Development of 3D-printed conducting microneedle-based electrochemical point-of-care device for transdermal sensing of chlorpromazine.

Despite the various benefits of chlorpromazine, its misuse and overdose may lead to severe side effects, therefore, creating a user-friendly point-of-care device for monitoring the levels of chlorpromazine drug to manage the potential side effects and ensure the effective and safe use of the medication is highly desired. In this report, we have demonstrated a simple and scalable manufacturing process for the development of a 3D-printed conducting microneedle array-based electrochemical point-of-care device for the minimally invasive sensing of chlorpromazine. We used an inkjet printer to print the carbon and silver ink onto a customized 3D-printed ultrasharp microneedle array for the preparation of counter, working, and reference electrodes.

Cost-effectiveness of finerenone therapy for patients with chronic kidney disease and type 2 diabetes in England & Wales: results of the FINE-CKD model.

Objective: Chronic kidney disease (CKD) is the leading cause of kidney failure, end-stage kidney disease (ESKD), and cardiovascular (CV) events in patients with type 2 diabetes (T2D). The FIDELIO-DKD trial demonstrated that finerenone lowered the risk of renal and CV events in patients with CKD and T2D, regardless of cardiovascular disease history. This study evaluated the cost-effectiveness of finerenone added to background treatment (finerenone + BT) versus background treatment (BT) alone in patients with CKD and T2D from the perspective of the National Health Service in England and Wales.

Developing Topics.

Background: Apathy in Alzheimer's disease improves with methylphenidate (MPH) but treatment response was found to vary depending on clinical factors. Here, we explored whether underlying biological factors assessed by blood-based biomarkers of neurodegeneration, inflammation and oxidative stress affect apathy treatment response.

Method: A subset of participants from the Apathy in Dementia Methylphenidate Trial 2 (ADMET 2) were included in this study whose blood samples were available at baseline and at the 6-month treatment completion.

Developing Topics.

Background: Adverse social exposome (indexed by high national Area Deprivation Index [ADI]) is linked to structural inequities and increased risk of clinical dementia diagnosis, yet linkage to ADRD neuropathology remains largely unknown. Early work from single site brain banks suggests a relationship, but assessment in large national cohorts is needed to increase generalizability and depth, particularly for rarer neuropathology findings.

Objective: Determine the association between adverse social exposome by ADI and ADRD neuropathology for brain donors from 21 Alzheimer's Disease Research Center (ADRC) brain banks as part of the on-going Neighborhoods Study.

Developing Topics.

Background: Improving modifiable risk factors, like diet quality, can protect against Alzheimer's disease (AD). The association between diet and cognition in midlife as a function of APOE-e4 genotype, a strong risk factor for AD, remains unknown. Therefore, this study examined the relationship between dietary intake and executive function (EF) in middle-aged sedentary women with a family history of AD (FH+), and if the association was moderated by APOE-e4 carrier status.

Developing Topics.

Background: Current blood biomarkers of Alzheimer's disease (AD) neuropathology and neurodegeneration include the ratio of amyloid-β 42 to 40 (Aβ42/Aβ40), phosphorylated tau at threonine 181 (p-Tau181), neurofilament light (NfL) and glial fibrillary acidic protein (GFAP). Prior studies have reported that hypertension is cross-sectionally associated with lower levels of Aβ42/Aβ40 and longitudinally associated with faster accumulation of NfL. In this longitudinal investigation, we expanded on prior research by examining whether mid-life blood pressure status was associated with change in AD biomarkers from mid- to late-life.

Developing Topics.

Background: In APOE ε4 allele carriers at increased risk for Alzheimer's disease (AD), midlife (age 40-65 years) is a critical window when amyloid-β (Aβ) pathology could progress without overt cognitive decline, but AD-related biomarkers may be present. Blood measures of phosphorylated tau at Thr217 (p-tau217) indicate aggregated Aβ pathology in the preclinical stage of AD, whereas ApoE protein levels are associated with the clearance of Aβ. C-reactive protein (CRP) and serum amyloid A (SAA) are acute phase reactants within the inflammatory pathway, but SAA is also related to ApoE levels and Aβ clearance.

Developing Topics.

Background: ApolipoproteinE ε4 carriers (ε4+) have a heightened risk for Alzheimer's disease (AD) and experience accelerated hippocampal volume (HV) loss during older adulthood, which tends to precede cognitive decline. Exercise interventions can increase HV in sedentary older adults, however it's currently unknown how exercise affects HV in sedentary middle-aged adults and if ε4 carrier status moderates this relationship.

Methods: A subset of 44 adults from an ongoing randomized controlled clinical trial (NIH/NIA: R01AG058919) completed baseline (pre), 6-month (mid), and 12-month (post) testing during a one-year exercise intervention (n = 29, 52% ε4+, 5 males, Age = 55.

Developing Topics.

Background: Mid-life and late-life cardiometabolic abnormality are known modifiable risk factors for late-life dementia. Neuroimaging-based "brain age" has shown as a surrogate marker for brain health. This study aims to investigate the relationship between effect of cardiometabolic risk factors (CMRF) and accelerated brain aging, METHOD: T1-weighted 3D MRIs from a total of 965 participants (47-81 years, 53% female) in the UKBiobank data were included in this study.

Alzheimer's Imaging Consortium.

Background: Weakened white matter (WM) integrity is highly associated with dementia risk. Still, not everyone with WM changes develops dementia, suggesting the important role modifiable lifestyle factors may have in reducing dementia risk. We investigated how social relationships in mid-life may modify the association between WM integrity and incident dementia risk within race and sex subgroups.

"Snakeskin" Bioinspired Design for Polymer Composite with Enhanced Positive Temperature-Dependent Thermal Conductivity.

Albeit there is widespread application of thermally conductive polymer composites, one challenge is their typical negative temperature dependence on thermal conductivity (TDTC) due to the mismatch in thermal expansion between the polymer and fillers, creating voids at the interfaces. Inspired by the hierarchical structure of snakeskin, where rigid scales and a soft intergap manage expansion, we designed a segregated structure by coating a high-expansion high impact polystyrene (HIPS)/graphite (Gt) composite with a copper alloy. We hypothesize that the Cu alloy restricts the thermal expansion of HIPS/Gt while forming a pseudoconductive network, enhancing TDTC and thermal conductivity (TC).

Alzheimer's Imaging Consortium.

Background: Residence in a disadvantaged neighborhood (e.g., high poverty rate, poor housing, etc.

Drug Development.

Background: Pharmacoepidemiologic studies assessing drug effectiveness for Alzheimer's disease and related dementias (ADRD) are increasingly popular given the critical need for effective therapies for ADRD. To meet the urgent need for robust dementia ascertainment from real-world data, we aimed to develop a novel algorithm for identifying incident and prevalent dementia in claims.

Method: We developed algorithm candidates by different timing/frequency of dementia diagnosis/treatment to identify dementia from inpatient/outpatient/prescription claims for 6,515 and 3,997 participants from Visits 5 (2011-2013; mean age 75.

Drug Development.

Background: There is an urgent need for new therapeutic and diagnostic targets for Alzheimer's disease (AD). Dementia afflicts roughly 55 million individuals worldwide, and the prevalence is increasing with longer lifespans and the absence of preventive therapies. Given the demonstrated heterogeneity of Alzheimer's disease in biological and genetic components, it is critical to identify new therapeutic approaches.

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.

Dementia Care Research and Psychosocial Factors.

Background: Caregiving for older adults requires balancing multiple tasks ranging in complexity and demand. While often characterized as burdensome, there are also positive outcomes related to caregiving including potential benefits to health outcomes. Although older adults are themselves often caregivers, the association between caregiving and cognitive outcomes has not been routinely studied.

Dementia Care Research and Psychosocial Factors.

Background: The scarcity of resources and caregiving services, a higher prevalence of health conditions, and financial concerns in rural areas in the United States have been well-documented. However, less research has compared experiences between caregivers of people with Alzheimer's disease and related dementias (ADRD) in rural versus urban areas. This study sought to address this gap by identifying those unmet service needs, explore factors associated with service use, and propose tailored strategies for better serving the needs of both rural and urban caregivers.

Dementia Care Research and Psychosocial Factors.

Background: Previous studies attest to a lack of awareness about Alzheimer's Disease (AD) and limited participation of Black Americans in AD clinical trials. The AHEAD Study is a multicenter trial focused on preventing AD by evaluating the effectiveness and safety of Lecanemab in individuals with preclinical AD. The study aims to recruit at least 15% from underrepresented populations, including Black Americans.

Dementia Care Research and Psychosocial Factors.

Background: Studies show that tube feeding does not improve clinical outcomes, and professional guidelines recommend against its use for individuals with advanced dementia. Yet, our preliminary work demonstrates a preference for tube feeding among Chinese-American dementia caregivers. We propose linguistic and cultural adaptation of "Making Choices: Feeding Options for Patients with Dementia (MCFODA) to create the Chinese version of this efficacious decision aid intervention.

Dementia Care Research and Psychosocial Factors.

Background: Our previous work has found that sexual and gender minority (SGM) or LGBTQIA+ caregivers of people living with Alzheimer's disease and related dementias (ADRD) experience higher levels of stigma, depressive symptoms, and stress than non-SGM caregivers and that these outcomes are associated with experiences of microaggressions related to their SGM identities. Guided by the Health Equity Promotion Model, we sought to explore the impact of the environmental context on psychosocial outcomes among SGM caregivers of people living with ADRD.

Methods: Data from a cross-sectional online survey using a non-probabilistic sample of SGM caregivers of people with ADRD recruited via social media (n = 284) were combined with publicly available data reporting composite equity climate index scores across five domains: legal/non-discrimination protections, youth/family support, political/religious attitudes, health access/safety, and work environment/employment.

Dementia Care Research and Psychosocial Factors.

Background: Previous What Matters Most (WMM) research identified and verified patient-important concepts among a diverse population of people living with Alzheimer's disease (PLWAD) and their care partners across all stages of Alzheimer's disease (AD). Additionally, a conceptual model of disease was developed using hypothesized domains and was further refined using qualitative data (Figure 1). This next phase of WMM research aims to quantify the importance of concepts, impacts, and outcomes and to determine priorities among PLWAD and care partners within a diverse sample including underrepresented ethnic and racial groups at each level of disease severity.

Dementia Care Research and Psychosocial Factors.

Background: Dementia compromises physical function, posing risks for falls. People living with dementia (PWD) have been historically excluded from intervention trials due to researchers' eligibility criteria. Exercise shows potential in enhancing physical function, but more evidence is needed.

Dementia Care Research and Psychosocial Factors.

Background: Commonly used screening measures of cognitive function such as the Montreal Cognitive Assessment (MoCA) are not sensitive to assess cognitive function among individuals with severe cognitive impairment due to floor effect. The Severe Cognitive Impairment Rating Scale (SCIRS) was designed to assess cognitive function in those with severe cognitive impairment, however, psychometric properties of its English version have not been reported.

Method: Using the existing data from StaN and tTED studies, floor and ceiling effects (percentage of minimal or maximal scores) of SCIRS and MoCA were examined, and the association between SCIRS and MoCA was evaluated.

Dementia Care Research and Psychosocial Factors.

Background: Exercise may improve dual-tasking and mobility impairments among people living with dementia (PWD), but more evidence is needed. The purpose of this pilot randomized controlled trial (RCT) was to determine the effect of six months of exercise on single- and dual-task mobility compared to usual care alone in PWD.

Method: This assessor-blinded RCT (1:1) included n = 21 PWD in the usual care and n = 21 PWD in the exercise group at two residential care facilities (Age = 82 years, 35% female, Montreal Cognitive Assessment (MoCA) = 10.

Measurement Invariance of the First Years Inventory (FYIv3.1) Across Age and Sex for Early Detection of Autism in a Community Sample of Infants.

The use of parent-report screeners for early detection of autism is time- and cost-efficient in clinical settings but their utility may vary by respondent characteristics. This study aimed to examine the degree to which infants' age and sex impacted parental reports of early behavioral signs of autism captured by the First Years Inventory Version 3.1 (FYIv3.