Drug Development.

Background: Impaired Aβ clearance plays a key role in the common, late-onset AD. Anti-Aβ immunotherapies are controversial, in part because of high rates of serious side effects including edema, microhemorrhages, and siderosis, highlighting the importance of the development of alternative Aβ clearance strategy. Here, we introduce a bioinspired nanoparticle named MG-PE3 crossing the human blood-brain barrier (BBB) and clearing Aβ with no adverse effect.

Drug Development.

Background: The accumulation of amyloidogenic proteins is recognized as a primary biomarker, initiator of pathology, and a potential therapeutic target for Alzheimer's disease (AD). An unbiased screening of a small molecule library was conducted to identify new chemical compounds exhibiting amyloid-dissociative properties.

Method: The ability of aryloxypropanolamine derivatives to dissociate amyloid-β (Aβ) aggregates was evaluated through in vitro assays.

Drug Development.

Background: Genome-wide association studies (GWAS) have identified close to one hundred loci associated with Alzheimer's disease (AD) risk. However, for most of these loci we do not understand the underlying mechanism leading to disease. Crispr genome editing in human induced pluripotent stem cells (hiPSCs) provides a model system to study the effects of these genetic variants in a disease relevant cell type.

Drug Development.

Background: Elevation of cerebrospinal fluid (CSF) tau is a feature of Alzheimer's disease (AD) and is being explored as a biomarker of AD and other tauopathies. The aim of this study was to elucidate the in vivo effects of DA-7503, a potent and selective tau aggregation inhibitor, and its pharmacodynamics on CSF tau in transgenic mouse models of Alzheimer's disease and primary tauopathies.

Method: TauP301L-BiFC mice expressing full-length human tau with the P301L mutation were orally administrated with DA-7503 for 1 month.

Drug Development.

Background: Neurofibrillary tangles (NFTs), along with amyloid beta plaque, are neuropathological aggregates of Alzheimer's Disease (AD). Hyperphosphorylated tau is responsible for the NFTs formation and further neurodegeneration in AD. The hippocampal region and the entorhinal cortex (EC) have been a major focus of AD research because the deposits of hyperphosphorylated tau protein and NFT in these regions are correlated with memory deficits.

Drug Development.

Background: Accumulating evidence suggests that the presynaptic protein α-synuclein (α-syn), is involved in the pathophysiology of AD and elevated in the cerebrospinal fluid (CSF). The role of Natural Killer (NK) cells of the innate immune system in AD has largely been overlooked. In a murine model, depletion of NK cells augmented the accumulation of pathological α-syn.

Drug Development.

Background: VY-TAU01 is a recombinant humanized IgG4 monoclonal antibody (mAb) directed against pathological tau for the treatment of patients with mild dementia or mild cognitive impairment due to Alzheimer's disease (AD). Both VY-TAU01 and its parental mouse IgG1 mAb Ab-01 target an epitope in the C-terminus of tau, bind pathological tau with high affinity and selectivity over wild-type tau, block paired helical filament seed-induced tau aggregates in vitro, and selectively stain tau tangles in AD and P301S mouse (C57/B6J-Tg[Thy1-MAPT*P301S]2541Godt) brain. Ab-01 robustly inhibits seeding and propagation of pathological tau in a P301S mouse seeding model.

Drug Development.

Background: Recruiting large numbers of study participants for Alzheimer's Disease (AD) drug trials remains a significant challenge in need of more effective approaches. Advertising can be an effective way to reach large numbers of prospective participants, but can suffer from low attendance rates. This study examined the relationship between the initial behaviors of prospective AD trial participants who did not attend their first scheduled appointment and their overall likelihood of eventually attending an in-person consultation.

Drug Development.

Background: Neurodegenerative diseases, including Alzheimer's disease (AD), have been long thought to be independent of the peripheral immune system, but their pathogenesis status is functionally influenced by various T cell subsets in the periphery. Especially Treg cells are emerging as an important dynamic population in the brain, but the detailed immunological molecular and cellular processes are poorly characterized METHOD: We reported that the cell surface protein Lrig1 is enriched in Treg cells and is an essential regulator of the functions of Treg cells in vitro and in vivo. To evaluate the functional importance of Treg cells in AD pathogenesis, the modulating mAb specific to Lrig1 (GTC 310-01) via intravenous injection route was administered into 5xFAD or 6xTg mice, the genetic mouse model of AD, and the various AD symptoms were investigated.

Drug Development.

Background: Recruitment challenges in people with and without Down syndrome (DS) can delay research progress and risk sample bias. This study identified and quantified differences in research attitudes across populations of research enrollment decision-makers for individuals with and without DS.

Method: We compared scores on the Research Attitudes Questionnaire (RAQ) of individuals enrolled in two recruitment registries: the UCI Consent to Contact [C2C (N = 4818)] and DS-Connect (N = 976).

Dementia Care Research and Psychosocial Factors.

Background: People with dementia of all ages have a human right to equal access to quality health care. Despite evidence regarding its effectiveness, many people living with dementia lack access to evidence-based rehabilitation for promoting function and quality of life. The aims of this study were to 1) explore barriers to access to dementia rehabilitation; and 2) identify solutions which improve access to rehabilitation.

Dementia Care Research and Psychosocial Factors.

Background: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive emerging tool to modulate brain activities and functional connectivity in various neuropsychiatric disorders. rTMS combined with cognitive training (rTMS-COG) has been showing cognitive enhancing effects compared to those of placebo in mild Alzheimer's disease (AD) in some previous studies. However, there is not much research to conclude how much each rTMS or COG contributes to therapeutic cognitive effects.

Outcomes of Immunotherapy Treatment in Sinonasal Mucosal Melanoma.

Background: Sinonasal mucosal melanoma has poor survival despite multimodality treatment. While the impact of immunotherapy (IT) on metastatic cutaneous melanoma is well-defined, there are relatively little data on sinonasal mucosal melanoma.

Objective: We sought to define immunotherapy outcomes in patients with sinonasal mucosal melanoma.

Dementia Care Research and Psychosocial Factors.

Background: Family caregivers of persons with dementia (PWD) suffer from constant caregiving burden resulting in poor sleep quality. Understanding sleep parameters (e.g.

Dementia Care Research and Psychosocial Factors.

Background: Sleep directly affects daily life, and lack of sleep affects cognitive function and mental health. So, this study analyzed the performance structures of daily activities affecting sleep using social network analysis.

Methods: The subjects were 313 people over 50 years old.

Dementia Care Research and Psychosocial Factors.

Background: Loneliness and depression among older adults are linked to a higher likelihood of chronic diseases, deterioration of physical function, and compromised quality of life. LGBTQ older adults are known to experience social isolation and mental distress at higher rates than their heterosexual counterparts, and those with cognitive impairment may be particularly susceptible to loneliness and depression. However, there is limited knowledge regarding the risk and protective factors for loneliness and depression among LGBTQ older adults living with cognitive impairment.

Dementia Care Research and Psychosocial Factors.

Background: Mealtime is a fundamental daily activity to ensure nutrition, social interaction, and enjoyment of food for people with dementia (PWD). Interventions addressing multilevel barriers are critical to optimize mealtime care and outcomes. This review aimed to synthesize existing interventions on mealtime care and outcomes in PWD and their caregivers.

Dementia Care Research and Psychosocial Factors.

Background: Medical history and healthcare utilization in preclinical Alzheimer's disease (AD) are not well characterized and may reveal indicators associated with asymptomatic stages of AD.

Methods: This retrospective observational study compared 246 Anti-Amyloid Treatment in Asymptomatic AD study (A4) individuals who met elevated brain amyloid eligibility criteria to 121 individuals in the companion Longitudinal Evaluation of Amyloid Risk and Neurodegeneration study (LEARN) who were eligible for A4 except did not meet elevated amyloid eligibility criteria. Matched-controls for A4/LEARN, using a 3:1 match of demographics, Medicare enrollment month, and frailty status, were randomly selected from Medicare beneficiaries without cognitive impairment/dementia claims.

Dementia Care Research and Psychosocial Factors.

Background: Self-rated health status goes beyond a mere indicator of one's well-being, encompassing biological, social, and functional aspects. It has emerged as a significant variable in predicting mortality. Against this backdrop, understanding the impact of subjective health status on anxiety symptoms is crucial for individuals with dementia.

Dementia Care Research and Psychosocial Factors.

Background: Dementia care management programs, including the Care Ecosystem, have been shown to improve patient and caregiver outcomes, reduce unnecessary healthcare expenditures, and are the focus of Medicare's new GUIDE payment model. Until now, prior research has focused on evaluating the effectiveness of participating for a short (eg, 12-month) time frame. The purpose of this study was to evaluate the effects of the Care Ecosystem when delivered for up to 5 years or end of life.

Dementia Care Research and Psychosocial Factors.

Background: Marital status is an important but often overlooked sociodemographic factor that could shape cognitive health in late adulthood. Being married is shown to be linked to lower risk of dementia, but less is understood about underlying mechanisms contributing to this relationship, such as brain reserve (BR) and cognitive reserve (CR). Further, less is known about how living arrangement, independent of marital status, is associated with late-life cognition.

Dementia Care Practice.

Background: Boosting shared decision-making (SDM) for individuals with dementia is a critical aspect of patient-centered care. This collaborative approach respects the autonomy and dignity of patients, even when they face challenges in communication or decision-making due to their medical condition. Understanding patients' values and preferences may be central to a successful SDM process.

Dementia Care Practice.

Background: Multispecialty Interprofessional Team (MINT) Memory Clinics build capacity for dementia care within primary care. This presentation will provide an overview of the MINT care model and results of a process evaluation of the implementation of the model in three provinces in Canada using the Research Medical Council framework for evaluating complex interventions.

Methods: 178 healthcare providers (HCP) were trained to establish 10 MINT clinics across three Canadian provinces.

Dementia Care Practice.

Background: The Medication Review in Cognitive Impairment and Dementia (MedRevCiD) checklist is a new tool designed to assist health care professionals in optimizing medication use in individuals with Mild Cognitive Impairment (MCI) or dementia. It consists of 6 domains, each of which addresses a specific medication use issue such as medication management and adherence. The primary objective of this study was to compare the mean number of drug-related problems (DRPs) identified with MedRevCiD Checklist to the Medication Appropriateness Index (MAI) in older adults attending a primary care-based memory clinic.

Dementia Care Practice.

Background: The use of potentially inappropriate medications (PIMs) in older adults with dementia and/or Mild Cognitive Impairment (MCI) has been associated with increased adverse events, drug-related problems (DRPs), prolonged hospitalization, risk of falls, and increased length of stay. This study aimed to identify which explicit tool, Beers criteria 2023 or Screening Tool of Older Persons Potentially Inappropriate Prescriptions (STOPP) 2023, identifies more PIM use among older adults with MCI or dementia.

Methods: A cross-sectional study was conducted at a Multispecialty Interprofessional Team-based (MINT) memory clinic.