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Depression has been shown to negatively impact neurocognitive functions, particularly those governed by fronto-subcortical networks, such as executive functions. Converging evidence suggests that depression-related executive dysfunction is greater at older ages, however, this has not been previously confirmed by meta-analysis. We performed a systematic review and meta-analysis, using three-level models, on peer-reviewed studies that examined depression-related differences in cognitive control in healthy community-dwelling individuals of any age. We focused on studies of cognitive control as defined by the National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC) framework, which centers on goal-directed behavior, such as goal selection (updating, representations, maintenance), response selection (inhibition or suppression), and performance monitoring. In 16,806 participants aged 7 to 97 across 76 studies, both clinical depression and subthreshold depressive symptoms were associated with cognitive control deficits (Hedges' g = -0.31). This relationship was stronger in study samples with an older mean age. Within studies with a mean age of 39 years or higher, which represents the median age in our analyses, the relationship was stronger in clinical compared to subthreshold depression and in individuals taking antidepressant medication. These findings highlight the importance of clinicians screening for cognitive control dysfunction in patients with depression, particularly in later stages of adulthood.

Transcranial direct current stimulation (tDCS) has emerged as a promising new treatment for major depression. While recent randomised, sham-controlled studies found tDCS to have antidepressant effects, it remains to be determined whether a tDCS treatment course may also enhance cognitive function independent of mood effects in depressed patients. This systematic review and individual patient data (IPD) meta-analysis examined cognitive outcomes from randomised, sham-controlled trials of tDCS treatment for major depression. Seven randomised, sham-controlled trials (n = 478 participants, 260 in active and 218 in sham) of tDCS for major depression were included. Results showed no cognitive enhancement after active tDCS compared to sham for the 12 cognitive outcomes investigated. Active relative to sham tDCS treatment was associated with reduced performance gains on a measure of processing speed (β = -0.33, 95% CI -0.58; -0.08, p = 0.011). Active tDCS treatment for depression did not show cognitive benefits independent of mood effects. Rather, tDCS treatment relative to sham stimulation for major depression may instead be associated with a reduced practice effect for processing speed., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Repetitive transcranial magnetic stimulation (rTMS) is an approved therapeutic treatment of major depressive disorder and has increasing clinical use throughout the world. However, it remains unclear whether an rTMS course for depression may also produce cognitive enhancement. In a recent meta-analysis of sham-controlled randomized controlled studies (RCTs) conducted in patients with neuropsychiatric conditions, no evidence was found for generalized cognitive enhancing effects across cognitive domains with active compared to sham rTMS. Notwithstanding, there remains the possibility of cognitive effects following an rTMS course that are more highly specific, for example, in specific clinical conditions, or at the individual task level. This study aimed to determine whether a therapeutic rTMS course in patients with depression is associated with cognitive enhancing effects at the task level., Methods: A systematic review and meta-analysis of outcomes on individual neuropsychological tasks from sham-controlled RCTs where an rTMS course was administered to the dorsolateral prefrontal cortex (DLPFC) in patients with depression., Results: Eighteen studies met the inclusion criteria. Active rTMS treatment showed no specific enhancing effects on the majority of cognitive tasks. Modest effect size improvements with active compared to sham rTMS treatment were found for performance on the Trail Making Test Parts A (g = 0.28, 95% CI = 0.06-0.50) and B (g = 0.26, 95% CI = 0.06-0.47)., Conclusion: A therapeutic rTMS course administered to the prefrontal cortex for depression may produce modest cognitive enhancing effects specific to psychomotor speed, visual scanning, and set-shifting ability., (© 2017 Wiley Periodicals, Inc.)

Repetitive transcranial magnetic stimulation (rTMS) is increasingly used as a therapeutic intervention for neuropsychiatric illnesses and has demonstrated efficacy for treatment of major depression. However, an unresolved question is whether a course of rTMS treatment results in effects on cognitive functioning. In this systematic review and meta-analysis we aimed to quantitatively determine whether a course of rTMS has cognitive enhancing effects. We examined cognitive outcomes from randomised, sham-controlled studies conducted in patients with neuropsychiatric conditions where rTMS was administered to the dorsolateral prefrontal cortex (DLPFC) across repeated sessions, searched from PubMed/MEDLINE and other databases up until October 2015. Thirty studies met our inclusion criteria. Cognitive outcomes were pooled and examined across the following domains: Global cognitive function, executive function, attention, working memory, processing speed, visual memory, verbal memory and visuospatial ability. Active rTMS treatment was unassociated with generalised gains across the majority of domains of cognitive functioning examined. Secondary analyses revealed a moderate sized positive effect for improved working memory in a small number of studies in patients with schizophrenia (k = 3, g = 0.507, 95 % CI = [0.183-0.831], p < .01). Therapeutic rTMS when administered to the DLPFC in patients with neuropsychiatric conditions does not result in robust cognitive enhancing effects.

Magnetic seizure therapy (MST) is a novel neurotherapeutic intervention in development for the treatment of major affective disorders. Like other neurotherapeutic strategies such as electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS), a primary interest will be to monitor the associated neurocognitive effects. Thus, the purpose of this systematic review was to synthesize the available data on the neurocognitive effects of MST. The authors performed two independent literature searches with the following terms terms: MST, magnetic, magnetic seizure therapy, depression, neurocognition, cognitive, preclinical. We included in this review a total of eleven articles that mentioned MST and neurocognition in the abstract. The articles were divided into three methodological domains that included virtual computer simulations, preclinical studies, and clinical investigations. Collectively, the available evidence suggests MST has little to no adverse cognitive effects. Specifically, virtual computer simulations found the magnetic field was localized to grey matter, and preclinical studies found no neurocortical or neurocognitive sequelae. Clinical investigations found MST to be associated with rapid reorientation and intact anterograde and retrograde memory. Future investigations using translational methods are warranted to confirm these findings and to further determine the effects of MST on neurocognitive functions.

Background: Electroconvulsive therapy (ECT) is an effective treatment for major depression. Optimising efficacy and minimising cognitive impairment are goals of ongoing technical refinements., Aims: To compare the efficacy and cognitive effects of a novel electrode placement, bifrontal, with two standard electrode placements, bitemporal and right unilateral in ECT., Method: This multicentre randomised, double-blind, controlled trial (NCT00069407) was carried out from 2001 to 2006. A total of 230 individuals with major depression, bipolar and unipolar, were randomly assigned to one of three electrode placements during a course of ECT: bifrontal at one and a half times seizure threshold, bitemporal at one and a half times seizure threshold and right unilateral at six times seizure threshold., Results: All three electrode placements resulted in both clinically and statistically significant antidepressant outcomes. Remission rates were 55% (95% CI 43-66%) with right unilateral, 61% with bifrontal (95% CI 50-71%) and 64% (95% CI 53-75%) with bitemporal. Bitemporal resulted in a more rapid decline in symptom ratings over the early course of treatment. Cognitive data revealed few differences between the electrode placements on a variety of neuropsychological instruments., Conclusions: Each electrode placement is a very effective antidepressant treatment when given with appropriate electrical dosing. Bitemporal leads to more rapid symptom reduction and should be considered the preferred placement for urgent clinical situations. The cognitive profile of bifrontal is not substantially different from that of bitemporal.

Objective: To develop an individualized method for detecting cognitive adverse events (CAEs) in the context of an ongoing trial of electroconvulsive therapy for refractory agitation and aggression for advanced dementia (ECT-AD study). Methods: Literature search aimed at identifying (a) cognitive measures appropriate for patients with advanced dementia, (b) functional scales to use as a proxy for cognitive status in patients with floor effects on baseline cognitive testing, and (c) statistical approaches for defining a CAE, to develop CAEs monitoring plan specifically for the ECT-AD study. Results: Using the Severe Impairment Battery-8 (SIB-8), baseline floor effects are defined as a score of ≤5/16. For patients without floor effects, a decline of ≥6 points is considered a CAE. For patients with floor effects, a decline of ≥30 points from baseline on the Barthel Index is considered a CAE. These values were derived using the standard deviation index (SDI) approach to measuring reliable change. Conclusions: The proposed plan accounts for practical and statistical challenges in detecting CAEs in patients with advanced dementia. While this protocol was developed in the context of the ECT-AD study, the general approach can potentially be applied to other interventional neuropsychiatric studies that carry the risk of CAEs in patients with advanced dementia. [ABSTRACT FROM AUTHOR]

Ketamine treatment prompts a rapid antidepressant response in treatment-resistant depression (TRD). We performed an exploratory investigation of how ketamine treatment in TRD affects different cognitive domains and relates to antidepressant response. Patients with TRD (N = 66; 30 M/35F; age = 39.5 ± 11.1 years) received four ketamine infusions (0.5 mg/kg). Neurocognitive function and depressive symptoms were assessed at baseline, 24 h after the first and fourth ketamine infusion, and 5 weeks following end of treatment. Mixed effect models tested for changes in seven neurocognitive domains and antidepressant response, with post-hoc pairwise comparisons between timepoints, including follow-up. Relationships between change in neurocognitive function and antidepressant response over the course of treatment were tested with Pearson's correlation and mediation analyses. Associations between baseline neurocognitive performance and antidepressant response were tested with Pearson's correlation. Significant improvements in inhibition, working memory, processing speed, and overall fluid cognition were observed after the first and fourth ketamine infusion. Improvements in processing speed and overall fluid cognition persisted through follow-up. Significant improvements in depressive symptoms reverted towards baseline at follow-up. Baseline working memory and change in inhibition were moderately correlated with antidepressant response, however, improvements in neurocognitive performance were statistically independent from antidepressant response. Antidepressant ketamine leads to improved neurocognitive function, which persist for at least 5 weeks. Neurocognitive improvements observed appear independent of antidepressant response, suggesting ketamine may target overlapping but distinct functional brain systems. Limitations Research investigating repeated serial ketamine treatments is important to determine cognitive safety. This study is a naturalistic design and does not include placebo. • Improvements in neurocognitive function observed 24 h after first and fourth ketamine infusion • Improvements in processing speed and global fluid cognitive function through 5-week follow-up • Change in neurocognitive function independent from antidepressant response [ABSTRACT FROM AUTHOR]

Introduction: Electroconvulsive therapy (ECT) pulse amplitude, which determines the induced electric field magnitude in the brain, is currently set at 800-900 milliamperes (mA) on modern ECT devices without any clinical or scientific rationale. The present study assessed differences in depression and cognitive outcomes for three different pulse amplitudes during an acute ECT series. We hypothesized that the lower amplitudes would maintain the antidepressant efficacy of the standard treatment and reduce the risk of neurocognitive impairment.Methods: This double-blind investigation randomized subjects to three treatment arms: 600, 700, and 800 mA (active comparator). Clinical, cognitive, and imaging assessments were conducted pre-, mid- and post-ECT. Subjects had a diagnosis of major depressive disorder, age range between 50 and 80 years, and met clinical indication for ECT.Results: The 700 and 800 mA arms had improvement in depression outcomes relative to the 600 mA arm. The amplitude groups showed no differences in the primary cognitive outcome variable, the Hopkins Verbal Learning Test-Revised (HVLT-R) retention raw score. However, secondary cognitive outcomes such as the Delis Kaplan Executive Function System Letter and Category Fluency measures demonstrated cognitive impairment in the 800 mA arm.Discussion: The results demonstrated a dissociation of depression (higher amplitudes better) and cognitive (lower amplitudes better) related outcomes. Future work is warranted to elucidate the relationship between amplitude, electric field, neuroplasticity, and clinical outcomes. [ABSTRACT FROM AUTHOR]

Objectives: To review brief cognitive screening instruments for routine clinical monitoring in electroconvulsive therapy. Methods: Brief cognitive screening instruments specifically developed for electroconvulsive therapy and commonly used brief generalised cognitive screening instruments were reviewed with relative advantages and disadvantages highlighted. Results: Several brief cognitive screening tests designed for use in electroconvulsive therapy have been found sensitive for monitoring electroconvulsive therapy–related cognitive side effects. The choice of a brief generalised cognitive screening instrument for use in an electroconvulsive therapy clinical context comes with several pertinent considerations. Conclusion: Electroconvulsive therapy is a highly effective treatment for pharmacoresistant and severe neuropsychiatric illness although cognitive side effects can be a barrier for treatment. Routine monitoring using brief cognitive screening instruments has advantages in busy clinical settings and can assist with optimising patient outcomes. More detailed neuropsychological assessment is recommended if the results from brief cognitive screening raise concerns. [ABSTRACT FROM AUTHOR]

Background: Treatment-resistant bipolar depression can be treated effectively using electroconvulsive therapy, but its use is limited because of stigma and cognitive adverse effects. Magnetic seizure therapy is a new convulsive therapy with promising early evidence of antidepressant effects and minimal cognitive adverse effects. However, there are no clinical trials of the efficacy and safety of magnetic seizure therapy for treatment-resistant bipolar depression. Methods: Participants with treatment-resistant bipolar depression were treated with magnetic seizure therapy for up to 24 sessions or until remission. Magnetic seizure therapy was applied over the prefrontal cortex at high (100 Hz; n = 8), medium (50 or 60 Hz; n = 9) or low (25 Hz; n = 3) frequency, or over the vertex at high frequency (n = 6). The primary outcome measure was the 24-item Hamilton Rating Scale for Depression. Participants completed a comprehensive battery of neurocognitive tests. Results: Twenty-six participants completed a minimally adequate trial of magnetic seizure therapy (i.e., ≥ 8 sessions), and 20 completed full treatment per protocol. Participants showed a significant reduction in scores on the Hamilton Rating Scale for Depression. Adequate trial completers had a remission rate of 23.1% and a response rate of 38.5%. Per-protocol completers had a remission rate of 30% and a response rate of 50%. Almost all cognitive measures remained stable, except for significantly worsened recall consistency on the autobiographical memory inventory. Limitations: The open-label study design and modest sample size did not allow for comparisons between stimulation parameters. Conclusion: In treatment-resistant bipolar depression, magnetic seizure therapy produced significant improvements in depression symptoms with minimal effects on cognitive performance. These promising results warrant further investigation with larger randomized clinical trials comparing magnetic seizure therapy to electroconvulsive therapy. Clinical trial registration: NCT01596608; clinicaltrials.gov [ABSTRACT FROM AUTHOR]

Abstract Background Transcranial direct current stimulation (tDCS) has promising antidepressant effects, however, clinical trials have shown variable efficacy. Pre-treatment neurocognitive functioning has previously been identified as an inter-individual predictor of tDCS antidepressant efficacy. Objective In this international multicentre, sham-controlled study, we investigated this relationship while also assessing the influence of clinical and genotype (BDNF Val66Met and COMT Val158Met polymorphisms) factors as predictors of response to active tDCS. Methods The study was a triple-masked, parallel, randomized, controlled design across 6 international academic medical centers. Participants were randomized to active (2.5 mA) or sham (34 μA) tDCS for 30 min each session for 20 sessions. The anode was centered over the left dorsolateral prefrontal cortex at F3 (10/20 EEG system) and the cathode over the lateral right frontal area at F8. Results Better pre-treatment attentional processing speed on the Ruff 2 & 7 Selective Attention Test (Total Speed: β = 0.25, p <.05) and concurrent antidepressant medication use (β = 0.31, p <.05) predicted antidepressant efficacy with active tDCS. Genotype differences in the BDNF Val66Metand COMT Val158Met polymorphisms were not associated with antidepressant effects. Secondary analyses revealed that only participants in the highest performing Ruff 2 & 7 Total Speed group at pre-treatment in both active and sham tDCS conditions showed significantly greater antidepressant response compared to those with lower performance at both the 2 and 4 week treatment time points (p <.05). Conclusions These results suggest that high pre-treatment attentional processing speed may be relevant for identifying participants more likely to show better tDCS antidepressant response to both high (2.5 mA) and very low (34 μA) current intensity stimulation. Clinical trials registration www.clinicaltrials.gov , NCT01562184. Highlights • A predictor analysis from a multicentre trial of tDCS for depression is reported. • Pre-treatment processing speed and medication use predicted response to active tDCS. • Better cognitive performance predicted mood response in both tDCS conditions. • Processing speed may be an important predictor for tDCS antidepressant response. [ABSTRACT FROM AUTHOR]

Objective: Electroconvulsive therapy is effective in treatment-resistant schizophrenia (TRS) but use is limited due to stigma and concerns around cognitive adverse effects. Magnetic seizure therapy (MST) is a promising new neuromodulation technique that uses transcranial magnetic stimulation to induce therapeutic seizures. Studies of MST in depression have shown clinical improvement with a favorable adverse effect profile. No studies have examined the clinical utility of MST in schizophrenia. Methods: We conducted an open-label pilot clinical trial of MST in eight TRS patients. Up to 24 MST treatments were delivered depending on treatment response. We assessed clinical outcome through the Brief Psychiatric Rating Scale (BPRS) and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). Cognitive testing included a neuropsychological test battery, the Autobiographical Memory Inventory (AMI), Montreal Cognitive Assessment (MoCA), and reorientation time. results: Four patients completed the trial as per protocol. For all patients and for trial completers alone, there was a significant clinical and quality of life improvement. Three met pre-determined criteria for remission (total score ≤25 on the BPRS) and one met criteria for response (i.e., ≥25% BPRS improvement from baseline for two consecutive assessments). Pre and post neurocognitive data showed no significant cognitive adverse effects apart from a decrease in AMI scores. Conclusion: In this pilot study, MST demonstrated evidence for feasibility in patients with TRS, with promise for clinical efficacy and negligible cognitive side effects. Further study in larger clinical populations is needed. [ABSTRACT FROM AUTHOR]

Although bipolar disorder and substance dependence are both associated with treatment non-adherence and cognitive impairment, no studies have investigated relationships between treatment adherence and cognitive functioning in this population. As part of a clinical trial, baseline performance on two neuropsychological tests in 120 outpatients with bipolar disorder and cocaine dependence was used to examine whether cognitive functioning was associated with appointment attendance, medication adherence, and return of medication bottles. This study found that higher baseline cognitive functioning measured by the Stroop Color–Word condition predicted better treatment adherence. However, this study also reports measurement sensitivity of cognition as it relates to treatment adherence when applied to this dual diagnosis population. Poorer performance in simple visual attention tasks as assessed by the Stroop Word condition was inversely associated with some measures of adherence. Future studies are warranted that include a comprehensive neuropsychological battery and advanced medication adherence measures to confirm these findings. [ABSTRACT FROM AUTHOR]

Introduction: Patients with Major Depressive Disorder (MDD) referred for electroconvulsive therapy (ECT) have poorer Health Related Quality of Life (HRQOL), compared with other patients with MDD, but ECT is associated with significant and durable improvement in HRQOL. However, no prior research has focused exclusively on elderly patients with MDD receiving ECT.Methods: HRQOL data from 240 depressed patients over the age of 60 was measured with the Medical Outcomes Study Short Form 36 (SF-36). The SF-36 was measured before and after a course of acute ECT. Predictors of change in HRQOL scores were identified by generalized linear modeling.Results: At baseline, participants showed very poor HRQOL. After treatment with ECT, the full sample showed marked and significant improvement across all SF-36 measures, with the largest gains seen in dimensions of mental health. Across all participants, the Physical Component Summary (PCS) score improved by 2.1 standardized points (95% CI, 0.61,3.56), while the Mental Component Summary (MCS) score improved by 12.5 points (95% CI, 7.2,10.8) Compared with non-remitters, remitters showed a trend toward greater improvement in the PCS summary score of 2.7 points (95%CI, -0.45, 5.9), while the improvement in the MCS summary score was significantly greater (8.5 points, 95% CI, 4.6,12.3) in the remitters than non-remitters. Post-ECT SF-36 measurements were consistently and positively related to baseline scores and remitter/non-remitter status or change in depression severity from baseline. Objective measures of cognitive function had no significant relationships to changes in SF-36 scores.Limitations: This study's limitations include that it was an open label study with no comparison group, and generalizability is limited to elderly patients.Discussion: ECT providers and elderly patients with MDD treated with ECT can be confident that ECT will result in improved HRQOL in the short-term. Attaining remission is a key factor in the improvement of HRQOL. Acute changes in select cognitive functions were outweighed by improvement in depressive symptoms in determining the short term HRQOL of the participants treated with ECT. [ABSTRACT FROM AUTHOR]