The Effect and Mechanism of Exercise Training on Rats with Poststroke Depression Based on the Intestinal Flora

Depression of poststroke depression (PSD) is the most common neuropsychiatric complication after stroke. Patients with PSD had higher mortality, more cognitive disorder, lower quality of life, and higher suicidal tendency. The pathogenesis of PSD mainly involves neurotransmitter inflammatory factors, HPA and BDNF. Enteral dysfunction and intestinal flora disorders caused by stroke can participate in the pathogenesis of PSD through various ways, such as immune, endocrine, and nervous system. In this experiment, we used exercise training as an intervention means to explore the curative effect and possible mechanism by observing the changes of behavior, inflammatory factors, and intestinal flora in rats. The results show that the mechanism of exercise training to improve the depressive behavior of rats may be related to inhibiting the expression of proinflammatory factors and increasing the number of lactic acid bacteria in the intestine.

Baicalein Ameliorates Aβ-Induced Memory Deficits and Neuronal Atrophy via Inhibition of PDE2 and PDE4

Inhibition of phosphodiesterase 2 and 4 (PDE2A and PDE4) increases the intracellular cAMP and/or cGMP levels, which may prevent Amyloid β 42 oligomers (Aβ) related cognitive impairment and dementias. Baicalein, one of natural flavones found in the root of Scutellaria baicalensis Georgi, has a wide range of pharmacological activities including antioxidant and anti-inflammatory effects. However, no studies suggest whether baicalein mediated anti-Alzheimer’s disease (AD) events involve PDEs subtypes-mediated neuroprotective pathways. The present study examined whether memory enhancing effects of baicalein on Aβ- induced cognitive impairment are related to regulating neuroplasticity via PDE2 and PDE4 subtypes dependent cAMP/cGMP neuroprotective pathway. The results suggested that microinjected of Aβ into CA1 of hippocampus induced cognitive and memory impairment in mice, as evidenced by decreased recognition index in the novel object recognition (NOR) task, impaired memory acquisition, retention and retrieval in the Morris water maze (MWM) and shuttle box tests. These effects were reversed by treatment with baicalein for 14 days. Moreover, Aβ-induced neuronal atrophy and decreased expression of two synaptic proteins, synaptophysin and PSD 95, were prevented by baicalein. The increased expression of PDE2A and PDE4 subtypes (PDE4A, PDE4B and PDE4D), and decreased levels of cAMP/cGMP, pCREB/CREB and BDNF induced by Aβ were also blocked by chronic treatment of baicalein for 14 days. These findings suggest that baicalein’s reversal of Aβ-induced memory and cognitive disorder may involve the regulation of neuronal remodeling via regulation of PDE2/PDE4 subtypes related cAMP/cGMP -pCREB-BDNF pathway.

Stakeholders’ Perspectives regarding Participation in Neuromodulation-Based Dementia Intervention Research

This study evaluated stakeholders’ perspectives regarding participation in two hypothetical neuromodulation trials focused on individuals with Alzheimer's disease and related disorders (ADRDs). Stakeholders (i.e., individuals at risk for ADRDs [ n = 56], individuals with experience as a caregiver for someone with a cognitive disorder [ n = 60], and comparison respondents [ n = 124]) were recruited via MTurk. Primary outcomes were willingness to enroll (or enroll one's loved one), feeling lucky to have the opportunity to enroll, and feeling obligated to enroll in two protocols (transcranial magnetic stimulation, TMS; deep brain stimulation, DBS). Relative to the Comparison group, the At Risk group endorsed higher levels of “feeling lucky” regarding both research protocols, and higher willingness to participate in the TMS protocol. These findings provide tentative reassurance regarding the nature of decision making regarding neurotechnology-based research on ADRDs. Further work is needed to evaluate the full range of potential influences on research participation.

An Innovative Transitions Model of Care for Delirium: “DDEFY Delirium” A Pilot Feasibility Randomized Trial

In current standard practice, without a structured process for delirium follow up, older individuals and their family caregivers seemed to be lost, as they transitioned from hospital to home. The aim of this study was to pilot test a theoretical post-hospital model of care (DDEFY delirium) to mitigate the complications in patients who had hospital delirium. This is a pilot feasibility randomized controlled trial for patients with hospital delirium. The intervention was carried out by a delirium transitions nurse with personalized interdisciplinary team recommendations. DDEFY delirium intervention encompasses: Diagnose cognitive disorder; review Drugs; Educate patient/family; assess Function; Your health goals. During COVID-19 pandemic a virtual intervention group was created. Thus, three groups were analyzed: control, intervention, and virtual intervention. Among the 35 participants (mean age 80 years (SD10), 40% Black, 46% female), 40% had a diagnosis of dementia, mean Charles Deyo score was 6.4, mean number of medications 11.4 (3.2), and a mean anticholinergic medication burden was 2.4. The intervention group and virtual intervention group rates were: recruitment: 44.6 %vs8.8%, feasibility: 97%vs97%, fidelity:100%vs100%, 30-day readmission 28.6%vs0%, and 30-day ED visits: 0 vs.1. There were no differences in 30-day readmission rates between control vs intervention (p=1.0), control vs virtual intervention (p=.53), nor comparing all 3 groups (p=.49). The results of this pilot study determined that delivering DDEFY intervention to patients with delirium is feasible. Lessons learned from conducting this study will help us design a larger trial with modifications for older patients with delirium who transition from hospital to home.

Differences in care between younger and older patients in the 2019 English national memory service audit

Aims and method This paper analyses how practice varied between patients aged <65 and ≥65 years in the 2019 UK national memory service audit. Results Data on 3959 patients were analysed. Those aged <65 (7% of the sample) were less likely than those aged ≥65 to be diagnosed with dementia (23 v. 67%) and more likely to receive a functional, psychiatric or no diagnosis. Younger patients were more likely to have magnetic resonance imaging; use of dementia biomarkers was low in both groups. Frontotemporal dementia and functional cognitive disorder were diagnosed infrequently. Use of dementia navigators/advisors and carer psychoeducation was similar between groups; younger patients were less likely to be offered but more likely to accept cognitive stimulation therapy. Clinical implications Memory services seeing younger people need expertise in functional cognitive disorder, alongside clinical skills and technologies to diagnose rarer forms of dementia. Further work is needed to understand why cognitive stimulation therapy is less frequently offered to younger people.

Human Cytomegalovirus Immediate Early Protein 2 Protein Causes Cognitive Disorder by Damaging Synaptic Plasticity in Human Cytomegalovirus-UL122-Tg Mice

Human cytomegalovirus (HCMV) infection is very common in the human population all around the world. Although the majority of HCMV infections are asymptomatic, they can cause neurologic deficits. Previous studies have shown that immediate early protein 2 (IE2, also known as UL122) of HCMV is related with the cognitive disorder mechanism. Due to species isolation, a HCMV-infected animal model could not be established which meant a study into the long-term effects of IE2 on neural development could not be carried out. By establishing HCMV-UL122-Tg mice (UL122 mice), we explored the cognitive behavior and complexity of neuron changes in this transgenic UL122 mice that could consistently express IE2 protein at different ages (confirmed in both 6- and 12-month-old UL122 mice). In the Morris water maze, cognitive impairment was more pronounced in 12-month-old UL122 mice than in 6-month-old ones. At the same time, a decrease of the density of dendritic spines and branches in the hippocampal neurons of 12-month-old mice was observed. Moreover, long-term potentiation was showed to be impaired in 12-month-old UL122 mice. The expressions of several synaptic plasticity-regulated molecules were reduced in 12-month-old UL122 mice, including scaffold proteins postsynaptic density protein 95 (PSD95) and microtubule-associated protein 2 (MAP2). Binding the expression of IE2 was increased in 12-month-old mice compared with 6-month-old mice, and results of statistical analysis suggested that the cognitive damage was not caused by natural animal aging, which might exclude the effect of natural aging on cognitive impairment. All these results suggested that IE2 acted as a pathogenic regulator in damaging synaptic plasticity by downregulating the expression of plasticity-related proteins (PRPs), and this damage increased with aging.

Metacognitive Performance on Memory and Visuospatial Tasks in Functional Cognitive Disorder

Functional Cognitive Disorder (FCD) is a common diagnosis at the memory clinic. FCD is characterised by significant self-reported cognitive symptoms in the absence of external evidence of cognitive dysfunction. A potential explanation for this is a deficit in metacognition, the process by which we internally judge our own abilities. Here we investigated differences in accuracy, confidence, and metacognition between people with FCD (N = 20), neurodegenerative mild cognitive impairment (nMCI; N = 14), and healthy controls (N = 23). The groups were assessed on forced choice memory and perceptual tasks, with trial by trial confidence ratings. FCD and nMCI participants showed lower accuracy on the memory task (means FCD 63.65%, nMCI 63.96%, HC 71.22%), with a significant difference between the FCD and HC groups after controlling for age and sex. There were no between-group differences in memory task confidence (means FCD 3.19, nMCI 3.59, HC 3.71). The FCD group showed greater confidence when longer time was allowed on the memory task. No between group differences in perceptual task accuracy (means FCD 63.97%, nMCI 64.50%, FCD 65.86%) or confidence (means FCD 3.71, nMCI 3.43, HC 3.88) were found. No differences in metacognitive efficacy emerged between the groups, either on the memory or perceptual task (Memory Meta-d’/d’:FCD 0.63, nMCI 0.94 HC 0.85; Perceptual Meta-d’,d’: FCD 0.50, nMCI 0.51, HC 0.72). Participants showed greater metacognitive efficacy on the memory task compared to the perceptual task. The difficulties experienced by people with FCD do not appear to be due to metacognitive deficits. Their performance was similar to people with nMCI over aspects of the memory tasks, which suggests that the primary issue may lie with memory encoding or retrieval, rather than with their judgement of performance accuracy.