Neuronal stimulation‐regulated RNA splicing defects in tauopathies are corrected by treatment with a p75 NTR modulator

Activity-Induced Long-Term Potentiation of Excitatory Synapses in Developing Zebrafish Retina In Vivo

BackgroundDespite the growing number and proportion of the immigrant population in the US, there is a lack of knowledge on healthcare expenditures among immigrants with cognitive limitations or Alzheimer’s disease and related dementias (ADRD). This study estimated differences in total healthcare expenditures between US‐born and foreign‐born individuals by the presence of ADRD and/or cognitive limitations. This study also examined the differences in healthcare expenditures by service types, including inpatient stays, office‐based visits, emergency department (ED) visits, home healthcare, and prescription drugs.MethodThe study used nationally representative data from the 2007‐2020 Medical Expenditure Panel Survey (MEPS). Generalized linear regression models were used to estimate differences in healthcare expenditures between US‐born and foreign‐born individuals with ADRD, cognitive limitations without ADRD, and without ADRD or cognitive limitations. Analyses were also implemented by the immigrants’ duration of residence in the US, classified as foreign‐born living less than 10 years in the US and more than 10 years in the US. The study sample included all community‐dwelling adult Americans and had separate subpopulation analyses on the elderly population aged 65 and above. Survey weights were applied to all estimates.ResultForeign‐born individuals with cognitive limitations or ADRD had substantially higher total healthcare expenditures than their counterparts. Compared to US‐born individuals with ADRD, foreign‐born individuals with ADRD spent significantly more on home healthcare ($4,456.1, p = 0.029). Among individuals without ADRD or cognitive limitations, foreign‐born individuals spent significantly less than their US‐born counterparts in most healthcare services. Compared to their US‐born counterparts, immigrants with ADRD who had lived in the US for more than 10 years encountered significantly higher home healthcare costs ($4,245.6, p = 0.031), whereas those who had lived in the US for less than 10 years incurred significantly lower costs on office‐based visits (‐$1,833.8, p<0.001) and ED visits (‐$514.4, p<0.001). In contrast, immigrants with no ADRD and cognitive limitations spent significantly less than their US‐born counterparts on healthcare regardless of residence duration in the US.ConclusionForeign‐born individuals with cognitive limitations or ADRD had substantially higher total healthcare expenditures than their US‐born counterparts, while foreign‐born individuals without ADRD or cognitive limitations spent significantly less than their US‐born counterparts.

Herpes zoster (HZ) is a painful condition that is managed with a combination of antivirals, steroids, and pain medications. Nursing home residents with Alzheimer’s disease and related dementias (ADRD) may have difficulty expressing HZ symptoms, thus affecting medication management. This study compared prescription and non-prescription medication use in nursing home residents with HZ by ADRD diagnosis. We conducted a retrospective cohort study using nursing home electronic health record data from 2017-2022. Residents with HZ and ADRD were identified using ICD-10 codes as of the HZ diagnosis date. Administration for pain medications, antivirals, and steroids were measured before and after the HZ diagnosis date in periods of time (e.g., 1-7, 8-14, and 15-30 days before/after diagnosis). To assess relative changes in medication prevalence over time, administrations 15-30 days prior to HZ represented the baseline period. We identified 4,719 residents with HZ (31.5% had ADRD). Among residents without ADRD, oxycodone increased from 1.6% to 3.4% (vs. ADRD=0.5% to 0.8%) and gabapentin from 13.4% to 33.9% (vs. ADRD=12.6% to 25.6%) between baseline and 0-7 days after HZ diagnosis. In the 0-7 days after HZ diagnosis, prednisone use was 1.74 times greater in residents without ADRD (10.3%) vs. with ADRD (5.9%), and acyclovir use was similar between groups (without ADRD=28.5%; with ADRD=27.1%). Differences in medications, especially prednisone, between residents with and without ADRD may reflect undertreatment of HZ symptoms in residents with ADRD.

BackgroundThe annual cost of Alzheimer’s disease and related dementias (ADRD) in the US is $355 billion; that rate is expected to triple by 2050. Individuals ADRD accrue higher healthcare utilization costs than peers without ADRD, including those with comorbid conditions (e.g., cancer, coronary artery disease, diabetes). Although research examining prevalence of ADRD in American Indians/Alaskan Natives (AI/AN) is limited, recent data suggest the prevalence of ADRD in the AI/AN population is 49% higher than in the Non‐Hispanic White population. Only one study has evaluated the healthcare utilization of AI/ANs, which showed greater utilization rates among those with (versus without) ADRD diagnosis and a rapid increase in utilization following ADRD diagnosis. We have yet to comprehensively analyze the additive cost of ADRD within the US among AI/ANs.MethodPost‐paid electronic health record data from Wisconsin Department of Health Services were retrospectively analyzed to compare non‐Tribal and Indian Health Service utilization costs among Medicaid enrolled AI/ANs, ages 40 and older, based on the presence or absence of ADRD throughout data review (7/1/2015 through 7/1/2020). Three separate analyses were completed, separated by payer programs: fee‐for‐service, HMO, and long‐term care. In each analysis, controls (individuals without ADRD) were matched to cases (individuals with ADRD) using exact matching across the subclasses defined by crossings of age group, sex, diabetes status, and emphysema status (Tables 1‐3). Weighted Wilcoxon rank sum tests were then used to compare total payable costs per capita. Tests accounted for both the subclass sampling strata and weights produced through the matching process. Weighted Chi‐square tests of association were also employed to confirm balance was achieved across age groups, sex, diabetes status, and emphysema status in the matching process; no weighted imbalances occurred.ResultAmong all three programs, AI/ANs with dementia had significantly higher healthcare utilization costs than those without dementia, after matching for age, gender, diabetes and emphysema status.ConclusionAI/ANs with ADRD accrued at $25,000 more over 5 years, on average, compared to those without ADRD. The greatest cost disparity was in long‐term care waiver programs ($50,879). Cost‐effective interventions aimed at ADRD prevention and treatment among AI/ANs are greatly needed.

BackgroundAmerican Indian and Alaska Native (AI/AN) peoples face a rising burden of Alzheimer's disease and related dementia (ADRD). The 2024 Lancet Commission identified modifiable risk factors for dementia for the general population; however, a comprehensive understanding of risk factors associated with ADRD among AI/AN peoples is missing. This study utilizes a national database to estimate the prevalence of health conditions associated with ADRD and examine disparities between older AI/AN and White populations.MethodWe analyzed 2019 Medicare Master Beneficiary Summary File data for Medicare beneficiaries aged 68 and older, including all AI/AN beneficiaries and a 5% random sample of White beneficiaries. Two types of health conditions were examined: Lancet risk factors available in the Medicare data and other conditions that have been associated with ADRD (Table 1). Prevalence of ADRD and each condition was reported. Bivariate and multivariate logistic regressions assessed the associations between health conditions and ADRD.ResultAmong 112,280 AI/AN and 1,010,862 White beneficiaries, the former had higher age‐adjusted prevalence of ADRD (15.6 % vs. 13.3%), and substantially higher prevalence of 5 out of 9 Lancet risk factors, including diabetes, alcohol use disorder (AUD), tobacco use disorder, visual impairment, and hearing loss; similar prevalence of hypertension, depression, and traumatic brain injury (TBI); but a lower prevalence of hyperlipidemia (Table 1). Bivariate analyses revealed that all conditions were associated with higher ADRD odds in both populations, with TBI, depression, and AUD showing the strongest association with ADRD (Table 2). In multivariate regressions, the associations for TBI (odds ratio (OR) = 8.00), AUD (OR=3.30), visual impairment (OR=2.38), and hearing loss (OR = 1.34) were stronger in AI/AN beneficiaries, while depression, diabetes, and hypertension had stronger associations in Whites (Figure 1).ConclusionOlder AI/AN Medicare beneficiaries compared to their White counterparts, exhibit a higher prevalence of ADRD and 5 of the 9 Lancet risk factors. Furthermore, several conditions had stronger associations with ADRD among AI/AN beneficiaries, underscoring the importance of addressing disparities in ADRD risk factors to mitigate ADRD risk among AI/AN peoples. Further research using longitudinal data with social and behavioral determinants is essential to better understand and reduce these disparities.

BackgroundEscalating drug costs are likely to disproportionately burden individuals with Alzheimer’s disease and related dementias (ADRD) as they often have multiple chronic conditions (MCC). This study aimed to estimate the incremental total and out‐of‐pocket (OOP) drug costs associated with ADRD and MCC across the drug cost distributions.MethodThe study used a nationally representative cross‐sectional dataset from 2003 to 2021 Medical Expenditure Panel Survey. The study sample comprised of 83,667 elderly community dwelling individuals aged 65 and above, among which 3,046 individuals had ADRD diagnosis and 2,710 had both ADRD and MCC. To address the skewed distribution of the drug costs, quantile regression models were used to examine the associations between prescription drug costs and having ADRD/MCC across the drug cost distributions at 25th, 50th, 75th, and 90th percentiles, after adjustment for other sociodemographic factors. MCC was defined as having two or more chronic conditions. Survey weights were applied to all estimates.ResultADRD patients and those with ADRD and MCC had significantly higher incremental costs at the upper end of the total and OOP drug cost distributions than at the lower end of the distributions, compared to those who had no ADRD diagnosis. The incremental OOP drug costs of ADRD at the 90th percentile were over 14 times higher than that at the 25th percentile ($624.43, p<0.001, 90th percentile; $42.66, p<0.001, 25th percentile), while the incremental total drug costs of ADRD at the 90th percentile was about 9 times higher than that of ADRD at the 25th percentile ($3,372.27, p<0.001, 90th percentile; $381.31, p<0.001, 25th percentile). Similarly, the incremental OOP drug costs among individuals with ADRD and MCC at the 90th percentile were 11 times more than that at the 25th percentile ($756.91 vs. $68.55, respectively), while the incremental cost difference for the total drug costs was 7 times higher among individuals with ADRD and MCC at the 90th percentile than those at the 25th percentile ($3,940.53 vs. $548.80, respectively).ConclusionThe results of the study highlighted that ADRD patients with and without MCC who are heavy prescription drug users face a disproportionately greater burden in OOP payments.

Aging populations in low‐ and middle‐income countries (LMICs) are growing more rapidly than those in high income countries (HICs). Thus, globally, the burden of Alzheimer’s disease and related dementias (ADRD) profoundly impacts LMICs, with greater burden and risk for late‐life women than men. LMICs are unable to meet diagnostic challenges with underfunded healthcare infrastructure, low numbers of clinicians with training and expertise in ADRD, and a lack of culturally and linguistically sensitive screening assessments. Emerging social and societal factors that are important risk and protective factors for later life ADRD and are differentially experienced by gender/sex are relatively understudied, yet essential in LMICs. Typical samples in neuroscience studies have been small and highly selected. They have been biased toward Western, Educated, Industrialized, Rich, and Democratic (WEIRD) samples and do not apply well to target populations in LMICs. In addition, levels‐of‐analysis across social/societal and biological determinants of disease are not typically integrated, and social/societal factors such as sociocultural (e.g., culture, religion, gender norms, access to education, discrimination, social aspects of pandemics, disability), political (e.g., governments and policies; migrants and displaced persons; war and conflict; reproductive health, justice, and agency), environmental (e.g., climate change and pollution), and economic factors (e.g., poverty), and their co‐occurrence, have been minimally considered for their role and impact on ADRD. To better understand gender/sex differences in ADRD in LMICs, we review how these social and societal factors may be important to ADRD using an integrated Population Neuroscience and Syndemics framework. Population neuroscience considers the brain in context using multiple levels of analyses, a life course perspective, and tools to enhance internal and external validity, while Syndemics suggest that diseases and social conditions may cluster and interact in populations with syndemic risk factors—sociocultural, political, economic, and environmental factors which promote stress pathways. We lay out a model in which syndemic risk and protective factors contribute to or protect from stress and biological aging and ultimately ADRD risk, both directly and indirectly through physical and mental health conditions. We close with recommendations for future aging and ADRD research based on this integrated Population Neuroscience‐Syndemics of ADRD framework.

Abstract. Increasing awareness of Alzheimer’s disease and related dementias (ADRD) may contribute to anxiety about the prospect of a dementia-related diagnosis (dementia-related anxiety). In an online study, we examined variables believed to predict interest in ADRD testing: family ADRD history, self-perceived ADRD risk, dementia-related anxiety, and coping styles. Logistic regression analysis indicated family ADRD history, being in a relationship, and greater tendency toward monitoring style of coping were significantly associated with greater likelihood of interest in ADRD testing. In a second model, a significant interaction suggested that greater tendency toward monitoring coping style and greater self-perceived ADRD risk predict greater interest in ADRD testing. In the second model, dementia-related anxiety predicted interest in ADRD testing. Implications and future directions are discussed.

Research ObjectiveTo explore racial differences in the nursing home (NH) placement among Medicare‐Medicaid dual‐eligible home and community‐based service (HCBS) users with Alzheimer's disease and related dementias (ADRD), and determine the extent to which HCBS generosity may be influential.Study DesignThe following 2010‐2013 national data were linked at the individual level: Medicaid Analytic eXtract (MAX) Personal Summary (PS) file and Other Therapy (OT) file, the Minimum Data Set (MDS) 2.0/3.0 and Medicare Beneficiary Summary File and MedPAR.Dually eligible fee‐for‐service Medicare and Medicaid beneficiaries were identified using MBSF. Diagnosis of ADRD was based on the MBSF chronic condition file. New users were defined as those who did not have HCBS episodes in a prior 30‐day look‐back period, based on the OT records.The outcome variable was any NH admission within one year after the HBCS use, defined based on the MDS data. The main variables of interest were race (ie, white, black, other), the intensity of HCBS among ADRD population at the county level (the average monthly spending per HCBS user with ADRD in a county, based on MAX PS file), and the interaction terms between the intensity of ADRD and race. A linear probability model with county fixed‐effect and robust standard errors were estimated, accounting for individual covariates (eg, demographic characteristics, chronic conditions, prior use of institutional care).Population Studied1 527 974 new users of HCBS with ADRD during CY2010 to 2013.Principal FindingsThe intensity of HCBS among individuals with ADRD varies widely across counties, the 25th percentile, median, and the 75th percentile was $654, $827, and $1099, respectively. The overall NH admission rate among HCBS users with ADRD was 67%, 55%, and 36% for whites, blacks, and others, respectively. After accounting for individual covariates, whites continued to exhibit a higher NH admission rate, as compared with two other race groups. However, while a higher intensity of HCBS reduced the likelihood of NH placement for whites, it increased the risk among blacks. NH admission rate for blacks was 7.2 percentage points (P < 0.01) lower than for whites in a county with a median HCBS monthly spending. A one hundred dollars increase in monthly HCBS spending was associated with a 0.3 percentage points (P < 0.01) decrease in admission rate among whites, but a 0.3 percentage points (P < 0.01) increase among blacks.ConclusionsOur findings suggest that among dual‐eligible HCBS users with ADRD, whites were more likely to have NH admission within 1 year than non‐whites. Moreover, higher intensity of HCBS in a county was associated with lower a NH admission rate among whites, but a higher rate among blacks.Implications for Policy or PracticeStates have been promoting the use of HCBS as the means of rebalancing the cost of traditional institutional care while allowing more people to remain living in the community. However, the expansion of HCBS may have differential impact on NH admission risk for whites and blacks. Better understanding of racial differences in care needs is critical to inform the State Medicaid program design.Primary Funding SourceNational Institutes of Health.

BackgroundAlzheimer’s and Related Dementias (ADRD) affects close to half of older adults before death. The age‐adjusted rate of ADRD is disproportionately higher in racial/ethnic minority populations. There are also disparities in end‐of‐life care for racial minority older adults with ADRD, including the type of care, place of care, and place of death. Place of death is associated with the quality, type, and cost of care that patients may receive. Place of death is increasingly being recognized as an indicator of end‐of‐life care quality. In surveys of the U.S. population, older adults, including racial minority older adults, increasingly state a preference for death at home compared to a hospital or nursing home setting. In this study, we investigated factors associated with place of death among older adults with ADRD.MethodWe conducted a secondary analysis of a national dataset, the Health and Retirement Study (HRS), using HRS Exit interviews related to deceased participants’ data from 2002‐2019.ResultOf the 7,214 decedents, 13% had a diagnosis of ADRD, 30% had cognitive impairment suggesting undiagnosed ADRD, and 57% were cognitively intact. Among the 3,102 participants with ADRD, Black participants were 80% more likely to die in the hospital and 46% less likely to die in a nursing home compared to white participants. We did not observe any significant effect of race on hospice use. Additionally, married participants were 89% more likely to die at home compared to unmarried participants. For every 1‐year age increase, participants were 1.6% less likely to die in the hospital, 3.8% less likely to die at home, and 6% more likely to die in nursing homes.ConclusionOur findings indicate that race, marital status, and age are significant predictors of place of death among older adults living with ADRD. Black participants with ADRD were less likely to die at home compared to their white counterparts. There are considerable racial differences in which patients with ADRD die at home or in institutions. There is a need for further research to understand the reasons for these variations in the efficiency and type of end‐of‐life care delivered to racial minorities.

Healthy Lifestyles and the Risk of Alzheimer’s Disease and Related Dementias among Low-Income Black and White Americans

BackgroundHispanic/Latino (H/L) individuals have higher rates of Alzheimer’s disease and related dementias (ADRD) yet are less likely to be diagnosed with ADRD and engage in ADRD research. Almost 30% of the population is H/L in Denver, Colorado. We carried out the Boot Camp Translation (BCT) process with our local H/L community to increase awareness of medical issues and enhance the uptake of evidence‐based interventions.MethodDuring the BCT process, participants learn about a medical issue, share their personal expertise and knowledge, and create locally relevant, culturally informed health messages and plans for message dissemination. The Denver H/L BCT on ADRD was conducted over a series of virtual meetings led by two University of Colorado academic co‐facilitators and a real‐time Spanish interpreterResult16 H/L individuals with a broad array of lived experience participated in the Denver H/L BCT on ADRD. The group met over a period of 8 months. Four dominant themes emerged: 1) Awareness of ADRD; 2) Brain health; 3) ADRD risk reduction; and 4) Exclusion of H/Ls in the ADRD health care and research. The target audience for these messages included H/L middle age and older adults and undocumented individuals in Denver. The group worked with a local designer to create flyers and t‐shirts displaying the messages, which were disseminated through local mercados, churches, and libraries. After the project, 12 of the 16 members agreed to serve on a community advisory board (CAB) to help guide future community‐academic partnership work.ConclusionBCT is an effective approach to engaging H/L individuals in ADRD research. The Denver H/L BCT successfully conducted the BCT using virtual meetings and a live interpreter. The partnership developed during the BCT led to the formation of a CAB, which will provide infrastructure for sustainable community engaged ADRD work.

BackgroundAlzheimer’s disease and related dementias (ADRD) are leading causes of disability and often result in communication deficits that can complicate ADRD caregiving and clinical care. Augmentative and Alternative Communication (AAC) devices have been shown to provide assistance in communication for persons with ADRD, although many of these devices have been criticized for limited ability to customize content or design, and not addressing the impact of communication deficits on the larger family unit. This program of research has been informed by related theoretical frameworks: person‐centered (PCT) and family‐centered theories (FCT).MethodAn interdisciplinary team working with stakeholders are designing a novel information technology prototype with a touchscreen to promote communication and personhood for persons with ADRD. This improved ACC device is best described as an AAC Plus. The AAC Plus goes beyond traditional AAC in that it can be integrated into an existing healthcare delivery system and provide real‐time clinical data and health trends to the healthcare provider for early detection, intervention, and monitoring of clinical symptoms. In addition, the AAC Plus: (1) is designed to promote engagement and communication for interactions between the caregiver and person with ADRD using ubiquitous touchscreen technology; (2) facilitates tracking of behavioral and other clinical information about the person with ADRD, such as sleep and appetite; (3) has easily customizable interfaces for the caregiver and person with ADRD.ResultUsability and feasibility will be tested using common use case scenarios, user experience testing, alpha testing, and beta testing methodologies to evaluate ease‐of‐use and cognitive ergonomics for both caregivers and persons with ADRD. This will include evaluating the design layout, user flow, and integrated content for the device’s interfaces. Once usability and feasibility is established, the team will conduct a randomized trial of the AAC Plus, in collaboration with Memory Centers in the United States (R01 AG068572‐01).ConclusionThis presentation will provide content on the process of development and human‐computer interaction methodologies used to develop an evidence‐based, innovative technology for people with ADRD and their caregivers. Attention will also be given for developing technologies for ADRD care that integrate person and family‐centered design.

BackgroundWith increases in population aging and life expectancy, the burden of mild cognitive impairment (MCI), Alzheimer's disease, and related dementias (ADRDs) is projected to increase. Veterans, in particular, experience the same risk factors for MCI and ADRDs as the general U.S. population (e.g., aging, genetic risk) as well as service‐specific risk factors (e.g., traumatic brain injury, posttraumatic stress disorder [PTSD], occupational exposures) that may put them at greater risk.MethodThe current study aimed to examine the incidence and correlates of MCI and ADRDs in post‐9/11 veterans utilizing over 20 years of longitudinal data from the Millennium Cohort Study (n = 146,670). MCI and ADRD cases were ascertained through ICD‐9 and 10 codes obtained through Veterans Health Administration and Military Health System Data Repository electronic health records between 2001‐2024. Age‐ and sex‐adjusted rates were reported per 100,000 person‐years calculated from the date of birth and censored at the date of diagnosis, date of death, or end of the observation period (August 15th, 2024), whichever came first. Age‐ and sex‐adjusted rates by characteristic subgroups were estimated from direct standardization methods and standardized to the total military population in 2010.ResultDuring the study period, 1,759 veterans were diagnosed with MCI (25.82 cases per 100,000 person‐years, 95% CI=24.25, 27.38) and 661 veterans were diagnosed with ADRD (6.86 cases per 100,00 person‐years, 95% CI=6.17, 7.54). A majority of ADRDs did not have an identified etiology (e.g., unspecified dementias). Among those who did, Alzheimer's disease and vascular dementia were the most prevalent diagnoses within the cohort. Military characteristics, such as serving in the Army and in occupations with high risk for low‐level blast, were associated with higher age‐ and sex‐adjusted rates of MCI and ADRD diagnoses. Mental (e.g., PTSD, depression) and physical health (e.g., hearing loss, smoking) factors were also associated with higher rates of MCI and ADRDs.ConclusionFindings highlight potential unique military risk factors for the development of cognitive impairment and dementia. These findings may help to inform future policy and develop interventions aimed at reducing long‐term cognitive health consequences that may be associated with military service.

PDG38 Association between Satisfaction with Quality of Care and ANTI-Dementia Medication Adherence Among Elderly Adults with Alzheimer's Disease and Related Dementias