Drug Development.

Background: Developing drugs for treating Alzheimer's disease (AD) has been extremely challenging and costly due to limited knowledge on underlying biological mechanisms and therapeutic targets. Repurposing drugs or their combination has shown potential in accelerating drug development due to the reduced drug toxicity while targeting multiple pathologies.

Method: To address the challenge in AD drug development, we developed a multi-task machine learning pipeline to integrate a comprehensive knowledge graph on biological/pharmacological interactions and multi-level evidence on drug efficacy, to identify repurposable drugs and their combination candidates RESULT: Using the drug embedding from the heterogeneous graph representation model, we ranked drug candidates based on evidence from post-treatment transcriptomic patterns, mechanistic efficacy in preclinical models, population-based treatment effect, and Phase 2/3 clinical trials.

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: Global epidemiological studies involving over nine million participants have shown a 35% lower incidence of Alzheimer's Disease (AD) in older cancer survivors compared to those without a history of cancer. This inverse relationship, consistent across recent studies with methodological controls, suggests that cancer itself, rather than cancer treatments, may offer protective factors against AD. This insight opens avenues for novel therapeutic strategies targeting early AD by harnessing cancer-associated protective factors.

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: Non-human primates (NHP) serve as an important bridge for testing therapeutic agents that have been previously shown to be effective in transgenic mouse models. Our earlier published data using an NHP model of sporadic AD-related pathology that develops abundant cerebral amyloid angiopathy (CAA), squirrel monkeys (SQMs), indicates that chronic treatment with TLR9 agonist, class B CpG ODN, safely ameliorates CAA while promoting cognitive benefits. In the present study, we intended to delineate alterations in brain metabolome induced by chronic CpG ODN administration in order to provide further insight into CpG ODN immunomodulatory capabilities.

Dementia Care Research and Psychosocial Factors.

Background: Prior research has demonstrated the positive association between social support and cognition. Specifically, greater social support has been linked with improved cognitive performance and reduced risk of dementia. In particular, emotional support has been identified as a key dimension in the relationship between social support and cognition.

Dementia Care Research and Psychosocial Factors.

Background: The approval of anti-amyloid monoclonal antibodies (mAbs) provides a novel approach to the treatment of Alzheimer's disease. Infusions in alternative sites of care can benefit the patient financially and logistically, but coverage is largely payor dependent. The purpose of this study is to describe observations from this national complex specialty pharmacy around the safety of anti-amyloid mAb infusions in alternative sites of care, including the home.

Dementia Care Research and Psychosocial Factors.

Background: Cerebral amyloid angiopathy (CAA) is a significant contributor to hemorrhagic stroke, notably lobar intracerebral hemorrhage (ICH) and convexity subarachnoid hemorrhage (SAH), both of which have been observed in patients with MCI/AD. To evaluate all-cause mortality among veterans with mild cognitive impairment (MCI) and Alzheimer's dementia (AD) with/without Intracerebral hemorrhage and subarachnoid hemorrhage (ICH/SAH) in the United States (US) Veterans Affairs Healthcare System (VAHS).

Method: Veterans with MCI or AD were identified based on having clinical notes or diagnostic codes in the VAHS database (2010-2019).

Dementia Care Research and Psychosocial Factors.

Background: The goal of this study is to examine how gender of research participants affects informants assessments of cognitive functioning in older adults. Informant assessments are important tools when clinicians diagnose cognitive decline and dementia and have been used to characterize highly impaired adults in population studies. Contextual and social factors for men and women in different countries may make informants more or less likely to report changes in functioning and cognitive declines at different levels of cognitive impairment.

Dementia Care Research and Psychosocial Factors.

Background: Approximately 10% of people living with Alzheimer's dementia (PWD) experience depression, yet behavioral interventions remain scarce. We developed an innovative depression intervention, Caregiver-Provided Life Review (C-PLR) based on life review therapy. The purposes of this study were to evaluate the feasibility of training family caregivers in life review skills and evaluate the impact on depressive symptoms.

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: Globally, 47.5 million people were living with dementia in 2015. This figure is expected to reach 75.

Dementia Care Research and Psychosocial Factors.

Background: In recent years, brain banks have become a valuable resource for examining the molecular underpinnings of various neurological and psychological disorders such as Alzheimer's disease and Parkinson's disease; however, the availability of brain tissue has significantly declined. Proper collection, preparation, and preservation of post-mortem autopsy tissue are essential for optimal downstream brain tissue distribution and experimentation. Collaborations between brain banks through larger networks such as NeuroBioBank with centralized sample request mechanisms promote tissue distribution where brain donations are disproportionately lower.

Dementia Care Research and Psychosocial Factors.

Background: In Zambia, dementia prevalence is unknown due to limited community awareness and a lack of providers skilled in recognizing and diagnosing this disease. Community healthcare workers (CHWs) are widely utilized across sub-Saharan Africa to improve health care access, particularly HIV services. CHWs may be an untapped resource to raise awareness, screen for dementia, and support dementia care in the community.

Dementia Care Research and Psychosocial Factors.

Background: Occupation complexity during adulthood may contribute to cognitive reserve in later life. Research on occupational complexity and cognitive function has focused on high-income countries, where there is a large proportion of individuals with complex occupations. Thus, it is important to investigate this association in the context of low- and middle-income countries where there is greater variance in occupation complexity and where there is a higher proportion of lower-complexity occupations due to educational and other socioeconomic limitations.

Dementia Care Research and Psychosocial Factors.

Background: Due to the high prevalence of depressive symptoms and dementia in older Americans (≥65 years), we trained unpaid family caregivers in an evidence-based life review depression intervention virtually via Zoom and produced positive outcomes. The objective of this study was to examine the feasibility of training caregivers via online video and delivering the intervention at home.

Method: We recruited caregiver-care recipient dyads nationwide during the COVID-19 pandemic (N = 20 dyads).

Dementia Care Research and Psychosocial Factors.

Background: Cerebral amyloid angiopathy (CAA) is a significant contributor to hemorrhagic stroke, notably lobar intracerebral hemorrhage (ICH) and convexity subarachnoid hemorrhage (SAH). This study describes the natural occurrence of ICH and SAH events among veterans, including those with AD, within the United States Veterans Affairs Healthcare System (VAHS).

Method: The VAHS database was evaluated to identify ICD-10 codes for ICH (I61.

Dementia Care Research and Psychosocial Factors.

Background: Personality traits are long-standing characteristics of behavior and emotion. Personality might influence cognitive health in later life by affecting responses to stressful events and engagement in cognitively stimulating activities, such as interpersonal interaction. The current study examined associations between personality traits and cognition in late life, and potential mediation by positive and negative emotion, depression, and social connectedness.

Dementia Care Research and Psychosocial Factors.

Background: Although primary progressive aphasia (PPA) is considered a rarer form of dementia, individuals living with PPA are increasingly identified by healthcare professionals. Research investigating speech-language assessment and intervention in PPA has been conducted primarily in monolingual speakers and little is known about clinical decision-making of speech-language pathologists (SLPs) working with bilinguals with PPA.

Methods: A comprehensive survey containing questions regarding clinician confidence, prioritization, and ratings of basic competency for Volkmer, Cartwright, Ruggero et al.

Dementia Care Research and Psychosocial Factors.

Background: Among Black caregivers of persons living with Alzheimer's disease and related dementias (ADRD), the overlay of health disparities and systemic discrimination substantially contribute to heightened adverse health outcomes. Black dementia caregivers report experiencing challenges in providing care that may be exacerbated by them receiving fewer support services and having more unmet needs compared to their racial counterparts. Furthermore, historical systemic failures and disadvantages impacting Black dementia caregivers contribute to long-established stressors and vulnerabilities.

Dementia Care Research and Psychosocial Factors.

Background: A large body of research supports the benefits of older adults engaging in physical activity outdoors. However, a paucity of research explores factors associated with the frequency of older adults going outdoors. The aim of this study was to explore how factors including cognition, neighborhood characteristics, and physical ability were associated with community-dwelling older adults' outdoor frequency.

Dementia Care Research and Psychosocial Factors.

Background: Cognitive care planning-the process of regularly and systematically assessing patient needs and documenting recommendations to address them-improves health and quality of life among patients with cognitive impairments, like Alzheimer's disease and related dementias (ADRD). A cognitive care plan may promote physical exercise, social engagement, healthier eating, medication recommendations, and overall improvement in care management (e.g.

Dementia Care Practice.

Background: In the United States, Latino older adults are 1.5x more likely to develop Alzheimer's disease than non-Latino White older adults. Latino Family Caregivers (LFC) maintain home care for longer periods of time but use formal care less.

Dementia Care Practice.

The prevalence of Alzheimer's disease and related disorders (ADRD) is rising, and primary care providers (PCPs) will increasingly play a role in its detection. We developed an evidence-based intervention to facilitate cognitive evaluation in primary care. We then implemented it as a set of web-based trainings which were combined with specific tools embedded in the electronic health record (EHR) for PCPs to use in their practices.

Dementia Care Practice.

Current joint practice guidelines (PG) on genetic counseling and testing for Alzheimer's disease (AD), published in 2011 by the National Society of Genetic Counselors (NSGC) and American College of Medical Genetics), recommend against clinical APOE genetic testing. These recommendations were largely followed, as seen in a survey of AD Research Centers in 2019 where only 7% of centers reported disclosure of APOE to research participants. However, because the risk of amyloid related imaging abnormalities (ARIA) associated with anti-amyloid therapy is increased for those with one or two copies of APOE e4, the FDA now endorses APOE testing for those considering this treatment.