Transcranial direct current stimulation as an additional treatment to selective serotonin reuptake inhibitors in adults with major depressive disorder in Germany (DepressionDC): a triple-blind, randomised, sham-controlled, multicentre trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) has been proposed as a feasible treatment for major depressive disorder (MDD). However, meta-analytic evidence is heterogenous and data from multicentre trials are scarce. We aimed to assess the efficacy of tDCS versus sham stimulation as an additional treatment to a stable dose of selective serotonin reuptake inhibitors (SSRIs) in adults with MDD. METHODS: The DepressionDC trial was triple-blind, randomised, and sham-controlled and conducted at eight hospitals in Germany. Patients being treated at a participating hospital aged 18-65 years were eligible if they had a diagnosis of MDD, a score of at least 15 on the Hamilton Depression Rating Scale (21-item version), no response to at least one antidepressant trial in their current depressive episode, and treatment with an SSRI at a stable dose for at least 4 weeks before inclusion; the SSRI was continued at the same dose during stimulation. Patients were allocated (1:1) by fixed-blocked randomisation to receive either 30 min of 2 mA bifrontal tDCS every weekday for 4 weeks, then two tDCS sessions per week for 2 weeks, or sham stimulation at the same intervals. Randomisation was stratified by site and baseline Montgomery-Åsberg Depression Rating Scale (MADRS) score (ie, <31 or ≥31). Participants, raters, and operators were masked to treatment assignment. The primary outcome was change on the MADRS at week 6, analysed in the intention-to-treat population. Safety was assessed in all patients who received at least one treatment session. The trial was registered with ClinicalTrials.gov (NCT02530164). FINDINGS: Between Jan 19, 2016, and June 15, 2020, 3601 individuals were assessed for eligibility. 160 patients were included and randomly assigned to receive either active tDCS (n=83) or sham tDCS (n=77). Six patients withdrew consent and four patients were found to have been wrongly included, so data from 150 patients were analysed (89 [59%] were female and 61 [41%] were male). No intergroup difference was found in mean improvement on the MADRS at week 6 between the active tDCS group (n=77; -8·2, SD 7·2) and the sham tDCS group (n=73; -8·0, 9·3; difference 0·3 [95% CI -2·4 to 2·9]). Significantly more participants had one or more mild adverse events in the active tDCS group (50 [60%] of 83) than in the sham tDCS group (33 [43%] of 77; p=0·028). INTERPRETATION: Active tDCS was not superior to sham stimulation during a 6-week period. Our trial does not support the efficacy of tDCS as an additional treatment to SSRIs in adults with MDD. FUNDING: German Federal Ministry of Education and Research.

Does physical activity and inflammation mediate the job stress-headache relationship? A sequential mediation analysis in the ELSA-Brasil study.

BACKGROUND: Evidence indicates that physical activity reduces stress and promote a myriad of health-enhancing effects through anti-inflammatory mechanisms. However, it is unknown whether these mechanisms interfere in the association between psychosocial job stress and headache disorders. OBJECTIVE: To test whether physical activity and its interplay with the systemic inflammation biomarkers high-sensitivity C-reactive protein (hs-CRP) and acute phase glycoproteins (GlycA) would mediate the associations between job stress and headache disorders. METHODS: We cross-sectionally evaluated the baseline data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) regarding job stress (higher demand and lower control and support subscales), migraine and tension-type headache (ICHD-2 criteria), self-reported leisure-time physical activity, and plasma hs-CRP and GlycA levels. Conditional process analyses with a sequential mediation approach were employed to compute path coefficients and 95 % confidence intervals (CI) around the indirect effects of physical activity and biomarkers on the job stress-headache relationship. Separate models were adjusted for sex, age, and depression and anxiety. Further adjustments added BMI smoking status, and socioeconomic factors. RESULTS: In total, 7,644 people were included in the study. The 1-year prevalence of migraine and tension-type headache were 13.1 % and 49.4 %, respectively. In models adjusted for sex, age, anxiety, and depression, the association between job stress (lower job control) and migraine was mediated by physical activity [effect = -0.039 (95 %CI: -0.074, -0.010)] but not hs-CRP or GlycA. TTH was associated with higher job control and lower job demand, which was mediated by the inverse associations between physical activity and GlycA [Job Control: effect = 0.0005 (95 %CI: 0.0001, 0.0010); Job Demand: effect = 0.0003 (95 %CI: 0.0001, 0.0007]. Only the mediating effect of physical activity in the job stress-migraine link remained after further adjustments including socioeconomic factors, BMI, smoking, and the exclusion of major chronic diseases. CONCLUSION: In the ELSA-Brasil study, physical activity reversed the link between job stress and migraine independently of systemic inflammation, while the LTPA-mediated downregulation of GlycA was associated with lower job stress-related TTH.

Dose-dependent response of prefrontal transcranial direct current stimulation on the heart rate variability: An electric field modeling study.

Transcranial direct current stimulation (tDCS) of the prefrontal cortex (PFC) modulates the autonomic nervous system by activating deeper brain areas via top-down pathway. However, effects on the nervous system are heterogeneous and may depend on the amount of current that penetrates. Therefore, we aimed to investigate the variable effects of tDCS on heart rate variability (HRV), a measure of the functional state of the autonomic nervous system. Using three prefrontal tDCS protocols (1.5, 3 mA and sham), we associated the simulated individual electric field (E-field) magnitude in brain regions of interest with the HRV effects. This was a randomized, double-blinded, sham-controlled and within-subject trial, in which healthy young-adult participants received tDCS sessions separated by 2 weeks. The brain regions of interest were the dorsolateral PFC (DLPFC), anterior cingulate cortex, insula and amygdala. Overall, 37 participants were investigated, corresponding to a total of 111 tDCS sessions. The findings suggested that HRV, measured by root mean squared of successive differences (RMSSD) and high-frequency HRV (HF-HRV), were significantly increased by the 3.0 mA tDCS when compared to sham and 1.5 mA. No difference was found between sham and 1.5 mA. E-field analysis showed that all brain regions of interest were associated with the HRV outcomes. However, this significance was associated with the protocol intensity, rather than inter-individual brain structural variability. To conclude, our results suggest a dose-dependent effect of tDCS for HRV. Therefore, further research is warranted to investigate the optimal current dose to modulate HRV.

Efficacy and acceptability of noninvasive brain stimulation for treating posttraumatic stress disorder symptoms: A network meta-analysis of randomized controlled trials.

INTRODUCTION: Despite its high lifetime prevalence rate and the elevated disability caused by posttraumatic stress disorder (PTSD), treatments exhibit modest efficacy. In consideration of the abnormal connectivity between the dorsolateral prefrontal cortex (DLPFC) and amygdala in PTSD, several randomized controlled trials (RCTs) addressing the efficacy of different noninvasive brain stimulation (NIBS) modalities for PTSD management have been undertaken. However, previous RCTs have reported inconsistent results. The current network meta-analysis (NMA) aimed to compare the efficacy and acceptability of various NIBS protocols in PTSD management. METHODS: We systematically searched ClinicalKey, Cochrane Central Register of Controlled Trials, Embase, ProQuest, PubMed, ScienceDirect, Web of Science, and ClinicalTrials.gov to identify relevant RCTs. The targeted RCTs was those comparing the efficacy of NIBS interventions, such as transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), and transcutaneous cervical vagal nerve stimulation, in patients with PTSD. The NMA was conducted using a frequentist model. The primary outcomes were changes in the overall severity of PTSD and acceptability (to be specific, rates of dropouts for any reason). RESULTS: We identified 14 RCTs that enrolled 686 participants. The NMA demonstrated that among the investigated NIBS types, high-frequency rTMS over bilateral DLPFCs was associated with the greatest reduction in overall PTSD severity. Further, in comparison with the sham controls, excitatory stimulation over the right DLPFC with/without excitatory stimulation over left DLPFC were associated with significant reductions in PTSD-related symptoms, including depression and anxiety symptoms, and overall PTSD severity. CONCLUSIONS: This NMA demonstrated that excitatory stimulation over the right DLPFC with or without excitatory stimulation over left DLPFC were associated with significant reductions in PTSD-related symptoms. TRIAL REGISTRATION: PROSPERO CRD42023391562.

Availability of Electroconvulsive Therapy in Public Health Services in the Last Decade in Brazil.

OBJECTIVE: To identify the current treatment options for electroconvulsive therapy (ECT) therapy in public services linked to the Unified Health System in Brazil and compare them with data published in 2012 based on their availability. METHODS: In this retrospective observational study, we mapped institutions that perform ECT under public health services in Brazil. A questionnaire was administered to active and inactive service centers between August 2022 and June 2023. RESULTS: We identified 16 institutions that performed ECT, including 12 linked to public universities and 4 with various links. In the last decade, 2 new public services that perform ECT in the country have emerged, whereas 4 services have ceased function. In 2022, the number of individuals treated with ECT per 100,000 population was 1.86, whereas the number of procedures performed per 100,000 people was 6.55. CONCLUSIONS: Although 2 new public ECT services have been identified, 4 have turned inactive. Most services are linked to public universities, and inactive service points to financial issues as the main factor in service interruption. Brazil has one of the lowest rates of individuals treated with ECT per 100,000 population compared with countries in North America and Europe. Thus, it is essential to raise awareness to improve ECT adoption rates and bring it out of the shadows in Brazil.

Impact of data extraction errors in meta-analyses on the association between depression and peripheral inflammatory biomarkers: an umbrella review.

BACKGROUND: Accumulating evidence suggests that alterations in inflammatory biomarkers are important in depression. However, previous meta-analyses disagree on these associations, and errors in data extraction may account for these discrepancies. METHODS: PubMed/MEDLINE, Embase, PsycINFO, and the Cochrane Library were searched from database inception to 14 January 2020. Meta-analyses of observational studies examining the association between depression and levels of tumor necrosis factor-α (TNF-α), interleukin 1-ß (IL-1ß), interleukin-6 (IL-6), and C-reactive protein (CRP) were eligible. Errors were classified as follows: incorrect sample sizes, incorrectly used standard deviation, incorrect participant inclusion, calculation error, or analysis with insufficient data. We determined their impact on the results after correction thereof. RESULTS: Errors were noted in 14 of the 15 meta-analyses included. Across 521 primary studies, 118 (22.6%) showed the following errors: incorrect sample sizes (20 studies, 16.9%), incorrect use of standard deviation (35 studies, 29.7%), incorrect participant inclusion (7 studies, 5.9%), calculation errors (33 studies, 28.0%), and analysis with insufficient data (23 studies, 19.5%). After correcting these errors, 11 (29.7%) out of 37 pooled effect sizes changed by a magnitude of more than 0.1, ranging from 0.11 to 1.15. The updated meta-analyses showed that elevated levels of TNF- α, IL-6, CRP, but not IL-1ß, are associated with depression. CONCLUSIONS: These findings show that data extraction errors in meta-analyses can impact findings. Efforts to reduce such errors are important in studies of the association between depression and peripheral inflammatory biomarkers, for which high heterogeneity and conflicting results have been continuously reported.

Prevalence and risk factors of psychiatric symptoms and diagnoses before and during the COVID-19 pandemic: findings from the ELSA-Brasil COVID-19 mental health cohort.

BACKGROUND: There is mixed evidence on increasing rates of psychiatric disorders and symptoms during the coronavirus disease 2019 (COVID-19) pandemic in 2020. We evaluated pandemic-related psychopathology and psychiatry diagnoses and their determinants in the Brazilian Longitudinal Study of Health (ELSA-Brasil) São Paulo Research Center. METHODS: Between pre-pandemic ELSA-Brasil assessments in 2008-2010 (wave-1), 2012-2014 (wave-2), 2016-2018 (wave-3) and three pandemic assessments in 2020 (COVID-19 waves in May-July, July-September, and October-December), rates of common psychiatric symptoms, and depressive, anxiety, and common mental disorders (CMDs) were compared using the Clinical Interview Scheduled-Revised (CIS-R) and the Depression Anxiety Stress Scale-21 (DASS-21). Multivariable generalized linear models, adjusted by age, gender, educational level, and ethnicity identified variables associated with an elevated risk for mental disorders. RESULTS: In 2117 participants (mean age 62.3 years, 58.2% females), rates of CMDs and depressive disorders did not significantly change over time, oscillating from 23.5% to 21.1%, and 3.3% to 2.8%, respectively; whereas rate of anxiety disorders significantly decreased (2008-2010: 13.8%; 2016-2018: 9.8%; 2020: 8%). There was a decrease along three wave-COVID assessments for depression [ß = -0.37, 99.5% confidence interval (CI) -0.50 to -0.23], anxiety (ß = -0.37, 99.5% CI -0.48 to -0.26), and stress (ß = -0.48, 99.5% CI -0.64 to -0.33) symptoms (all ps < 0.001). Younger age, female sex, lower educational level, non-white ethnicity, and previous psychiatric disorders were associated with increased odds for psychiatric disorders, whereas self-evaluated good health and good quality of relationships with decreased risk. CONCLUSION: No consistent evidence of pandemic-related worsening psychopathology in our cohort was found. Indeed, psychiatric symptoms slightly decreased along 2020. Risk factors representing socioeconomic disadvantages were associated with increased odds of psychiatric disorders.

Inflammatory and oxidative stress markers in post-traumatic stress disorder: a systematic review and meta-analysis.

Post-traumatic stress disorder (PTSD) has been associated with persistent, low-degree inflammation, which could explain the increased prevalence of autoimmune conditions and accelerated aging among patients. The aim of the present study is to assess which inflammatory and oxidative stress markers are associated with PTSD. We carried out a meta-analytic and meta-regression analysis based on a systematic review of studies comparing inflammatory and oxidative stress markers between patients with PTSD and controls. We undertook meta-analyses whenever values of inflammatory and oxidative stress markers were available in two or more studies. Overall, 28,008 abstracts were identified, and 54 studies were included, with a total of 8394 participants. The Newcastle-Ottawa Quality Assessment Scale was used to evaluate the quality of the studies. Concentrations of C-reactive protein (SMD = 0.64; 95% CI: 0.21 to 1.06; p = 0.0031; k = 12), interleukin 6 (SMD = 0.94; 95% CI: 0.36 to 1.52; p = 0.0014; k = 32), and tumor necrosis factor-α (SMD = 0.89; 95% CI: 0.23 to 1.55; p = 0.0080; k = 24) were significantly increased in patients with PTSD in comparison with healthy controls. Interleukin 1ß levels almost reached the threshold for significance (SMD = 1.20; 95% CI: -0.04 to 2.44; p = 0.0569; k = 15). No oxidative stress marker was associated with PTSD. These findings may explain why PTSD is associated with accelerated aging and illnesses in which immune activation has a key role, such as cardiovascular diseases and diabetes. In addition, they pointed to the potential role of inflammatory markers as therapeutic targets.

Association between objective sleep measures and cognitive performance: a cross-sectional analysis in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) study.

Sleep disturbances often co-exist, which challenges our understanding of their potential impact on cognition. We explored the cross-sectional associations of insomnia and objective measures of sleep with cognitive performance in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) study stratified by middle-aged and older adults. Participants aged ≥55 years underwent cognitive evaluations, polygraphy for 1 night, and actigraphy for 7 days. Insomnia was evaluated using the Clinical Interview Scheduled Revised. Obstructive sleep apnea (OSA) and short sleep duration (SSD) were defined by an apnea-hypopnea index (AHI) of ≥15 events/h and <6 h/ night, respectively. In 703 participants (mean [SD] age 62 [6] years, 44% men), cognition was evaluated using a 10-word list, verbal fluency, and trail-making tests. The frequencies of insomnia, SSD, and OSA were 11%, 24%, and 33%, respectively. In all, 4% had comorbid OSA and insomnia, and 11% had both OSA and SSD. Higher wake after sleep onset (ß = -0.004, 95% confidence interval [CI] -0.008, -0.001) and the number of awakenings (ß = -0.006, 95% CI -0.012, -0.001) were associated with worse verbal fluency performance. Compared to those without insomnia, older participants with insomnia had worse global performance (ß = -0.354, 95% CI -0.671, -0.038). Insomnia was an effect modifier in the associations between AHI and executive function performance (p for the interaction between insomnia and AHI = 0.004) and between oxygen saturation <90% and memory performance (p for the interaction between insomnia and oxygen saturation = 0.02). Although some associations between sleep measures and cognition were significant, they should be considered with caution due to the large sample size and multiple testing performed in this study.

Distorted thoughts as a mediator of depressive symptoms in patients with major depressive disorder: a longitudinal study.

BACKGROUND: Distorted thoughts are common in Major Depressive Disorder (MDD), and can impact patients' perceptions of depression severity, and predict chronicity and treatment response. This study aimed to investigate whether distorted thoughts mediate depressive symptoms in MDD over a 6-month period. METHOD: These are secondary results from a study that followed 119 patients diagnosed with moderate to severe MDD for 6 months. Diagnoses were confirmed by the Structured Interview for DSM-IV (SCID-CV). The analysis was composed of results from the Hamilton Depression Rating Scale (HAMD-17), the Montgomery-Asberg Depression Rating Scale (MADRS), the second edition of the Beck Depression Inventory (BDI-II), and the Depression Thoughts Scale (DTS) collected at weeks 1, 8, 12 and 24. RESULTS: Results showed that the DTS mediated the relationship between depressive symptoms experienced approximately 3 months after starting antidepressant treatment. CONCLUSION: Cognitive distortions were linked as a mediator to depressive symptoms, highlighting the importance of early psychological interventions in patients with MDD who exhibit these distortions. TRIAL REGISTRATION: NCT02268487.

Potentially inappropriate medications and cognitive performance: cross-sectional results from the ELSA-Brasil study.

OBJECTIVES: Potentially inappropriate medications (PIM), especially those with potential effects on the central nervous system, can increase the risk of cognitive impairment. We investigated the association of the use of PIM and PIM that may impair cognition (PIM-Cog) with cognitive performance among older adults. METHODS: In this cross-sectional study with 2,626 participants, PIM and PIM-Cog were defined by the 2019 American Geriatrics Society Beers criteria. We calculated global cognition and memory, verbal fluency, and Trail Making Test B version (TMT-B) z-scores. Linear regression models adjusted for sociodemographic and clinical variables were used to investigate the association between PIM and cognition. RESULTS: 27% and 7% of the sample (mean age = 65.1 ± 4.1 years old, 54% women, and 61% White) used at least one PIM and PIM-cog, respectively. PIM was associated with poor performance in the TMT-B (ß = -0.17, 95% Cl = -0.29; -0.05, p = 0.007). PIM-Cog was also associated with poor TMT-B performance (ß = -0.08, 95% Cl = -0.15; -0.01, p = 0.025). CONCLUSION: The use of PIM and PIM-Cog was associated with poor executive function among older adults. The review of PIM use and the deprescription of these drugs may be an effective way to improve cognitive function.

White matter predicts tDCS antidepressant effects in a sham-controlled clinical trial study.

Transcranial direct current stimulation (tDCS) has been used as treatment for depression, but its effects are heterogeneous. We investigated, in a subsample of the clinical trial Escitalopram versus Electrical Direct Current Therapy for Depression Study (ELECTTDCS), whether white matter areas associated with depression disorder were associated with tDCS response. Baseline diffusion tensor imaging data were analyzed from 49 patients (34 females, mean age 41.9) randomized to escitalopram 20 mg/day, tDCS (2 mA, 30 min, 22 sessions), or placebo. Antidepressant outcomes were assessed by Hamilton Depression Rating Scale-17 (HDRS) after 10-week treatment. We used whole-brain tractography for extracting white matter measures for anterior corpus callosum, and bilaterally for cingulum bundle, striato-frontal, inferior occipito-frontal fasciculus and uncinate. For the rostral body, tDCS group showed higher MD associated with antidepressant effects (estimate = -5.13 ± 1.64, p = 0.002), and tDCS significantly differed from the placebo and the escitalopram group. The left striato-frontal tract showed higher FA associated with antidepressant effects (estimate = -2.14 ± 0.72, p = 0.003), and tDCS differed only from the placebo group. For the right uncinate, the tDCS group lower AD values were associated with higher HDRS decrease (estimate = -1.45 ± 0.67, p = 0.031). Abnormalities in white matter MDD-related areas are associated with tDCS antidepressant effects. Suggested better white matter microstructure of the left prefrontal cortex was associated with tDCS antidepressant effects. Future studies should investigate whether these findings are driven by electric field diffusion and density in these areas.

Deconstructing depression by machine learning: the POKAL-PSY study.

Unipolar depression is a prevalent and disabling condition, often left untreated. In the outpatient setting, general practitioners fail to recognize depression in about 50% of cases mainly due to somatic comorbidities. Given the significant economic, social, and interpersonal impact of depression and its increasing prevalence, there is a need to improve its diagnosis and treatment in outpatient care. Various efforts have been made to isolate individual biological markers for depression to streamline diagnostic and therapeutic approaches. However, the intricate and dynamic interplay between neuroinflammation, metabolic abnormalities, and relevant neurobiological correlates of depression is not yet fully understood. To address this issue, we propose a naturalistic prospective study involving outpatients with unipolar depression, individuals without depression or comorbidities, and healthy controls. In addition to clinical assessments, cardiovascular parameters, metabolic factors, and inflammatory parameters are collected. For analysis we will use conventional statistics as well as machine learning algorithms. We aim to detect relevant participant subgroups by data-driven cluster algorithms and their impact on the subjects' long-term prognosis. The POKAL-PSY study is a subproject of the research network POKAL (Predictors and Clinical Outcomes in Depressive Disorders; GRK 2621).

Association between chemosensory impairment with neuropsychiatric morbidity in post-acute COVID-19 syndrome: results from a multidisciplinary cohort study.

Preliminary methodologically limited studies suggested that taste and smell known as chemosensory impairments and neuropsychiatric symptoms are associated in post-COVID-19. The objective of this study is to evaluate whether chemosensory dysfunction and neuropsychiatric impairments in a well-characterized post-COVID-19 sample. This is a cohort study assessing adult patients hospitalized due to moderate or severe forms of COVID-19 between March and August 2020. Baseline information includes several clinical and hospitalization data. Further evaluations were made using several different reliable instruments designed to assess taste and smell functions, parosmia, and neuropsychiatric disorders (using standardized psychiatric and cognitive measures). Out of 1800 eligible individuals, 701 volunteers were assessed on this study. After multivariate analysis, patients reporting parosmia had a worse perception of memory performance (p < 0.001). Moderate/severe hypogeusia was significantly associated with a worse performance on the word list memory task (p = 0.012); Concomitant moderate/severe olfactory and gustatory loss during the acute phase of COVID-19 was also significantly associated with episodic memory impairment (p = 0.006). We found a positive association between reported chemosensory (taste and olfaction) abnormalities and cognition dysfunction in post-COVID-19 patients. These findings may help us identify potential mechanisms linking these two neurobiological functions, and also support the speculation on a possible route through which SARS-CoV-2 may reach the central nervous system.

Dissipating the fog: Cognitive trajectories and risk factors 1 year after COVID-19 hospitalization.

INTRODUCTION: Cognitive impairment is common after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, associations between post-hospital discharge risk factors and cognitive trajectories have not been explored. METHODS: A total of 1105 adults (mean age ± SD 64.9 ± 9.9 years, 44% women, 63% White) with severe coronavirus disease 2019 (COVID-19) were evaluated for cognitive function 1 year after hospital discharge. Scores from cognitive tests were harmonized, and clusters of cognitive impairment were defined using sequential analysis. RESULTS: Three groups of cognitive trajectories were observed during the follow-up: no cognitive impairment, initial short-term cognitive impairment, and long-term cognitive impairment. Predictors of cognitive decline after COVID-19 were older age (ß = -0.013, 95% CI = -0.023;-0.003), female sex (ß = -0.230, 95% CI = -0.413;-0.047), previous dementia diagnosis or substantial memory complaints (ß = -0.606, 95% CI = -0.877;-0.335), frailty before hospitalization (ß = -0.191, 95% CI = -0.264;-0.119), higher platelet count (ß = -0.101, 95% CI = -0.185;-0.018), and delirium (ß = -0.483, 95% CI = -0.724;-0.244). Post-discharge predictors included hospital readmissions and frailty. DISCUSSION: Cognitive impairment was common and the patterns of cognitive trajectories depended on sociodemographic, in-hospital, and post-hospitalization predictors. HIGHLIGHTS: Cognitive impairment after coronavirus disease 2019 (COVID-19) hospital discharge was associated with higher age, less education, delirium during hospitalization, a higher number of hospitalizations post discharge, and frailty before and after hospitalization. Frequent cognitive evaluations for 12-month post-COVID-19 hospitalization showed three possible cognitive trajectories: no cognitive impairment, initial short-term impairment, and long-term impairment. This study highlights the importance of frequent cognitive testing to determine patterns of COVID-19 cognitive impairment, given the high frequency of incident cognitive impairment 1 year after hospitalization.

Post-acute sequelae of SARS-CoV-2 infection: relationship of central nervous system manifestations with physical disability and systemic inflammation.

BACKGROUND: Despite the multitude of clinical manifestations of post-acute sequelae of SARS-CoV-2 infection (PASC), studies applying statistical methods to directly investigate patterns of symptom co-occurrence and their biological correlates are scarce. METHODS: We assessed 30 symptoms pertaining to different organ systems in 749 adults (age = 55 ± 14 years; 47% female) during in-person visits conducted at 6-11 months after hospitalization due to coronavirus disease 2019 (COVID-19), including six psychiatric and cognitive manifestations. Symptom co-occurrence was initially investigated using exploratory factor analysis (EFA), and latent variable modeling was then conducted using Item Response Theory (IRT). We investigated associations of latent variable severity with objective indices of persistent physical disability, pulmonary and kidney dysfunction, and C-reactive protein and D-dimer blood levels, measured at the same follow-up assessment. RESULTS: The EFA extracted one factor, explaining 64.8% of variance; loadings were positive for all symptoms, and above 0.35 for 16 of them. The latent trait generated using IRT placed fatigue, psychiatric, and cognitive manifestations as the most discriminative symptoms (coefficients > 1.5, p < 0.001). Latent trait severity was associated with decreased body weight and poorer physical performance (coefficients > 0.240; p ⩽ 0.003), and elevated blood levels of C-reactive protein (coefficient = 0.378; 95% CI 0.215-0.541; p < 0.001) and D-dimer (coefficient = 0.412; 95% CI 0.123-0.702; p = 0.005). Results were similar after excluding subjects with pro-inflammatory comorbidities. CONCLUSIONS: Different symptoms that persist for several months after moderate or severe COVID-19 may unite within one latent trait of PASC. This trait is dominated by fatigue and psychiatric symptoms, and is associated with objective signs of physical disability and persistent systemic inflammation.

Toward a neurocircuit-based taxonomy to guide treatment of obsessive-compulsive disorder.

An important challenge in mental health research is to translate findings from cognitive neuroscience and neuroimaging research into effective treatments that target the neurobiological alterations involved in psychiatric symptoms. To address this challenge, in this review we propose a heuristic neurocircuit-based taxonomy to guide the treatment of obsessive-compulsive disorder (OCD). We do this by integrating information from several sources. First, we provide case vignettes in which patients with OCD describe their symptoms and discuss different clinical profiles in the phenotypic expression of the condition. Second, we link variations in these clinical profiles to underlying neurocircuit dysfunctions, drawing on findings from neuropsychological and neuroimaging studies in OCD. Third, we consider behavioral, pharmacological, and neuromodulatory treatments that could target those specific neurocircuit dysfunctions. Finally, we suggest methods of testing this neurocircuit-based taxonomy as well as important limitations to this approach that should be considered in future research.

Sex differences in the association between alcohol intake and cognitive decline over 4 years in a middle-aged cohort: The Brazilian Longitudinal Study of Adult Health.

BACKGROUND AND PURPOSE: The association between alcohol intake and cognitive decline has been widely studied. Sex differences and cognitive domains affected by alcohol intake patterns make this topic complex. The objective of this study was to investigate the effect of alcohol intake on cognition in middle-aged participants in the Brazilian Longitudinal Study of Adult Health by sex during 4 years of follow-up. METHODS: A total of 7595 participants (55% women) aged between 50 and 75 years at baseline were assessed. Semantic and phonemic fluency, memory, and executive functions were assessed at baseline (2008-2010) and repeated during Visit 2. Linear mixed models were used to investigate the association between cognition and current abstainers, never drinkers, light drinkers, moderate drinkers, and heavy drinkers. RESULTS: Heavy alcohol intake accentuated the decline in executive functions for men (ß = -0.01, p < 0.05), and in semantic fluency (ß = -0.02, p < 0.05) and memory (ß = -0.02, p < 0.05) for women. Never drinker men also showed an accentuated decline in semantic fluency (ß = -0.02, p < 0.01). Moderate alcohol intake slowed cognitive decline in phonemic fluency for men (ß = 0.02, p < 0.01) and women (ß = 0.01, p < 0.01), and in executive functions (ß = 0.01, p < 0.05) for women. CONCLUSIONS: Having more than 14 drinks per week can impact executive functions in men and memory in women. In addition, alcohol consumption of seven to 14 drinks per week may have a protective effect on gender-specific cognitive functions. These findings should be considered in public health policies and guidelines on alcohol and cognitive aging.

Anticholinergic burden and cognitive performance: cross-sectional results from the ELSA-Brasil study.

OBJECTIVES: Using multiple drugs with anticholinergic properties is common and might lead to cumulative anticholinergic toxicity and increased risk of cognitive impairment. Therefore, we sought to investigate the association between the Anticholinergic Cognitive Burden (ACB) Scale and cognitive performance among middle-aged and older adults. METHODS: In this cross-sectional study with 13,065 participants from the baseline visit of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), mean age was 51.7 ± 9.0 years old, 55% women, and 53% white. The ACB was calculated based on the medications in use. We investigated the association of ACB with global cognition and memory, verbal fluency (VF), and trail-making test version B (TMT-B) z-scores, using multiple linear regression models adjusted for sociodemographic and clinical variables. RESULTS: Overall, 16% of participants had an ACB score greater than 0. ACB was associated with poor cognitive performance in all tests in crude analysis. After adjustment for sociodemographic characteristics, the association remained significant for the global cognitive score, as well as the memory and the TMT-B z-scores. However, after further adjustments for clinical variables, only trend associations of ACB with poor memory (ß = - 0.02, 95% Cl = - 0.05, 0.00, p = 0.056) and the TMT-B z-scores (ß = - 0.02, 95% Cl = - 0.04, 0.00, p = 0.054) were found. In stratified analyses by age groups, ACB was associated with poor cognitive performance on the TMT-B (ß = - 0.03, 95% Cl = - 0.05, - 0.01, p = 0.005) in individuals aged less than 65 years old. CONCLUSION: Although the ACB was associated with poor executive function only among middle-aged adults in adjusted analysis, residual confounding may partly explain our results.

Hearing Loss and Cognitive Function: Baseline Findings From the Brazilian Longitudinal Study of Adult Health: ELSA-Brasil.

OBJECTIVE: Hearing loss (HL) has been associated with cognitive impairment in high-income countries. However, no study has investigated this association in low- and middle-income countries. Therefore, our aim was to investigate the association between cognitive function and HL in the Brazilian Longitudinal Study of Adult Health. DESIGN: Cross-sectional analysis of Longitudinal Study of Adult Health (ELSA-Brasil) with 802 individuals (35-74 years old). Hearing was measured using pure-tone audiometry. A pure-tone average (s) of thresholds at 500, 1000, 2000, and 4000 Hz was calculated. HL was defined as a PTA above 25 dB in the better ear or either ear, as a categorical variable. Cognitive performance was measured using the Consortium to Establish a Registry for Alzheimer's Disease word list memory test, the semantic and phonemic verbal fluency (VF) tests, and the Trail Making test version B. To investigate the association between cognitive performance and HL, we used linear regression models adjusted for sociodemographic and clinical variables. RESULTS: Of the total of participants, 7.6% had HL. After adjustment for sociodemographic and health confounding variables, only VF was associated with HL; a 10 dB increase in the PTA in the better ear was associated with worse performance in the phonemic VF test (ß = -0.115 [95% CI, -0.203 to -0.027], p = 0.01). We found a significant interaction between HL and age in the VF domain ( p = 0.01). HL was related to poor VF performance among older adults only. CONCLUSION: In a community-dwelling sample of most middle-aged adults, objectively measured HL was associated with lower VF. These results should be evaluated with caution, given the likelihood of residual confounding and the fact that only VF showed an association with HL.