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.

Pre-K and Kindergarten Teacher Perception of School Readiness During the COVID-19 Pandemic.

In 2020, the COVID-19 pandemic caused a mandatory shift from in-person instruction to online learning for many young children. Teachers needed to adjust to virtual teaching, children were isolated from their peers, and parents played a bigger role in learning during the pandemic. In 2021, the shift back to in-person learning occurred. Research has already shown the negative influence COVID-19 had on students' mental health; however, limited research has examined the impact of the pandemic on school readiness. In this study, using the Head Start domains of school readiness, 154 Kindergarten and Pre-K teachers compared current student school readiness to the readiness of their students prior to the pandemic. Results showed that nearly 80% of teachers felt that overall student functioning was Worse or Much Worse than before the pandemic; no teachers reported functioning was overall much better. Teachers most frequently identified the Ready to Learn and Social-Emotional Development domains as the areas of greatest struggle for their students; Physical Development was the least frequently reported. Chi-square tests were used to examine the association between teacher demographics and overall school readiness and domain of greatest struggle; no significant relationships were found. Future directions and limitations of these results are discussed.

The Importance of Person-Centered Approaches to Managing Behavioral and Psychological Symptoms of Dementia: A Case Report.

Behavioral and psychological symptoms of dementia (BPSD) are common and associated with increased morbidity and mortality in dementia. In this report, we describe a patient with severe BPSD who was effectively managed with a variety of non-pharmacologic strategies. A 70-year-old Navy veteran and retired commercial flooring business owner with a history of dementia was admitted to the hospital with aggressive behavior. He was no longer manageable by his family. He required intermittent use of restraints and multiple antipsychotics during hospitalization. He spent much of his time crawling on the floor, "working" on floor tiles, which was often difficult for staff to safely accommodate. However, with time, interprofessional staff identified signs of distress and developed strategies to safely engage the patient's current perception of his situation. This case highlights how BPSD may be driven by a person's identities and roles from earlier stages of life. Approaching and managing these symptoms flexibly can enhance dementia care.

Treatment of behavioral and psychological symptoms of dementia using transcranial magnetic stimulation: a systematic review.

OBJECTIVE: Behavioral and psychological symptoms of dementia (BPSD) are a group of noncognitive symptoms that occur commonly among individuals with dementia. These symptoms worsen the morbidity and mortality among individuals with dementia and significantly increase the cost of caring for these individuals. Transcranial magnetic stimulation (TMS) has been shown to have some benefits in the treatment of BPSD. This review provides an updated summary of the effect of TMS on BPSD. METHODS: We conducted a systematic review of PubMed, Cochrane, and Ovid databases on the use of TMS to treat BPSD. RESULTS: We found 11 randomized controlled studies that evaluated the use of TMS among individuals with BPSD. Three of these studies examined the effect of TMS on apathy, two of which showed significant benefit. Seven studies showed that TMS significantly improves BPSD: six using repetitive transcranial magnetic stimulation (rTMS) and one using transcranial direct current stimulation (tDCS). Four studies, two evaluating tDCS, one evaluating rTMS, and one evaluating intermittent theta-burst stimulation (iTBS) showed a nonsignificant impact of TMS on BPSD. Adverse events were predominantly mild and transitory in all studies. CONCLUSION: Available data from this review indicate that rTMS is beneficial for individuals with BPSD, especially among individuals with apathy, and is well tolerated. However, more data are needed to prove the efficacy of tDCS and iTBS. Additionally, more randomized controlled trials with longer treatment follow-up and standardized use of BPSD assessments are needed to determine the best dose, duration, and modality for effective treatment of BPSD.

The Effect of Drains and Compressive Garments Versus Progressive Tensioning Sutures on Seroma Formation in Abdominoplasty.

Seroma is a common problem following abdominoplasty surgery. Both compressive garments with drains and progressive tension sutures have their advocates to minimise seroma formation. This is a retrospective study in which patients underwent an identical surgical procedure, except for use of drains and garments in comparison to progressive tension sutures between 2005 and 2020. Two hundred thirty-two patients were included in the study 61 in the drains and garment group (DG group), and 171 with progressive tension sutures (PTS group) alone. There was a lower incidence of seroma formation in the PTS group (X2 (1, N = 232) = 6.35, P = .012). The weight of tissue excised in the PTS group was greater than the DG group (P < .001). There was there a significantly higher tissue excision weights for patients who developed a seroma, compared with those who did not (P=.02). Patients, who developed a seroma in the PTS group, had significantly greater excision weights than the DG group. Liposuction did not change the incidence of seroma in each group (X2 (4, N = 232) = 6.701, P = .08 n/s). This study demonstrates the effectiveness of progressive tension sutures in reducing the incidence of seroma formation following abdominoplasty, particularly when large excision weights are involved. The addition of small volume liposuction distant to the abdominal flap does not increase the incidence of seroma formation.Level of Evidence III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Right Brain: A Medical Student's Reflections on Creating Space for Dementia Discussions.

The following narrative describes the experiences and reflections of a fourth-year medical student who longitudinally cared for a patient with dementia in an outpatient geriatric psychiatry clinic and inpatient medicine unit. The student, through these experiences, emphasizes the importance of creating space for honest and realistic discussions, balanced with empathic support, when discussing dementia diagnoses with patients and families. Additionally, she recognizes the importance of engaging families in these discussions to promote proactive care planning and reminding patients and families they are not at fault for their disease.

Synaptic alterations and immune response are sexually dimorphic in a non-pertussis toxin model of experimental autoimmune encephalomyelitis.

Multiple sclerosis is an autoimmune disorder of the central nervous system (CNS) characterized by locomotor impairments, cognitive deficits, affective disorders, and chronic pain. Females are predominately affected by MS compared to males and develop motor symptoms earlier. However, key symptoms affect all patients regardless of sex. Previous studies have shown that demyelination and axonal damage play key roles in symptom development, but it is unclear why sex differences exist in MS onset, and effective symptom treatment is still lacking. We here used a non-pertussis toxin (nPTX) experimental autoimmune encephalomyelitis (EAE) model in C57BL/6 mice, to explore chronic symptoms and sex differences in CNS autoimmunity. We observed that, like in humans, female mice developed motor disease earlier than males. Further, changes in pre- and post-synaptic protein expression levels were observed in a sexually dimorphic manner with an overall shift towards excitatory signaling. Our data suggest that this shift towards excitatory signaling is achieved through different mechanisms in males and females. Altogether, our study helps to better understand sex-specific disease mechanisms to ultimately develop better diagnostic and treatment tools.

Exogenous activation of tumor necrosis factor receptor 2 promotes recovery from sensory and motor disease in a model of multiple sclerosis.

Tumor necrosis factor receptor 2 (TNFR2) is a transmembrane receptor that promotes immune modulation and tissue regeneration and is recognized as a potential therapeutic target for multiple sclerosis (MS). However, TNFR2 also contributes to T effector cell function and macrophage-TNFR2 recently was shown to promote disease development in the experimental autoimmune encephalomyelitis (EAE) model of MS. We here demonstrate that systemic administration of a TNFR2 agonist alleviates peripheral and central inflammation, and reduces demyelination and neurodegeneration, indicating that protective signals induced by TNFR2 exceed potential pathogenic TNFR2-dependent responses. Our behavioral data show that systemic treatment of female EAE mice with a TNFR2 agonist is therapeutic on motor symptoms and promotes long-term recovery from neuropathic pain. Mechanistically, our data indicate that TNFR2 agonist treatment follows a dual mode of action and promotes both suppression of CNS autoimmunity and remyelination. Strategies based on the concept of exogenous activation of TNFR2 therefore hold great promise as a new therapeutic approach to treat motor and sensory disease in MS as well as other inflammatory diseases or neuropathic pain conditions.

Early TLR4 Blockade Attenuates Sterile Inflammation-mediated Stress in Islets During Isolation and Promotes Successful Transplant Outcomes.

BACKGROUND: During the isolation process, pancreatic islets are exposed to an environment of sterile inflammation resulting in an upregulated inflammatory state before transplantation. Toll-like receptor 4 (TLR4) has been identified as a major mediator of sterile inflammation. Therefore, we sought to determine whether early TLR4 blockade would be effective in reducing the inflammatory burden in islets pretransplant. METHODS: Islets from C57BL/6 mice were treated with a TLR4 antagonist during the pancreatic ductal perfusion and digestion steps of the isolation process. Islets were then analyzed for inflammation by RT-PCR and Western blot, and for viability and function in vitro. A syngeneic transplant model using a marginal mass of islets transplanted intraportally into mice with streptozotocin-induced diabetes was used to study transplant outcomes after early TLR4 blockade. RESULTS: Diabetic mice receiving 150 islets treated with early TLR4 blockade achieved euglycemia at a higher rate than mice receiving untreated islets (75% vs 29%; P < 0.05) and had improved long-term function (P < 0.05). Serum markers for islet damage and inflammation were significantly reduced posttransplant (P < 0.05). Both the expression of key inflammatory genes and the activation of mitogen-activated protein kinases were reduced by early TLR4 blockade. Islet viability was improved (P < 0.05) while preserving islet insulin secretory capacity postisolation. CONCLUSIONS: Early TLR4 blockade protects islets from sterile inflammation-mediated stress sustained during isolation and promotes positive transplant outcomes. Our findings support the use of early TLR4 blockade during clinical islet isolation procedures to reduce pretransplant inflammation and improve transplant outcomes.