Working and short-term memory in children with ADHD: an examination of prefrontal cortical functioning using functional Near-Infrared Spectroscopy (fNIRS).

Working memory impairments are an oft-reported deficit among children with ADHD, and complementary neuroimaging studies implicate reductions in prefrontal cortex (PFC) structure and function as a neurobiological explanation. Most imaging studies, however, rely on costly, movement-intolerant, and/or invasive methods to examine cortical differences. This is the first study to use a newer neuroimaging tool that overcomes these limitations, functional Near Infrared Spectroscopy (fNIRS), to investigate hypothesized prefrontal differences. Children (aged 8-12) with ADHD (N = 22) and typically developing (N = 18) children completed phonological working memory (PHWM) and short-term memory (PHSTM) tasks. Children with ADHD evinced poorer performance on both tasks, with greater differences observed in PHWM (Hedges' g = 0.67) relative to PHSTM (g = 0.39). fNIRS revealed reduced hemodynamic response among children with ADHD in the dorsolateral PFC while completing the PHWM task, but not within the anterior or posterior PFC. No between-group fNIRS differences were observed during the PHSTM task. Findings suggest that children with ADHD exhibit an inadequate hemodynamic response in a region of the brain that underlies PHWM abilities. The study also highlights the use of fNIRS as a cost-effective, noninvasive neuroimaging technique to localize/quantify neural activation patterns associated with executive functions.

Development and cadherin-mediated control of prefrontal corticostriatal projections in mice.

Action-outcome associations depend on prefrontal cortex (PFC) projections to the dorsal striatum. To assess how these projections form, we measured PFC axon patterning, synapse formation, and functional maturation in the postnatally developing mouse striatum. Using Hotspot analysis, we show that PFC axons form an adult-like pattern of clustered terminations in the first postnatal week that remains largely stable thereafter. PFC-striatal synaptic strength is adult-like by P21, while excitatory synapse density increases until adulthood. We then tested how the targeted deletion of a candidate adhesion/guidance protein, Cadherin-8 (Cdh8), from corticostriatal neurons regulates pathway development. Mutant mice showed diminished PFC axon targeting and reduced spontaneous glutamatergic synaptic activity in the dorsal striatum. They also exhibited impaired behavioral performance in action-outcome learning. The data show that PFC-striatal axons form striatal territories through an early, directed growth model and they highlight essential contributions of Cdh8 to the anatomical and functional features critical for the formation of action-outcome associations.

Development of prefrontal corticostriatal connectivity in mice.

Rational decision making is grounded in learning to associate actions with outcomes, a process that depends on projections from prefrontal cortex to dorsomedial striatum. Symptoms associated with a variety of human pathological conditions ranging from schizophrenia and autism to Huntington's and Parkinson's disease point toward functional deficits in this projection, but its development is not well understood, making it difficult to investigate how perturbations in development of this circuitry could contribute to pathophysiology. We applied a novel strategy based on Hotspot Analysis to assess the developmental progression of anatomical positioning of prefrontal cortex to striatal projections. Corticostriatal axonal territories established at P7 expand in concert with striatal growth but remain largely unchanged in positioning through adulthood, indicating they are generated by directed, targeted growth and not modified extensively by postnatal experience. Consistent with these findings, corticostriatal synaptogenesis increased steadily from P7 to P56, with no evidence for widescale pruning. As corticostriatal synapse density increased over late postnatal ages, the strength of evoked PFC input onto dorsomedial striatal projection neurons also increased, but spontaneous glutamatergic synaptic activity was stable. Based on its pattern of expression, we asked whether the adhesion protein, Cdh8, influenced this progression. In mice lacking Cdh8 in PFC corticostriatal projection neurons, axon terminal fields in dorsal striatum shifted ventrally. Corticostriatal synaptogenesis was unimpeded, but spontaneous EPSC frequency declined and mice failed to learn to associate an action with an outcome. Collectively these findings show that corticostriatal axons grow to their target zone and are restrained from an early age, do not undergo postnatal synapse pruning as the most dominant models predict, and that a relatively modest shift in terminal arbor positioning and synapse function has an outsized, negative impact on corticostriatal-dependent behavior.

Development of a Web-Based Training Platform for School Clinicians in Evidence-Based Practices for ADHD.

Lack of training for school clinicians in evidence-based practices (EBPs) contributes to underutilization of such services for youth with attention-deficit/hyperactivity disorder (ADHD). Advances in web-based technology and videoconferencing have allowed for expanded access to and optimization of training. We describe the development and outcomes of a novel web-based platform for training school clinicians to gain skills in EBPs for school-age youth with ADHD. The training platform is adapted from an empirically supported, in-person training for a school-home behavioral intervention (Collaborative Life Skills program) and includes skill modules for working with teachers, parents, and students. Training methods include web-accessed manuals/handouts, skill example video clips, automated progress monitoring tools, and consultation/in-session coaching via videoconferencing. We gathered stakeholder qualitative and quantitative feedback during discovery and design phases of the iterative development. We then evaluated the usability, acceptability, fidelity and clinician and student outcomes of the remote training program. Focus group themes and qualitative feedback identified clinician preferences for remote training features (e.g., interactive, brief, role-plays/coaching methods), video tools (recorded samples of skills and therapy sessions), and progress monitoring tools (e.g., clear, easy to use). Clinician usability ratings of the platform were high with most components rated as moderately to very useful/easy to use. Clinician ratings of usability, fidelity implementing the treatment, and their EBP knowledge and confidence following training were favorable. Student's outcomes were similar to those achieved in prior studies of clinician in-person training. Results support the promise of remote, web-based clinician training for the dissemination of evidence-based practices.

Pain, mood, and suicidal behavior among injured working adults in Chile.

BACKGROUND: Chronic pain is comorbid with psychiatric disorders, but information on the association of chronic pain with depressive symptoms, generalized anxiety, and suicidal behavior among occupational cohorts is inadequate. We investigated these associations among employed Chilean adults. METHODS: A total of 1946 working adults were interviewed during their outpatient visit. Pain was assessed using the Short Form McGill Pain questionnaire (SF-MPG) while depression and generalized anxiety were examined using the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), respectively. The Columbia-Suicide Severity Rating Scale was used to assess suicidal behavior and suicidal ideation. Multivariable logistic regression models were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (95%CI) for the association of chronic pain with mood disorders, as well as suicidal behavior. RESULTS: High chronic pain (SF-MPG > 11) was reported by 46% of participants. Approximately two-fifths of the study participants (38.2%) had depression, 23.8% generalized anxiety, 13.4% suicidal ideation, and 2.4% suicidal behavior. Compared to those with low pain (SF-MPG ≤11), participants with high chronic pain (SF-MPG > 11) had increased odds of experiencing depression only (aOR = 2.87; 95% CI: 2.21-3.73), generalized anxiety only (aOR = 2.38; 95% CI: 1.42-3.99), and comorbid depression and generalized anxiety (aOR = 6.91; 95% CI: 5.20-9.19). The corresponding aOR (95%CI) for suicidal ideation and suicidal behavior were (aOR = 2.20; 95% CI: 1.58-3.07) and (aOR = 2.18 = 95% CI: 0.99-4.79), respectively. CONCLUSIONS: Chronic pain is associated with increased odds of depression, generalized anxiety, and suicidal behavior. Mental health support and appropriate management of patients experiencing chronic pain are critical.

Poor sleep Quality and Obstructive Sleep Apnea are Associated with Maternal Mood, and Anxiety Disorders in Pregnancy.

BACKGROUND: Previous studies suggest sleep quality and obstructive sleep apnea (OSA) may be associated with psychiatric symptoms, including depression, anxiety, and posttraumatic stress disorder (PTSD). However, few studies have examined the relationship between sleep quality and OSA with maternal psychiatric symptoms during pregnancy, a state of vulnerability to these disorders. OBJECTIVE: The objective of our study is to examine the association between poor sleep quality and sleep apnea with antepartum depression, anxiety, and PTSD among pregnant women. METHODS: A cross-sectional study was conducted among women seeking prenatal care in Lima, Peru. Sleep quality was measured using the Pittsburgh Sleep Quality Index, and the Berlin questionnaire was used to identify women at high risk for OSA. Depression, generalized anxiety, and PTSD symptoms were measured using the Patient Health Questionnaire-9, Generalized Anxiety Disorder Assessment, and PTSD Checklist - Civilian Version. Multivariate logistic regression procedures were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (95% CI). RESULTS: Approximately 29.0X% of women had poor sleep quality, and 6.2% were at high risk for OSA. The prevalence of psychiatric symptoms was high in this cohort with 25.1%, 32.5%, and 30.9% of women reporting symptoms of antepartum depression, antepartum anxiety, and PTSD, respectively. Women with poor sleep quality had higher odds of antepartum depression (aOR = 3.28; 95%CI: 2.64-4.07), generalized anxiety (aOR = 1.94; 95%CI: 1.58-2.38), and PTSD symptoms (aOR = 2.81; 95% CI: 2.28-3.46) as compared with women who reported good sleep quality. Women with a high risk of OSA had higher odds of antepartum depression (aOR = 2.36; 95% CI: 1.57-3.56), generalized anxiety (aOR = 2.02, 95% CI: 1.36-3.00), and PTSD symptoms (aOR = 2.14; 95%CI: 1.43-3.21) as compared with those with a low risk of sleep apnea. CONCLUSIONS: Poor sleep quality and high risk of OSA are associated with antepartum depression, generalized anxiety, and PTSD symptoms among pregnant women. Further characterizations of the associations of these prevalent sleep, mood, and anxiety conditions among pregnant women could aid in evaluating and delivering optimal perinatal care to women with these comorbidities.

Evaluating the performance of the Pain Interference Index and the Short Form McGill Pain Questionnaire among Chilean injured working adults.

BACKGROUND: Chronic pain can lead to economic instability, decreased job productivity, and poor mental health. Therefore, reliable identification and quantification of chronic pain is important for clinical diagnosis and treatment. OBJECTIVE: To determine the psychometric properties of the Spanish language versions of the Pain Interference Index (PII) and the Short Form McGill Pain Questionnaire (SF-MPG) among a population of working adults who experienced injury in Santiago, Chile. METHODS: A total of 1,975 participants with work-related injuries were interviewed to collect sociodemographic, occupational, and chronic pain characteristics. Construct validity and factorial structure of the PII and SF-MPG were assessed through exploratory factor analyses (EFA). Cronbach's alpha was used to evaluate internal consistency. RESULTS: The PII mean score was 3.84 ± 1.43 among all participants. The SF-MPG median score was 11 [IQR: 6-16] in this study population. Cronbach's alpha for the PII was 0.90 and 0.87 for the SF-MP. EFA resulted in a one factor solution for the PII. A two-factor solution was found for the SF-MPG. The two-factors for SF-MPG were sensory and affective subscales with Cronbach's alpha of 0.82 and 0.714, respectively. When the two scales were combined, an EFA analysis confirmed the PII and SF-MPG measure different aspects of chronic pain. CONCLUSIONS: The PII and SF-MPG had good construct validity and reliability for assessing different aspects of chronic pain among working Chilean adults.

Verbal Memory Interference in Attention-Deficit Hyperactivity Disorder: A Meta-Analytic Review.

OBJECTIVE: Interference control is used to overcome conflict among competing memory representations and may contribute to memory difficulties in ADHD. This meta-analytic review examined memory interference to evaluate susceptibility to proactive, retroactive, and memory control interference among those with ADHD. METHOD: Twenty studies (1987-2019) examining verbal memory interference in ADHD met inclusion criteria (age: 8-36 years). Proactive and retroactive interference indices were extracted from list-learning tasks, and memory control indices were extracted from experimental paradigms (e.g., directed-forgetting). RESULTS: Children with ADHD were less affected by proactive interference (g=-0.53, 95% CI [-0.75, -0.31]), whereas no significant differences were found in adults (g=0.13, 95% CI [-0.02, 0.28]). Adults and children with ADHD exhibited more retroactive interference (g=0.17, 95% CI [0.05, 0.29]) and performed worse on memory control tasks (g=0.35, 95% CI [0.08, 0.62]) relative to controls. CONCLUSION: Differences in verbal memory interference control in ADHD were observed but effects were different depending upon interference type and participant age.

Association of morningness-eveningness with psychiatric symptoms among pregnant women.

In the present study, we examined associations between circadian preference and psychiatric symptoms among 1,796 pregnant women from Lima, Peru. One quarter were classified as evening types. Compared to morning types, evening type pregnant women had increased odds of generalized anxiety (OR = 1.44; 95%CI: 1.12-1.86) and posttraumatic stress disorder (OR = 1.38; 95%CI: 1.07-1.78). Although there was a positive trend, evening chronotype was not significantly associated with elevated odds of depression (OR = 1.23; 95%CI: 0.94-1.61). Future studies are warranted to help understand the underlying behavioral, biological, and genetic pathways of these associations. Assessing circadian preference may help clinicians identify pregnant women at risk for psychiatric symptoms.

Commentary: Global Alzheimer's disease and Alzheimer's disease related dementia research funding organizations support and engage the research community throughout the COVID-19 pandemic.

The COVID-19 pandemic has disproportionately affected more vulnerable populations, including those living with dementia. Over 50 million individuals worldwide are living with Alzheimer's disease (AD) or other dementia, and it is crucial to continue the fight against the condition during the global pandemic. Since the start of mandated lockdowns in March 2020, charity and non-profit organizations that fund AD and related dementia research continue to respond to the needs of the AD research community, ensuring the momentum continues and accelerates. Members of the International Alzheimer's and Related Dementia Research Funder Consortium, a group of nearly 40 funding organizations that informally convene throughout the year to share updates and information, have taken a number of steps to ensure the continued support of the research community. Even during times of uncertainty, it is essential that the field moves forward to uncover preventions, diagnoses, and treatments for these diseases that affect many millions globally.

Patterns of Parental Adherence and the Association to Child and Parenting Outcomes Following a Multicomponent School-Home Intervention for Youth With ADHD.

The goal of the present study was to evaluate the role of parent adherence in the Collaborative Life Skills (CLS) program, a multicomponent school-home intervention, for predicting child and parenting outcomes. A sample of 129 children (63% male; M age = 8.22, SD = 1.10; grades 2-5) with attention-deficit/hyperactivity disorder (ADHD) and their parents participated in CLS, which included 10 weekly behavioral parent training group sessions. Each week, parents provided information on their CLS skill use between sessions (at home) as part of the intervention. Outcome measures included parent and teacher ratings of child behavior and parenting at post-intervention and 6 months follow-up. Growth mixture models examining weekly parent skill use trajectories throughout the intervention significantly predicted parent- and teacher-reported outcomes including parent-rated child behavior, teacher-rated academic competence, and positive parenting behaviors. Fifty-two percent of parents displayed moderate skill use throughout the intervention, whereas the remaining parents had either low (20%) or high (28%) initial levels of use but demonstrated high skill utilization by the middle of the intervention. Results highlight the importance of examining individual differences in parents between session strategy use for behavioral parent training interventions targeting child and parenting outcomes.

Value-Generating Exploratory Trials in Neurodegenerative Dementias.

Drug development for Alzheimer disease and other neurodegenerative dementias, including frontotemporal dementia, has experienced a long history of phase 2 and phase 3 clinical trials that failed to show efficacy of investigational drugs. Despite differences in clinical and behavioral characteristics, these disorders have shared pathologies and face common challenges in designing early-phase trials that are predictive of late-stage success. Here, we discuss exploratory clinical trials in neurodegenerative dementias. These are generally phase 1b or phase 2a trials that are designed to assess pharmacologic effects and rely on biomarker outcomes, with shorter treatment durations and fewer patients than traditional phase 2 studies. Exploratory trials can establish go/no-go decision points, support proof of concept and dose selection, and terminate drugs that fail to show target engagement with suitable exposure and acceptable safety profiles. Early failure saves valuable resources including opportunity costs. This is especially important for programs in academia and small biotechnology companies but may be applied to high-risk projects in large pharmaceutical companies to achieve proof of concept more rapidly at lower costs than traditional approaches. Exploratory studies in a staged clinical development program may provide promising data to warrant the substantial resources needed to advance compounds through late-stage development. To optimize the design and application of exploratory trials, the Alzheimer's Drug Discovery Foundation and the Association for Frontotemporal Degeneration convened an advisory panel to provide recommendations on outcome measures and statistical considerations for these types of studies and study designs that can improve efficiency in clinical development.

Can School Mental Health Providers Deliver Psychosocial Treatment Improving Youth Attention and Behavior in Mexico? A Pilot Randomized Controlled Trial of CLS-FUERTE.

BACKGROUND: Despite well-established Evidence-Based Treatments (EBTs) for Attention-Deficit/Hyperactivity Disorder (ADHD) and Oppositional Defiant Disorder (ODD), many low-resource settings lack EBT access. METHODS: We conducted a school-clustered randomized controlled pilot of CLS-FUERTE (a multicomponent behavioral EBT adapted for children in Mexico) with 58 students. We randomly assigned four schools to receive CLS-FUERTE and four to receive school services as usual. We compared groups post-treatment on parent- and teacher-rated ADHD/ODD symptoms and impairment. RESULTS: CLS-FUERTE fidelity, attendance, engagement, and acceptability was high and students receiving CLS-FUERTE showed greater improvement in teacher-rated ADHD, ODD, and impairment, as well as parent-rated ADHD and impairment, compared to students receiving usual services. CONCLUSIONS: Pilot results suggest that psychosocial EBTs can be successfully implemented by School Mental Health Providers in Mexico.

Working Memory Capacity and ADHD Symptoms in Boys: Examining the Heterogeneity of Working Memory Functioning Using Latent Profile Analysis.

Recent studies demonstrate that working memory (WM) is integral to etiological models of ADHD; however, significant questions persist regarding the relation between WM performance across tasks with varying cognitive demands and ADHD symptoms. The current study incorporates an individual differences approach to WM heterogeneity (i.e., latent profile analysis) to (a) identify differential profiles of WM across the phonological and visuospatial WM subsystems; and (b) characterize differences in symptom presentation among WM profiles. Parent and teacher ratings of child behavior, obtained for boys with (n=51) and without (n=38) a diagnosis of ADHD, were compared across latent classes of visuospatial and phonological WM performance. Latent profile analysis identified three classes of WM functioning: Low WM, Moderate WM, and High WM. Membership in the Low and Moderate WM classes was associated with greater levels of parent- and teacher-rated inattentive and hyperactive symptoms. While 84% of the ADHD group were assigned to the Low and Moderate WM classes, more than a quarter of children without ADHD exhibited Moderate WM limitations. Collectively, these findings extend prior work suggesting that there is substantial heterogeneity in WM functioning in children with and without ADHD and that these differences contribute to the expression of symptoms of inattention and hyperactivity.

Do Parents' ADHD Symptoms Affect Treatment for their Children? The Impact of Parental ADHD on Adherence to Behavioral Parent Training for Childhood ADHD.

Nearly half of all youth with Attention-Deficit Hyperactivity Disorder (ADHD) have at least one parent who also meets criteria for the disorder, and intergenerational ADHD is a significant risk factor for poor outcomes following evidence-based behavioral parent training (BPT) programs. Given that BPT is predicated on consistent parental involvement, symptoms of ADHD in parents may be a significant barrier to effective engagement with BPT treatment. In the present investigation, we examine the effect of parental ADHD symptoms on BPT treatment engagement for children with ADHD-predominantly inattentive presentation (N = 148, ages 7-11). We examine the following parent- and clinician-rated treatment engagement domains: between-session skill adherence, in-session participation, perceived skill understanding, treatment-engagement attitudes, and session attendance. Parent- and clinician-rated between-session adherence was the only treatment engagement domain related significantly to parental ADHD symptoms. This finding was robust and remained even after accounting for symptoms of parental anxiety and depression, child ADHD symptom severity, and various sociodemographic factors (parental education level, household income, employment status, and being a single parent). These findings suggest that targeting parental ADHD symptoms in the context of parenting interventions may be a promising approach for improving adherence and treatment outcomes for BPT interventions.

The Use of Wearable Technology to Objectively Measure Sleep Quality and Physical Activity Among Pregnant Women in Urban Lima, Peru: A Pilot Feasibility Study.

INTRODUCTION: Sleep quality and physical activity can affect the mental and physical health of pregnant women and their babies in utero. METHODS: We investigated the feasibility of objectively assessing sleep quality and physical activity among resource-constrained, pregnant women in urban Lima, Peru. Twenty pregnant women were asked to complete written sleep logs and wear ActiSleep, a wristwatch-like device that records sleep quality (consecutive minutes of uninterrupted sleep) and physical activity (steps), for seven consecutive days. Sociodemographic data and pregnancy characteristics were also collected. RESULTS: Of twenty women, 13 (65%) had sufficient data collected for analysis. The mean age of study participants was 26.3 years (SD = 3.9), with a mean sleep duration of 6.9 h (SD = 1.4). The median time for sleep onset was 21:15. The mean time for sleep latency was 17.3 min; and wake after sleep onset was 116 min. The mean number of awakenings was 20.4 (SD = 6.7); and sleep efficiency was 77.9%. For physical activity, participants averaged of 6,029 steps per day (SD = 3,087). DISCUSSION: Objective assessment of sleep quality and physical activity among pregnant women in a resource-constrained setting was promising, despite modest data collection completeness. Wearable technology could be used in health interventions to improve sleep quality and physical activity among this population.

Association of stress-related sleep disturbance with psychiatric symptoms among pregnant women.

BACKGROUND: Physiological changes during pregnancy are often accompanied by reduced sleep quality, sleep disruptions, and insomnia. Studies conducted among men and non-pregnant women have documented psychiatric disorders as common comorbidities of insomnia and other sleep disorders. However, no previous study has examined the association between stress-related sleep disturbances and psychiatric disorders among pregnant women. METHODS: This cross-sectional study included a total of 2051 pregnant women in Peru. The Spanish-language version of the Ford Insomnia Response to Stress Test (FIRST-S) was used to assess sleep disruptions due to stressful situations. Symptoms of antepartum depression, generalized anxiety disorder, and posttraumatic stress disorder (PTSD) were examined using the Patient Health Questionnaire-9, Generalized Anxiety Disorder Scale-7 and PTSD Checklist - Civilian Version, respectively. High risk for psychosis was assessed using the Prodromal Questionnaire. Multivariable logistic regression procedures were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CI). RESULTS: Stress-related sleep disturbance was reported by 33.2% of women. Of all women, 24.9% had antepartum depression, 32.2% had generalized anxiety disorder, 30.9% had PTSD, and 27.6% were assessed as having a high risk of psychosis. After adjusting for confounders, women with stress-related sleep disturbances were more likely to experience antepartum depression (OR = 2.74; 95%CI: 2.22-3.38), generalized anxiety disorder (OR = 2.48; 95%CI: 2.04-3.02), PTSD (OR = 2.36; 95%CI: 1.93-2.88), and high risk for psychosis (OR = 2.07; 95%CI: 1.69-2.54) as compared to women without stress-related sleep disturbances. CONCLUSIONS: Stress-related sleep disturbances during pregnancy are associated with increased odds of psychiatric disorders. Inquiring about stress related sleep disturbances during antenatal care may be beneficial for identifying and caring for women at high risk of psychiatric disorders.

Association of social support and antepartum depression among pregnant women.

BACKGROUND: Few investigators have evaluated the association between early pregnancy social support and depression; however, increased social support may improve mental health during pregnancy. Our objective is to examine whether in early pregnancy there is an association between social support and maternal depression among women in Peru. METHODS: 2,062 pregnant women participated in structured interviews. Early pregnancy social support was measured using the Social Support Questionnaire (SSQ-6). We evaluated the number of individuals that participants could turn to in different situations (Social Support Number Score; SSQN) and their satisfaction with support received (Social Support Satisfaction Score; SSQS). Median SSQN and SSQS characterized participants according to high and low levels of support. SSQN family vs. non-family support were also evaluated separately. Antepartum depression was assessed using the Patient Health Questionnaire-9. Multivariable logistic regression procedures were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: 39.6% of women reported high SSQN and 45.5% reported high SSQS. Approximately 25% had antepartum depression. Women with high SSQN had 22% lower odds of antepartum depression (OR = 0.78; 95%CI: 0.63-0.97). Similarly, women with high SSQS scores had 45% lower odds of antepartum depression (OR = 0.55; 95%CI: 0.45-0.68). Women with high SSQN non-family scores had 30% lower odds antepartum depression compared to those with low SSQN non-family scores (OR = 0.70; 95%CI: 0.57-0.86). The association between SSQN family scores and antepartum depression did not reach statistical significance. CONCLUSION: Increased social support may improve maternal mental health during pregnancy and this association should be assessed in longitudinal studies.

An update on the utility and safety of cholinesterase inhibitors for the treatment of Alzheimer's disease.

Introduction: Alzheimer's disease (AD) is the most common cause of major neurocognitive disorders with a prevalence in the US of about 5.7 million in 2018. With the disease burden projected to increase dramatically in the coming years, it is imperative to review the current available treatment regimens for their safety and utility. The cholinesterase inhibitors (ChEIs) have continued to play a pivotal role in managing the symptoms and possibly slowing the rate of progression of AD since 1993. Owing to their being a mainstay in the treatment of AD, the safety and efficacy of prescribing these drugs needs to be reviewed often, especially with the approval of new formulations and doses.Areas covered: The three ChEIs currently approved by the FDA are donepezil, rivastigmine and galantamine. This article will review the safety and tolerability of these ChEIs and analyze the potential disease modifying properties of these drugs. The authors have reviewed all recent literature including review articles, meta-analyzes, clinical trials and more.Expert opinion: These ChEIs differ subtly in their mechanisms of action, in their tolerability and safety and FDA-approved indications. All are considered first-line, symptomatic treatments of the various phases of AD and may even have potentially disease-modifying effects.