Alteration in amygdala subfield volumes and their association with cognition in mild cognitive impairment.

BACKGROUND: The amygdala has an important role in cognitive and affective functions. The involvement of amygdala and related limbic structures is implicated in many aspects of memory and emotion in mild cognitive impairment (MCI). In the present study, we aimed to compare the volumetric measurements of amygdala and its subfields as well as their association with cognitive functions in stable MCI (sMCI). METHODS: We performed Addenbrooke's cognitive examination III (ACE-III) test, as well as high-resolution T1-weighted images from 31 participants with sMCI and 31 age-matched healthy controls. The amygdala subfield volumes were extracted using Freesurfer software, and group differences were assessed using general linear model (GLM) with age, gender, education and estimated intracranial volume (ICV) as covariates. Partial correlation was also calculated between cognitive scores and volumes of amygdala subfields in healthy controls and sMCI participants controlling for estimated ICV. RESULTS: sMCI participants exhibited significantly reduced volumes in most of the right amygdala subfields, including basal nucleus, accessory basal nucleus, central nucleus, medial nucleus, corticoamygdaloid transition area, and whole amygdala, as well as significantly reduced right amygdala/hippocampus ratio compared to healthy controls. In addition, our results revealed statistically significant positive correlations between ACE memory scores and the volumes of right central nucleus, right medial nucleus, right cortical nucleus, and the right whole amygdala, in sMCI. CONCLUSIONS: Our findings revealed volumetric reductions in most of the right amygdala subfields along with its association with the memory functions in sMCI. These findings provide valuable insights into the underlying anatomical factors contributing to neurocognitive symptoms in MCI.

Dysregulated Cerebrospinal Fluid Proteome of Spinocerebellar Ataxia Type 2 and its Clinical Implications.

BACKGROUND: Abnormalities in ataxin-2 associated with spinocerebellar ataxia type 2 (SCA2) may lead to widespread disruptions in the proteome. This study was performed to identify dysregulated proteome in SCA2 and to explore its clinical-radiological correlations. METHODS: Cerebrospinal fluid (CSF) samples from 21 genetically confirmed SCA2 were subjected to shotgun proteome analysis using mass spectrometry (MS) and tandem mass tag (TMT)-based multiplexing. Proteins with at least 1.5-fold change in abundance were identified. Their relative abundance was measured using parallel reaction monitoring (PRM) and correlated against disease-related factors. RESULTS: Eleven proteins were significantly upregulated in SCA2. They belonged to the family of cell adhesion molecules and granins. Their fold changes showed significant clinical, genetic, and radiological correlations. CONCLUSIONS: Significant dysregulation of CSF proteome is seen in SCA2. The dysregulated protein may have potential use in clinical evaluation of patients with SCA2. © 2024 International Parkinson and Movement Disorder Society.

Transcranial direct current stimulation-efficacy in mild cognitive impairment: A meta-analysis.

Objectives: Mild cognitive impairment (MCI) is a transition state in which individuals have cognitive abilities that are in between those of normal aging and dementia. Although not everyone with MCI develops dementia, the risk of progression to dementia is higher in people with MCI. Interventions at this stage can prevent or delay the onset of dementia. In recent years, studies on non-invasive brain stimulation techniques, namely transcranial direct current stimulation (tDCS), have gained momentum for cognitive enhancement in MCI. Since there are very few studies that also report varied results, it becomes important to analyze the effect of tDCS in MCI. The aim of this study was to systematically review the available evidence about using tDCS for MCI and to assess its efficacy using meta-analysis. Materials and Methods: Eight single- or double-blinded randomized controlled trials were included in the study. Montreal cognitive assessment (MoCA) and mini-mental state examination (MMSE) for global cognition; and digit span test forward and backward, trail-making test (TMT) A and B; and logical memory test (LMT) assessing specific cognitive domains were considered. A random-effects model was used wherein the standardized mean difference (SMD) and its 95% confidence intervals were reported. Results: The effect of the active tDCS (MoCA [SMD 0.37, 95% CI -0.22-0.95], MMSE [SMD 0.26, 95% CI 0.25-0.77], TMT-A [SMD -0.01, 95% CI -0.42-0.40], and LMT [SMD 0.80, 95% CI -0.24-1.83]) when compared with the sham tDCS was statistically insignificant. Conclusion: The current meta-analysis identified insignificant improvement in cognitive performance with active tDCS treatment as compared to sham tDCS among people with MCI.

Association between multilingualism and cognitive performance among older adults in rural southern India.

Objectives: Recent studies have shown that multilingualism may play an important role in enhancing cognitive health. The process of language acquisition constitutes a form of natural brain training, which in turn is hypothesized to increase neuroplasticity and hence, maintains the cognitive reserve. The study aimed to analyze the relationship between the number of languages known to an individual and its effect on cognitive functioning in both healthy and cognitively impaired study participants. Materials and Methods: This study utilized cross-sectional (baseline) data from Srinivasapura Aging, Neuro Senescence and COGnition study, which is an ongoing community-based, longitudinal aging cohort study conducted in a rural setting in southern India. A total of 3725 participants were considered for the study. The participants were separated into two groups, namely, monolinguals (participants knowing one language) and multilingual (participants knowing more than one language). The cognitive performance of the participants was assessed using the Clinical Dementia Rating (CDR) Scale. In addition, bivariate analyses and binary logistic regression analyses were carried out. Results: The result of CDR scores with respect to language category shows that, among the monolingual participants, 86.5% were healthy individuals and 13.5% were with mild cognitive impairment (MCI). Similarly, among the multilingual, 94.3% were healthy and 5.7% were with MCI. The odds ratio value derived from logistic regression (0.69 95% CI (0.5-0.9)) that an individual has a higher chance of developing cognitive impairment if he/she is a monolingual. Conclusion: This study highlights that knowing more than one language might have a profound positive impact on cognitive health, thereby reducing the likelihood of developing cognitive decline.

Therapeutic Potential of Buprenorphine in Depression: A Meta-Analysis of Current Evidence.

Background: Emerging research indicates buprenorphine, used in management of opioid use disorder, has attracted interest for its potential in treating a variety of psychiatric conditions. This meta-analysis aimed to determine the efficacy of buprenorphine in treating symptoms of depression. Methods: Using Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, a search was conducted of several databases until April 25, 2022, for English language articles related to buprenorphine and its use in treating various mental health conditions. Standardized mean differences (SMDs) and its 95% confidence intervals (CIs) were reported for the Hamilton Rating Scale for Depression (HAM-D) and the Montgomery-Asberg Depression Rating Scale (MADRS) scores. Statistical analyses were performed using Cochrane RevMan 5. Results: Of the 1,347 identified studies, six clinical trials were included. MADRS-10 least square mean difference (LSMD) inter-group assessment favored buprenorphine over placebo, but it lacked statistical significance. Similarly, MADRS scores as well as HAM-D inter-group assessment were in favor of buprenorphine, however, were not statistically significant. These findings suggest a potential therapeutic role for buprenorphine in treating depression, albeit with caution due to the observed lack of statistical significance and the potential for confounding factors. Conclusions: Preliminary evidence suggests potential efficacy of buprenorphine at lower doses in improving improving outcomes specifically related to depression. However, due to limitations in statistical significance and possible confounding factors, entail cautious interpretation. Further rigorous research is needed to investigate the long-term effects, optimal dosing, and determine the role of adjuvant drug therapy.

Comparative efficacy of repetitive transcranial magnetic stimulation protocols for obsessive-compulsive disorder: A network meta-analysis.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has been found to be helpful for the treatment of obsessive-compulsive disorder (OCD). However, the relative efficacy of different rTMS protocols is unclear. OBJECTIVE: To conduct a systematic review and network meta-analysis (NMA) of published literature to compare the relative efficacy of different rTMS protocols for decreasing Yale-Brown Obsessive Compulsive Severity (Y-BOCS) scores in patients with OCD. METHOD: Relevant articles published between 1985 to September 2023 were searched from the Cochrane Central Register of Controlled Trials, PubMed and PsycInfo. Double or single-blinded randomized controlled studies conducted on patients with OCD comparing an active rTMS protocol with either another active or sham rTMS protocol were included. Network meta-analysis (NMA) was conducted using a frequentist approach. Standardized mean difference (SMD) of change in Y-BOCS scores was calculated employing Hedge's g. Pairwise meta-analysis using random effects model was conducted which was extended to the NMA using restricted maximum likelihood estimation procedure. Surface under the cumulative ranking (SUCRA) probabilities were used to rank the interventions. RESULTS: Excitatory rTMS of the bilateral dorsolateral prefrontal cortex (DLPFC), inhibitory rTMS of right DLPFC, inhibitory as well as excitatory rTMS of bilateral medial prefrontal cortex/anterior cingulate cortex (mPFC/ACC) and inhibitory rTMS of bilateral supplementary motor area (SMA) were superior to sham stimulation. The DLPFC and mPFC/ACC protocols had a higher probability of being among the top-ranked interventions. The majority of studies had a modest sample size and at least some concerns in the risk of bias assessment. CONCLUSION: rTMS targeting either the medial or lateral prefrontal cortices is a promising intervention for resistant OCD. There is a need to confirm these findings in large systematic studies.

Effectiveness of Short-Term Lifestyle Modification on Reducing Body- Weight-Related Parameters in Persons with Severe Mental Illness: A Randomized Controlled Trial.

Background: Persons with severe mental illness (SMI) reportedly have a high mortality rate due to metabolic syndrome (MS). However, lifestyle modification (LM) offers effective management of some components of MS. This study aimed to evaluate the effectiveness of LM in reducing body-weight-related parameters in SMIs. Method: Eighty participants with SMI were assigned randomly to either LM (n = 40) or treatment as usual (TAU; n = 40) groups using block randomization (eight blocks of n = 10). The LM group and their caregivers received a structured LM package that included nutrition counselling, recommendations on a balanced diet, and physical activity. The two groups were assessed on body weight, body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), and quality of life (QOL) at baseline and after three months. Thirty-one LM and 33 TAU participants completed the study. Results: The LM and TAU groups were comparable on sociodemographic and clinical characteristics and baseline variables of body weight, BMI, WC, and WHR (all P > 0.08). Repeated-measures analysis of variance (RM ANOVA) showed that the LM group had significantly reduced body weight, BMI, WC, and WHR (all P < 0.001) than the TAU group. Similarly, the LM group also showed improvement in their QOL (P < 0.001), whereas TAU showed no improvement. Conclusions: LM is an effective way to reduce body-weight-related parameters of MS and improves the QOL among persons with SMI in the short term. The caregivers' inclusion during LM contributed to the weight reduction. However, the long-term effect of the intervention could not be assessed.

Sex difference in evolution of cognitive decline: studies on mouse model and the Dominantly Inherited Alzheimer Network cohort.

Women carry a higher burden of Alzheimer's disease (AD) compared to men, which is not accounted entirely by differences in lifespan. To identify the mechanisms underlying this effect, we investigated sex-specific differences in the progression of familial AD in humans and in APPswe/PS1ΔE9 mice. Activity dependent protein translation and associative learning and memory deficits were examined in APPswe/PS1ΔE9 mice and wild-type mice. As a human comparator group, progression of cognitive dysfunction was assessed in mutation carriers and non-carriers from DIAN (Dominantly Inherited Alzheimer Network) cohort. Female APPswe/PS1ΔE9 mice did not show recall deficits after contextual fear conditioning until 8 months of age. Further, activity dependent protein translation and Akt1-mTOR signaling at the synapse were impaired in male but not in female mice until 8 months of age. Ovariectomized APPswe/PS1ΔE9 mice displayed recall deficits at 4 months of age and these were sustained until 8 months of age. Moreover, activity dependent protein translation was also impaired in 4 months old ovariectomized APPswe/PS1ΔE9 mice compared with sham female APPswe/PS1ΔE9 mice. Progression of memory impairment differed between men and women in the DIAN cohort as analyzed using linear mixed effects model, wherein men showed steeper cognitive decline irrespective of the age of entry in the study, while women showed significantly greater performance and slower decline in immediate recall (LOGIMEM) and delayed recall (MEMUNITS) than men. However, when the performance of men and women in several cognitive tasks (such as Wechsler's logical memory) are compared with the estimated year from expected symptom onset (EYO) we found no significant differences between men and women. We conclude that in familial AD patients and mouse models, females are protected, and the onset of disease is delayed as long as estrogen levels are intact.

Multivariate Bayesian Arm-Based Network Meta-Analysis of Pharmacological Interventions for the Treatment of Acute Bipolar Mania in Adults.

Background: In a network meta-analysis (NMA), multiple treatments can be compared simultaneously by aggregating pieces of evidence from direct as well as indirect treatment comparisons in different randomized controlled trials (RCTs). Conventional NMA are performed using a normal approximation approach and can be applied for arm-level binary outcome data as well. This study aimed to estimate the treatment effects within a Bayesian framework using a binomial likelihood for a multivariate NMA model. Methods: The dataset consists of 57 RCTs comparing the effect of ten pharmacological drugs and a placebo for acute bipolar mania in adults. The binary outcomes of interest were treatment response and all-cause dropouts measured three weeks from the baseline. Binomial distribution was adopted for the number of events and the probability of event occurrence modeled on the logit scale. Jeffrey's Beta prior was considered for the heterogeneity and inconsistency of standard deviation (SD) parameters. Cholesky and spherical decomposition strategies were adopted for the between-study variance-covariance matrix. Deviance information criterion (DIC) indices were computed to determine the model fit. All results pertaining to Markov chain Monte Carlo simulations and all analyses were carried out in WinBUGS software. Results: The estimated common heterogeneity SDs were similar, and the DIC values did not provide any evidence for superiority between the two decomposition strategies. The correlation (95% credible interval) between the outcomes was estimated as -0.31 (-0.71, -0.02) and -0.37 (-0.73, -0.03) for the Cholesky and spherical decompositions, respectively. Gelman-Rubin convergence statistics were stable, and Monte Carlo errors for all the parameters were around 0.005. Overall, olanzapine, paliperidone, and quetiapine were both significantly more effective and acceptable than a placebo when both the study outcomes were considered simultaneously. Conclusions: The findings favoring olanzapine, paliperidone, and quetiapine possess an excellent concordance with the one adopted in clinical practice, and the Canadian Network for Mood and Anxiety Treatments and Royal Australian and New Zealand College of Psychiatrists guidelines recommend these as first-line drugs for treating bipolar disorder.

Treatment strategies for serotonin reuptake inhibitor-resistant obsessive-compulsive disorder: A network meta-analysis of randomised controlled trials.

OBJECTIVES: Treatment-resistant obsessive-compulsive disorder is a chronic debilitating illness. We conducted a network meta-analysis [NMA] to compare the efficacy of all interventions in SRI-resistant OCD from published Randomised controlled trials [RCT]. METHODS: We performed an NMA of RCTs in SRI resistant OCD from all modalities of treatments; pharmacological, psychological, neuromodulation, neurosurgery including deep brain stimulation. The design-by-treatment interaction inconsistency model within the frequentist framework was adopted with a change in Yale-Brown Obsessive-Compulsive Scale score as the primary outcome. We conducted sensitivity analyses excluding studies examining neurosurgical interventions, deep brain stimulation, studies in the paediatric population, and studies from a single geographical region. We also conducted analyses of interventions categorised into treatment groups. RESULTS: 55 RCTs examining 19 treatments or placebo involving 2011 participants were included in the NMA. Ondansetron [Standardised mean difference -2.01 (95% CI: -3.19, -0.83)], deep TMS [- 1.95 (-3.25, -0.65)], therapist administered Cognitive Behavioural Therapy [CBT-TA] [-1.46 (-2.93, 0.01)] and aripiprazole [-1.36 (-2.56, -0.17)] were ranked as the best four treatments on using the Surface Under the Cumulative Ranking [SUCRA] percentage values (85.4%, 83.2%, 80.3%, 67.9% respectively). While all four interventions had large effect sizes, CBT[TA] narrowly missed statistical significance in our analysis. In sensitivity analyses, deep TMS was ranked as the best treatment strategy for SRI-resistant OCD. The small number of subjects in individual studies, higher confidence interval limits, and wider prediction interval for most agents warrant a cautious interpretation. CONCLUSIONS: Considering the principal analysis and sensitivity analyses together, deep TMS, ondansetron, CBT[TA], and aripiprazole may be considered a first-line intervention for SRI-resistant OCD in adults. OTHER: This work was not funded. The NMA has been registered with PROSPERO, [Registration number: CRD42020173589].

A systematic review and meta-analysis of early childhood intervention programs for developmental difficulties in low-and-middle-income countries.

Early acknowledgment of developmental difficulties in young children strengthens both preventive and therapeutic approaches. Despite their feasibility, early intervention services are limited in Low-and-Middle-Income (LAMI) countries compared to high income countries. The aim of this study was to examine the evidence for early childhood intervention programs for developmental difficulties in children below five years in LAMI countries through a systematic review and meta-analysis. In this background, original studies published in peer-reviewed journals from 2010 to 2019 with a focus on developmental difficulties including delays and deviances; randomized research design with a clear description of the intervention and measurable outcomes, and conducted in LAMI countries were considered for the systematic review. Electronic databases, including ProQuest, PubMed, Ovid, EBSCOhost, and Google Scholar, were searched using a combination of specific keywords. PRISMA guidelines were followed to include the studies. Each of the selected study was assessed for quality before applying appropriate statistics to synthesize the data. Fourteen publications were identified from 2697 publications for the systematic review, out of which four were found compatible for a meta-analysis. The studies reviewed were conducted in Bangladesh, India, Pakistan, Uganda, Vietnam, and Zambia. A meta-analysis of four studies provided considerable evidence for the effects of early developmental intervention. This systematic review provides an evidence for early childhood intervention programs in LAMI countries. Implications of these findings for the early childhood programs are discussed in this article.

Phonatory Characteristics of Male Patients with Classic Essential Tremor.

OBJECTIVE: Voice tremor (VT) is one of the characteristics of essential tremor (ET). This study was designed to describe the group and phonatory characteristics of classic ET patients with VT. METHODS: This retrospective case-control study compared classic ET patients with age and sex-matched controls. The ET population was subgrouped based on auditory perceptual voice analysis. Electroglottography and acoustic voice samples obtained from both groups were analyzed for contact quotient (CQ) and multidimensional voice program parameters, i.e., fundamental frequency (F0), perturbation, noise, and tremor parameters. RESULTS: The CQ, F0, perturbation, noise, and tremor characteristics significantly increased from the moderate VT group to the severe VT group. CONCLUSION: The CQ, F0, and noise characteristics reflected the vocal folds' functionality. The perturbation and tremor parameters variation were reasoned considering the tremor-related changes occurring in the laryngeal, vocal tract, and expiratory muscles in patients with ET. Thus, phonatory analysis may help in monitoring the progression of ET.

Impact of lifestyle modification on some components of metabolic syndrome in persons with severe mental disorders: A meta-analysis.

BACKGROUND: Metabolic syndrome (MS) is reportedly associated with high mortality from mostly cardiovascular causes in patients with severe mental disorders (SMD). Lifestyle interventions augment effective management of MS in patients with SMD. The present meta-analysis aims at updating the recent evidence on the effectiveness of lifestyle intervention for MS in patients with SMD. METHOD: A literature search for English Language publications of randomized controlled trials (RCTs) from 2001 to 2016 comparing lifestyle modification (LM) with treatment as usual (TAU) in the management of MS were identified. Using PRISMA guidelines, 19 RCTs reporting data on 1688 SMD and MS patients and providing data on change in Body Weight, Body Mass Index (BMI) and waist circumference (WC) were included. Using random effects model, standardized mean difference between LM and TAU for the mean baseline-to-endpoint change in body weight, BMI and WC was calculated with a 95% confidence limit, on RevMan 5.3. The study was registered with PROSPERO (CRD42016046847). RESULTS: LM had significantly superior efficacy in the reducing weight (-0.64, 95% CI -0.89, -0.39, Z = 5.03, overall effect p < 0.00001), BMI (-0.68, 95% CI -1.01, -0.35, Z = 4.05, overall effect p < 0.0001), and WC (-0.60, 95% CI -1.17, -0.03, Z = 2.06; overall effect p = 0.04), compared to TAU. LM was significantly more effective than TAU even in short duration (p = 0.0001) and irrespective of the treatment setting. CONCLUSION: Interventions targeting LM in persons with SMD and MS are effective in reducing body weight, BMI and WC. It must be routinely recommended to all patients with SMD, ideally during commencement stage of second generation antipsychotic treatment.