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.

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.

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.

Distribution of biochemical and haematological parameters in an aging population from southern India: A cross-sectional analysis.

BACKGROUND: Examining the distribution of biochemical and haematological tests in different age groups of rural population is necessary to ensure that health care facilities are equipped to address the prevalent health conditions and manage age-related illness effectively. Hence, this study is aimed at seeing the distributions of blood biochemical and haematological parameters in rural population. METHODS: This cross-sectional study investigated the distribution of 26 different haematological and biochemical parameters in longitudinal cohort study (Srinivaspura Aging, NeuoSenescence and COGnition - SANSCOG), from the villages of Srinivaspura, Kolar district, India. A total of 2592 participants (1240 males and 1352 females), aged ≥45 years who are cognitively healthy were included for the analysis. Mean, 2.5th, 5th, 25th, 50th, 75th, 95th and 97.5th percentiles were calculated for the entire sample. Additionally, median and percentiles were determined for both gender and age categories (45-54, 55-64, 65-74, and ≥75 years). RESULTS: We observed the distinct distributions of various haematological and biochemical parameters, with elevated levels of glycaemic, lipid, liver, and thyroid parameters. CONCLUSION: Findings revealed the notable variations from the established reference ranges, indicating the potential undiagnosed cases and highlighting the gaps in health awareness and health seeking behaviour.

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.