Search

Introduction: Little is known regarding genetic factors associated with treatment outcome of psychotic depression. We explored genomic associations of remission and relapse of psychotic depression treated with pharmacotherapy. Methods: Genomic analyses were performed in 171 men and women aged 18–85 years with an episode of psychotic depression who participated in the Study of the Pharmacotherapy of Psychotic Depression II (STOP-PD II). Participants were treated with open-label sertraline plus olanzapine for up to 12 weeks; those who achieved remission or near-remission and maintained it following 8 weeks of stabilization were eligible to participate in a 36-week randomized controlled trial that compared sertraline plus olanzapine with sertraline plus placebo in preventing relapse. Results: There were no genome-wide significant associations with either remission or relapse. However, at a suggestive threshold, SNP rs1026501 (31 kb from SYNPO2) in the whole sample and rs6844137 (within the intronic region of SYNPO2) in the European ancestry subsample were associated with a decreased likelihood of remission. In polygenic risk analyses, participants who had greater improvement after antidepressant treatments showed a higher likelihood of reaching remission. Those who achieved remission and had a higher polygenic risk for Alzheimer’s disease had a significantly decreased likelihood of relapse. Conclusion: Our analyses provide preliminary insights into the genetic architecture of remission and relapse in a well-characterized group of patients with psychotic depression.

Evidence-based treatment options for late-life treatment-resistant depression (TRD) are limited. Ketamine is a promising treatment for TRD; however, there is a paucity of data on its safety and efficacy in older adults.In this pilot clinical trial, 25 adults aged ≥60 years with TRD received IV ketamine openly twice a week for 4 weeks; partial responders at the end of this acute phase were eligible to receive weekly infusions for 4 more weeks in a continuation phase. Acceptability, tolerability, and safety, including adverse and serious adverse events (AEs and SAEs), blood pressure changes, dissociation, craving, in addition to rates of depression response and remission were evaluated. The NIH Toolbox Cognitive Battery was used to assess specific measures of executive function (EF) and overall fluid cognition.Completion rates were 88% for the acute phase and 100% for the continuation phase. No AEs resulted in participant discontinuation, and there were no SAEs. Treatment-emergent elevation of blood pressure, dissociation, and craving were transient and did not result in any participant discontinuation. Depressive symptoms improved significantly and 48% of participants responded. During the acute phase, the EF measures and the fluid cognition composite score improved (Cohen's d = 0.61), and these improvements were sustained in the continuation phase.This pilot study suggests that repeated IV ketamine infusions are well-tolerated and are associated with improvement in depression and EF in older adults with TRD. These promising findings need to be confirmed and extended in a larger randomized controlled trial.

Psychotic depression has a high rate of relapse. The study aims were to identify a prediction model of risk of relapse of psychotic depression and examine whether predictors moderated the effect of treatment on relapse. One hundred and twenty-six men and women aged 18-85 years, who experienced sustained remission or near-remission of psychotic depression with sertraline plus olanzapine, participated in a 36-week randomized controlled trial that compared sertraline plus olanzapine with sertraline plus placebo in preventing relapse (NCT01427608). Cox regression analyses were performed to identify significant predictors of relapse and to model the combined role of significant predictors. Concordance statistic was calculated to determine the accuracy of the best fit multivariable models in predicting relapse. Finally, interaction terms were tested for each significant predictor to examine whether they moderated the effect of treatment on risk of relapse. Lifetime number of depressive episodes, severity of residual depressive symptoms at the time of randomization, and psychomotor disturbance both at acute enrollment when participants were depressed and at the time of randomization predicted risk of relapse. Multivariable models had 69-70% accuracy in predicting relapse. Psychomotor disturbance was associated with increased risk of relapse in the sertraline plus olanzapine group compared with sertraline plus placebo, whereas the other predictors did not moderate the effect of treatment on relapse. Future research is needed to determine whether a combination of clinical and biological variables can further increase the accuracy of prediction of relapse of psychotic depression.

Background Electroconvulsive therapy (ECT) is a procedural treatment that is potentially life-saving for some patients with severe psychiatric illness. At the start of the global coronavirus disease 2019 (COVID-19) pandemic, ECT practice was remarkably disrupted, putting vulnerable individuals at increased risk of symptom exacerbation and death by suicide. This study aimed to capture the self-reported experiences of psychiatrists based at healthcare facilities across Canadian provinces who were delivering ECT treatments during the first phase of the COVID-19 pandemic (i.e., from mid-March 2020 to mid-May 2020). Methods A multidisciplinary team of experts developed a survey focusing on five domains: ECT unit operations, decision-making, hospital resources, ECT procedure, and mitigating patient impact. Responses were collected from psychiatrists providing ECT at 67 ECT centres in Canada, grouped by four geographical regions (Ontario, Quebec, Atlantic Canada, and Western Canada). Results Clinical operations of ECT programs were disrupted across all four regions – however, centres in Atlantic Canada were able to best preserve outpatient and maintenance care, while centres in Western Canada were able to best preserve inpatient and acute care. Similarly, Atlantic and Western Canada demonstrated the best decision-making practices of involving the ECT team and clinical ethicists in the development of pandemic-related guidelines. Across all four regions, ECT practice was affected by the redeployment of professionals, the shortage of personal protective equipment, and the need to enforce social distancing. Attempts to introduce modifications to the ECT delivery room and minimize bag-valve-mask ventilation were consistently reported. All four regions developed a new patient prioritization framework, and Western Canada, notably, aimed to provide ECT to only the most severe cases. Conclusions The results suggest that ECT provision was disproportionately affected across different parts of Canada. Possible factors that could explain these interregional differences include population, distribution of urban vs. rural areas, pre-pandemic barriers in access to ECT, number of cases, ability to control the spread of infection, and the general reduction in physicians’ activities across different areas of health care. Studying these factors in the future will inform how medical centres should respond to public health emergencies and pandemic-related circumstances in the context of procedural treatments.

Recent work suggests that APOEɛ4/4 females with Alzheimer's disease (AD) are more susceptible to developing neuropsychiatric symptoms (NPS).To examine the interaction of sex and APOEɛ4 status on NPS burden using two independent cohorts: 1) patients at risk for AD with mild cognitive impairment and/or major depressive disorder (n = 252) and 2) patients with probable AD (n = 7,261).Regression models examined the interactive effects of sex and APOEɛ4 on the number of NPS experienced and NPS Severity. APOEɛ3/4 and APOEɛ4/4 were pooled in the at-risk cohort due to the sample size.In the at-risk cohort, there was a significant sex*APOEɛ4 interaction (p = 0.007) such that the association of APOEɛ4 with NPS was greater in females than in males (incident rate ratio (IRR) = 2.0). APOEɛ4/4 females had the most NPS (mean = 1.9) and the highest severity scores (mean = 3.5) of any subgroup. In the clinical cohort, APOEɛ4/4 females had significantly more NPS (IRR = 1.1, p = 0.001, mean = 3.1) and higher severity scores (b = 0.31, p = 0.015, mean = 3.7) than APOEɛ3/3 females (meanNPS = 2.9, meanSeverity = 3.3). No association was found in males.Our study suggests that sex modifies the association of APOEɛ4 on NPS burden. APOEɛ4/4 females may be particularly susceptible to increased NPS burden among individuals with AD and among individuals at risk for AD. Further investigation into the mechanisms behind these associations are needed.

Healthcare providers caring for people living with dementia may experience moral distress when faced with ethically challenging situations, such as the inability to provide care that is consistent with their values. The COVID-19 pandemic produced conditions in long-term care homes (hereafter referred to as ‘care homes’) that could potentially contribute to moral distress. We conducted an online survey to examine changes in moral distress during the pandemic, its contributing factors and correlates, and its impact on the well-being of care home staff. Survey participants (n = 227) working in care homes across Ontario, Canada were recruited through provincial care home organizations. Using a Bayesian approach, we examined the association between moral distress and staff demographics and roles, and characteristics of the long-term care home. We performed a qualitative analysis of the survey’s free-text responses. More than 80% of care home healthcare providers working with people with dementia reported an increase in moral distress since the start of the pandemic. There was no difference in the severity of distress by age, sex, role, or years of experience. The most common factors associated with moral distress were lack of activities and family visits, insufficient staffing and high turnover, and having to follow policies and procedures that were perceived to harm residents with dementia. At least two-thirds of respondents reported feelings of physical exhaustion, sadness/anxiety, frustration, powerlessness, and guilt due to the moral distress experienced during the pandemic. Respondents working in not-for-profit or municipal homes reported less sadness/anxiety and feelings of not wanting to go to work than those in for-profit homes. Front-line staff were more likely to report not wanting to work than those in management or administrative positions. Overall, we found that increases in moral distress during the pandemic negatively affected the well-being of healthcare providers in care homes, with preliminary evidence suggesting that individual and systemic factors may intensify the negative effect.

Theta-gamma coupling (TGC) is a neurophysiologic mechanism that supports working memory (WM). TGC is associated with N-back performance, a WM task. Similar to TGC, theta and alpha event-related synchronization (ERS) and desynchronization (ERD) are also associated with WM. Few studies have examined the longitudinal relationship between WM performance and TGC, ERS, or ERD. This study aimed to determine if changes in WM performance are associated with changes in TGC (primary aim), as well as theta and alpha ERS or ERD over 6 to 12 weeks. Participants included 62 individuals aged 60 and older with no neuropsychiatric conditions or with remitted Major Depressive Disorder (MDD) and no cognitive disorders. TGC, ERS, and ERD were assessed using electroencephalography (EEG) during the N-back task (3-back condition). There was an association between changes in 3-back performance and changes in TGC, alpha ERD and ERS, and theta ERS in the control group. In contrast, there was only a significant association between changes in 3-back performance and changes in TGC in the subgroup with remitted MDD. Our results suggest that the relationship between WM performance and TGC is stable over time, while this is not the case for changes in theta and alpha ERS and ERD.

Objectives The COVID-19 pandemic has disrupted the provision of essential and potentially life-saving procedural treatments such as electroconvulsive therapy (ECT). We surveyed ECT providers across Canada to understand how the first wave of the pandemic affected ECT delivery between mid-March 2020 and mid-May 2020. Methods The survey was administered to ECT team members and decision makers at 107 Canadian health care centers with a focus on 5 domains: operations, decision-making, hospital resources, ECT procedure, and patient impact. Responses were obtained from 72 institutions, and collected answers were used to derive representative responses reflecting the situation at each ECT center. For specific domains, responses were split into 2 databases representing the perspective of psychiatrists (n = 67 centers) and anesthesiologists (n = 24 centers). Results Provision of ECT decreased in 64% centers and was completely suspended in 27% of centers after the onset of the pandemic. Outpatient and maintenance ECT were more affected than inpatient and acute ECT. Programs reported a high level of collaboration between psychiatry and hospital leadership (59%) but a limited input from clinical ethicists (18%). Decisions were mostly made ad hoc leading to variability across institutions in adopted resource allocation, physical location of ECT delivery, and triaging frameworks. The majority of centers considered ECT to be aerosol-generating and incorporated changes to airway management. Conclusions Electroconvulsive therapy services in Canada were markedly disrupted by the COVID-19 pandemic. The variability in decision-making across centers warrants the development of a rational approach toward offering ECT in pandemic contexts.

Objective To evaluate the safety, tolerability, and effectiveness of repeated doses of intravenous (IV) ketamine in older adults (i.e., ≥60 years of age) with treatment-resistant depression. Method In this case series, fifty-three older adults (Mage = 67, SD = 6; 57% female [n = 30]) received 4 IV ketamine infusions, administered over 1–2 weeks. Effectiveness of IV ketamine was measured using the Quick Inventory for Depressive Symptomatology–Self Report 16 (QIDS-SR16) approximately 2 days after infusions 1–3, and 1–2 weeks after infusion 4. Safety was measured as hemodynamic changes before, during, immediately after, and 20 minutes after each infusion. Tolerability was assessed via systematic reporting of treatment-emergent adverse events during and after each infusion, in addition to symptoms of dissociation measured using the Clinician Administered Dissociative States Scale. Partial response (25%–50% symptomatic improvement from baseline), response (≥50% symptomatic improvement from baseline), clinically significant improvements (≥25% symptomatic improvement from baseline), and remission rates (QIDS-SR16 ≤5) were also calculated. Results Participants reported significant decreases in depressive symptoms (i.e., as measured by the QIDS-SR16) with repeated ketamine infusions (F(4, 92) = 7.412, p Conclusion Ketamine was associated with transient treatment-emergent hypertension. Response and remission rates were comparable to those reported in general adult samples. Findings are limited by the open-label, chart review nature of this study.

Objective To examine the effect of older versus younger age on change in anthropometric and metabolic measures during extended treatment of psychotic depression with sertraline plus olanzapine. Methods Two hundred and sixty-nine men and women aged 18–85 years with an episode of psychotic depression were treated with open-label sertraline plus olanzapine for up to 12 weeks. Participants who remained in remission following an 8-week stabilization phase were eligible to participate in a 36-week randomized controlled trial (RCT) that compared the efficacy and tolerability of sertraline plus olanzapine with sertraline plus placebo. Weight, waist circumference and plasma lipids, glucose, HbA1c, and insulin were measured at regular intervals during the acute, stabilization and randomized phases of the study. Linear mixed models were used to analyze the trajectories of anthropometric and metabolic measures. Results Participants aged 60 years or older experienced less weight gain and less increase in cholesterol during the combined acute and stabilization phases of the study compared with those aged 18–59 years. At the acute-stabilization termination visit, mean weight in older participants was 6.5 lb. less than premorbid weight, whereas it was 17.9 lb. more than premorbid weight in younger participants. In the RCT, there was a significant interaction of treatment and age group for the trajectory of weight, but the post hoc tests that compared age groups within each treatment arm were not statistically significant. There were no clinically significant differences between younger and older participants in glycemic measures. Conclusion Older patients with psychotic depression experienced less increase in weight and total cholesterol than their younger counterparts during acute and stabilization treatment with sertraline plus olanzapine. In the older group, weight gained during the acute and stabilization phases appeared to be partial restoration of weight lost during the index episode of depression, whereas weight gain in younger participants was not.

IntroductionThere has been growing interest in using real-time location systems (RTLS) in residential care settings. This technology has clinical applications for locating residents within a care unit and as a nurse call system, and can also be used to gather information about movement, location, and activity over time. RTLS thus provides health data to track markers of health and wellbeing and augment healthcare decisions. To date, no reviews have examined the potential use of RTLS data in caring for older adults with cognitive impairment living in a residential care setting.ObjectiveThis scoping review aims to explore the use of data from real-time locating systems (RTLS) technology to inform clinical measures and augment healthcare decision-making in the care of older adults with cognitive impairment who live in residential care settings.MethodsEmbase (Ovid), CINAHL (EBSCO), APA PsycINFO (Ovid) and IEEE Xplore databases were searched for published English-language articles that reported the results of studies that investigated RTLS technologies in persons aged 50 years or older with cognitive impairment who were living in a residential care setting. Included studies were summarized, compared and synthesized according to the study outcomes.ResultsA total of 27 studies were included. RTLS data were used to assess activity levels, characterization of wandering, cognition, social interaction, and to monitor a resident’s health and wellbeing. These RTLS-based measures were not consistently validated against clinical measurements or clinically important outcomes, and no studies have examined their effectiveness or impact on decision-making.ConclusionThis scoping review describes how data from RTLS technology has been used to support clinical care of older adults with dementia. Research efforts have progressed from using the data to track activity levels to, most recently, using the data to inform clinical decision-making and as a predictor of delirium. Future studies are needed to validate RTLS-based health indices and examine how these indices can be used to inform decision-making.

In the 1980s, the response rate of major depressive disorder with psychotic features (MDD-Psy) to placebo pills was reported to be close to 0%. To our knowledge, this placebo response rate has not been systematically reassessed. We undertook a systematic review of randomized controlled trials (RCTs) that have used a placebo or sham control group for MDD-Psy.We searched MEDLINE and identified 9 relevant publications reporting on 10 studies comparing a placebo or sham interventions versus an active intervention. We extracted reported rates of response or of dropout for all causes associated with placebo versus active intervention(s) and aggregated response and dropout rates across trials.Two sham-controlled electroconvulsive therapy (ECT) trials did not provide response rates. In the 3 pharmacotherapy studies published in the 1980s, 0 of 12 participants (0%) responded to placebo versus 13 of 38 (34.2%) responding to the active interventions. In contrast, 5 RCTs published in the 2000s, 114 of 339 participants (33.6%) randomized to placebo responded versus 149 of 373 participants (39.9%) randomized to active interventions; dropout rates were 71/236 (30.1%) for placebo versus 84/282 (29.8%) for the active interventions.As expected, response rates to placebo pills in RCTs for MDD-Psy increased markedly from the 1980s to the 2000s. Methodological issues in the design and conduct of more recent RCTs may have contributed to the high placebo response. However, one needs to consider this placebo response rate when interpreting the result of recent trials of MDD-Psy, which typically have not included a "pure" placebo condition.

BackgroundLittle is known about the relationship between psychomotor disturbance (PMD) and treatment outcome of psychotic depression. This study examined the association between PMD and subsequent remission and relapse of treated psychotic depression.MethodsTwo hundred and sixty-nine men and women aged 18–85 years with an episode of psychotic depression were treated with open-label sertraline plus olanzapine for up to 12 weeks. Participants who remained in remission or near-remission following an 8-week stabilization phase were eligible to participate in a 36-week randomized controlled trial (RCT) that compared the efficacy and tolerability of sertraline plus olanzapine (n = 64) with sertraline plus placebo (n = 62). PMD was measured with the psychiatrist-rated sign-based CORE at acute phase baseline and at RCT baseline. Spearman's correlations and logistic regression analyses were used to analyze the association between CORE total score at acute phase baseline and remission/near-remission and CORE total score at RCT baseline and relapse.ResultsHigher CORE total score at acute phase baseline was associated with lower frequency of remission/near-remission. Higher CORE total score at RCT baseline was associated with higher frequency of relapse, in the RCT sample as a whole, as well as in each of the two randomized groups.ConclusionsPMD is associated with poorer outcome of psychotic depression treated with sertraline plus olanzapine. Future research needs to examine the neurobiology of PMD in psychotic depression in relation to treatment outcome.

Purpose/background Electroconvulsive therapy (ECT) is effective in the treatment of acute episodes of psychotic depression. However, no adequately powered studies have directly investigated the efficacy of antipsychotic pharmacotherapy in relapse prevention of psychotic depression after ECT. In the absence of such literature, we reviewed the clinical practice of 4 academic medical centers that have made research contributions in the treatment of psychotic depression over the past 20 years. Methods/procedures We reviewed medical records of patients with a diagnosis of psychotic depression who received 1 or more acute courses of ECT over the span of 3 years. Chi-square tests were used to compare pharmacotherapy prescribed at the time of completion of ECT. Findings/results A total of 163 patients received 176 courses of ECT for separate episodes of psychotic depression. The combination of an antidepressant plus an antipsychotic was the most common regimen, ranging from 61.9% to 85.5% of all prescriptions. One center added lithium in 45.5% of cases treated with the combination of an antidepressant plus an antipsychotic. An antipsychotic alone was prescribed in less than 10% of cases. An antidepressant alone or other drug combinations were rare. Implications/conclusions The combination of an antidepressant plus an antipsychotic was the most commonly prescribed regimen at the completion of ECT for relapse prevention in patients with psychotic depression acutely treated with ECT. Although this report offers a view of the clinical practice of 4 academic medical centers, it also points to the need of randomized controlled trials on continuation pharmacotherapy after treatment of psychotic depression with ECT.

Objective This study tested the hypotheses that, in older adults with remitted major depression, a history of psychotic features and poorer neuropsychological performance would be independently associated with poorer everyday functioning, but that neuropsychological performance would explain more of the variance in functioning than history of psychotic features. Methods This cross-sectional study included 73 patients aged 50 years or older with remitted psychotic major depression or nonpsychotic major depression. The dependent variables were subjective and objective measures of function. The independent variables were history of psychotic features during one or more major depressive episodes in the previous 10 years and neuropsychological performance. Linear regression models examined the association of independent variables with function, controlling for pertinent covariates. Effect sizes were calculated for the magnitude of difference in function between the patient participants and an age- and gender-matched nonpsychiatric group, and distribution of functioning scores were compared between groups. Results In separate models, history of psychotic features and poorer processing speed, executive function, and verbal learning were independently associated with poorer participant-reported functioning and performance-based functioning. However, the association of psychotic features with functioning was no longer statistically significant when tested in the same models as neuropsychological measures. Effect sizes of the difference in functioning between patients and the nonpsychiatric group were significantly larger for the remitted psychotic than the remitted nonpsychotic depression group; functioning scores were more heterogeneous in the remitted psychotic depression group. Conclusion Patients with remitted psychotic depression exhibit greater, and clinically important, impairment in everyday functioning than those with remitted nonpsychotic depression. Neuropsychological impairment appears to contribute to this relationship.

Impaired insight into delusions is associated with a lower probability of remission of psychotic depression, independent of illness severity. The relationship between participant characteristics and impaired insight into delusions in remitted psychotic depression, and whether impaired insight is associated with risk of relapse of psychotic depression during continuation pharmacotherapy were examined.Data were analyzed from 126 participants in the STOP-PD II study who experienced sustained remission of psychotic depression during 8-week stabilization treatment with sertraline plus olanzapine and were then randomized to 36 weeks of continuation treatment with sertraline plus either olanzapine or placebo. Insight into delusions was assessed with the Resolution of Delusions Scale (RODS). Linear regression analyses examined the associations between participant characteristics and insight into delusions. Cox proportional-hazards models examined whether i) change in RODS during stabilization treatment; or ii) RODS at the end of stabilization treatment predicted risk of relapse during 36 weeks of continuation treatment.Severity of psychosis before initiation of treatment was the only participant characteristic associated with the change in insight during stabilization treatment. Neither change in insight during stabilization treatment nor insight at the end of stabilization treatment was associated with risk of relapse.Insufficient statistical power and the lack of variability in RODS scores at the time of randomization may have contributed to the absence of a relationship between RODS and risk of relapse.Residual or reemergent insight impairment following acute treatment does not preclude patients from sustaining remission of psychotic depression in a randomized placebo-controlled trial.

Background By the time Alzheimer's disease and related disorders (ADRD) are diagnosed, efficacy of treatments is limited. Preventive interventions are urgently needed. Objective To design a randomized controlled trial to assess a novel intervention that aims to prevent ADRD in high-risk groups. Methods We report on the rationale and describe the design of a multisite randomized controlled trial that aims to prevent ADRD in older persons with: (1) mild cognitive impairment (MCI); (2) remitted major depressive disorder (MDD) without MCI; or (3) remitted MDD with MCI. Results PACt-MD (Prevention of Alzheimer's dementia with Cognitive remediation plus transcranial direct current stimulation in Mild cognitive impairment and Depression) is a trial that randomized 375 older participants with MCI, MDD, or MCI + MDD to cognitive remediation (CR) plus transcranial direct current stimulation (tDCS) or sham-CR + sham-tDCS for 5 days/week for 8 weeks followed by boosters for 5 days/week once every 6 months until participants progress to MCI or ADRD, or the end of the study. Between boosters, participants are asked to train on CR daily. At baseline, end of 8 weeks, and yearly from baseline, participants undergo clinical, cognitive, and functional assessments. The primary aims are to compare the efficacy of CR + tDCS versus sham + sham in preventing: 1) long-term cognitive decline; and 2) incidence of ADRD or MCI. The secondary aim is to assess for cognitive improvement after the 8-week course. We will also explore the moderating and mediating effects of several biomarkers collected from the participants. Conclusion PACt-MD is unique in combining brain stimulation and a psychosocial intervention to prevent ADRD. PACt-MD is also a platform for studying multi-domain biomarkers that will advance our understanding of the relationships among MCI, MDD, and ADRD.

A history of depression is a risk factor for dementia. Despite strong epidemiologic evidence, the pathways linking depression and dementia remain unclear. We assessed structural brain alterations in white and gray matter of frontal-executive and corticolimbic circuitries in five groups of older adults putatively at-risk for developing dementia- remitted depression (MDD), non-amnestic MCI (naMCI), MDD+naMCI, amnestic MCI (aMCI), and MDD+aMCI. We also examined two other groups: non-psychiatric (“healthy”) controls (HC) and individuals with Alzheimer’s dementia (AD). Magnetic resonance imaging (MRI) data were acquired on the same 3T scanner. Following quality control in these seven groups, from diffusion-weighted imaging (n = 300), we compared white matter fractional anisotropy (FA), mean diffusivity (MD), and from T1-weighted imaging (n = 333), subcortical volumes and cortical thickness in frontal-executive and corticolimbic regions of interest (ROIs). We also used exploratory graph theory analysis to compare topological properties of structural covariance networks and hub regions. We found main effects for diagnostic group in FA, MD, subcortical volume, and cortical thickness. These differences were largely due to greater deficits in the AD group and to a lesser extent aMCI compared with other groups. Graph theory analysis revealed differences in several global measures among several groups. Older individuals with remitted MDD and naMCI did not have the same white or gray matter changes in the frontal-executive and corticolimbic circuitries as those with aMCI or AD, suggesting distinct neural mechanisms in these disorders. Structural covariance global metrics suggested a potential difference in brain reserve among groups.

Objective The objective of this study is to characterize functional competence (measure of assistance needed for independence) on Performance Assessment of Self-Care Skills (PASS) Cognitively Mediated Instrumental Activities of Daily Living (C-IADL), in individuals with amnestic mild cognitive impairment (aMCI). It aims to determine: (1) the association of functional competence on PASS C-IADL tasks with neurocognitive test performance in aMCI, (2) its ability to discriminate individuals with aMCI from healthy control (HC) individuals, and (3) its added value in discriminating aMCI from HC individuals when combined with neurocognitive test performance. Design Cross-sectional secondary analysis of baseline data from a cohort of individuals enrolled in a clinical trial (NCT02386670). Setting Five university-affiliated outpatient clinics in Toronto, Canada. Participants aMCI (N = 137) and HC (N = 51) participants, all aged 60 years or older. Methods We assessed the relationship between functional competence on three C-IADL PASS tasks (shopping, bill paying, and checkbook balancing) and neurocognitive tests in 137 participants with aMCI using multiple linear regressions. Additionally, we constructed receiver operating characteristic curves to assess the role of PASS functional competence in discriminating between 137 aMCI and 51 HC participants. Results Functional competence on PASS was significantly associated with tests of verbal memory, information processing speed, and executive function. It demonstrated 79% accuracy in discriminating aMCI from HC participants. Combining functional competence on PASS with individual neurocognitive tests significantly increased the discriminant accuracy of individual tests, and neurocognitive test scores combined with functional competence on PASS had the highest discriminant accuracy (94%). Conclusion Functional competence on PASS is predicted by the underlying cognitive deficits and possibly captures additional element of effort that could improve the diagnostic accuracy of aMCI when combined with neurocognitive tests. Thus, PASS appears to be a promising tool for assessment of functional competence in aMCI in clinical or research settings. J Am Geriatr Soc 68:1787-1795, 2020.

Major depressive disorder with psychotic features (psychotic depression) is a severe disorder. Compared with other psychotic disorders such as schizophrenia, relatively few studies on the neurobiology of psychotic depression have been pursued. Neuroimaging studies investigating psychotic depression have provided evidence for distributed structural brain abnormalities implicating the insular cortex and limbic system. We examined structural brain networks in participants (N = 245) using magnetic resonance imaging. This sample included healthy controls (n = 159) and the largest cross-sectional sample of patients with remitted psychotic depression (n = 86) collected to date. All patients participated in the Study of Pharmacotherapy of Psychotic Depression II randomized controlled trial. We used a novel, whole-brain, data-driven parcellation technique-non-negative matrix factorization-and applied it to cortical thickness data to derive structural covariance networks. We compared patients with remitted psychotic depression to healthy controls and found that patients had significantly thinner cortex in five structural covariance networks (insular-limbic, occipito-temporal, temporal, parahippocampal-limbic, and inferior fronto-temporal), confirming our hypothesis that affected brain networks would incorporate cortico-limbic regions. We also found that cross-sectional depression and severity scores at the time of scanning were associated with the insular-limbic network. Furthermore, the insular-limbic network predicted future severity scores that were collected at the time of recurrence of psychotic depression or sustained remission. Overall, decreased cortical thickness was found in five structural brain networks in patients with remitted psychotic depression and brain-behavior relationships were observed, particularly between the insular-limbic network and illness severity.

The common requirement to set the time to "10 past 11" on the Clock Drawing Test is intended to elicit a stimulus bound response (SBR), in which the responder is "pulled" to the salient stimulus "10," resulting in hands set at "10 before 11." SBRs are considered markers of executive dysfunction, although this assumption has not yet been validated. We compared SBR and other time-setting errors on inhibitory control tests, hypothesizing that they represent related constructs. The role of semantic dysfunction in the formation of those errors was also investigated. We examined baseline test performance of participants with Mild Cognitive Impairment or a history of depression, and control participants, enrolled in a dementia prevention study. Among 258 participants, we identified clocks with SBRs (

Investigating effects of aging on neurophysiological mechanisms underlying working memory provides a better understanding of potential targets for brain intervention to prevent cognitive decline. Theta-gamma coupling (TGC) indexes the ability to order information processed during working memory tasks. Frontal theta event-related synchronization (ERS) and parietal alpha event-related desynchronization (ERD) index cognitive control and interference inhibition, respectively. Relative contributions of TGC, theta ERS, and alpha ERD in relation to stimulus presentation are not characterized. Further, differential effect of normal aging on pre- or post-stimulus processes is unknown. Electroencephalography was recorded in 66 younger and 41 older healthy participants while performing 3-back working memory task. We assessed relationships between 3-back task performance and each of post-stimulus TGC, pre-stimulus parietal alpha ERD, and pre-stimulus frontal theta ERS in each age group. While older adults performed worse on 3-back task than younger adults, TGC, alpha ERD, or theta ERS did not differ between the two groups. TGC was positively associated with 3-back performance in both age groups; pre-stimulus alpha ERD was associated with performance among younger adults; and pre-stimulus theta ERS was not associated with performance in either group. Our findings suggest that both pre-stimulus interference inhibition and post-stimulus ordering of information are important for working memory in younger adults. In contrast, performance in older adults appears to depend only on post-stimulus ordering of information. These specific contributions of neurophysiological resources may explain the poorer performance of older adults and suggest different targets to enhance working memory in age groups. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11357-022-00577-5.

Major depressive disorder (MDD) is associated with an increased risk of developing dementia. The present study aimed to better understand this risk by comparing resting state functional connectivity (rsFC) in the executive control network (ECN) and the default mode network (DMN) in older adults with MDD or mild cognitive impairment (MCI). Additionally, we examined the association between rsFC in the ECN or DMN and cognitive impairment transdiagnostically. We assessed rsFC alterations in ECN and DMN in 383 participants from five groups at-risk for dementia-remitted MDD with normal cognition (MDD-NC), non-amnestic mild cognitive impairment (naMCI), remitted MDD + naMCI, amnestic MCI (aMCI), and remitted MDD + aMCI-and from healthy controls (HC) or individuals with Alzheimer's dementia (AD). Subject-specific whole-brain functional connectivity maps were generated for each network and group differences in rsFC were calculated. We hypothesized that alteration of rsFC in the ECN and DMN would be progressively larger among our seven groups, ranked from low to high according to their risk for dementia as HC, MDD-NC, naMCI, MDD + naMCI, aMCI, MDD + aMCI, and AD. We also regressed scores of six cognitive domains (executive functioning, processing speed, language, visuospatial memory, verbal memory, and working memory) on the ECN and DMN connectivity maps. We found a significant alteration in the rsFC of the ECN, with post hoc testing showing differences between the AD group and the HC, MDD-NC, or naMCI groups, but no significant alterations in rsFC of the DMN. Alterations in rsFC of the ECN and DMN were significantly associated with several cognitive domain scores transdiagnostically. Our findings suggest that a diagnosis of remitted MDD may not confer functional brain risk for dementia. However, given the association of rs-FC with cognitive performance (i.e., transdiagnostically), rs-FC may help in stratifying this risk among people with MDD and varying degrees of cognitive impairment.

Data consists of baseline clinical assessments of gait, mobility, and fall risk at the time of admission of 54 adults with dementia. Furthermore, it includes the participants' daily medication intake in three medication categories, and frequent assessments of gait performed via a computer vision-based ambient monitoring system.

Background Some patients with major depression continue to demonstrate deficits in health-related quality of life (HRQL) following remission. No data exist, however, regarding HRQL in remitted psychotic depression. In this study, we aimed to characterize HRQL in patients with psychotic depression receiving controlled pharmacotherapy. Methods This is a secondary analysis of a randomized controlled trial studying continuation pharmacotherapy of psychotic depression. We compared participants’ HRQL (measured using the SF-36) between baseline and remission and to population norms. We also compared SF-36 scores stratified by age and gender and examined the correlation between SF-36 scores and medical burden, depression score and neuropsychological performance in remission. Results SF-36 scores were significantly lower than population norms at baseline, but improved following remission to the level of population norms. Neither SF-36 scores nor magnitude of SF-36 improvement differed substantially between genders or between younger and older participants. In remission, depression scores were correlated with most SF-36 scales and medical burden was correlated with SF-36 scales measuring physical symptoms. Neuropsychological measures were generally not correlated with SF-36 scores. Limitations This study was a secondary analysis not powered specifically to measure HRQL as an outcome variable and the SF-36 was the only HRQL measure used. Conclusions Participants with remitted psychotic depression demonstrated levels of HRQL comparable to population norms, despite marked impairment in HRQL when acutely ill. This finding suggests that, when treated in a rigorous manner, many patients with this severe illness improve significantly from a clinical and HRQL perspective.

Background Gait impairments contribute to falls in people with dementia. In this study, we used a vision-based system to record episodes of walking over a 2-week period as participants moved naturally around their environment, and from these calculated spatiotemporal, stability, symmetry, and acceleration gait features. The aim of this study was to determine whether features of gait extracted from a vision-based system are associated with falls, and which of these features are most strongly associated with falling. Methods Fifty-two people with dementia admitted to a specialized dementia unit participated in this study. Thirty different features describing baseline gait were extracted from Kinect recordings of natural gait over a 2-week period. Baseline clinical and demographic measures were collected, and falls were tracked throughout the participants’ admission. Results A total of 1,744 gait episodes were recorded (mean 33.5 ± 23.0 per participant) over a 2-week baseline period. There were a total of 78 falls during the study period (range 0–10). In single variable analyses, the estimated lateral margin of stability, step width, and step time variability were significantly associated with the number of falls during admission. In a multivariate model controlling for clinical and demographic variables, the estimated lateral margin of stability (p = .01) was remained associated with number of falls. Conclusions Information about gait can be extracted from vision-based recordings of natural walking. In particular, the lateral margin of stability, a measure of lateral gait stability, is an important marker of short-term falls risk.

Background Previous studies examining the link between neuropsychiatric symptoms (NPS) and biomarkers of Alzheimer's disease (AD) may be confounded by remitted or past history of psychiatric illness, which in itself is associated with AD biomarkers such as reduced medial temporal lobe (MTL) volume. Objective We examined associations between mood and anxiety-related NPS and MTL in older adults with mild cognitive impairment (MCI) free of lifetime history of depression. We hypothesized an inverse relationship between NPS severity and MTL. Methods Forty-two MCI participants without current or past history of depression or other major psychiatric illness were assessed using the Neuropsychiatric Inventory-Questionnaire (NPI-Q). Correlation and regression analyses were performed between selected NPI-Q items and regional MTL volumes from structural magnetic resonance imaging. Results Sleep disturbances were inversely associated with several regional volumes within the MTL. Sleep disturbances remained significantly correlated with left hippocampal and amygdala volume following correction for multiple comparisons. In contrast, depression and anxiety were not correlated with MTL. Conclusions The relationship between reduced MTL and sleep, but not with depressed or anxious states, in MCI free of lifetime history of depression, suggests a potential mechanism for sleep as a risk factor for AD. The current findings highlight the importance of accounting for remitted psychiatric conditions in studies of the link between NPS and AD biomarkers and support the need for further research on sleep as clinical biomarker of AD and target for AD prevention.

While several studies have found that neural oscillations play a key role in the functioning of working memory, the nature of aberrant oscillatory activity underlying working memory impairments in Alzheimer's disease (AD) and mild cognitive impairment (MCI) remains largely unexplored. These individuals often display structural alterations in brain regions and pathways involved in working memory processes and therefore may also display altered oscillatory activity during memory activation. Electroencephalographic (EEG) activity was recorded during the N-back working memory task in three groups: AD (n = 29), MCI (n = 100), and healthy controls (HCs; n = 40). Theta (4-7 Hz) and alpha (7.5-12 Hz) modulation was measured in response to the stimulus presentation during correct and incorrect responses. This modulation represents the change in EEG activity associated with the stimulus onset and was measured as a ratio of post stimulus power to pre stimulus power. We also assessed the relationship between change in oscillatory power and working memory performance. Compared to HCs, the AD group demonstrated the lowest working memory accuracy and a smaller theta ratio for correct responses on the 2-back condition; the MCI group demonstrated a smaller theta ratio for correct responses on the 3-back condition. Finally, we observed that the theta ratio, but not the alpha ratio, was a significant predictor of working memory performance in the three groups for all conditions. Taken together, these behavioral and electrophysiological results suggest that in addition to impairments in working memory performance, modulation of theta, but not alpha power, may be impaired in MCI and AD.

The CORE instrument is commonly used to measure psychomotor disturbance. We examined the factor structure of the CORE in 266 adults with an acute episode psychotic depression, a disorder with a high rate of psychomotor disturbance. Exploratory factor analysis identified a two-factor solution: Factor 1 corresponded to the CORE's retardation and non-interactiveness items and Factor 2 corresponded to its agitation items. Internal consistency was excellent for Factor 1 but questionable for Factor 2. These findings suggest that the CORE's retardation and non-interactiveness items should be combined in one subscale when assessing patients with an acute episode of psychotic depression.

Objectives:To compare the prevalence of select cardiovascular risk factors (CVRFs) in patients with mild cognitive impairment (MCI) versus lifetime history of major depression disorder (MDD) and a normal comparison group using baseline data from the Prevention of Alzheimer’s Dementia with Cognitive Remediation plus Transcranial Direct Current Stimulation (PACt-MD) study.Design:Baseline data from a multi-centered intervention study of older adults with MCI, history of MDD, or combined MCI and history of MDD (PACt-MD) were analyzed.Setting:Community-based multi-centered study based in Toronto across 5 academic sites.Participants:Older adults with MCI, history of MDD, or combined MCI and history of MDD and healthy controls.Measurements:We examined the baseline distribution of smoking, hypertension and diabetes in three groups of participants aged 60+ years in the PACt-MD cohort study: MCI (n = 278), MDD (n = 95), and healthy older controls (n = 81). Generalized linear models were fitted to study the effect of CVRFs on MCI and MDD as well as neuropsychological composite scores.Results:A higher odds of hypertension among the MCI cohort compared to healthy controls (p < .05) was noted in unadjusted analysis. Statistical significance level was lost on adjusting for age, sex and education (p > .05). A history of hypertension was associated with lower performance in composite executive function (p < .05) and overall composite neuropsychological test score (p < .05) among a pooled cohort with MCI or MDD.Conclusions:This study reinforces the importance of treating modifiable CVRFs, specifically hypertension, as a means of mitigating cognitive decline in patients with at-risk cognitive conditions.

OBJECTIVE This study compared diagnostic rates and clinical predictors of discrepancies between diagnoses conferred via: 1) a comprehensive neuropsychological evaluation and National Institute on Aging–Alzheimer's Association (NIA-AA) criteria versus 2) a cognitive screener and Diagnostic Statistical Manual of Mental Disorders (DSM-5) criteria. DESIGN Cross-sectional examination of baseline data from the P revention of Al zheimer's dementia (AD) using C ognitive remediation and t ranscranial direct current stimulation in Mild Cognitive Impairment (MCI) and D epression (PACt-MD; ClinicalTrials.gov Identifier: NCT02386670) trial. SETTING Five geriatric psychiatry and memory clinics located at academic hospitals affiliated with the Department of Psychiatry, University of Toronto. PARTICIPANTS Older adults (N = 431) with a history of major depressive disorder (MDD) in remission, MCI, or both. MEASUREMENTS Main outcome was a comparison of NIA-AA diagnostic rates of MCI or dementia versus DSM-5 rates of mild or major neurocognitive disorder. Secondary analyses examined demographic, race, gender, premorbid intellectual ability, psychosocial, health-related, and genetic predictors of discrepancy between DSM-5 and NIA-AA diagnoses. RESULTS There were 103 (23.8%) discrepant cases, with most (91; 88.3%) of these discrepant cases reflecting more impairment with the detailed neuropsychological testing and NIA-AA criteria. Discrepancies were more likely in individuals with a history of MDD or who had at least one ApoE4 allele. CONCLUSION The NIA-AA criteria, in conjunction with comprehensive neuropsychological testing, identified a greater prevalence of cognitive impairment than DSM-5 criteria, in conjunction with the Montreal Cognitive Assessment. Detailed neuropsychological evaluations are recommended for older adults who have a history of MDD or a genetic vulnerability to dementia.

Introduction: Major depressive disorder (MDD) is associated with hypothalamic-pituitary-adrenal axis dysfunction that may persist into remission. Preliminary evidence suggests that this dysfunction may be associated with impaired neuropsychological performance in remitted MDD. MDD with psychotic features (“psychotic depression”) is associated with greater neuropsychological and functional impairment than nonpsychotic depression, including in remission. Therefore, the aim of this exploratory study was to examine the relationships among hair cortisol concentration (HCC) – a marker of longer term endogenous cortisol exposure – and history of psychotic features, neuropsychological performance, and functioning in remitted MDD. Methods: This cross-sectional study compared the relationship between HCC and (i) history of psychosis, (ii) neuropsychological performance, and (iii) everyday functioning in a group of 60 participants with remitted later-life MDD using Pearson’s correlation coefficients. This study also measured HCC in a group of 36 nonpsychiatric volunteers to examine the clinical significance of HCC in the patient group. Results: There were no statistically significant correlations between HCC and history of psychotic features, neuropsychological performance, or functioning. Furthermore, there was no clinically meaningful difference in HCC between patients and nonpsychiatric volunteers. Conclusion: This study is the first to examine HCC in psychotic depression. The results do not support the hypothesis that impaired neuropsychological performance, and everyday function in remitted psychotic depression is due to a sustained elevation of cortisol.

Objectives Validated diagnostic interviews are required to classify depression status and estimate prevalence of disorder, but screening tools are often used instead. We used individual participant data meta-analysis to compare prevalence based on standard Hospital Anxiety and Depression Scale – depression subscale (HADS-D) cutoffs of ≥8 and ≥11 versus Structured Clinical Interview for DSM (SCID) major depression and determined if an alternative HADS-D cutoff could more accurately estimate prevalence. Methods We searched Medline, Medline In-Process & Other Non-Indexed Citations via Ovid, PsycINFO, and Web of Science (inception-July 11, 2016) for studies comparing HADS-D scores to SCID major depression status. Pooled prevalence and pooled differences in prevalence for HADS-D cutoffs versus SCID major depression were estimated. Results 6005 participants (689 SCID major depression cases) from 41 primary studies were included. Pooled prevalence was 24.5% (95% Confidence Interval (CI): 20.5%, 29.0%) for HADS-D ≥8, 10.7% (95% CI: 8.3%, 13.8%) for HADS-D ≥11, and 11.6% (95% CI: 9.2%, 14.6%) for SCID major depression. HADS-D ≥11 was closest to SCID major depression prevalence, but the 95% prediction interval for the difference that could be expected for HADS-D ≥11 versus SCID in a new study was −21.1% to 19.5%. Conclusions HADS-D ≥8 substantially overestimates depression prevalence. Of all possible cutoff thresholds, HADS-D ≥11 was closest to the SCID, but there was substantial heterogeneity in the difference between HADS-D ≥11 and SCID-based estimates. HADS-D should not be used as a substitute for a validated diagnostic interview.

Highlights • What is the primary question addressed by this study? What strategies can used in the nursing home setting to ensure the safe, effective, and compassionate quarantine of dementia patients with symptoms of COVID-19? • What is the main finding of this study? While there is a clear ethical and legal basis for the involuntary confinement of people with dementia, the potential for unintended harm with these interventions is high, and there is little guidance for nursing homes on how to isolate safely, while maintaining the human dignity and personhood of the individual with dementia. To address these gaps, there needs to be an urgent investment in proper staffing, training, and safe equipment in the nursing home sector. • What is the meaning of the finding? Nursing homes that have not yet been impacted by COVID-19 have a narrow window of opportunity to prepare for the isolation of residents with dementia and front-line staff are now looking to their leadership and government bodies to help prepare to take these actions as safely and compassionately as possible, Nursing homes are facing the rapid spread of COVID-19 among residents and staff and are at the centre of the public health emergency due to the COVID-19 pandemic. As policy changes and interventions designed to support nursing homes are put into place, there are barriers to implementing a fundamental, highly effective element of infection control, namely the isolation of suspected or confirmed cases. Many nursing home residents have dementia, associated with impairments in memory, language, insight and judgment that impact their ability to understand and appreciate the necessity of isolation and to voluntarily comply with isolation procedures. While there is a clear ethical and legal basis for the involuntary confinement of people with dementia, the potential for unintended harm with these interventions is high, and there is little guidance for nursing homes on how to isolate safely, while maintaining the human dignity and personhood of the individual with dementia. In this commentary, we discuss strategies for effective, safe and compassionate isolation care planning, and present a case vignette of a person with dementia who is placed in quarantine on a dementia unit.

Objective We conducted a 12-week double-blind study of stabilization pharmacotherapy in patients with remitted psychotic depression (PD). Methods Seventy-one persons aged 18 years or older who had achieved remission of PD when randomized to either olanzapine plus sertraline or olanzapine plus placebo were continued on the double-blind treatment associated with remission. Symptoms of depression and psychosis, and weight, were measured once every 4 weeks. Cholesterol, triglycerides, and glucose were measured at stabilization phase baseline and Week 12/termination. Results The effect of treatment did not significantly change with time for depression, weight, or metabolic measures in the stabilization phase. Eight of the 71 participants (11.3%; 95% CI: 5.8, 20.7) experienced a relapse of major depression, psychosis, or both. Treatment groups did not differ in the frequency of relapse. In the entire study group, the adjusted estimate for change in weight was an increase of 1.66 kg (95% CI: 0.83, 2.48) and the adjusted estimate for change in total cholesterol was a decrease of 14.8 mg/dL (95% CI: 3.5, 26.1) during the 12-week stabilization phase; the remaining metabolic measures did not significantly change. Conclusion Continuation of acute treatment was associated with stability of remission.

Purpose of review This article provides a synopsis of the current understanding of the pathophysiology of anxiety disorders, the biological and environmental risk factors that contribute to their development and maintenance, a review of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic criteria, and a practical approach to the treatment of anxiety disorders in adults. Recent findings Despite the ubiquity of anxiety, the evidence is that most individuals with an anxiety disorder are not identified and do not receive guideline-level care. In part, this may be because of the manifold clinical presentations of anxiety disorders and clinicians' lack of confidence in accurately diagnosing and treating these conditions, especially in nonpsychiatric settings. Anxiety disorders represent the complex interplay between biological, psychological, temperamental, and environmental factors. Converging lines of evidence point to dysfunction in regulating activity in the "threat circuit" in the brain as a putative common pathophysiology underlying anxiety disorders. Evidence-based treatments for anxiety disorders, such as cognitive-behavioral therapy and antidepressant medications, have been shown to regulate activity in this circuit, which consists of reciprocal connections between the dorsomedial prefrontal cortex, insula, and amygdala. Summary Anxiety disorders are the most common class of emotional disorders and a leading cause of disability worldwide. A variety of effective treatment strategies are available, which may exert their therapeutic benefits from top-down or bottom-up modulation of the dysfunctional brain activity associated with anxiety disorders.

Although the antidepressant efficacy of ECT is well documented, patient-reported outcomes after this treatment are less well characterized. The aims of the current meta-analysis are to quantify the impact of an acute course of ECT on health-related quality of life (HRQoL) and to identify related moderators, specifically post-ECT depressive symptom remission and patient age.We searched PubMed, PsycINFO, and Web of Science databases for randomized and nonrandomized studies that report on changes in HRQoL measures after an acute course of ECT. Only studies that used the Medical Outcomes Study Short Form 36 (SF-36) instrument were included. A random effects model using the Hedges' g effect size was used in calculating the pre-post ECT outcomes on all 8 SF-36 subscales and the SF-36 total scores including the physical and mental composite scores. Subgroup analyses were conducted using remission status and age as moderators.Four studies contributed to this analysis. Significant improvements across all subscales of the SF-36 were observed. Large and very large effect sizes were present for both the SF-36 physical component score (PCS) and mental health component score (MCS), with the change in MCS being statistically superior to the PCS (MCS, Hedges' g = 1.28; 95% confidence interval, 1.15-1.42; PCS, Hedges' g = 0.97; 95% confidence interval, 0.86-1.07). Medium, large, and very large effect sizes were observed for SF-36 subscales scores. Post-ECT depression remission status was related to HRQoL improvement, with statistically significant differences present between remitters and nonremitters for PCS, MCS, and most SF-36 subscale scores. No significant differences were observed in improvement in HRQoL with ECT based on patient age.An acute course of ECT for depressive symptoms produces medium to very large effect size improvements in HRQoL across multiple components and subscales measured by the SF-36. The magnitude of the effects reported by ECT patients is greater than those that have been reported in other open-label studies of brain stimulation techniques. This study confirms that ECT plays a vital role in the treatment of the most severely ill patients with depressive disorders.

Falls are viewed as a preventable cause of injury, functional loss, and death in older adults with dementia, and have been used as a marker of quality of care in long-term care facilities. Despite intensive intervention around fall prevention in these settings, falls and injury remain frequent, particularly among residents in the advanced stages of dementia. In this clinical review, we consider the common challenges and pitfalls in both the management of falls and the provision of palliative care in advanced dementia. We then describe a palliative approach to falls in advanced dementia that involves identifying individuals who would benefit from this care approach, framing falls and loss of mobility as a quality of life issue, and devising an individualized symptom assessment and management plan. A palliative approach can lead to recognition and acceptance that recurrent falls are often symptomatic of advanced dementia, and that not all falls are preventable. We conclude that falls in the advanced stage of dementia can be sentinel events indicating the need for a palliative approach to care. Rather than replace falls prevention activities, a palliative approach to falls prompts us to select dementia stage-appropriate interventions with a focus on symptom management, comfort, and dignity.