepen our knowledge of the pathophysiology of OCD and the brain mechanisms underlying the effects of antidepressants.

Perioperative esketamine administration for prevention of postpartum depression after the cesarean section: A systematic review and meta-analysis.

BACKGROUND: Postpartum Depression (PPD) exerts a substantial negative effect on maternal well-being post-delivery, particularly among Cesarean Section (C/S) recipients. In this study, we aimed to review the efficacy of perioperative esketamine, the S-enantiomer of ketamine, in preventing PPD incidence and depressive symptoms as measured with the Edinburgh Postnatal Depression Scale (EPDS) after C/S. METHODS: A systematic search for relevant articles was conducted in Scopus, PubMed, Web of Sciences, and PsycINFO until April 6, 2024. Meta-analyses were conducted using random-effect models to compare the PPD incidence and EPDS scores via log odds ratio and Hedge's g, respectively, during the first week post-C/S and at 42 days post-C/S in the esketamine and control group. RESULTS: Fourteen studies, including 12 randomized controlled trials and 2 retrospective cohorts, were reviewed. Our meta-analyses found lower PPD incidence during the first week (log odds ratio: -0.956 [95 % confidence interval: -1.420, -0.491]) and at day 42 post-C/S (log odds ratio: -0.989 [95 % confidence interval: -1.707, -0.272]) among patients administered esketamine compared to controls. Additionally, EPDS scores for the esketamine group were significantly lower than controls during the first week (Hedge's g: -0.682 [95 % confidence interval: -1.088, -0.276]) and at day 42 post-C/S (Hedge's g: -0.614 [95 % confidence interval: -1.098, -0.129]). LIMITATIONS: Presence of various concomitant medications and heterogeneous study designs. CONCLUSION: Our review highlights the potential impact of esketamine in PPD prevention, as well as in alleviating depressive symptoms post-C/S, regardless of PPD occurrence, therefore suggesting the benefits of adding esketamine to peri-C/S analgesic regimen.

Effects of routine repetitive transcranial magnetic stimulation on the sleep duration of patients with treatment-resistant depression: A prospective cohort study.

Aim: The aim of this study was to evaluate the short-term and long-term effects of routine repetitive transcranial magnetic stimulation (rTMS) on the sleep duration, depressive symptoms, and quality of life of patients with treatment-resistant depression (TRD). Methods: In this prospective cohort study, 25 participants with TRD were assessed using the Insomnia Severity Index (ISI) and four sleep duration components of the Pittsburgh Sleep Quality Index (PSQI). Depression severity was measured with Hamilton's Depression Rating Scale (HDRS) and Beck's Depression Inventory (BDI-II), and patient-perceived quality of life with the 36-Item Short-Form Survey (SF-36). All of these measures were evaluated at baseline (T0), and immediately (T1), 6 weeks (T2), and 12 weeks (T3) after the end of intervention. Results: At T1 endpoint, HDRS, BDI, SF-36, ISI, and three PSQI items (time to wake up, time taken to fall asleep, and Real Sleep Time) significantly improved, though these gains were reduced at follow-up endpoints (T2 and T3). Adjusting for confounders (age, sex, occupational status, BMI, and hypnotic medication) revealed that only improvements in HDRS, BDI, and time taken to fall asleep at T1 remained statistically significant. Linear regression analyses showed no significant association between reduced time taken to fall asleep and depression symptoms, suggesting rTMS can independently enhance this parameter, irrespective of depression resolution. Conclusion: Routine rTMS therapy can potentially enhance sleep duration in TRD individuals, alongside improved depressive symptoms and quality of life. However, these benefits tend to decrease over long-term follow-up, emphasizing a more pronounced short-term efficacy of rTMS.

Effect of spaceflight experience on human brain structure, microstructure, and function: systematic review of neuroimaging studies.

Spaceflight-induced brain changes have been commonly reported in astronauts. The role of microgravity in the alteration of the brain structure, microstructure, and function can be tested with magnetic resonance imaging (MRI) techniques. Here, we aim to provide a comprehensive overview of Spaceflight studies exploring the potential role of brain alterations identified by MRI in astronauts. We conducted a search on PubMed, Web of Science, and Scopus to find neuroimaging correlates of spaceflight experience using MRI. A total of 20 studies (structural MRI n = 8, diffusion-based MRI n = 2, functional MRI n = 1, structural MRI and diffusion-weighted MRI n = 6, structural MRI and functional MRI n = 3) met our inclusion criteria. Overall, the studies showed that regardless of the MRI techniques, mission duration significantly impacts the human brain, prompting the inclusion of various brain regions as features in the analyses. After spaceflight, notable alterations were also observed in the superior occipital gyrus and the precentral gyrus which show alterations in connectivity and activation during spaceflight. The results provided highlight the alterations in brain structure after spaceflight, the unique patterns of brain remodeling, the challenges in drawing unified conclusions, and the impact of microgravity on intracranial cerebrospinal fluid volume.

Global prevalence and incidence of Young Onset Parkinson's disease: A systematic review and meta-analysis.

BACKGROUND: There is a lack of enough evidence regarding the epidemiology of Young-onset Parkinson's disease (YOPD) which is needed by clinicians and healthcare policymakers. AIM: Herein, in this systematic review and meta-analysis, we aimed to estimate the global prevalence and incidence rates of YOPD. METHODS: We searched the literature in PubMed, Scopus, and Web of Science in May 2022. We included retrospective, prospective, cross-sectional observational population-based studies that reported the prevalence or incidence of PD in individuals younger than 40 years with known diagnostic criteria. RESULTS: After two-step screening, 50 studies were eligible to be included in our study. The age-standardized prevalence of YOPD was 10.2 per 100,000 persons globally while it was 14.7 per 100,000 population in European countries. Age-standardized prevalence estimates for 5-year age bands showed that the YOPD prevalence estimates varied from 6.1 per 100,000 population in the group aged 20-24 to 16.1 per 100,000 population in the group aged 35-39. Also, the age-standardized incidence of YOPD was 1.3 per 100,000 person-years population worldwide and 1.2 per 100,000 person-years in the European population. CONCLUSION: Based on this systematic review and meta-analysis, the overall prevalence of YOPD is 10.2 per 100,000 population, although estimates of the prevalence and incidence in low-income countries remain scarce. To improve monitoring and certain diagnoses of YOPD, healthcare providers and policymakers should be aware that much more effective tools are required.

Advanced nanoparticle strategies for optimizing RNA therapeutic delivery in neurodegenerative disorders.

Neurodegenerative diseases affect many people worldwide, and as the population ages, the incidence of these conditions increases. Alzheimer's disease (AD) and Parkinson's disease (PD) are the most prevalent neurodegenerative disorders worldwide. Different medicines are being used to control symptoms related to these conditions, but no treatment has yet been approved. Both genetic and environmental factors are involved in disease pathogenesis, and research on the pathophysiological pathways is still ongoing. The role of subcellular pathways and dysregulation in RNA pathways has been highlighted in pathophysiological studies, and treatment strategies focused on these pathways can be a promising approach. Many experiments have been conducted on delivering RNA cargo to the CNS to modulate various pathways involved. Yet another challenge to be faced is the effective transport of desired molecules to targets, which can be greatly hindered by distinct barriers limiting transport to the CNS, most noticeably the blood-brain barrier (BBB). Nanotechnology and the use of different nano-carriers for the delivery of nucleotides, peptides, proteins, and drug molecules are currently of great interest as these carriers help with better delivery and protection and, as a result, improve the effectiveness of the cargo. Nanocarriers can protect susceptible RNA molecules from possible degradation or destruction and improve their ability to reach the brain by enhancing BBB penetration. Different mechanisms for this process have been hypothesized. This review will go through the therapeutic application of RNA molecules in the treatment of AD and PD and the role of nanocarriers in overcoming delivery challenges and enhancing efficacy.

Machine Learning for prediction of violent behaviors in schizophrenia spectrum disorders: a systematic review.

Background: Schizophrenia spectrum disorders (SSD) can be associated with an increased risk of violent behavior (VB), which can harm patients, others, and properties. Prediction of VB could help reduce the SSD burden on patients and healthcare systems. Some recent studies have used machine learning (ML) algorithms to identify SSD patients at risk of VB. In this article, we aimed to review studies that used ML to predict VB in SSD patients and discuss the most successful ML methods and predictors of VB. Methods: We performed a systematic search in PubMed, Web of Sciences, Embase, and PsycINFO on September 30, 2023, to identify studies on the application of ML in predicting VB in SSD patients. Results: We included 18 studies with data from 11,733 patients diagnosed with SSD. Different ML models demonstrated mixed performance with an area under the receiver operating characteristic curve of 0.56-0.95 and an accuracy of 50.27-90.67% in predicting violence among SSD patients. Our comparative analysis demonstrated a superior performance for the gradient boosting model, compared to other ML models in predicting VB among SSD patients. Various sociodemographic, clinical, metabolic, and neuroimaging features were associated with VB, with age and olanzapine equivalent dose at the time of discharge being the most frequently identified factors. Conclusion: ML models demonstrated varied VB prediction performance in SSD patients, with gradient boosting outperforming. Further research is warranted for clinical applications of ML methods in this field.

Growth-Associated Protein 43 and Tensor-Based Morphometry Indices in Mild Cognitive Impairment.

Growth-associated protein 43 (GAP-43) is found in the axonal terminal of neurons in the limbic system, which is affected in people with Alzheimer's disease (AD). We assumed GAP-43 may contribute to AD progression and serve as a biomarker. So, in a two-year follow-up study, we assessed GAP-43 changes and whether they are correlated with tensor-based morphometry (TBM) findings in patients with mild cognitive impairment (MCI). We included MCI and cognitively normal (CN) people with available baseline and follow-up cerebrospinal fluid (CSF) GAP-43 and TBM findings from the ADNI database. We assessed the difference between the two groups and correlations in each group at each time point. CSF GAP-43 and TBM measures were similar in the two study groups in all time points, except for the accelerated anatomical region of interest (ROI) of CN subjects that were significantly greater than those of MCI. The only significant correlations with GAP-43 observed were those inverse correlations with accelerated and non-accelerated anatomical ROI in MCI subjects at baseline. Plus, all TBM metrics decreased significantly in all study groups during the follow-up in contrast to CSF GAP-43 levels. Our study revealed significant associations between CSF GAP-43 levels and TBM indices among people of the AD spectrum.

Risk of MS relapse and deterioration after COVID-19: A systematic review and meta-analysis.

BACKGROUND: Upper respiratory viral infections have long been considered triggers for multiple sclerosis (MS) relapse and exacerbation. The possible effects of SARS-CoV-2 infection on MS relapse and deterioration remain controversial. METHODS: We systematically searched PubMed, Scopus, Embase, Cochrane, and Web of Science databases to find relevant studies assessing changes in relapse rates or Expanded Disability Status Scale (EDSS) following COVID-19 in people with MS. Meta-analyses were performed, and to investigate sources of heterogeneity, subgroup analysis, meta-regression, and sensitivity analysis were conducted. RESULTS: We included 14 studies in our systematic review and meta-analysis. The meta-analysis demonstrated that COVID-19 was not associated with a rise in relapse rate (risk ratio (RR): 0.97, 95 % confidence interval (CI): 0.67, 1.41, p-value: 0.87) or a rise in EDSS (standardized mean difference (SMD): -0.09, 95 % CI: -0.22, 0.03, p-value: 0.13). The analysis of EDSS changes indicated a significant heterogeneity (I2: 55 %, p-value: 0.01). Other analyses were not statistically significant. CONCLUSIONS: COVID-19 infection was not associated with an increased risk of relapse and clinical deterioration in people with MS.

Microstructural white matter alterations associated with social anxiety disorders: A systematic review.

BACKGROUND: Social anxiety disorder (SAD) is a psychiatric condition characterized by impaired social functioning that negatively impacts individuals' quality of life. Previous neuroimaging studies have revealed morphological and functional changes in various brain regions associated with SAD. Recent advances in diffusion tensor imaging (DTI) and diffusion-weighted imaging (DWI) have enabled the investigation of microstructural white matter (WM) alterations in SAD. This study aims to provide an overview of DTI/DWI studies exploring WM microstructure changes in SAD. METHODS: A systematic search on PubMed, Scopus, Web of Science, and PsycINFO was conducted for relevant records on July 8, 2023. An exploratory meta-analysis was also performed. RESULTS: Eight studies were reviewed. Consistent findings indicated reduced fractional anisotropy and increased diffusivity measures in different WM tracts in SAD patients compared to healthy controls. These alterations were mostly observed within regions of the fronto-limbic network, like uncinate fasciculus (UF) and superior and inferior longitudinal fasciculi (SLF and ILF). Finally, our exploratory meta-analysis on four studies utilizing a voxel-wise analytic approach yielded no significant differences between SAD patients and controls. LIMITATIONS: Limited number of studies, small sample sizes, and heterogeneity in analysis methods. CONCLUSIONS: Patients with SAD exhibited altered WM integrity, particularly in the UF, SLF, and ILF, compared to healthy controls. However, due to the limited number of included studies, our meta-analysis yielded no significant differences between SAD patients and controls. Therefore, future research is crucial to unravel the link between altered WM structure and the involvement of other limbic and cortical structures in SAD pathogenesis.