Treatment Of Cognitive Decline Research Articles

Instrumental activities of daily living function and cognitive status among Chinese older adults: a serial multiple mediation model.

This study aimed to develop and validate a serial multiple mediation model to investigate the association between instrumental activities of daily living (IADL) function and cognitive status among older adults while exploring the underlying mechanisms. This cross-sectional study involved 3,665 individuals aged 60 years and older who participated in the China Health and Retirement Longitudinal Survey (CHARLS). A serial multiple mediation model was utilized to explore the direct and indirect relationship between IADL function and cognitive status and whether sleep duration, social engagement, and depressive symptoms mediated this relationship. Decreased IADL function was associated with worse cognitive status [effect = -0.620, 95% CI: (-0.692, -0.540)]. Sleep duration, social participation (SP), and depressive symptoms all acted as mediators in the relationship between IADL function and cognitive status. This study found both direct and indirect associations between IADL function and cognitive status, providing new insights into the effective prevention and intervention of cognitive decline among older adults.

CHALLENGES AND NOVEL SOLUTIONS TO PROMOTING ADHERENCE TO HOME-BASED COGNITIVE ASSESSMENT

Abstract New technologies now allow for home-based self-assessment of cognition to promote the early detection and treatment of cognitive decline. Early detection has a multitude of benefits for the individual and for our scientific understanding of cognitive impairments and possible treatments. However, for these solutions to be effective, they will likely require long-term adherence to assessment protocols to detect longitudinal change, and like many health behaviors, adherence can be a major challenge. This presentation will provide an overview of the Adherence Promotion with Person-centered Technology (APPT) project, which aims to develop a tailored, smart reminder system that infers participants’ contexts and motivations to provide just-in-time support to facilitate cognitive assessment adherence. Among other studies, this overview will include discussion of a recently completed focus group study (N = 42) that was used to understand motivations and potential barriers to home-based assessment and preferences for adherence support, a recently completed pilot study (N = 44) in which the adherence support system was initially tested and refined, and a series of survey studies (total N > 200) that examined older adults’ attitudes toward wearable technologies to detect cognitive decline. The talk will conclude with discussion of an upcoming randomized controlled trial to test the efficacy of the newly developed system with respect to promoting long-term adherence to cognitive assessment via smartphone technologies.

Sleep spindle architecture associated with distinct clinical phenotypes in older adults at risk for dementia

Sleep spindles are a hallmark of non-REM sleep and play a fundamental role in memory consolidation. Alterations in these spindles are emerging as sensitive biomarkers for neurodegenerative diseases of ageing. Understanding the clinical presentations associated with spindle alterations may help to elucidate the functional role of these distinct electroencephalographic oscillations and the pathophysiology of sleep and neurodegenerative disorders. Here, we use a data-driven approach to examine the sleep, memory and default mode network connectivity phenotypes associated with sleep spindle architecture in older adults (mean age = 66 years). Participants were recruited from a specialist clinic for early diagnosis and intervention for cognitive decline, with a proportion showing mild cognitive deficits on neuropsychological testing. In a sample of 88 people who underwent memory assessment, overnight polysomnography and resting-state fMRI, a k-means cluster analysis was applied to spindle measures of interest: fast spindle density, spindle duration and spindle amplitude. This resulted in three clusters, characterised by preserved spindle architecture with higher fast spindle density and longer spindle duration (Cluster 1), and alterations in spindle architecture (Clusters 2 and 3). These clusters were further characterised by reduced memory (Clusters 2 and 3) and nocturnal hypoxemia, associated with sleep apnea (Cluster 3). Resting-state fMRI analysis confirmed that default mode connectivity was related to spindle architecture, although directionality of this relationship differed across the cluster groups. Together, these results confirm a diversity in spindle architecture in older adults, associated with clinically meaningful phenotypes, including memory function and sleep apnea. They suggest that resting-state default mode connectivity during the awake state can be associated with sleep spindle architecture; however, this is highly dependent on clinical phenotype. Establishing relationships between clinical and neuroimaging features and sleep spindle alterations will advance our understanding of the bidirectional relationships between sleep changes and neurodegenerative diseases of ageing.

Yigong Powder regulates CXCL12/CXCR4 signaling to reduce glutamate release and prevent cognitive decline in mouse model of aging

This study aims to explore the effect of preventive administration of Yigong Powder on the learning and memory abilities of the mouse model of aging induced by D-galactose and decipher the underlying mechanism, so as to provide a basis for the application of Yigong Powder in the prevention and treatment of cognitive decline. Forty KM mice were randomized into control, model, donepezil(1.5 mg·kg~(-1)), and high-dose(7.5 g·kg~(-1)) and low-dose(3.75 g·kg~(-1)) Yigong Powder groups. The mice in other groups except the control group were injected with D-galactose(200 g·kg~(-1)) at the back of the neck for the modeling of aging. At the same time, the mice were administrated with corresponding drugs by gavage for one month. Morris water maze was used to examine the learning and memory abilities of the mice. Hematoxylin-eosin staining was employed to observe the pathological and morphological changes of the hippocampus. The immunofluorescence assay was employed to detect the expression of ionized calcium-binding adapter molecule 1(IBA1), glial fibrillary acidic protein(GFAP), chemokine C-X-C-motif ligand 12(CXCL12), chemokine C-X-C-motif receptor 4(CXCR4) in the hippocampus and observe the positional relationship between IBA1, GFAP, and CXCR4. Western blot was employed to determine the protein levels of extracellular regulated kinase(ERK), p-ERK, and tumor necrosis factor receptor 1(TNFR1). Enzyme-linked immunosorbent assay was employed to measure the levels of glutamate and tumor necrosis factor(TNF-α) in the brain tissue and the level of TNF-α in the serum and spleen. Yigong Powder significantly shortened the escape latency, increased the times crossing platforms, and prolonged the cumulative time in quadrants of the aging mice. It alleviated the nerve cell disarrangement, increased intercellular space, and cell degeneration or death in the hippocampus and reduced the pathology score of the damaged nerve. Moreover, Yigong Powder reduced the positive area of IBA1 and GFAP, reduced the levels of TNF-α in the brain tissue, serum, and spleen, and decreased spleen index. Furthermore, Yigong Powder decreased the average fluorescence intensity of CXCL12 and CXCR4, reduced CXCR4-positive astrocytes and microglia, down-regulated the protein levels of p-ERK/ERK and TNFR1, and lowered the level of glutamate in the brain tissue. This study showed that the preventive administration of Yigong Powder can ameliorate the learning and memory decline of the D-galactose-induced aging mice by regulating the immune function of the spleen and the CXCL12/CXCR4 signaling in the brain to reduce glutamate release. However, the mechanism of Yigong San in preventing and treating dementia via regulating spleen and stomach function remains to be studied.

Abstract 152: Exploring Age‐related Changes in Brain Metabolism among Individuals with Cardiovascular Risk Factors: An FDG‐PET Analysis

Introduction Patients with cognitive impairment often have a history of cardiovascular disease (CVD) or multiple cardiovascular risk factors (CRFs) such as hypertension, obesity, and hypercholesterolemia. The literature reports that CVD with CRFs may increase the risk of developing vascular dementia and Alzheimer’s Disease. 18F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) allows for the in vivo study of cerebral glucose metabolism, and can detect metabolic alterations in several neurological diseases. As we age, the brain undergoes both structural and functional changes; the regional distribution of these alterations mirrors cognitive decline. This study aims to assess the effect of aging on regional glucose uptake in subjects with known cardiovascular risk factors. Methods In total, 40 subjects (mean age 55.9 ± 11.89 years, 50% males) with known cardiovascular risk factors underwent FDG‐PET scanning, and 70 whole brain structures were analyzed in each subject. Participants were recruited from a group of patients with chest pain syndromes who were referred for coronary CT angiography. All subjects underwent whole‐body FDG‐PET/CT imaging 180 minutes after the administration of 4.0 MBq/kg dose of FDG. The quantitative regional analysis of PET images was performed using MIMneuro version 7.1.5 (MIM Software, Inc., Cleveland, Ohio). MIMneuro provides region‐based analysis, with z‐scores generated by comparing the patient to the selected age‐matched set of normal controls. Pearson’s R was calculated and evaluated for significance in all variables. The threshold for significance was set at P < 0.05. Results Various significant associations between age and FDG uptake across all 70 brain regions of interest were observed. In particular, age was found to have an inverse correlation with regional metabolism in the middle temporal gyrus (r= ‐0.364, p=0.021), superior frontal gyrus (r= ‐0.433, p=0.005), superior parietal lobule (r= ‐0.354, p=0.025), supplementary motor area (r= ‐0.436, p=0.005), and temporal operculum (r= ‐0.370, p=0.019). Conclusion The results demonstrate a significant inverse correlation between age and FDG uptake in five regions among individuals with cardiovascular risk factors. This information may be useful in the determination of whether such scans might be useful in the evaluation of patients with a history of CVD/CRF or with mild cognitive impairment (MCI). Previous literature has reported that increased medial temporal gyrus atrophy is a predictor of dementia in subjects with MCI, and alterations within this lobe mark the beginning of the disease process. Our strongest inverse correlation, the superior frontal gyrus, has been shown to be related to working memory; hypometabolism in this region has previously correlated with severity of cognitive impairments in attention, executive function, and language. Further research is needed to determine the potential for using FDG‐PET imaging as a tool for early detection and intervention for cognitive decline. If patients with CVD or CRFs can be properly diagnosed, if there exists a metabolic signature of regional functional change, intervention may prove highly beneficial for cognitive function, quality of life, and overall well‐being.

Peripheral inflammatory biomarkers are associated with cognitive function and dementia: Framingham Heart Study Offspring cohort.

Inflammatory protein biomarkers induced by immune responses have been associated with cognitive decline and the pathogenesis of Alzheimer's disease (AD). Here, we investigate associations between a panel of inflammatory biomarkers and cognitive function and incident dementia outcomes in the well-characterized Framingham Heart Study Offspring cohort. Participants aged ≥40 years and dementia-free at Exam 7 who had a stored plasma sample were selected for profiling using the OLINK proteomics inflammation panel. Cross-sectional associations of the biomarkers with cognitive domain scores (N = 708, 53% female, 22% apolipoprotein E (APOE) ε4 carriers, 15% APOE ε2 carriers, mean age 61) and incident all-cause and AD dementia during up to 20 years of follow-up were tested. APOE genotype-stratified analyses were performed to explore effect modification. Higher levels of 12 and 3 proteins were associated with worse executive function and language domain factor scores, respectively. Several proteins were associated with more than one cognitive domain, including IL10, LIF-R, TWEAK, CCL19, IL-17C, MCP-4, and TGF-alpha. Stratified analyses suggested differential effects between APOE ε2 and ε4 carriers: most ε4 carrier associations were with executive function and memory domains, whereas most ε2 associations were with the visuospatial domain. Higher levels of TNFB and CDCP1 were associated with higher risks of incident all-cause and AD dementia. Our study found that TWEAK concentration was associated both with cognitive function and risks for AD dementia. The association of these inflammatory biomarkers with cognitive function and incident dementia may contribute to the discovery of therapeutic interventions for the prevention and treatment of cognitive decline.

Potential Role of Glucagon-like Peptide-1 Receptor Agonists in the Treatment of Cognitive Decline and Dementia in Diabetes Mellitus

Dementia is a permanent illness characterized by mental instability, memory loss, and cognitive decline. Many studies have demonstrated an association between diabetes and cognitive dysfunction that proceeds in three steps, namely, diabetes-associated cognitive decrements, mild cognitive impairment (MCI; both non-amnesic MCI and amnesic MCI), and dementia [both vascular dementia and Alzheimer’s disease (AD)]. Based on this association, this disease has been designated as type 3 diabetes mellitus. The underlying mechanisms comprise insulin resistance, inflammation, lipid abnormalities, oxidative stress, mitochondrial dysfunction, glycated end-products and autophagy. Moreover, insulin and insulin-like growth factor-1 (IGF-1) have been demonstrated to be involved. Insulin in the brain has a neuroprotective role that alters cognitive skills and alteration of insulin signaling determines beta-amyloid (Aβ) accumulation, in turn promoting brain insulin resistance. In this complex mechanism, other triggers include hyperglycemia-induced overproduction of reactive oxygen species (ROS) and inflammatory cytokines, which result in neuroinflammation, suggesting that antidiabetic drugs may be potential treatments to protect against AD. Among these, glucagon-like peptide-1 receptor agonists (GLP-1RAs) are the most attractive antidiabetic drugs due to their actions on synaptic plasticity, cognition and cell survival. The present review summarizes the significant data concerning the underlying pathophysiological and pharmacological mechanisms between diabetes and dementia.

Still Alice, Always Elena: New Stories about Dementia

ABSTRACT As a hospice social worker and tenured professor of Russian literature, I have seen how the stories we tell and re-tell affect how patients, caregivers, and medical professionals live with many different diseases. My essay explores one aspect of this: how the stories we tell about dementia shape our understanding and treatment of cognitive decline. Through an analysis of the novels Still Alice (by Lisa Genova) and The Kukotsky Case (by Liudmila Ulitskaia; English translation by Diane Nemec Ignashev, 2016), I show how telling a story about the possibilities of dementia can help us to reshape our conception of dementia and that, in turn, can change the experience of caregivers, patients, and medical professionals. I argue that fiction can be a powerful agent of transformation, both personal, and, in time, societal. A deep dive into two novels and one condition reveals more than a broader analysis would as these two novels demand close readings. The implications of the essay are larger as I invite medical professionals to think about story and narrative skill in understanding all kinds of disease-and indeed, how “medicalizing” and/or pathologizing conditions such as dementia can work against deeper connections and engagement.

Investigating the Impact of Epilepsy on Cognitive Function: A Narrative Review.

It has been noted that people who have epilepsy have an increased propensity for cognitive dysfunction. We explored 25 relevant articles on PubMed and Cochrane Library after implementing inclusion criteria. Different factors have been postulated and studied that may cause cognitive dysfunction in these patients; structural brain abnormalities, polypharmacy of antiepileptic medication, and neuropsychiatric disorders are the most common causes. Cognitive assessments such as Montreal Cognitive Assessment (MOCA) and Mini-Mental State Exam (MMSE) are the mainstay tools used to diagnose the degree of cognitive decline, and alterations in EEG (electroencephalogram) parameters have also been noted in people with cognitive decline. The mechanisms and treatments for cognitive decline are still being studied, while attention has also been directed toward preventive and predictive methods. Early detection and treatment of cognitive impairment can help minimize its impact on the patient's quality of life. Regular cognitive assessments are essential for epileptic patients, particularly those on multiple antiepileptic drugs. While proper management of epilepsy and related comorbidities would reduce cognitive decline and improve the overall quality of life for people with epilepsy.

Original research: longitudinal evaluation of cognitively demanding daily function using performance-based functional assessment highlights heterogeneous trajectories in cognitive and functional abilities in people with Parkinson's disease.

Longitudinal assessment of functional abilities in Parkinson's disease (PD) is needed to determine the efficacy of cognitive interventions in providing meaningful improvements in daily life. Additionally, subtle changes in instrumental activities of daily living may precede a clinical diagnosis of dementia and could aid earlier detection of and intervention for cognitive decline. The primary goal was to validate the longitudinal application of the University of California San Diego Performance-Based Skills Assessment (UPSA). An exploratory secondary goal was to determine whether UPSA may identify individuals at higher risk of cognitive decline in PD. Seventy participants with PD completed the UPSA with at least one follow-up visit. Linear mixed effects modeling was used to identify associations between baseline UPSA score and cognitive composite score (CCS) over time. Descriptive analysis of four heterogeneous cognitive and functional trajectory groups and individual case examples was performed. Baseline UPSA score predicted CCS at each timepoint for functionally impaired and unimpaired groups (p < 0.01) but did not predict the rate change in CCS over time (p = 0.83). Participants displayed heterogenous trajectories in both UPSA and CCS during the follow-up period. Most participants maintained both cognitive and functional performance (n = 54), though some displayed cognitive and functional decline (n = 4), cognitive decline with functional maintenance (n = 4), and functional decline with cognitive maintenance (n = 8). The UPSA is a valid measure of cognitive functional abilities over time in PD. Given the heterogeneity of functional and cognitive trajectories, this performance-based assessment did not predict cognitive decline with this relatively short follow-up. Further work is needed to understand longitudinal functional assessments in PD-associated cognitive impairment.

The application scenarios study on the intervention of cognitive decline in elderly population using metaverse technology

China is facing the peak of an ageing population, and there is an increase in demand for intelligent healthcare services for the elderly. The metaverse, as a new internet social communication space, has shown infinite potential for application. This paper focuses on the application of the metaverse in medicine in the intervention of cognitive decline in the elderly population. The problems in assessment and intervention of cognitive decline in the elderly group were analyzed. The basic data required to construct the metaverse in medicine was introduced. Moreover, it is demonstrated that the elderly users can conduct self-monitoring, experience immersive self-healing and health-care through the metaverse in medicine technology. Furthermore, we proposed that it is feasible that the metaverse in medicine has obvious advantages in prediction and diagnosis, prevention and rehabilitation, as well as assisting patients with cognitive decline. Risks for its application were pointed out as well. The metaverse in medicine technology solves the problem of non-face-to-face social communication for elderly users, which may help to reconstruct the social medical system and service mode for the elderly population.

Hemerocallis citrina Baroni ameliorates chronic sleep deprivation-induced cognitive deficits and depressive-like behaviours in mice

Sleep deprivation (SD) is common during spaceflight. SD is known to cause cognitive deficits and depression, requiring treatment and prevention. Hemerocallis citrina Baroni (Liliaceae) is a perennial herb with antidepressant, antioxidant, antitumor, anti-inflammatory, and neuroprotective effects.The aim of our study was to investigate the effects of H. citrina extract (HCE) on SD-induced cognitive decline and depression-like behavior and possible neuroinflammation-related mechanisms. HCE (2 g/kg/day, i.g.) or vortioxetine (10 mg/kg/day, i.g.) were given to mice by oral gavage for a total of 28 days during the SD process. HCE treatment was found to ameliorate SD-induced impairment of short- and long-term spatial and nonspatial memory, measured using Y-maze, object recognition, and Morris water maze tests, as well as mitigating SD-induced depression-like behaviors, measured by tail suspension and forced swimming tests. HCE also reduced the levels of inflammatory cytokines (IL-1β, IL-18, and IL-6) in the serum and hippocampus. Furthermore, HCE suppressed SD-induced microglial activation in the prefrontal cortex (PFC) and the CA1 and dentate gyrus (DG) regions of the hippocampus. HCE also inhibited the expression of phosphorylated NF-κB and activation of the NLRP3 inflammasome. In summary, our findings indicated that HCE attenuated SD-induced cognitive impairment and depression-like behavior and that this effect may be mediated by the inhibition of inflammatory progression and microglial activation in the hippocampus, as well as the down-regulation of NF-κB and NLRP3 signaling. The findings of these studies showingTthese results indicate that HCE exerts neuroprotective effects and are consistent with the findings of previous studies, suggesting that HCE is beneficial for the prevention and treatment of cognitive decline and depression in SD.

Use of Hericium erinaceus as a potential therapeutic of mental disorders: a systematic review

Introduction: Hericium erinaceus (HE), often known as Lion's Mane, is an edible fungus that has been extensively explored for its many functions. The use of this mushroom in traditional Chinese medicine dates back many years, and it is now being tested in the treatment of cognitive decline and Alzheimer's disease, and mental diseases like depression, anxiety, schizophrenia. Methods: We followed 2020 PRISMA statement for systematic reviews. The three selected databases were Worldcat®, Cochrane Library®, and PubMed®. On March 7, 2022, a search for articles was conducted. The search sources' descriptions were Hericium erinaceus AND (mental disorders OR cognitive impairment OR depression OR anxiety). "English" was the sole filter applied to the data sources. Results: Three Japanese randomized double-blind controlled trials were included in the review. Although the data demonstrated that HE can be useful in treating symptoms of cognitive impairment and moderate cognitive impairment, it was not effective in treating depression/anxiety symptoms. Conclusions: More studies are needed in countries besides Japan, lasting at least 12 weeks, since shorter periods do not demonstrate significant improvement of symptoms. Incorporating HE into a patient's daily diet may produce favorable benefits by alleviating cognitive decline.

AMES: An Automated Self-Administered Scale to Detect Incipient Cognitive Decline in Primary Care Settings.

Early identification and intervention of cognitive decline could be effective to prevent progression to dementia. We developed a self-delivered cognitive screening tool, Automated Memory and Executive Screening (AMES), to assess cognitive domains including memory, language, and executive function. 189 participants with diagnoses of mild cognitive impairment (MCI, n = 43), subjective cognitive decline (SCD, n = 29), objectively-defined subtle cognitive decline (obj-SCD, n = 18), and normal controls (NC, n = 99) completed the study. AMES had good convergent validity with conventional scales, and was good to discriminate patients with MCI (area under the curve [AUC] = 0.88; sensitivity = 86%; specificity = 80%) and obj-SCD (AUC = 0.78; sensitivity = 89%; specificity = 63%) from NC. These findings support that AMES is an easy to administer and effective instrument to screen for early cognitive impairment in community-based settings.

Metabolic syndrome and adiposity: Risk factors for decreased myelin in cognitively healthy adults

Metabolic syndrome (MetS) is a cluster of conditions that affects ∼25% of the global population, including excess adiposity, hyperglycemia, dyslipidemia, and elevated blood pressure. MetS is one of major risk factors not only for chronic diseases, but also for dementia and cognitive dysfunction, although the underlying mechanisms remain poorly understood. White matter is of particular interest in the context of MetS due to the metabolic vulnerability of myelin maintenance, and the accumulating evidence for the importance of the white matter in the pathophysiology of dementia. Therefore, we investigated the associations of MetS risk score and adiposity (combined body mass index and waist circumference) with myelin water fraction measured with myelin water imaging. In 90 cognitively and neurologically healthy adults (20–79 years), we found that both high MetS risk score and adiposity were correlated with lower myelin water fraction in late-myelinating prefrontal and associative fibers, controlling for age, sex, race, ethnicity, education and income. Our findings call for randomized clinical trials to establish causality between MetS, adiposity, and myelin content, and to explore the potential of weight loss and visceral adiposity reduction as means to support maintenance of myelin integrity throughout adulthood, which could open new avenues for prevention or treatment of cognitive decline and dementia.

Effectiveness of Nootropics in Combination with Cholinesterase Inhibitors on Cognitive Function in Mild-to-Moderate Dementia: A Study Using Real-World Data.

The clinical benefits of nootropics in the treatment of cognitive decline has been either limited or controversial. This study aimed to observe the effectiveness of cholinesterase inhibitor (ChEI) and nootropics combination in the treatment of cognitive impairment in dementia. Data were based on electronic medical records in a university health system. Patients with mild-to-moderate dementia and no history of prior cognitive enhancer use were included (n = 583). The subjects were categorized into the ChEI only group and the ChEI and nootropics combination group. The primary outcome measure was the change in cognitive function, as assessed by the mini-mental state examination (MMSE) from baseline to 300–400 days after the first ChEI prescription. Subsequent analyses were conducted in consideration of the dementia type, medical adherence, and type of nootropics. The changes in MMSE scores from baseline to endpoint were not significantly different between the two groups. In Alzheimer’s dementia, the combination group showed significantly less deterioration in MMSE language subscale scores compared to the ChEI only group (F = 6.86, p = 0.009), and the difference was consistent in the highly adherent subjects (F = 10.16, p = 0.002). The choline alfoscerate and the ginkgo biloba extract subgroups in Alzheimer’s dementia showed more significant improvements in the MMSE language subscale scores compared to the other nootropics subgroup (F = 7.04, p = 0.001). The present study showed that the effectiveness of ChEI and nootropics combination on cognition may appear differently according to the dementia type. This emphasizes the need for well-controlled studies to generalize the effectiveness of nootropics across various clinical settings.

Menopausal Hormone Therapy and the Mind: The Role of Hormone Replacement in the Prevention and Treatment of Cognitive Decline, Dementia, and Cognitive Dysfunction of Depression.

After participating in this activity, learners should be better able to:• Outline the clinical recommendations for menopausal hormone treatment related to cognitive concerns• Debate and discuss the various research pieces on the use of menopausal hormone therapy cognitive decline, dysfunction, and dementia. Menopause has been associated with subjective cognitive dysfunction and elevated rates of depression. While menopausal hormone therapy (MHT) is Food and Drug Administration-approved for the treatment of vasomotor symptoms related to menopause, a potential role for MHT in treating and preventing cognitive decline, dysfunction, and dementia has remained unclear and a topic of continued interest and debate across decades of research. Increasing numbers of patients are seeking help for subjective cognitive decline, and those with poorer mental health are substantially more likely to perceive themselves to be at high risk of developing dementia; thus, mental health professionals are likely to encounter such patients and may be asked to provide advice concerning MHT, cognition, and indications for MHT use. Here, we synthesize the neurobiological effects of MHT, make recommendations for its use in current clinical practice in the contexts of cognitive dysfunction associated with major depressive disorder, cognitive decline, and Alzheimer's disease, and discuss the frontiers being explored by ongoing research on this topic. We conclude that MHT to improve cognitive functioning has only a few scenarios where it would be recommended and that particular caution may be warranted for carriers of the APOE ε4 allele.

Inhibition of NLRP3 inflammasome-mediated neuroinflammation alleviates electroconvulsive shock-induced memory impairment via regulation of hippocampal synaptic plasticity in depressive rats

Electroconvulsive shock has been considered one of the most effective treatment modalities for major depressive disorder. The association of acute transitory neuroinflammation in the hippocampus following electroconvulsive therapy with transient learning and memory impairment limits its clinical application. Whereas the NLRP3 inflammatory pathway is deemed to serve a key role in neuroinflammatory regulation, we aimed to examine if NLRP3 inflammasome activation was linked to electroconvulsive shock (ECS)-induced neuroinflammation and cognitive deficits. The depressed rats were modeled with chronic unpredictable mild stress. Their depression-like behaviors and cognitive performance were evaluated via sucrose preference test, forced swim test, open field test, and Morris water maze test. The NLRP3 expression was determined by western blot. The hippocampal CA1 region was immunohistochemically and electron-microscopically examined, respectively, for the activation of Iba-1 positive microglia and the ultrastructure of synapses. In this work, we found that ECS induced microglial activation in the rat hippocampal CA1 region. Pharmacological inhibition of NLRP3 inflammasome with MCC950 (NLRP3 inhibitor) in vivo significantly alleviated ECS-induced spatial learning and memory impairment, partially reversed neuroinflammation, and synaptic structural plasticity in the damaged hippocampal CA1 region, and reduced synapse associated protein expression and microglial activation. It offers a potential new approach for the prevention and treatment of cognitive decline following electroconvulsive therapy.

Aims of the Adherence Promotion With Person-Centered Technology (APPT) Project

The APPT project supports the early detection and treatment of age-related cognitive decline and dementia by 1) enhancing adherence to cognitive intervention and assessment protocols, 2) improving understanding of barriers to long-term adherence, and 3) developing algorithms for predicting and preventing adherence failures. Two randomized controlled trials will test an adaptive technology support system predicted to boost adherence to cognitive protocols over a period of six months within samples of older adults with and without cognitive impairment. These studies will provide insight into the benefits of adherence support, and individual difference factors that should shape the adherence protocol, informing the process of identifying individuals who would benefit from additional support and predicting and preventing extended adherence failures before they happen. These studies should improve early detection and treatment of cognitive decline, extend functional independence, and improve lives of those with cognitive impairment as well as the lives of their families.

Aims of the Adherence Promotion With Person-Centered Technology (APPT) Project

To mitigate the effects of COVID-19, Health Ministries across Canada have enacted numerous public health measures. Our mixed methods study examined the effect of COVID-19 related public health messaging and measures for family caregivers (FCGs) of people living with dementia (PLWD). Of the 230 FCGs completing the survey, most frequently used information sources were television, family/friends, and websites. FCGs over 60 more often used television, newspaper and radio versus websites and social media. FCGs rated public health messaging as good-excellent (64%) especially messaging around the disease spread, symptoms, and finding information. 46% believe the restrictions in long-term care facilities went beyond necessary with 97% reporting restrictions have negatively impacted them. 84% were willing to undertake personal protective equipment and infection control training to ensure continued access to PLWD. Focus groups highlighted concerns about continued access to PLWD, quality of care provision, and increased social isolation’s impact on dementia progression.