Alzheimer's disease (AD) is the most common cause for dementia worldwide. Until recently, all approved treatments for AD were symptomatic and not disease modifying. On 7 June 2021, the US FDA ...approved aducanumab, a human IgG1 anti-Aβ monoclonal antibody selective for Aβ aggregates, as the first disease-modifying treatment for AD. Aducanumab is approved in the United States for the treatment of mild cognitive impairment or mild-dementia stage of AD. In this Editorial, we review the trial data for aducanumab in the treatment of AD and the controversies that its approval has generated.
Accumulating evidence demonstrates that metabolic changes in the brain associated with neuroinflammation, oxidative stress, and mitochondrial dysfunction play an important role in the pathophysiology ...of mild cognitive impairment (MCI) and Alzheimer’s disease (AD). However, the neural signatures associated with these metabolic alterations and underlying molecular mechanisms are still elusive. Accordingly, we reviewed the literature on in vivo human brain 1H and 31P-MRS studies and use meta-analyses to identify patterns of brain metabolic alterations in MCI and AD. 40 and 39 studies on MCI and AD, respectively, were classified according to brain regions. Our results indicate decreased N-acetyl aspartate and creatine but increased myo-inositol levels in both MCI and AD, decreased glutathione level in MCI as well as disrupted energy metabolism in AD. In addition, the hippocampus shows the strongest alterations in most of these metabolites. This meta-analysis also illustrates progressive metabolite alterations from MCI to AD. Taken together, it suggests that 1) neuroinflammation and oxidative stress may occur in the early stages of AD, and likely precede neuron loss in its progression; 2) the hippocampus is a sensitive region of interest for early diagnosis and monitoring the response of interventions; 3) targeting bioenergetics associated with neuroinflammation/oxidative stress is a promising approach for treating AD.
•Neuroinflammation and oxidative stress (OS) may occur in the early stages of AD.•Neuroinflammation and OS likely precede neuronal loss in AD.•The hippocampus is the most vulnerable brain region in the progression of AD.
Current prescribing practices for major depressive disorder (MDD) produce limited treatment success. Although pharmacogenomics may improve outcomes by identifying genetically inappropriate ...medications, studies to date were limited in scope. Outpatients (N = 1167) diagnosed with MDD and with a patient- or clinician-reported inadequate response to at least one antidepressant were enrolled in the Genomics Used to Improve DEpression Decisions (GUIDED) trial – a rater- and patient-blind randomized controlled trial. Patients were randomized to treatment as usual (TAU) or a pharmacogenomics-guided intervention arm in which clinicians had access to a pharmacogenomic test report to inform medication selections (guided-care). Medications were considered congruent (‘use as directed’ or ‘use with caution’ test categories) or incongruent (‘use with increased caution and with more frequent monitoring’ test category) with test results. Unblinding occurred after week 8. Primary outcome was symptom improvement change in 17-item Hamilton Depression Rating Scale (HAM-D17) at week 8; secondary outcomes were response (≥50% decrease in HAM-D17) and remission (HAM-D17 ≤ 7) at week 8. At week 8, symptom improvement for guided-care was not significantly different than TAU (27.2% versus 24.4%, p = 0.107); however, improvements in response (26.0% versus 19.9%, p = 0.013) and remission (15.3% versus 10.1%, p = 0.007) were statistically significant. Patients taking incongruent medications prior to baseline who switched to congruent medications by week 8 experienced greater symptom improvement (33.5% versus 21.1%, p = 0.002), response (28.5% versus 16.7%, p = 0.036), and remission (21.5% versus 8.5%, p = 0.007) compared to those remaining incongruent. Pharmacogenomic testing did not significantly improve mean symptoms but did significantly improve response and remission rates for difficult-to-treat depression patients over standard of care (ClinicalTrials.gov NCT02109939).
The rapidly increasing population living with dementia presents a unique economic and public health challenge. However, primary care physicians, despite their position as first-line providers, often ...lack the time, support, and training to systematically screen for, diagnose, and treat dementia, as well as provide adequate psychosocial support to unpaid caregivers. Models of collaborative care, which have found success in reducing symptom severity and increasing quality of life for other chronic illnesses, have been studied for feasibility, efficacy, and cost effectiveness in treating individuals with dementia and supporting caregivers. A review of initial data from several models suggests that enrollment in a collaborative care program for dementia is associated with benefits such as reduction in behavioral symptoms of dementia, improved functioning and quality of life, less frequent utilization of acute medical services, and decrease in caregiver burden. These evidence-based models, if implemented widely, stand to facilitate delivery of highly effective dementia care while reducing associated total medical expense. In this narrative review, we examine the key components of collaborative care teams, summarize outcomes of prior studies and discuss barriers and opportunities for wider dissemination of collaborative care models that are partnered with and/or based within primary care settings.
This meta-analysis of randomized controlled trials (RCTs) examined the efficacy and safety of the combination of electroconvulsive therapy (ECT) and antipsychotic medication (except for clozapine) ...versus the same antipsychotic monotherapy for treatment-resistant schizophrenia (TRS). Two independent investigators extracted data for a random effects meta-analysis and pre-specified subgroup and meta-regression analyses. Weighted and standard mean difference (WMD/SMD), risk ratio (RR) ±95% confidence intervals (CIs), number needed to treat (NNT), and number needed to harm (NNH) were calculated. Eleven studies (n = 818, duration = 10.2±5.5 weeks) were identified for meta-analysis. Adjunctive ECT was superior to antipsychotic monotherapy regarding (1) symptomatic improvement at last-observation endpoint with an SMD of -0.67 (p<0.00001; I2 = 62%), separating the two groups as early as weeks 1–2 with an SMD of -0.58 (p<0.00001; I2 = 0%); (2) study-defined response (RR = 1.48, p<0.0001) with an NNT of 6 (CI = 4–9) and remission rate (RR = 2.18, p = 0.0002) with an NNT of 8 (CI = 6–16); (3) PANSS positive and general symptom sub-scores at endpoint with a WMD between -3.48 to -1.32 (P = 0.01 to 0.009). Subgroup analyses were conducted comparing double blind/rater-masked vs. open RCTs, those with and without randomization details, and high quality (Jadad≥adadup analyses were Jadad<3) studies. The ECT-antipsychotic combination caused more headache (p = 0.02) with an NNH of 6 (CI = 4–11) and memory impairment (p = 0.001) with an NNH of 3 (CI = 2–5). The use of ECT to augment antipsychotic treatment (clozapine excepted) can be an effective treatment option for TRS, with increased frequency of self-reported memory impairment and headache.
CRD42014006689 (PROSPERO).
Objectives
In the coming generation, older adults with bipolar disorder (BD) will increase in absolute numbers as well as proportion of the general population. This is the first report of the ...International Society for Bipolar Disorder (ISBD) Task Force on Older‐Age Bipolar Disorder (OABD).
Methods
This task force report addresses the unique aspects of OABD including epidemiology and clinical features, neuropathology and biomarkers, physical health, cognition, and care approaches.
Results
The report describes an expert consensus summary on OABD that is intended to advance the care of patients, and shed light on issues of relevance to BD research across the lifespan. Although there is still a dearth of research and health efforts focused on older adults with BD, emerging data have brought some answers, innovative questions, and novel perspectives related to the notion of late onset, medical comorbidity, and the vexing issue of cognitive impairment and decline.
Conclusions
Improving our understanding of the biological, clinical, and social underpinnings relevant to OABD is an indispensable step in building a complete map of BD across the lifespan.
IMPORTANCE: Whether ketamine is as effective as electroconvulsive therapy (ECT) among patients with major depressive episode remains unknown. OBJECTIVE: To systematically review and meta-analyze data ...about clinical efficacy and safety for ketamine and ECT in patients with major depressive episode. DATA SOURCES: PubMed, MEDLINE, Cochrane Library, and Embase were systematically searched using Medical Subject Headings (MeSH) terms and text keywords from database inception through April 19, 2022, with no language limits. Two authors also manually and independently searched all relevant studies in US and European clinical trial registries and Google Scholar. STUDY SELECTION: Included were studies that involved (1) a diagnosis of depression using standardized diagnostic criteria, (2) intervention/comparator groups consisting of ECT and ketamine, and (3) depressive symptoms as an efficacy outcome using standardized measures. DATA EXTRACTION AND SYNTHESIS: Data extraction was completed independently by 2 extractors and cross-checked for errors. Hedges g standardized mean differences (SMDs) were used for improvement in depressive symptoms. SMDs with corresponding 95% CIs were estimated using fixed- or random-effects models. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed. MAIN OUTCOMES AND MEASURES: Efficacy outcomes included depression severity, cognition, and memory performance. Safety outcomes included serious adverse events (eg, suicide attempts and deaths) and other adverse events. RESULTS: Six clinical trials comprising 340 patients (n = 162 for ECT and n = 178 for ketamine) were included in the review. Six of 6 studies enrolled patients who were eligible to receive ECT, 6 studies were conducted in inpatient settings, and 5 studies were randomized clinical trials. The overall pooled SMD for depression symptoms for ECT when compared with ketamine was −0.69 (95% CI, −0.89 to −0.48; Cochran Q, P = .15; I2 = 39%), suggesting an efficacy advantage for ECT compared with ketamine for depression severity. Significant differences were not observed between groups for studies that assessed cognition/memory or serious adverse events. Both ketamine and ECT had unique adverse effect profiles (ie, ketamine: lower risks for headache and muscle pain; ECT: lower risks for blurred vision, vertigo, diplopia/nystagmus, and transient dissociative/depersonalization symptoms). Limitations included low to moderate methodological quality and underpowered study designs. CONCLUSIONS AND RELEVANCE: Findings from this systematic review and meta-analysis suggest that ECT may be superior to ketamine for improving depression severity in the acute phase, but treatment options should be individualized and patient-centered.
Current treatments for behavioral and psychological symptoms of dementia (BPSD) are of limited efficacy. Electroconvulsive therapy (ECT) is an effective and safe treatment for a range of psychiatric ...disorders, with some limited data suggesting a role in treating BPSD. We sought to expand this growing literature by examining-in a rigorous way with a larger sample size than in previous reports-the potential of ECT as a treatment for comorbid depression and dementia.
Drawing on nationally representative 2014-2015 Medicare claims data, propensity score methods were used to create two comparable cohorts consisting of ECT-treated patients (n = 147) and controls (n = 415) who were hospitalized with a principal psychiatric diagnosis. Functional outcomes were compared before and after hospitalization (when ECT was initiated for the ECT cohort).
Both cohorts generally declined in all functional outcomes over the time period observed. The ECT cohort had a slower rate of functional decline in bathing (Cohen
= -0.05 vs 0.38;
< .001) and transferring (
= 0.18 vs 0.45;
= .031) compared to matched controls. In multivariate analysis, ECT patients also fared better in the overall activities of daily living summary score at 180 days (coefficient = -0.10; 95% CI, -0.19 to 0.01), though these effects were small. No difference was seen in cognition or ambulation.
: Receiving ECT does not worsen the trajectory of functional outcomes compared to not receiving ECT in older adults with comorbid depression. Randomized clinical trials are needed to more definitively examine the causal effect of ECT on functional outcomes of individuals with dementia.
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