Drug Development.

Background: Clinical trials should strive to yield results that are clinically meaningful rather than solely relying on statistical significance. However, the determination of clinical meaningfulness of dementia clinical trials lacks standardization and varies based on the trial's nature. To tackle this issue, a proposed approach involves assessing the time saved before reaching a specific threshold in cognitive status.

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: Blood pressure (BP) management is an accessible therapeutic target for dementia prevention. BP variability (BPV) is a newer aspect of BP control recently associated with cognitive decline, dementia and Alzheimer's disease (AD), independent of traditionally targeted mean BP levels. Most of this work has relied on largely non-Hispanic White study samples in observational cohorts.

Drug Development.

It is well recognised that Alzheimer's disease and related dementia disorders (ADRD) are associated with very high societal costs. The total global costs of dementia have been estimated to over 1.3 trillion US$ annually (Wimo, Seeher et al.

Drug Development.

Background: Iron is vital for metabolism but can act as a catalyst for oxidative damage. Elevated brain iron, determined from biomarkers of iron (CSF ferritin and quantitative susceptibility mapping MRI) and from post-mortem measurement of brain iron, has been associated with accelerated cognitive decline in multiple Alzheimer's disease (AD) clinical, cohorts. These findings supported the hypothesis that treatment with the brain-permeable iron chelator deferiprone may be associated clinical benefit in AD.

Drug Development.

Background: Mivelsiran (ALN-APP) is an investigational, intrathecally administered RNA interference therapeutic designed to lower levels of amyloid-β (Aβ) peptide, a key driver of Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA) pathogenesis, by reducing upstream production of amyloid precursor protein (APP). We report additional safety, pharmacodynamic, and biomarker data from the double-blind, placebo-controlled, single ascending dose part of the ongoing mivelsiran Phase 1 study (NCT05231785).

Method: Patients with early-onset AD (symptom onset <65 years of age, Clinical Dementia Rating global score 0.

Drug Development.

Background: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the impairment of cognitive development and disruption of neurocognitive function. This neuropathological condition is marked by neurodegeneration, loss of neural tissue, and the formation of neurofibrillary tangles and Aβ plaques. Various studies reported the utilization of phytoconstituents like fisetin, quercetin, berberine, and xanthohumol for the treatment of AD.

Drug Development.

Background: The first disease-modifying treatments (DMTs) for Alzheimer's disease (AD) have been approved in the USA, marking profound changes in AD-diagnosis and treatment. This will bring new challenges in terms of clinician-patient communication. We aimed to collect the perspectives of memory clinic professionals regarding the most important topics to address and what (tools) would support professionals and their patients and care partners to engage in a meaningful conversation on whether (or not) to initiate treatment.

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.

Correction: Camptothecin-based prodrug nanomedicines for cancer therapy.

Correction for 'Camptothecin-based prodrug nanomedicines for cancer therapy' by Renshuai Zhang , , 2023, , 17658-17697, https://doi.org/10.1039/D3NR04147F.

Drug Development.

Background: The Mini-Mental State Examination (MMSE) is a common screening tool in Alzheimer's disease (AD) clinical trials. MMSE score inflation at inclusionary visits poses challenges by potentially amplifying placebo responses and complicating the detection of treatment effects. Despite these concerns, prior research (e.

Drug Development.

Background: Recruitment of demographically diverse participants into Alzheimer's disease (AD) clinical trials, encompassing both screening and randomization, remains a consistent and persistent challenge contributing to underrepresentation of certain groups. Despite the exciting prospects of identifying therapeutic interventions for biomarker-eligible, cognitively unimpaired individuals, these studies grapple with the inherent complexities of AD trials coupled with intricate and time-consuming screening processes. Addressing this the issue of underrepresentation necessitates concerted and intentional efforts that prioritize inclusivity and equitable access to enroll adults meeting study criteria, reflecting the demographic and social diversity of North America.

Clinical Characteristics and Outcomes of Deep Vein Thrombosis in Relation to Location: A Retrospective Analysis Study.

Deep vein thrombosis (DVT) is a leading cause of death disability. DVT can be classified based on the location and extent of the clot into isolated distal DVT (iDDVT), isolated proximal DVT (iPDVT), or mixed DVT. The aim of this study is to explore the baseline characteristics and clinical outcomes of patients with different types of DVT.

Drug Development.

Numerous drugs (including disease-modifying therapies, cognitive enhancers and neuropsychiatric treatments) are being developed for Alzheimer's and related dementias (ADRD). Emerging neuroimaging modalities, and genetic and other biomarkers potentially enhance diagnostic and prognostic accuracy. These advances need to be assessed in real-world studies (RWS).

Drug Development.

Background: Recruiting and retaining older adults for clinical trials is challenging, especially in low-resource settings. Such challenges led to a systematic exclusion of such participants from clinical trials, compromising the generalizability of the results obtained in high income countries.

Objective: Here we describe the strategies we used in the PROAME study for recruiting and retaining illiterate older adults from low socioeconomical levels in a non-pharmacological trial.

Drug Development.

Background: Agitation is a common and disabling symptom of Alzheimer's dementia (AD). Pharmacological treatments are recommended if agitation is not responsive to psychosocial intervention. Citalopram was effective in treating agitation in AD but was associated with cognitive and cardiac risks linked to its R- but not S-enantiomer.

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.

Introduction: The United States is undergoing a demographic shift with increasing proportions of older adults. Currently, one in three older adults pass away with a form of Alzheimer's disease or related dementias (ADRD). This figure is higher in underrepresented and underserved groups including older adults in rural Appalachian communities.

Drug Development.

In Japan, the regulatory authority approved the drug in September 2023, and on December 20, it became available for prescription country-wide under the health insurance system. However, there are strict patient, physician, and facility requirements for the prescription of Lecanemab, and various problems are anticipated in its future implementation and widespread use in society. Lecanemab is the first anti-Aβ antibody in Japan, and even dementia specialists do not have sufficient knowledge and experience in its introduction, evaluation of efficacy, and evaluation and handling of side effects.

Drug Development.

Real-world data on the uptake, effectiveness and safety of new diagnostics and disease-modifying (DMT) treatments for Alzheimer's Disease (AD) are imperative. This can be achieved through patient registries. A major challenge is how to embed registry data capture into routine clinical practice.

Sex-related differences in the morphology of rectal mucosa-associated lymphoid tissues in C57BL/6NCrSlc mice.

Sex hormones regulate gut function and mucosal immunity; however, their specific effects on the mucosa-associated lymphoid tissue (MALT) in the rectum of mammals remain unclear. Here, we aimed to investigate the influence of sex on MALT in the rectum of mammals by focusing on the rectal mucosa-associated lymphoid tissues (RMALTs) of C57BL/6NCrSIc mice. Histological analysis revealed that RMALTs were predominantly located in the lamina propria and submucosa of the rectal mucosa, with a significant sex-related difference in the distance from the anorectal junction to the first appearance of the RMALT.

Drug Development.

Background: To bolster clinical trial infrastructure, there is a need to develop novel, valid, and reliable patient-reported outcome (PRO) measures capable of tracking clinically-relevant changes in Alzheimer's disease (AD), Mild Cognitive Impairment (MCI) and dementia over time. This research describes the development and validation of the Alzheimer's Disease-Health Index (AD-HI) as a tool to measure how patients feel and function in response to therapeutic intervention.

Method: We previously conducted semi-structured qualitative interviews and a national cross-sectional study with individuals with AD, MCI and dementia to ascertain the most prevalent and impactful symptoms identified by the participants.

Drug Development.

Background: The LatAm-FINGERS trial marks a pioneering initiative as the first non-pharmacological clinical trial encompassing participants from 12 Latin American countries, including Argentina, Brazil, Bolivia, Chile, Colombia, Costa Rica, Ecuador, Dominican Republic, Mexico, Peru, Puerto Rico, and Uruguay. This initiative represents a significant advancement in promoting inclusivity and diversity in clinical trial recruitment, particularly in underserved populations.

Method: The LatAm-FINGERS trial is a multicenter randomized clinical trial evaluating a lifestyle intervention tailored for the Latin American population.

Drug Development.

Real-World data platforms for Alzheimer's Disease (AD) offer a unique opportunity to improve health equity through better understanding of health disparities and inclusivity in research, which is critical to translatability of research findings. AD research in the US and globally remains largely inaccessible to many individuals due to individual-level, study-level, investigator-level and larger systemic barriers. ALZ-NET, a US-based registry to evaluate longitudinal outcomes of patients being evaluated for or treated with novel FDA-approved AD therapy, and New IDEAS, an observational US-based longitudinal study of amyloid PET clinical utility, both offer opportunities for examining care, inclusivity, and disparities.

Drug Development.

Background: It is essential that both drug and lifestyle-based interventions aimed at delaying the functional decline in conditions like Alzheimer's disease and related dementias (ADRDs) capture change in functioning that incorporates the person's voice. Such brain health priorities can vary across populations and it is unclear to what degree findings from the ePSOM program in the UK might apply to the US.

Methods: We conducted an online nationwide study to understand what matters to people aged 50 and older about their brain health in the US.