Dexmedetomidine for agitation in dementia: Current data and future direction.

BACKGROUND: The incidence and prevalence of dementia, and thus dementia-related behavioral and psychological symptoms, are increasing significantly. Currently, there are limited safe and efficacious options for treating these symptoms. Dexmedetomidine has been used for agitation related to delirium and showed significant benefit in prior studies. This raises the question whether dexmedetomidine could also provide a safe and effective treatment for BPSD, including agitation related to dementia. METHODS: Our team searched PubMed, Cochrane Database, and Ovid with the terms dexmedetomidine and dementia. Only studies published in English language journals, or with official English language translations, and human studies were included. All reports of dexmedetomidine for dementia were included regardless of study type. RESULTS: No completed studies on dexmedetomidine for agitation in dementia were identified. The TRANQUILITY study is in progress, although results are yet to be published. CONCLUSION: Dexmedetomidine has shown benefit for hospital delirium and for agitation in schizophrenia and bipolar disorder. However, there are no completed studies published on dexmedetomidine for agitation in dementia. Controlled studies with larger sample sizes are needed to assess the efficacy, safety, and the best route of administration for this drug in managing BPSD including agitation.

The Utilization of Preoperative Steroids Safely Decreases the Risk of Postoperative Delirium in Geriatric Patients After Hip Fracture Surgery: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVES: Postoperative delirium is an acute neurocognitive complication that can have adverse effects on outcomes of geriatric patients after undergoing hip fracture surgery. The objective of this study was to examine the efficacy of preoperative steroids in preventing postoperative delirium after hip fracture surgery. DATA SOURCES: A systematic review and meta-analysis was performed using PubMed, SPORTDiscus, CINAHL, MEDLINE, and Web of Science from database inception until September 28, 2023. STUDY SELECTION: Inclusion criteria were randomized controlled trials of patients who underwent surgical intervention for hip fracture, were examined for postoperative delirium, and used preoperative steroids. DATA EXTRACTION: Data included the risk of postoperative delirium, postoperative all-cause infection, and postoperative hyperglycemia. Articles were graded via the Cochrane Collaboration's tool. DATA SYNTHESIS: Statistical analysis included a random-effects binary model with relative risk, 95% confidence intervals along with a defined "number needed to treat" threshold (number needed to treat). RESULTS: Four randomized controlled trials were included from 128 articles initially retrieved. Patients (n = 416; average age: 82.2 ± 2.2 years) underwent surgical intervention for hip fracture after receiving either preoperative steroids (n = 209) or control interventions (n = 207). There was a statistically significant decrease in the incidence of postoperative delirium among patients who received preoperative steroids (12.9%; 27 cases) as compared with patients who received control interventions (26.7%; 55 cases) after hip fracture surgery ( P < 0.001; RR: 0.84). The absolute risk difference was 13.8%, and the number needed to treat was 7.2 patients. There was no statistically significant difference in the risk of postoperative all-cause infection among patients who received preoperative steroids as compared with patients who received normal saline as placebo after hip fracture surgery ( P = 0.850; RR: 0.96). CONCLUSIONS: The utilization of preoperative steroids seems to decrease the risk of postoperative delirium after hip fracture surgery in elderly adults. Furthermore, this decreased risk of postoperative delirium was not associated with a significant increase in postoperative infection, indicating possible safety of preoperative steroid administration. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Social connections as determinants of cognitive health and as targets for social interventions in persons with or at risk of Alzheimer's disease and related disorders: a scoping review.

BACKGROUND: Social connections have a significant impact on health across age groups, including older adults. Loneliness and social isolation are known risk factors for Alzheimer's disease and related dementias (ADRD). Yet, we did not find a review focused on meta-analyses and systematic reviews of studies that had examined associations of social connections with cognitive decline and trials of technology-based and other social interventions to enhance social connections in people with ADRD. STUDY DESIGN: We conducted a scoping review of 11 meta-analyses and systematic reviews of social connections as possible determinants of cognitive decline in older adults with or at risk of developing ADRD. We also examined eight systematic reviews of technology-based and other social interventions in persons with ADRD. STUDY RESULTS: The strongest evidence for an association of social connections with lower risk of cognitive decline was related to social engagement and social activities. There was also evidence linking social network size to cognitive function or cognitive decline, but it was not consistently significant. A number of, though not all, studies reported a significant association of marital status with risk of ADRD. Surprisingly, evidence showing that social support reduces the risk of ADRD was weak. To varying degrees, technology-based and other social interventions designed to reduce loneliness in people with ADRD improved social connections and activities as well as quality of life but had no significant impact on cognition. We discuss strengths and limitations of the studies included. CONCLUSIONS: Social engagement and social activities seem to be the most consistent components of social connections for improving cognitive health among individuals with or at risk for ADRD. Socially focused technology-based and other social interventions aid in improving social activities and connections and deserve more research.

Why Does the US Overly Rely on International Medical Graduates in Its Geriatric Psychiatric Workforce?

International medical graduates (IMGs) tend to choose careers in geriatric psychiatry likely because high-quality training and robust mentorship opportunities from other IMGs are available. Geriatric psychiatry offers stable career prospects and opportunities to express humanitarian impulses by working closely with elders. IMGs currently constitute almost a quarter of the psychiatry workforce and approximately 53% of the geriatric psychiatry work force in the United States. However, the number of IMGs entering psychiatry residencies-and, subsequently, geriatric psychiatry fellowships-has recently declined. Overreliance on IMGs in the US geriatric psychiatric workforce means these shortages will further burden an already-limited geriatric mental health care workforce and further compromise US health system capacity to meet its elders' needs.

Electroconvulsive therapy in individuals with dementia/major NCD presenting with behavioral symptoms: a systematic review.

OBJECTIVE: This study aims to systematically review the literature on using electroconvulsive therapy (ECT) in patients with dementia/major NCD (Neuro cognitive disorder) presenting with behavioral symptoms. DESIGN: We conducted a PRISMA-guided systematic review of the literature. We searched five major databases, including PubMed, Medline, Embase, Cochrane, and registry (ClinicalTrials.gov), collaborating with "ECT" and "dementia/major NCD" as our search terms. MEASUREMENTS: Out of 445 published papers and four clinical trials, only 43 papers and three clinical trials met the criteria. There were 22 case reports, 14 case series, 4 retrospective chart reviews, 1 retrospective case-control study, 1 randomized controlled trial, and 2 ongoing trials. We evaluated existing evidence for using ECT in dementia/major NCD patients with depressive symptoms, agitation and aggression, psychotic symptoms, catatonia, Lewy body dementia/major NCD, manic symptoms, and a combination of these symptoms. SETTINGS: The studies were conducted in the in-patient setting. PARTICIPANTS: Seven hundred and ninety total patients over the age of 60 years were added. RESULTS: All reviewed studies reported symptomatic benefits in treating behavioral symptoms in individuals with dementia/major NCD. While transient confusion, short-term memory loss, and cognitive impairment were common side effects, most studies found no serious side effects from ECT use. CONCLUSION: Current evidence from a systematic review of 46 studies indicates that ECT benefits specific individuals with dementia/major NCD and behavioral symptoms, but sometimes adverse events may limit its use in these vulnerable individuals.

Propranolol for the management of behavioural and psychological symptoms of dementia.

Propranolol is a ß-adrenergic antagonist used in the management of hypertension, cardiac arrhythmia, and angina pectoris. There is some evidence that propranolol may benefit individuals with behavioural and psychological symptoms of dementia (BPSD). A total of three case series, one randomized controlled trial and one case report were identified (from a literature search of three major databases: PubMed, Ovid, and Cochrane collaboration) that assessed the use of propranolol for the management of BPSD. From these studies, it appears that propranolol improves BPSD, including agitation and aggression. Propranolol is also well tolerated with no significant bradycardia or hypotension noted in these studies. Current data on the use of propranolol for the management of BPSD are limited in comparison to other pharmacological agents (atypical antipsychotics, antidepressants, acetylcholinesterase inhibitors, memantine, and cannabinoids) and treatment modalities (repetitive transcranial magnetic stimulation and electroconvulsive therapy). The efficacy and safety of these treatments among individuals with BPSD has been evaluated in multiple controlled studies. In clinical practice, the routine use of propranolol among people with BPSD cannot be recommended at this time given the limited data. However, propranolol can be trialled among individuals with BPSD when symptoms have not responded adequately to other medications. Propranolol may also be used prior to embarking on trials of repetitive transcranial magnetic stimulation and electroconvulsive therapy among people with BPSD given the greater acceptance of this medication in the general population.

Substance Use Disorders in the Elderly.

The population of elderly in the United States with substance use disorders (SUDs) is growing appreciably. SUDs among the elderly are often associated with poor outcomes and are frequently underdiagnosed. The current diagnostic criteria are less sensitive in identifying SUDs among the elderly. Routine screening with validated screening tools may improve the diagnosis of SUDs among the elderly. There is a dearth of data from controlled studies on SUDs among the elderly and the use of pharmacologic agents for treatment, although data indicate that older adults with SUDs respond well to treatments that are specifically designed for this age group.

Dementia Is More Than Memory Loss: Neuropsychiatric Symptoms of Dementia and Their Nonpharmacological and Pharmacological Management.

Neuropsychiatric symptoms of dementia (NPS) are a group of noncognitive symptoms that occur in over 90% of individuals with dementia. NPS seem to result from a complex interaction among various biological, psychosocial, and environmental factors, and they are associated with greater morbidity and mortality, higher caregiver burden and burnout, high risk of nursing home placement, and increased cost of care for patients with dementia. Use of standardized assessment tools like the Neuropsychiatric Inventory can assist with qualifying and quantifying NPS. In this review, the authors evaluate the evidence for efficacy and safety of nonpharmacological and pharmacological interventions for treating NPS, mostly based on published meta-analyses. Commonly prescribed medications include atypical antipsychotics, acetylcholinesterase inhibitors, memantine, antidepressants, and mood stabilizers. There are also limited data on cannabinoids, repetitive transcranial magnetic stimulation, and ECT in individuals with NPS. Available evidence indicates that several nonpharmacological interventions are beneficial in the management of NPS and are recommended as first-line treatments. Pharmacotherapy should be reserved for the treatment of more severe or refractory NPS or where nonpharmacological management is not feasible. Atypical antipsychotics have shown mostly modest benefit in reducing NPS, and their use is limited by their adverse effect profiles. Recent investigations suggest potential strategies for preventing or at least reducing the risk of dementia and NPS. The authors conclude with brief guidelines for clinical practice as well as future research.

Managing Behavioral and Psychological Symptoms of Dementia (BPSD) in the Era of Boxed Warnings.

PURPOSE OF REVIEW: To provide a comprehensive overview on the evaluation and management of behavioral and psychological symptoms of dementia (BPSD) using evidence from literature. RECENT FINDINGS: Evidence indicates efficacy for some non-pharmacological techniques including education of caregivers and cognitive stimulation therapy and pharmacological agents like antidepressant and antipsychotics for the management of BPSD. The use of antipsychotics has generated controversy due to the recognition of their serious adverse effect profile including the risk of cerebrovascular adverse events and death. BPSD is associated with worsening of cognition and function among individuals with dementia, greater caregiver burden, more frequent institutionalization, overall poorer quality of life, and greater cost of caring for these individuals. Future management strategies for BPSD should include the use of technology for the provision of non-pharmacological interventions and the judicious use of cannabinoids and interventional procedures like ECT for the management of refractory symptoms.

Prazosin for the management of behavioural and psychological symptoms of dementia.

Prazosin, a centrally acting α1 adrenoceptor antagonist, has been included in two published algorithms amongst the list of medications that may be used in the management of behavioural and psychological symptoms of dementia (BPSD). However, a review of PubMed, Ovid and Cochrane Collaboration found that there was only one small published randomized controlled trial (RCT) that evaluated the use of prazosin amongst individuals with BPSD. Evidence from this good quality RCT indicates that prazosin appears to benefit individuals with agitation and aggression amongst individuals with BPSD and this medication is well tolerated. When compared to other treatments for BPSD, including atypical antipsychotics, antidepressants, acetylcholinesterase inhibitors, memantine, repetitive transcranial magnetic stimulation and electroconvulsive therapy, where there are multiple studies for each of these treatment modalities, the data for the use of prazosin for BPSD are limited to just one good quality RCT. Given the limitations in available data, the routine use of prazosin for the treatment of BPSD cannot be recommended at this time. However, prazosin may be used for the management of agitation and aggression amongst individuals with dementia when other medication classes, like acetylcholinesterase inhibitors, memantine, antidepressants and/or atypical antipsychotics, have been ineffective or not tolerated.

Perspectives on the Clinical Use of Pharmacogenetic Testing in Late-Life Mental Healthcare: A Survey of the American Association of Geriatric Psychiatry Membership.

OBJECTIVE: To assess perspectives on pharmacogenetic (PGx) testing among members of the American Association of Geriatric Psychiatry (AAGP). DESIGN: Cross-sectional survey. PARTICIPANTS: Members of the AAGP. MEASUREMENTS: Anonymous web-based survey consisting of 41 items covering experiences, indications, barriers, facilitators and ethical, legal and social implications for PGx testing. RESULTS: A total of 124 surveys were completed (response rate = 13%). Most respondents (60%) had used PGx testing but an equal proportion (58%) was uncertain about the clinical usefulness of PGx testing in late-life mental health. Despite self-reported confidence in the ability to order and interpret PGx testing, 60% of respondents felt there was not enough clinical evidence for them to use PGx testing in their practice. This was compounded by uncertainties related to their ethical obligation and legal liability when interpreting and using (or not using) PGx testing results. Respondents strongly affirmed that clinical and legal guidelines for PGx testing in older adults are needed and would be helpful. CONCLUSION: The findings suggest additional PGx research and physician education in late-life mental healthcare settings is required to reconcile uncertainties related to the clinical efficacy and ethico-legal aspects of PGx testing as well as address current knowledge barriers to testing uptake. These efforts would be further facilitated by the development of clinical practice guidelines to ensure equitable access to testing and standardized implementation of PGx-informed prescribing in older adults.

Is there evidence for using anticonvulsants in the prevention and/or treatment of delirium among older adults?

OBJECTIVE: This systematic review aims to identify published randomized controlled trials (RCTs) that evaluated the use of anticonvulsants for the prevention and/or treatment of delirium among older adults. METHODS: A comprehensive search of databases: MEDLINE ALL (Ovid), Embase (Ovid), PsycINFO (Ovid), Web of Science Core Collection and Cochrane Central Register of Controlled was conducted. RESULTS: The search identified four RCTs that evaluated the use of anticonvulsants among older adults with delirium. One RCT evaluated the perioperative use of gabapentin among individuals undergoing spinal surgery and the development of postoperative delirium. One RCT evaluated the relationship between the use of perioperative gabapentin and the development of postoperative delirium among individuals undergoing spinal surgery and hip and knee arthroplasty. Two post-hoc analyses of RCTs evaluated the use of gabapentin and pregabalin among individuals undergoing total knee arthroplasty (TKA) and total hip arthroplasty (THA). The perioperative use of gabapentin reduced the incidence of postoperative delirium among older adults undergoing spinal surgery. The perioperative use of gabapentin did not reduce the rates, severity or duration of postoperative delirium among older adults who were undergoing spine and hip and knee arthroplasty. The perioperative use of gabapentin did not reduce the incidence or duration of postoperative delirium among older adults undergoing elective TKA. The perioperative use of pregabalin did not reduce the incidence of postoperative delirium among older adults undergoing elective THA. Gabapentin and pregabalin were well tolerated among the individuals enrolled in these trials. There were no RCTs identified that evaluated the use of other anticonvulsants for the prevention and/or treatment of delirium among older adults. CONCLUSIONS: Based on current evidence, the routine use of anticonvulsants for the prevention and/or treatment of delirium among older adults cannot be recommended.

Aducanumab: evidence from clinical trial data and controversies.

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-Aß monoclonal antibody selective for Aß 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.