bluuebunny/crossref_metadata_2025 huggingface dataset:
Fast and insightful: triage‐level cognitive screening captures risks beyond delirium in emergency care for older adults
Authors: de Moraes Gabriel Stanziola , Curiati Pedro Kallas , Avelino‐Silva Thiago J , Morinaga Christian Valle , Suemoto Claudia Kimie , Aliberti Márlon Juliano Romero
Published: January 2025

Background

Although delirium is a powerful tool for identifying high‐risk older patients at the emergency department (ED), the feasibility and importance of cognitive screening beyond delirium remain debated in fast‐paced healthcare settings. We estimated the effect of comprehensive but pragmatic cognitive screening, capturing delirium and preexisting cognitive impairment, on predicting adverse outcomes within 90 days of admission in older adults at the ED.

Method

We conducted a prospective cohort study comprising patients aged ≥65 years who were consecutively admitted to the ED of a large general hospital in Sao Paulo, Brazil. Trained healthcare professionals administered the brief Confusion Assessment Method (bCAM) and, for those without delirium, also the 10‐point Cognitive Screener (10‐CS), a practical 2‐minute tool validated for detecting preexisting cognitive impairment. Cognitive status was defined as normal (negative bCAM and 10‐CS>5), preexisting cognitive impairment (negative bCAM, but 10‐CS≤5), or delirium (positive bCAM). Investigators blinded to baseline data conducted telephone interviews to assess health outcomes, including functional decline in activities of daily living (ADL) and mortality over 90 days post‐admission. We used proportional hazards models to investigate associations between cognitive status and outcomes after adjusting for sociodemographic and clinical factors.

Result

Among 830 patients (mean age = 80±9 years; women = 47%), 434 (52%) were classified as normal cognition and 396 (48%) as cognitive impairment (165 [20%] had delirium and 231 [28%] had preexisting cognitive impairment without delirium) (Table 1). Interestingly, 52% of patients with preexisting cognitive impairment without delirium had neither been diagnosed with dementia nor reported memory complaints. Patients with preexisting cognitive impairment without delirium, similar to those with delirium, showed an increased risk of functional decline in ADL (sub‐HR = 1.59; 95% CI = 1.01‐2.49) and mortality (HR = 2.19; 95% CI = 1.18‐4.09) within 90 days of admission, compared to patients with normal cognition (Figures 1‐2).

Conclusion

In older patients at the ED, preexisting cognitive impairment without delirium emerges as a crucial risk factor for adverse outcomes, underscoring the need for comprehensive yet expedient cognitive screening in fast‐paced healthcare settings. The 10‐CS battery, swift and practical, is ideal for detecting frequently overlooked preexisting cognitive impairments, enabling the quick identification of high‐risk acutely ill older patients.
Discontinuity of unmet social support among US adults with potential cognitive impairment before and after the confirmed diagnosis of dementia: an matched ambidirectional cohort study
Authors: Chen Shanquan , Zhang Huanyu , Underwood Benjamin R
Published: January 2025

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. The index date was set as either the entry date into HRS or the start of the study, depending on which came later, and follow‐up lasted until death, withdrawal, or study end. Eligibility was limited to participants with potential cognitive impairment during follow‐up, identified through a validated HRS‐based dementia algorithm.

The study divided participants into two groups: the exposure group with a confirmed dementia diagnosis during follow‐up, and the control group, matched by age, sex, race/ethnicity, and survey wave, but without a confirmed diagnosis.

Our primary outcome was unmet social support, defined as reporting physical disability without receiving corresponding social support. We applied a controlled interrupted time series(CITS) model to assess the continuity of unmet social support pre and post‐diagnosis.

Results

From 2000 to 2018, our study involved 1,261 dementia patients in the exposure group and 12,604 in the control group. Following diagnosis, Hispanics showed a significant rise in unmet Basic Activities of Daily Living(BADL) support needs (coef = 0.74, 95%CI[0.03,1.46]), particularly for eating assistance (coef = 1.58, 95% CI[0.17,2.99]). Blacks experienced significant increased unmet BADL needs in toileting (coef = 1.52, 95%CI[0.57,2.47]) and Instrumental ADL (IADL) support (coef = 0.09, 95%CI[0.00,0.17]). Whites saw a significant rise in unmet IADL needs (coef = 0.11,95% CI[0.08,0.14]), especially for making phone calls (coef = 0.83, 95%CI[0.19,1.47]). Further analysis suggested these increases in unmet support were mainly due to a greater rise in disabilities compared to corresponding social support.

Conclusions

Our study identifies a disconnect in the care provided to individuals with dementia before and after their diagnosis. Notably, post‐diagnosis, we observed substantial disparities in unmet social support needs across various racial groups. This highlights the need for more cohesive and equitable care strategies in the dementia care continuum.
The effects of culturally adapted recruitment strategies for Black/ African Americans' engagement with Alzheimer’s Disease Research in New York City
Authors: Browne Laurel Y , Bubu Omonigho Michael , Dominguez Joanna , Sogade Anamarie , Weisgerber Elizabeth , Dharmapuri Anhiti , McBride Julian , Cesar Oliver , Gills Joshua L , Barry Fatoumata
Published: January 2025

Background

In the United States, Black people represent 12% of the total US population and account for 19.3% of dementia cases. Social determinants of health (SDOH) and vascular comorbidities contribute to Black/African Americans having a higher risk of Alzheimer’s disease and related dementias (ADRD). More importantly, Black community underrepresentation in clinical research studies continues to be an issue. We aimed to employ culturally adapted recruitment methods to increase engagement of older Black/African Americans ages 55‐85 in ADRD research studies.

Method

To mitigate the underrepresentation of Black/African Americans in ADRD studies, the Aging Research in Sleep Equity & Dementia Prevention Program (ARISE‐DP) at NYU Langone Health utilized multiple streams of recruitment with a focus on cultural inclusivity and humility. Recruitment methods included community outreach events, stakeholders, referrals, and recruitment companies (BuildClinical). In addition, a community liaison was utilized to form relationships, build trust, and increase engagement between the Black community in NYC & the ARISE‐DP Program. We compared previous recruitment methods, such as cold calls and mychart, to forming bonds and increasing literacy. The specific study’s recruitment goal for Black/African Americans was 125.

Result

Recruitment efforts occurred from September 2023 to January 2024. As a result of the culturally adapted recruitment strategies, engagement with ARISE‐DP increased by 100%. Each strategy advanced the total number of people reached (N = 616): community outreach events (N = 297), stakeholders (N = 59), referrals (N = 34), and BuildClinical (N = 226). Individuals who expressed interest in participating in ARISE‐DP clinical trials were screened and, based on meeting eligibility criteria (age, cognition, and comfortability), were invited to be enrolled (N = 74) with a ratio of 44 Black women and 30 Black men recruited. BuildClinical (N = 22), community outreach events (N = 20), and stakeholders (N = 19) were the most effective recruitment strategies, followed by referrals (N = 12). As a result, we have met 59% of our recruitment goal in 3 months.

Conclusion

Representation, education, culturally responsive methods, and including the community in recruitment increase trust and engagement in research studies. Recruitment strategies that acknowledge the historical barriers to Black/African American involvement in clinical studies and provide a holistic approach lead to an equitable, racially inclusive research environment.
Engaging and Recruiting Latino‐led Community Organizations to Build Workforce Capacity in AD/Brain Health Prevention Research
Authors: Diaz‐Santos Mirella
Published: January 2025

Background

AD prevention and early detection are crucial to reduce prevalence projections in Latinos. Despite these projections, our community partners in Los Angeles County continue to disclose barriers in accessing culturally and linguistically congruent bilingual programs activating behavioral modifications for AD prevention and early identification of cognitive changes. In this study, we partnered with community organizations to co‐design and pilot a brain health prevention program tailored to the needs of their constituents.

Method

We used a mixed‐methods design using quantitative data from surveys, and qualitative data from informal short interviews in Spanish and English with Latino community organizations and their constituents. We implemented Community‐Based Participatory Research (CBPR) and Human Centered Design (HCD) principles, anchoring the program in the cognitive reserve theory, tailored to cultural values, traditions, and needs of Latinos in Los Angeles County. Spanish and English‐speaking Latino members requested brain health and early detections materials easy to comprehend. Four Spanish and English brochures were designed. We also design a communication training toolkit to improve delivery of the program from our research team, employing oral storytelling techniques with cultural metaphors explaining brain structure/functions and cognitive functioning/decline.

Results

Between June and December 2023, our team received invitations to participate in 11 community engagement and outreach events across Los Angeles County. A team of 3 bilingual trained research assistants engaged with approximately 475 Spanish and English‐speaking community members with an average of 43 individuals per event. Average distance traveled averaged 37 miles roundtrip total per event. Total printing cost per event was approximately $292, with an additional $30 for giveaways. In the 6 months of implementation, a total of thirty community‐based organizations requested formal presentations and trainings for their staff. Overarching qualitative themes included the community‐centeredness of the program, it’s cultural, linguistically and health literacy appropriateness, and the culturally competent communication skills showcased by bilingual research staff.

Conclusion

Following CBPR, and HCD principles, we showed respect for community needs, while empowering the members to be an integral part of the design and pilot. Our approach engaged and recruited 30 Latino‐led community organizations interested in building their own workforce capacity in brain health prevention and early detection.
Pragmatic Implementation of a Comprehensive Dementia Care Management Program in a Large Health System: The Cedars‐Sinai C.A.R.E.S. Program Preliminary Data
Authors: Tan Zaldy S , Qureshi Nabeel , Spivack Erica , Rhinehart Deana , Gatmaitan Dyane , Guinto Augustine , Kremen Sarah , Sicotte Nancy
Published: January 2025

Background

The United States faces a growing challenge with over 6.5 million people living with dementia (PLwD). PLwD and their caregivers struggle with cognitive, functional, behavioral, and psychosocial issues. As dementia care shifts to home settings, caregivers receive inadequate support but bear increasing responsibilities, leading to higher healthcare costs. In response, the Centers for Medicare & Medicaid Services (CMS) introduced the Guiding an Improving Dementia Experience (GUIDE) Model. The study explores the real‐world implementation of the Cedars‐Sinai C.A.R.E.S. Program, a pragmatic dementia care model, detailing its recruitment process and initial outcomes.

Methods

The Cedars‐Sinai C.A.R.E.S. Program was integrated into the Epic electronic health record system, and focused on proactive patient identification, engagement, interdisciplinary collaboration, care transitions, and ongoing care management. Eligible patients aged 65 and older with a dementia diagnosis were identified through electronic health record and invited to join the program. Nurse practitioners with specialized training in dementia care performed comprehensive assessments using the novel CEDARS‐6 tool, leading to personalized care plans developed in consultation with primary care providers. Patients benefit from a multidisciplinary team and support from care navigators.

Results

Of the 781 eligible patients identified, 431 were enrolled in the C.A.R.E.S. Program. Enrollees were racially diverse, with lower caregiver strain and patient behavioral and psychological symptoms of dementia (BPSD) severity compared to other programs. Healthcare utilization, including hospitalizations, emergency department (ED) admissions, and urgent care visits showed a downward trend over time. Completion of advanced directives and Physician Order of Life Sustaining Treatment (POLST) increased after enrollment.

Conclusion

The Cedars‐Sinai C.A.R.E.S. Program offers a promising approach to dementia care. Its real‐world implementation demonstrates the feasibility of enrolling a diverse population and achieving positive outcomes for PLwD and their caregivers, supporting the goals of national dementia care initiatives.
Common Mechanisms of Long COVID and Vascular Dementia
Authors: Talkington Grant , Ismael Saifudeen , Hall Gregory W , Bix Gregory J
Published: January 2025

Background

Vascular dementia (VaD), the second most common cause of dementia, is characterized by cognitive decline due to reduced cerebral blood flow and blood‐brain barrier disruption. Current evidence demonstrates that not only are VaD patients at higher risk of severe COVID‐19 illness and mortality, but also that pre‐existing cognitive dysfunction/dementia is associated with increased COVID‐19 incidence. Conversely, SARS‐CoV‐2 infection alone worsens dementia‐related mild cognitive impairment (MCI) and increases risk of cognitive decline, supported by similar fMRI findings demonstrating hypoperfusion. Therefore, we hypothesize that both vascular dementia and long COVID bear a common vascular mechanism.

Method

To investigate, we conducted a chronic‐phase COVID‐19 study utilizing an innovative non‐transgenic mouse model with Mouse Adapted 10 (MA‐10) strain of SARS‐CoV‐2 following bilateral carotid artery stenosis (BCAS) to model VaD. We inoculated 12‐week‐old C57 mice intranasally with 1×10^4 PFU of MA‐10 and followed them to 15 days post‐infection.

Result

Bulk RNA sequencing on brain tissues and analysis with Ingenuity Pathway Analysis (IPA) revealed substantial net alterations to several signaling pathways including IL‐6, IL‐1B, and Pathogen‐associated molecular response patterns, providing critical insights into the mechanisms underpinning acute and chronic COVID‐19 morbidities.

Conclusion

Our findings confirm a significant mechanistic interaction between VaD and long COVID, suggesting that existing therapies targeting VaD may also be effective in long COVID.
VXX‐301, a muti‐epitope active immunotherapy targeting Tau, induces antibodies with favorable binding to Tau and exhibits efficacy in vivo
Authors: Boyd Justin , Dodart JC , Prokop Stefan
Published: January 2025

Background

Vaxxinity is developing an active immunotherapy targeting Tau for Alzheimer’s disease (AD) and other tauopathies. VXX‐301 is a multi‐epitope vaccine designed to target the N‐terminal and repeat domains of Tau. This design enables targeting multiple forms of Tau thought to contribute to Tau associated pathologies. Such a vaccine would be well positioned for the treatment and prevention of neuropathology induced by Tau.

Method

VXX‐301 comprises a mixture of two Tau targeting peptides (p5555kb and p5187kb) each conjugated to Vaxxinity’s proprietary T helper carrier peptide and formulated with CpG and AdjuPhos. Antibody titers against specific targeted Tau regions in immunized rats were quantified and compared to single epitope targeting vaccines, p5555kb and p5187kb. Additionally, antibody titers against full length 2N4R rTau monomers and preformed fibrils were quantified. IgG isotyping was also conducted. The binding properties of VXX‐301‐derived antibodies were characterized by Western blot and immunohistochemistry. Epitope mapping was also conducted to confirm binding to targeted regions. In vitro activity was performed to quantify VXX‐301 antibodies in Tau aggregation and Tau uptake assays. In vivo efficacy was measured by evaluating the onset of ataxia and survival of P301L mice.

Result

VXX‐301 induces high antibody titers against specific regions of Tau. Antibodies are primarily of the IgG1 isotype in rats and exhibit high binding potency to full length monomeric and PFF Tau. Additionally, antibodies bind to multiple recombinant Tau preparations, including 2N4R, 2N3R, 2N4R P301S, and K18 (P301L). Epitope mapping analyses confirm that VXX‐301‐derived antibodies bind to the intended epitopes of Tau. In vitro, VXX‐301‐derived antibodies block Tau cellular uptake as well as Tau aggregation. Finally, P301L transgenic mice immunized with VXX‐301 exhibit protection from ataxia onset and death.

Conclusion

Here we present preclinical data indicating that VXX‐301 is immunogenic and induces antibodies with favorable characteristics. VXX‐301 antibodies exhibit binding to specific targeted regions as well as multiple forms of full‐length Tau. Moreover, we show that VXX‐301 antibodies bind to Tau in human brain tissue samples. VXX‐301 demonstrates both in vitro and in vivo efficacy against Tau‐dependent phenotypes, supporting the further development of this vaccine as a treatment and prevention of AD and other tauopathies.
The Scale of Benefit and Cost Effectiveness of the Care Ecosystem for Alzheimer’s Disease relative to Lecanemab
Authors: Atkins Kelly J , Kahn James G , Possin Katherine L
Published: January 2025

Background

Only a small proportion of people living with Alzheimer’s Disease (AD) are eligible for disease modifying therapies such as Lecanemab. Dementia care management programs, such as Care Ecosystem, provide care navigation and specialist resources to people with dementia and their caregivers, with broad eligibility criteria. We first estimated the lifetime health and economic outcomes of adults with MCI or mild dementia due to AD who receive Care Ecosystem, compared to Lecanemab. We then estimated the benefits of each intervention when scaled to the eligible US population.

Method

We employed a decision analytic model to a simulation sample of 1,000 people (52% female) aged 71 years at the commencement of one of three intervention states: 1) usual care, 2) Lecanemab or 3) Care Ecosystem. Next, we applied our model outcomes to all people with MCI or dementia due to AD who were eligible for each intervention. Primary outcomes were quality‐adjusted life years (QALYs); remaining life years (LYs); and costs in 2024 US dollars.

Result

Per‐person LYs increased by 0.39 per person with Lecanemab compared to Care Ecosystem and usual care. Lifetime QALYs for Lecanemab were 0.45 higher than usual care, due to disease slowing. Lifetime QALYs for the Care Ecosystem were 0.23 higher than usual care, due to improved quality of life (Figure 1). The per‐person cost of Lecanemab was $105,581 higher than usual care, driven primarily by drug costs. The per‐person cost of the Care Ecosystem was $11,304 lower than usual care, reflecting savings to Medicare associated with dementia care management. In the US in 2024, we estimated ∼765,000 people were eligible for Lecanemab and 6.1 million for Care Ecosystem. The population benefit of Lecanemab was 760,000 QALYs and cost $80 billion compared to usual care. The population benefit of Care Ecosystem was 6,160,000 QALYs with savings of $69 billion (Figure 2).

Conclusion

Lecanemab offers a larger QALY gain per‐person than provided by Care Ecosystem. When scaled to eligible populations, the QALY gains of Care Ecosystem far exceed Lecanemab, with a net cost reduction. Universal access to dementia care management should be a priority of health care policy.
Identifying Dementia Care Partner Supports as a Public Health Priority: Addressing Equity and Unmet Population Health Needs
Authors: Reed Jenn Hollandsworth , Gelmon Sherril B , Dawson Walter D
Published: January 2025

Background

The wellbeing of over 11 million care partners of people living with Alzheimer’s disease and related dementias (ADRD) in the United States is increasingly recognized as a public health priority. Addressing care partners’ needs for support and services is particularly important, as care partner burden is associated with negative health outcomes in care partners and people living with ADRD. Care partners from marginalized populations experience inequities in research participation, care burden, and access to supports and services. The goals of this study were 1) to determine supports needed by care partners of people living with ADRD, by empowering population groups historically and currently underserved in ADRD research and services; and 2) to recommend public health policies and interventions to improve care partner wellbeing through social supports and services.

Methods

Caregiving‐related priorities of care partners from four populations underserved in ADRD research and services (Asian, Black, Indigenous, and Latinx Americans) were determined using 5 focus groups and 24 in‐depth interviews with care partners and organizations that support people living with dementia in Oregon. Key governmental and nonprofit organizational leaders (N = 40) participated in a modified Delphi process to identify priorities for supporting care partners through policies and programs. Data were collected from October 2022 through August 2023.

Results

Care partners were generally satisfied with clinical ADRD care but identified opportunities for new supports and improved equity in access to services. Eight themes relating to care partner needs were identified: supports, programs and services, information resources, care coordination, technology, financing, workforce development, and policy. Specific needs varied across populations due to cultural traditions, systemic inequities, and structural racism.

Conclusions

Supporting care partners is a public health strategy that can improve personal wellbeing of care partners and reduce or delay institutional living for people living with ADRD. To ensure equitable supports across diverse populations, policymakers at all levels of government must engage with care partners from marginalized communities to enhance and expand access to services, especially culturally appropriate services. Policies and programs should also be leveraged to address the social determinants of health for care partners in an equitable way.
Association of Complementary and Integrative Health Use with Risk of Long‐Term Institutionalization, Hospitalization, or Death in Patients with ADRD
Authors: Shao Yijun , Cheng Yan , Ahmed Ali , Zamrini Edward , Zeng Qing
Published: January 2025

Background

Complementary and Integrative Health (CIH) encompass many therapeutic modalities including physical, nutritional, psychological, and combination therapies. Small clinical trials on Tai‐Chi, yoga, and acupuncture reported improved cognitive functions. However, there is a knowledge gap regarding effectiveness on long‐term outcomes in patients with Alzheimer’s disease and related dementias (ADRD).

Method

We began by randomly selecting 50,000 patients with ADRD from the Veterans Affairs (VA) electronic health record (EHR) database. We used an NLP tool developed by our team to identify the use of CIH modalities (acupuncture, biofeedback, guided imagery, meditation, Tai‐Chi, yoga) after first ADRD diagnosis. For CIH users, the index date was the date of first CIH use after first ADRD diagnosis. For non‐users, the index date was the encounter date matching the index date of an CIH user with the same ADRD diagnosis year. Then we collected their demographics and clinical data including comorbidities and healthcare utilization from the 5 years before index date.

Next, we matched the non‐users to the CIH users on the propensity scores calculated using the demographics, comorbidities and healthcare utilizations data. On this matched cohort, we performed survival analysis for the combined endpoint of long‐term institutionalization (LTI), hospitalization, or death.

Result

Overall, 4064 (8.1% of 50,000) patients were CIH users. Compared to non‐users, CIH users were younger (78.4 vs. 83.3) with higher proportions of females (3.6% vs. 2.1%) and African Americans (14.8% vs. 10.9%), had higher prevalence in almost all comorbidities, had nearly twice as many visits and hospitalizations per year, and had 4 times longer cumulative hospitalizations during the 5 years before index date (Table 1).

On the propensity score‐matched cohort, the survival analysis yielded a hazard ratio of 0.61 (95% CI: 0.57–0.64) for CIH use (Figure 1). There were some differences between acupuncture users and Tai‐Chi/yoga users (Figure 2).

Conclusion

Our results suggest that CIH treatments in the VA ADRD population are often reserved for patients with more comorbidities and higher healthcare utilizations. In the propensity matched cohort, CIH use is associated with a lower risk in the combined outcome of LTI, hospitalization, or death as the endpoint.
The perspective of soft‐robotics for people with neurodegenerative diseases: Can we develop robotic solutions using soft material?
Authors: Biswas Bijetri , Coulthard Elizabeth , Roudaut Anne
Published: January 2025

Background

We investigate perceptions of soft robotics in individuals with neurodegenerative diseases (NDD) from diverse communities. Soft robotics is made from soft, flexible materials to make it safer for users. It is a fast‐emerging medical field with applications ranging from diagnosis to rehabilitation practices. However, this area is underinvestigated in the older population with neurological disorders.

Method

We recruited individuals with NDD, e.g. dementia, Parkinson’s and mild cognitive impairment, via Bristol Brain Centre, charities, personal contacts, and social media advertisements. We aim to understand better user requirements and their views on such innovative technologies. In this ongoing study, we interviewed individuals with NDD, careers and clinicians to find the gap in designing soft robotics and conducted co‐design sessions with each group. To conclude the study, we will collect all the designs, create a prototype and gather iterative feedback.

Result

Preliminary results from the semi‐structured interviews have shown that interaction with soft robotics technologies, such as smart pillows, prosthetics, and others, needs further exploration but is challenging. Therefore, individuals found it difficult to think or acknowledge what could help them improve their quality of life. It also highlights the importance of technologies that can help carers facilitate patients' needs. Interviews with clinicians also emphasised carers' needs and technology that can promote independence and improve well‐being. Another interesting finding from the study is that previously, individuals were unaware of creating technologies personalised to them. Furthermore, co‐designing with this population showed that involving them in the ideation and designing process is critical for empowerment.

Conclusion

Do‐it‐yourself (DIY) practice offers a higher engagement in developing complex technologies, and the user‐centric design process using the Arduino prototyping platform improves the engagement rate. Cultural and ethnic diversity in the study population was another challenge, as it was challenging to get a clear view of their needs due to the language barrier. However, they overcame this by expressing their ideas by drawing. We aim to understand user requirements better and their views on such innovative technologies, present developments in soft robotics technology, and research challenges associated with our population to highlight research directions to understand this emerging field better.
The Impact of Neighborhood‐Level Area Deprivation on Picture Naming Ability and Decline in Alzheimer’s Disease
Authors: Biro Tifani , Hamilton Roy
Published: January 2025

Background

The cortex responsible for language processing is among the earliest areas affected by Alzheimer’s Disease (AD), manifesting speech and language abnormalities even before formal diagnosis. Language decline in AD is clinically significant, often parallel to a loss in basic daily living abilities. Research endeavors to detect AD early through automated speech analysis, emphasizing the need to comprehend factors influencing language disruption. Previous studies suggest that higher socioeconomic status (SES) may mitigate dementia and cognitive impairments. Our study explores the link between neighborhood‐level area deprivation and language decline in AD patients.

Method

We utilized data from the University of Pennsylvania’s Integrated Neurodegenerative Disease Database (INDD). Inclusion criteria encompassed consensus diagnoses from multiple assessments for AD patients and individuals with normal cognition. Subjects' address information facilitated the derivation of State and National Area Deprivation Index (ADI) ranks based on 12‐digit Federal Information Processing System (FIPS) codes. Our analysis employed weighted linear mixed effects models to assess the impact of ADI Ranks on Boston Naming Task performance across patients with or without AD and among AD patients at various stages post‐symptom onset (2‐8 years).

Result

Our analysis revealed an inverse relationship between ADI National and State Ranks and Boston Naming Scores, evident in both AD and non‐AD individuals. AD patients consistently demonstrated lower Boston Naming Task scores than their counterparts, with disparities widening as ADI Ranks increased. In AD patients, language decline correlated with disease progression, occurring earlier and intensifying with higher ADI National and State Ranks. These findings concur with prior research, underscoring the predictive utility of the Boston Naming Test for cognitive decline.

Conclusion

Our study unveils the complex interplay between area deprivation and language decline in AD patients. Those residing in more deprived areas experienced accelerated language deterioration, highlighting the impact of socioeconomic disparities. These insights advance discussions on early AD detection and intervention strategies, underscoring environmental factors' role in disease trajectories and the potential for targeted interventions to enhance patient care.
Evaluation of Novel GLP‐1 analogue in the treatment of Alzheimer’s disease
Authors: Edison Paul
Published: January 2025

Background

Liraglutide is a glucagon‐like peptide‐1 (GLP‐1) analogue licensed for the treatment of type 2 diabetes mellitus (T2DM). Preclinical evidence in transgenic models of Alzheimer’s disease suggests that liraglutide exerts neuroprotective effects by reducing amyloid oligomers, normalising synaptic plasticity and cerebral glucose uptake, and increasing the proliferation of neuronal progenitor cells.

Method

This is a multi‐centre, randomised, double‐blind, placebo‐controlled, phase IIb trial of liraglutide in participants with mild to moderate Alzheimer’s dementia, conducted at several centres in the UK.

As a part of this study, MRI brain scans of all patients were performed at baseline and after 12 months treatment with liraglutide or matching placebo along with neuropsychometric evaluation and [18F]FDG PET. A total of 204 Alzheimer’s participants were randomised to receive either liraglutide or placebo as a daily subcutaneous injection for 12 months. All subjects had regular clinical visits and neuropsychometric evaluation at regular intervals. Repeat scans were performed in all subjects who completed 52 weeks of treatment. Volumetric changes from baseline to follow‐up in MRI scans were evaluated using both regional volume analysis and voxel‐based morphometric analysis.

Result

MRI analysis demonstrated a slower decline of temporal lobe volume and total grey matter volume in liraglutide‐treated patients compared to the placebo group. Voxel‐based morphometry (VBM) analysis demonstrated that liraglutide‐treated participants showed a slower reduction in whole cortical grey matter, frontal, temporal and parietal lobe volume in participants treated with liraglutide compared to placebo. This was associated with slower decline in cognitive function.

Conclusion

These findings highlight the potential of GLP‐1 analogues in the treatment of Alzheimer’s disease

Authors:

Edison P, Femminella GD, Ritchie C, Holmes C, Nowell J, Walker Z, Ridha B., Raza S, Livingston NR, Frangou E, Love S, Williams G, Lawrence R, Mcfarlane B, Archer H, Coulthard E, Underwood B. R, Koranteng P, Karim S, Bannister C, Perneczky R, Prasanna A, Junaid K, McGuinness B, Nilforooshan R, Macharouthu A, Donaldson A, Thacker S, Russell G, Malik N, Mate V, Knight L, Kshemendran S, Holscher C, Mansouri A, Mae Chester‐Jones L, Holmes J, Tan T, Williams S, Brooks DJ, Harrison J, Hinz R, Tadros G, Passmore AP, Ballard C.
Defy Dementia: Mobilizing a Public Health Awareness Campaign for Dementia Prevention
Authors: Sekuler Allison B. , Aleong Rosanne , Rashid Shusmita , Boutcher Faith , Anderson Nicole D. , Dubroqua Sylvain , Leventhal Natalie
Published: January 2025

Background

While age is the most significant risk factor for dementia, increased awareness and understanding of other modifiable risk factors of dementia, coupled with proactive lifestyle behavior changes, hold the potential to prevent dementia and improve the quality of life for older adults.

Defy Dementia is a public health initiative, led by the Baycrest Academy for Research and Education (BARE) and funded by the Public Health Agency of Canada. It involves curating, co‐designing, and disseminating a series of knowledge products to raise public awareness of dementia prevention and reduce stigma associated with dementia. These knowledge products, including podcasts, minute‐videos, and infographics, aim to raise awareness about modifiable risk factors associated with dementia and empower individuals to take proactive measures.

Method

To assess the impact of our knowledge products our evaluation consisted of two main components: a) quantitative data obtained through an online survey on the project website (convenience sample); and b) qualitative data obtained through 4 focus groups (each with a selected group of 4‐8 participants, derived from the first convenience sample and event participants). Quantitative data will be exported from REDCap and explored through descriptive statistics using SAS System version 9.4 or R version 4.2. Thematic analysis of the focus group data will be performed using NVivo R.

Result

Based on our hypothesis, we anticipate that individuals who engage with the knowledge products or attend an event will experience an improvement in their awareness and understanding of the modifiable risk factors associated with dementia, have enhanced knowledge about dementia prevention, exhibit behaviour change and have changed attitudes about PLWD.

Conclusion

We will demonstrate how meaningfully engaging older adults, persons living with dementia, and their care partners in the design and dissemination of knowledge can not only improve the relevance and uptake of the knowledge but also foster empathy and reduce stigma associated with dementia. We will also engage the audience to consider how increased awareness of modifiable risk factors for dementia, coupled with action, has the potential to lower the risk of developing dementia, ultimately leading to its prevention or delay and enhancing the quality of life for older adults.
Associations Between Cognitive, Physical, and Mental Health and Baseline MIND Diet Scores in the U.S. POINTER Trial
Authors: Ventrelle Jennifer , Katula Jeffrey A. , Tangney Christy C , Garcia Katelyn R , Krueger Kristin R , Graef Sarah , Wilmoth Sharon , Heinrich Allison , Lopez Desiree , Baker Laura D
Published: January 2025

Background

The Mediterranean‐Dash Intervention for Neurodegenerative Delay (MIND) diet, featuring emphasis on green leafy and other colorful vegetables, berries, unsaturated fats, fish, and whole grains is a major component of the U.S. POINTER multi‐domain lifestyle intervention. The purpose of this study is to examine the associations among MIND diet screener scores, and measures of cognitive function, and physical and mental health at baseline.

Method

U.S. POINTER is a randomized controlled trial of two multidomain lifestyle interventions. (n = 2112; mean age = 68.18±5.15y). Cognitive function measures included global, episodic memory, executive function, and processing speed, derived from the U.S. POINTER modified Neuropsychological Test Battery. Physical and mental health were assessed using measures of BMI, hypertension, diabetes, dyslipidemia, physical activity, the Geriatric Depression Scale, the Pittsburgh Sleep Quality Index (PSQI) and symptoms of psychological distress. Pearson correlations were used to estimate bivariate associations among variables. Generalized linear regression models were used to examine associations while controlling for demographic variables.

Result

Baseline MIND diet screener scores were inversely associated with BMI (r = ‐0.09, p<.0001), diastolic blood pressure (DBP) (r = ‐0.10, p<.0001), depression (r = ‐0.12, p<.0001), and PSQI (r = ‐0.09, p<0.0001). MIND diet scores were positively associated with frequency of moderate‐intensity exercise (r = 0.10, p<.000) and total health score (r = 0.09, p<.0001). Linear models revealed that after controlling for demographics, MIND diet scores remained associated with BMI, DBP, frequency of exercise, depression, and sleep quality and total health (See Table 1). MIND diet scores were not associated with measures of cognition.

Conclusion

In U.S. POINTER, MIND diet scores were not associated with cognition; however, those with higher MIND diet scores had lower BMI, DBP depression and PSQI scores, as well as higher frequency of moderate‐intensity exercise, higher self‐reported health.
Mild Cognitive Impairment and Dementia Diagnoses after an Annual Wellness Visit in a Large Primary Care Network
Authors: Suchsland Monica Zigman , Fitzpatrick Annette L. , Raetz Jaqueline G. , McKiddy Sarah , Hsu Amy P , Gaster Barak
Published: January 2025

Background

The increasing incidence of cognitive impairment in older adults poses significant, complex challenges for patients and their families. While specialists have traditionally addressed this care, there is an urgent need to shift diagnosis and management of mild cognitive impairment (MCI) and dementia to primary care. The annual wellness visit for Medicare recipients provides an excellent opportunity for primary care providers (PCPs) to assess patients who may need a cognitive evaluation.

Method

We aimed to describe the timing of dementia‐related diagnoses in a large primary care network from electronic health record (EHR) data. All coded encounter data for patients 65 years and older seen in one of 14 primary care clinics at the University of Washington from January 1, 2019‐ August 1, 2023 were extracted from the EHR system and summarized.

Result

A total of 40,524 medical encounters for a Medicare annual wellness visit (AWV), billing code of G0439, were identified representing 17,179 unique patients. Of these, 187 (1.1%) had a first diagnosis of MCI, dementia or other cognitive impairment based on ICD 10 codes at a following clinic visit. The top diagnoses included dementia unspecified (36.9%), impaired cognition or other pre‐dementia diagnoses (26.2%), and Alzheimer’s Disease (23.0%). A median of 287 days (IQR 0‐587 days) elapsed between the AWV and coding of a dementia‐related diagnosis. Among encounters during which new dementia‐related diagnoses were documented, in 73% the primary diagnosis of the visit was a dementia‐related ICD‐10 diagnosis code; 27% listed other primary diagnoses (Table 1). Following a new dementia‐related diagnosis, a median of 3.3 (IQR 2‐5) primary care visits/year were made. Major comorbidities recorded in these visits included hypertension, diabetes, other cardiovascular conditions, chronic pulmonary disease, renal failure, other neurological disorders, and depression. The median weighted Charlson Comorbidity Index was 2.0 (IQR 0‐2).

Conclusion

These data may be helpful baseline measures to evaluate future trends in dementia‐related diagnosis following AWV. As programs designed to provide training and support for diagnosis and management of cognitive impairment in primary care settings are implemented, it will be important to understand the role the AWV serves as a tool for PCPs.
Metabolomics approaches for capturing the chemical exposome and its influences on cognitive function and brain health
Authors: Moseley M Arthur , Fiehn Oliver , Dorrestein Pieter , Hyotylainen Tuulia , Oresic Matej , Wishart David , Zhao Nina , Kaddurah‐Daouk Rima F. ,   Alzheimer's Gut Microbiome Project Consortium (AGMP)
Published: January 2025

Background

There is growing interest in the role of environmental factors (i.e., exposome) in the pathogenesis of Alzheimer’s diseases. The exposome includes three categories: internal (e.g., metabolism, gut microbiome, inflammation), specific external (e.g., environmental pollutants, diet, drugs, occupational), and general external (e.g., socioeconomic status, education, climate). The metabolome provides a readout of the influences of the exposome, capturing the presence of a large number of chemical exposures and allowing an interrogation of the influences of these chemicals on cognition and brain imaging changes.

Method

Four centers of excellence in metabolomics have used mass spectrometry‐based capabilities to provide broad coverage of the chemical exposome. A ‘ring trial’ was performed to determine the coverage of the metabolome/exposome using state‐of‐the‐art analytical tools. Human serum/plasma standards from diseased individuals ‐ Alzheimer’s, COPD, IBS, osteoarthritis, and Type 2 diabetes (BioIVT), and NIST standards (1950 and 1958) were analyzed, using LC‐MS/MS (targeted and untargeted), Direct Flow‐MS/MS and/or ICP‐MS. Similarly, we are measuring the exposome/metabolome in large studies of AD patients, including ADNI, ADRCs and the ROSMAP brain collection.

Result

Compounds were classified by chemical class (ClassyFire), toxicity/source groups (EPA CompTox DB)), and disease association (Comparative Toxicogenomics DB). Using the available InChiKey and CAS numbers available, ClassyFire sorted compounds into 184 chemical classes, EPA CompTox DB sorted 1179 unique InChiKey descriptors into 93 groups (toxicity class and/or exposure source), including DrugBank, Hazardous Substances DB 2019, BLOOD Toxic Substances Control Act, COSMO cosmetics and FDA Food Substances. These included 7 neurological groups with over 100 ring trial compounds. These compounds were classified as endogenous compounds, foods, medications, industrial chemicals, surfactants, plasticizers, personal care, and pesticides (Figure 1). Identical studies are being performed using large cohorts of brain and blood samples, including from ADRCs and the ROSMAP collection. We will present highlights of the brain chemical exposome and its links to cognition.

Conclusion

Big data is being generated to capture the influences of the exposome on brain health, connecting these peripheral influences on brain metabolic health and disease, facilitating the development of novel therapeutic approaches targeting the exposome and its effect on brain health.
Ethyl acetate fruit fraction of tetrapleura tetraptera modulates cholinergic anti‐inflammatory pathways: an invivo and insilico study
Authors: Onimisi Oyinoyi Bethel , Ochai Joy , Salifu Boniface , Ekpo Ubong Udeme , Sadisu Muhammad , Idris Sherifat Banke , Oderinde Gbenga Peter , Danladi Jibrin
Published: January 2025

Background

Studies suggest a potential link between stroke and Alzheimer’s disease wherein stroke may serve as a trigger for the onset or acceleration of Alzheimer’s pathogenesis as damage to the brain’s blood vessels may lead to the accumulation of amyloid beta protein which is a hallmark of Alzheimer’s disease. Recent research has shown that stroke treatment may hold the key to treating Alzheimer’s disease. The anti‐inflammatory potentials of Cholinergic signaling are a novel therapeutic target in memory decline associated with Alzheimer’s. Therefore, cholinergic agonists which play a crucial role in increasing the synaptic levels of acetylcholine could in turn downregulate inflammatory mediators as well as modulate Cholinergic signaling thereby improving cognition

Method

Molecular docking analysis of TT‐Fruits ligand against Iba1(PDB ID: 2d58), IL‐6 (PDB ID: 1Alu), and AChE (PDB ID: 5hfa) was conducted using Pyrex, Autodock Vina option with Galantamine and minocycline (MNC) as a control drugs to evaluate the molecular interactions between the ligands present in EAFFTT and inflammatory mediators implicated in stroke pathology. In‐vivo study was conducted as follows: 50 Male adult Wistar rats (200 – 220g) were randomly distributed into five groups: Group I‐Sham, and Group II‐V were subjected to Ischemia/Reperfusion (I/R) for 30 minutes and then treated daily with H2O, EAFFTT 200 mg/kg, EAFFTT 100 mg/kg, or MNC 50 mg/kg respectively, orally for seven days. Following this, the brains were extracted and processed for IL‐6 and AChE ELISA and IBA 1 immunohistochemistry for reactive microglia.

Result

molecular docking results predicted Aridanin and Echinocystic acid as the lead ligands in EAFFTT with a higher binding affinity with the proteins (Iba1, IL‐6, and AChE) than the control drugs. In the experimental study, I/R without treatment showed a significant increase in IL‐6, AChE, and the number of activated microglia. However, a significant decrease in IL‐6, AChE, and the number of reactive microglia was observed in I/R +EAFFTT (100 and 200 mg/kg), and I/R +MNC (50 mg/kg) ‐treated groups

Conclusion

Tetrapleura tetraptera fruit phenolics docked well with IBA1, IL‐6 and AChE, thereby modulating their expression, as EAFFTT is a potential neurotherapeutic agent against stroke‐induced neuroinflammation