Drug Development.

Background: The DL-3-n-butylphthalide (NBP), a multi-target neuroprotective drug, improving cognitive impairment in patient with vascular cognitive impairment has been confirmed. The efficacy of NBP in patients with cognitive impairment due to Alzheimer's disease (AD) remains unknown. This study aimed to evaluate the efficacy and safety of NBP in patients with mild cognitive impairment (MCI) due to AD though a clinical randomized controlled trail.

Drug Development.

Background: The initiation of amyloid plaque deposition signifies a crucial stage in Alzheimer's disease (AD) progression, which often coincides with the disruption of neural circuits and cognitive decline. While the role of excitatory-inhibitory balance is increasingly recognized in AD pathophysiology, targeted therapies to modulate this balance remain underexplored. This study investigates the effect of perampanel, a selective non-competitive AMPA receptor antagonist, in modulating neurophysiological changes in hAPP-J20 transgenic Alzheimer's mice.

Drug Development.

Background: Selecting the optimal dose for clinical development is especially problematic for drugs directed at CNS-specific targets. For drugs with a novel mechanism of action, these problems are often greater. We describe Xanamem's clinical pharmacology, including the approach to dose selection and proof-of-concept studies.

Drug Development.

Background: Individuals with type 2 diabetes mellitus (T2DM) face an increased risk of dementia. Recent discoveries indicate that SGLT2 inhibitors, a newer class of anti-diabetic medication, exhibit beneficial metabolic effects beyond glucose control, offering a potential avenue for mitigating the risk of Alzheimer's disease (AD). However, limited evidence exists regarding whether the use of SGLT2 inhibitors effectively reduces the risk of AD.

Drug Development.

Background: The well-accepted statistical efficacy inference approach for Alzheimer's disease (AD) clinical trials compares the absolute difference in change from baseline at the last study visit using MMRM (henceforth referred to as MMRM-Last-Visit). Recent AD clinical trials have shown that treatment effects may be manifested prior to 18 months. The objective is to evaluate models estimating an overall treatment effect across all post-baseline visits that may characterize disease modifying effects in contemporary early AD clinical trials.

Drug Development.

Background: Effective early intervention of mild cognitive impairment (MCI) is the key for preventing dementia. However, there is currently no drug for MCI. As a multi-targeted neuroprotective agent, butylphthalide has been demonstrated to repair cognition in patients with vascular cognitive impairment, and has the potential to treat MCI due to Alzheimer's disease (AD).

Drug Development.

Background: Alzheimer's disease (AD) is complex in pathogenesis and related to aging biology, especially in late-onset AD. We identified a novel synthetic curcumin analog TML-6 through the platform of 6 biomarkers of anti-aging, anti-inflammation, and anti-Aβ as the potential AD drug candidate. TML-6 exhibits multi-target effects on AD pathogenesis, including the activation of NrF-2, the regulation of autophagic machinery through mTOR, the inhibition of APP synthesis and reduction of Aβ, the upregulation of ApoE, and the inhibition of microglial activation.

Drug Development.

Background: Recent growth in the functionality and use of technology has prompted an increased interest in the potential for remote or decentralised clinical trials in dementia. There are many potential benefits associated with decentralised medication trials, but the field is currently lacking specific recommendations for their delivery in the dementia field.

Method: A modified Delphi method engaged a panel with substantial expertise in dementia trial design and delivery and backgrounds that included neurology, psychiatry, pharmacology and psychology, to develop recommendations for the conduct of decentralised medication trials in dementia prevention.

Drug Development.

Background: Findings regarding the protective effect of Angiotensin II receptor blockers (ARBs) against Alzheimer's disease and related dementias (ADRD) and cognitive decline have been inconclusive.

Method: A total of 6,390,826 hypertensive individuals were included in this study from Optum's de-identified Clinformatics® Data Mart. We identified antihypertensive medication (AHM) drug classes and subclassified ARBs by blood-brain barrier (BBB) permeability.

Drug Development.

Background: Apolipoprotein E4 (apoE4) has been identified as the major genetic risk factor for late onset Alzheimer's disease (AD). Our lab has demonstrated that chronic administration of Aβ12-28P, a synthetic peptide that blocks apoE4/Aβ binding, in middle-aged transgenic AD mice significantly ameliorates pathology progression, resulting in reduced Aβ plaques deposition and cerebral amyloid angiopathy (CAA) along with improved memory and cognition. However, whether blocking apoE4/Aβ interaction by Aβ12-28P also has an ameliorating effect on the neuronal and cognitive function of old AD mice where Aβ pathology has been extensively developed remains unknown.

Drug Development.

Background: Increased APP gene dosage is both necessary and sufficient to result in Down Syndrome Alzheimer's Disease (DSAD) in humans and AD-related degenerative changes in mouse models of DS.

Method: We tested antisense oligonucleotides (ASOs) designed to suppress APP expression via RNAseH1-mediated degradation in the Dp(16)1Yey or Dp(16) model of Down Syndrome. Dp(16) is trisomic for human chromosome 21 syntenic regions on murine chromosome 16, containing 115 genes including APP.

Drug Development.

Background: Microglial activation is one of the neuropathological hallmarks of Alzheimer's disease (AD). Evidence suggest that chronic activation of microglia cause neuroinflammation and neuronal injuries, contributing to cognitive impairment. Therefore, modulation of microglial pathway like CSF-1R represents an attractive therapeutic strategy.

Dementia Care Research and Psychosocial Factors.

Background: Aging associates with decreased functional connectivity between brain regions linked to musical rhythm perception. Producing rhythmic music may result in strengthened functional connectivity of these regions, but more evidence is needed to support intervention design. Currently, few studies directly contrast younger and older adults' rhythmic music performance to understand brain-behavior relationships.

Dementia Care Research and Psychosocial Factors.

Background: Caring for family caregivers of dementia patients has grown to an important topic. Social media platforms, like Twitter, provide great resources for studying the needs of caregivers. It would be beneficial to understand the caregivers' interested or concerned topics from their tweets.

Dementia Care Research and Psychosocial Factors.

Background: Older adults with cognitive impairments will benefit from multicomponent interventions include cognitive training, exercise, and lifestyle modifications. Many digital therapeutic products predominantly focus on computerized cognitive training, lacking effective approaches to other crucial interventions. This study aimed to investigate the long term effects of multidimensional comprehensive cognitive intervention training program - Brain and Body Rehab Training (BBRT), which integrates multidomain cognitive training with physical-cognitive training and multidimensional lifestyle interventions on cognitive performance in participants with cognitive impairment after a 8-month follow-up.

Dementia Care Research and Psychosocial Factors.

Background: Social health factors have been robustly associated with better cognitive health in older adults; however, less is known about how social network size affects the relationship between in-vivo biomarkers of Alzheimer's disease (AD) pathology and brain aging outcomes. We examined the independent and interactive relationships between plasma pTau181 and social network size on memory function and medial temporal lobe (MTL) volume in older adults.

Method: Participants were 58 community-dwelling older adults (mean age = 75.

Dementia Care Research and Psychosocial Factors.

Background: The effects of the COVID-19 pandemic extend beyond the viral impact and include social and psychological effects of the ensuing lockdowns and restrictions. Australia's lengthy lockdowns present an opportunity to study changes in the physical and mental wellbeing of older adults resulting from extended social isolation, a known risk factor for dementia, in the absence of high infection or mortality rates.

Method: Sydney Memory and Ageing Study, Sydney Centenarian Study, and CogSCAN study participants were mailed questionnaires about in-person and remote social contact and access to resources during the 2020 Sydney lockdown.

Dementia Care Research and Psychosocial Factors.

Background: Lexical retrieval therapy (LRT) has been proven to be an effective speech therapy for individuals with semantic variant primary progressive aphasia (svPPA) and semantic cue plays an important ingredient in LRT. In recent findings, differential performance in using and choosing noun-classifiers amongst Chinese individuals with the three subtypes of PPA were observed. The current study aims to explore the treatment effect of employing noun-classifier as a semantic cue of LRT for Cantonese-speaking svPPA.

Dementia Care Research and Psychosocial Factors.

Background: In the context of heightened attention to dementia, research gaps persist in the seamless integration of clinical and non-clinical care, including long-term support. This study aims to examine potential gaps in social support for US adults with cognitive impairment, focusing on the transition before and after a dementia diagnosis.

Methods: In this ambidirectional cohort study, we examined data from the Health and Retirement Survey(HRS) for US adults over 50, using data from 2000 to 2018.

Dementia Care Research and Psychosocial Factors.

Background: The global increase in dementia cases underscores the need for community-based services, particularly for older adults who spend significant time in their neighborhoods. This context profoundly influences cognitive function and quality of life, especially in those at high risk of cognitive impairment. Despite its importance, neighborhood cohesion has not been extensively studied in this group.

Dementia Care Research and Psychosocial Factors.

Background: This study uses the data collected from the "Partnership in Implementation Science for Geriatric Mental Health (PRISM)" project, a randomized trial designed to test implementation support strategies for the delivery of the Reducing Disability in Alzheimer's Disease (RDAD) program, an evidence-based multi-component exercise and behavioral/psychosocial intervention for older adults with dementia and their family caregivers in Thailand.

Method: A total of 353 dyads of persons with dementia (PwD) and behavioral and psychological symptoms of dementia (BPSD) and their family caregivers received a 12-week RDAD intervention and were assessed at baseline, and at 3- and 6-months post-treatment. Longitudinal analyses were conducted using paired-sample t-tests to estimate the changes in each of the outcomes by treatment groups.

Electrocatalytic Mapping of Metal Fatigue with Persistent Slip Bands.

Metal fatigue, characterized by the accumulation of dislocation defects, is a prevalent failure mode in structural materials. Nondestructive early-stage detection of metal fatigue is extremely important to prevent disastrous events and protect human life. However, the lack of a precise quantitative method to visualize fatigue with spatiotemporal resolution poses a significant obstacle to timely detection.

Enhanced Near-Infrared Fluorescence Emission near a Graphene-Metal Hybrid Structure.

Plasmon resonance plays an important role in improving the detection of biomolecules, and it is one of the focuses of research to use metal plasmon resonance to achieve fluorescence enhancement and to improve detection sensitivity. However, the problems of nondynamic tuning and fluorescence quenching of metal plasmon resonance need to be solved. Graphene surface plasmon resonance can be dynamically controlled, and the graphene adsorption of fluorescent molecules can avoid fluorescence quenching and greatly improve the fluorescence emission intensity.

Dementia Care Research and Psychosocial Factors.

Background: Persons with cognitive impairment may experience difficulties with language and cognition that interfere with their ability to make and communicate decisions. We developed an online visual tool to facilitate conversations about their preferences concerning supportive care.

Methods: We conducted Zoom interviews with persons with mild cognitive impairment (MCI) and mild to moderate dementia, using storytelling and a virtual tool designed to facilitate discussion.

One-Pot Domino Catalysis to Construct Alkyl/Aryl Pyrroles Initiated by Pd-TMM Annulation of Unactivated Imines.

Herein, a one-pot domino catalyzed three-component process is described, which is initiated by a palladium/zinc cooperatively catalyzed cycloaddition between trimethylenemethane (TMM) and unactivated alkyl/aryl imines, followed by one-pot isomerization and Zn(OTf)-catalyzed DDQ oxidation, furnishing valuable substituted pyrroles. We disclose that the palladium/zinc cooperative catalysis affords a dual-Zn(OTf)-stabilized azapalladacycle, wherein the Pd-N bond is polarized by Zn(OTf), facilitating a unique outer-sphere allylic amination. Moreover, subsequent DDQ dehydrogenation can be feasibly promoted by zinc catalysis.