bluuebunny/crossref_metadata_2025 huggingface dataset:
Cognitive symptoms and medical history prior to mild cognitive impairment and dementia diagnosis: a retrospective case‐control study using Dutch primary care data
Authors: Baak Brenda N. , de Boer Casper , Nooralishahi Mahsa , van Harten Argonde C. , Vijverberg Everard G.B. , van der Flier Wiesje M. , Herings Ron M.C.
Published: January 2025

Background

General practitioners (GPs) play a crucial role in recognizing cognitive deficits and diagnosing dementia. Currently, dementia diagnosis in primary care is prone to be missed or delayed. Electronic health records from GPs can offer insights into the trajectory leading up to a dementia diagnosis. Our aim was to characterize prior medical history of health conditions known to be associated with dementia and cognitive concerns in dementia cases and controls using Dutch primary care data.

Method

In this retrospective case‐control study using data from the ABOARD‐GP Cohort (2011‐2022), we identified dementia cases and an equal number of controls (matched on birth year, sex, general practice and registration year). A prior medical history of cardiovascular disease, diabetes, hypercholesterolemia, cerebrovascular disease, psychiatric conditions, sleep disturbances, osteoporosis/arthritis, and fracture was assessed. Cognitive concerns mentioned during a GP consultation was operationalized as mentioning of (1) memory/concentration/orientation complaints/disorders, (2) overall decline, and/or (3) Mini‐Mental State Examination. Logistic regression compared each condition in medical history between dementia cases and controls. Time from first recorded cognitive concern to dementia diagnosis was estimated.

Result

We identified 70,628 dementia cases and 70,628 controls (mean age 80 years, 60% female) (Table 1). We found significant associations between all conditions in medical history and a dementia diagnosis. Cerebrovascular disease and psychiatric conditions, the two strongest associations, corresponded to a 58% and 59% higher odds of having a dementia diagnosis. Prior cognitive concerns mentioned during GP consultations were recorded in 47% of dementia cases (Table 2), indicating that over half had no documented history of cognitive concerns. For those with mentioning of a cognitive concern, the mean time from first cognitive concern to diagnosis was 2.14 years.

Conclusion

This study using GP data shows that cases with dementia were more likely to have pre‐existing health conditions than controls. One hypothesis for this could be that these conditions are known risk factors for dementia. Alternatively, individuals with these other conditions have previously sought medical attention from a GP, facilitating the detection of cognitive concerns. These results underscore the importance of timely recognition of cognitive symptoms and addressing risk factors to reduce the impact on cognitive health.
Blarcamesine in Early Alzheimer Disease Phase 2b/3 Randomized Clinical Trial
Authors: Sabbagh Marwan N. , Chezem William R. , Jin Kun , Missling Christopher U ,   Anavex Life Sciences Research Group
Published: January 2025

Background

There are no approved oral disease‐modifying treatments for Alzheimer disease (AD). This study was intended to assess efficacy and safety of blarcamesine (ANAVEX®2‐73), an orally available small‐molecule activator of the sigma‐1 receptor (SIGMAR1) designed to exert neuroprotection through restoration of cellular homeostasis including autophagy enhancement.

Method

ANAVEX®2‐73‐AD‐004 is a multicenter (52 medical research centers/hospitals in 5 countries), randomized, double‐blind, placebo‐controlled, 48‐week phase 2b/3 trial that enrolled 508 participants with early AD (mild cognitive impairment/mild dementia) from July 2018 to June 2021 (last patient visit in June 2022). Participants were randomized to receive blarcamesine (n = 338) or placebo (n = 170) oral capsules once daily for 48 weeks.

The co‐primary cognitive and functional outcomes were the change in ADAS‐Cog13 and ADCS‐ADL scores from baseline to 48 weeks. Additional clinical outcomes include the secondary outcome CDR‐SB and the exploratory outcome CGI‐I. All clinical endpoints were analyzed using a mixed model for repeated measures (MMRM).

Result

The blarcamesine group demonstrated improvement compared to the placebo group in all clinical endpoints at 48 weeks: when comparing least‐squares mean (LSM) change in ADAS‐Cog13 score (difference, −1.783 [95% CI, −3.314 to −0.251]; P = 0.0226), LSM change in ADCS‐ADL score (difference, 1.019 [95% CI, −0.66 to 2.70]; P = 0.234), LSM change in CDR‐SB score (difference, −0.456 [95% CI, −0.831 to −0.080]; P = 0.0175), and LSM change in CGI‐I score (difference, −0.285 [95% CI, −0.474 to −0.095]; P = 0.0033). Participants with ≥1 serious treatment‐emergent adverse events (TEAEs) occurred in 56 participants (16.7%) in the blarcamesine group and 17 (10.1%) in the placebo group. Common treatment‐emergent adverse events included dizziness, which was mostly mild to moderate in severity.

Conclusion

In this phase 2b/3 randomized clinical trial, we found that among participants with early AD, blarcamesine significantly slowed clinical progression on prespecified primary outcome global and cognitive measures at 48 weeks in the ITT population. These results suggest that blarcamesine may be an effective, safe, and novel scalable oral treatment for early AD.
APOE‐ε4 associations with smartphone‐based cognitive markers
Authors: Rosická Anna M , Fittipaldi Sol , Gallagher Eoghan , Hanlon Anna K , Ibáñez Agustín , Bridgeman Katie , Muniz‐Terrera Graciela , Ritchie Karen , Ritchie Craig W , O'Brien John T , Koychev Ivan , Lawlor Brian , Naci Lorina , Gillan Claire M
Published: January 2025

Background

Smartphone‐based assessments are a promising tool for early detection of cognitive decline in midlife. Previous research has shown such cognitive markers can be sensitive to a range of potentially modifiable dementia risk factors even in healthy adults. However, their sensitivity to genetic risk factors like APOE‐ε4 is likely to differ by cognitive domain, with evidence of strong negative effects on wayfinding tasks but mixed for other domains. We investigated the associations between a set of previously validated smartphone‐based cognitive markers and APOE‐ε4.

Method

N = 87 cognitively unimpaired, APOE‐genotyped participants (aged 44‐67, 57.5% female) of the PREVENT study completed a self‐administered module in the smartphone application Neureka, including gamified cognitive tasks and memory self‐evaluation (completion rates: 81%–99%). Controlling for age, gender, education, and parental history of dementia, we compared APOE‐ε4 carriers (n = 35) with non‐carriers in their performance on five cognitive measures: model‐based planning, visual working memory, processing speed (∼Trails A), cognitive flexibility (∼Trails B), and subjective memory problems. We conducted receiver operating characteristic (ROC) analysis to assess if APOE‐ε4 status can be predicted from norm‐adjusted cognitive scores, i.e., the difference between observed cognitive performance and what we would predict for given demographics based on an additional benchmark sample (N = 3,376, aged 18‐84, 65% female).

Result

In univariate analyses, APOE‐ε4 carriers did not significantly differ from non‐carriers in their demographic characteristics or cognitive scores except for visual working memory, which was better in carriers (t(63.226) = 2.245; p = .028). After controlling for covariates, APOE‐ε4 status was not significantly linked to, which was better in APOE‐ε4 carriers (β[bootstrapped 95% CI] = ‐0.29[‐0.53,‐0.06]; t = ‐2.30; p = .025). In ROC‐analysis, norm‐adjusted visual working memory scores modestly differentiated between carriers and non‐carriers (AUC(SE) = .648(0.067); bootstrapped 95% CIs = 0.515–0.774).

Conclusion

The non‐significant associations between APOE‐ε4 and most cognitive markers suggest limited sensitivity to genetic risk. Interestingly, APOE‐ε4 carriers outperformed non‐carriers in visual working memory, which could be due to antagonistic pleiotropy effects, but needs to be replicated in larger samples. The current study shows limited evidence for the clinical utility of our cognitive markers as indicators of genetic risk in middle‐aged cognitively unimpaired adults.
Identifying common disease trajectories of Alzheimer’s disease with electronic health records
Authors: Fu Mingzhou , Chang Timothy S ,   UCLA Precision Health Data Discovery Repository Working Group
Published: January 2025

Background

Alzheimer’s disease (AD), a leading cause of dementia, poses a growing global public health challenge. While recent studies have identified AD risk factors, they often focus on specific comorbidities, neglecting the complex interrelations and temporal dynamics. Our study addresses this by analyzing AD progression through longitudinal trajectories, utilizing clinical diagnoses over time. Using machine learning and network analysis, we created a computational framework to identify common AD progression patterns.

Method

We analyzed patient diagnoses from UCLA Health’s Electronic Health Records, coded with the International Classification of Diseases, version 10 (ICD‐10). Using the Fine and Gray model to detect significant temporal risk factors between diagnoses, we examined associations between diagnosis pairs and refined the patients' diagnostic trajectories, eliminating irrelevant disease transitions and delineating all possible trajectory combinations. These refined trajectories were compared using Dynamic Time Warping and grouped into clusters with hierarchical clustering. We investigated common AD trajectories through network analysis and compared patient demographics, AD manifestations, and genetic profiles across clusters. The Greedy Equivalence Search algorithm helped infer causal relationships within these trajectories.

Result

Our analysis included 6,969 eligible AD patients, narrowing down to 1,486 patients with 3,372 unique AD progression trajectories after refinement. We identified four trajectory clusters: 1) a mental disorder cluster centered around major depressive disorder (MDD) (e.g., anxiety disorder → MDD) (N_patient = 525); 2) a cerebrovascular disease cluster (e.g. hypertensive crisis → other cerebrovascular diseases) (N_patient = 348); 3) a neurodegenerative disease cluster characterized (e.g., Parkinson’s disease → other degenerative disease of nervous system) (N_patient = 742); and 4) an outlier cluster predominantly involving external causes like infectious diseases (N_patient = 7). Significant differences were observed in race‐ethnicity, age at AD onset, disease duration, and the polygenic risk score (PRS) for AD across clusters. For example, patients in the cerebrovascular disease cluster exhibited higher mean AD PRS compared to other clusters (p = 0.05). Causal analysis indicated that 56.1% (47 out of 91) of the identified trajectory connections were causal.

Conclusion

We uncovered AD diagnosis trajectories, incorporating temporal aspects and causal relationships. These insights could improve understanding of AD development, aid in subtype classification, and enhance risk assessment, which could significantly benefit patient care and medical research.
User Perceptions of a Robot‐based Music Intervention System for Dementia Care
Authors: Morris Tyler , Walker Sydney P. , Holder Laython V. , Vaughan Eric , Petrovsky Darina , Swaminathan Sai , Zhao Xiaopeng
Published: January 2025

Background

To address the rapid increase in the number of persons with Alzheimer’s disease or related dementia (PwADRD), we seek to combine the benefits of music intervention with the adaptability of social robotics. Our system, the Music intervention Using Socially Engaging robotics (MUSE) system, seeks to provide a structured music intervention session to a group of PwADRD using the social robot Pepper. As seen in Figure 1, the Pepper robot leads the PwADRD through a 3‐step music intervention session. To assess the user perception of the MUSE system, we conducted two workshops with PwADRD.

Method

We gathered groups of PwADRD with mild to moderate Alzheimer’s/dementia at assisted living facilities in the Knoxville, Tennessee area. Within these groups, the PwADRD participated in a MUSE session guided by the social robot. Afterward, they filled out a brief survey (5‐point Likert Scale questions) and participated in a semi‐structured interview.

Result

From the workshops conducted, we had a total of 15 participants. Regarding Pepper robot, the average survey score for all questions was 3.58/5 with a standard deviation of 1.12. These questions covered various design aspects of the robot’s design. Furthermore, the survey showed positive results for the MUSE app. Covering the activities of the MUSE session, participants gave an average score of 3.86/5 with a standard deviation of 0.89. Additionally, in the interview, participants proclaimed their admiration for the system. However, most participants did note that it was difficult to hear the robot at times and that the tablet interface was difficult to see.

Conclusion

The workshops showed that the MUSE system was positively received by the target community. As the research team observed participants engaging with the system, we found that most PwADRD enjoyed the musical activities and the robot that presented them. However, we also found ways to improve the MUSE system. Moving forward, we seek to address these issues and hopefully improve the user acceptance of the MUSE. Nonetheless, the workshops prove that the MUSE system can and will be positively received by the PwADRD community and therefore is a viable way to provide a meaningful intervention to PwADRD.
Perspectives from Underrepresented Patients and Families Following Biomarker‐Informed ADRD Diagnoses: Insights from the PARADE Study
Authors: Knox Melissa L , Witbracht Megan G. , Grill Joshua D , Lingler Jennifer H
Published: January 2025

Background

As the landscape of ADRD diagnoses evolves to include biomarker testing, there is a pressing need to understand the unique experiences, challenges, and support needs of families undergoing evaluations of cognitive decline, particularly in a manner that prioritizes cultural considerations from voices historically underrepresented in ADRD research. The current study aims to understand the AD biomarker disclosure journey of persons from underrepresented groups with the goal of informing culturally responsive approaches to the care of patients and their families navigating the complexities of ADRD diagnoses.

Method

Virtual focus groups are being conducted over a secure video conferencing platform, with a trained facilitator guiding the discussion. Participants represent a purposively selected subsample of those enrolled in Patient And family member Reactions to biomarker‐informed ADRD DiagnosEs (PARADE NIH RF1AG080591), a current add‐on to the New IDEAS study, a CMS coverage with evidence development study of amyloid PET with an explicit objective to represent diverse patients by enrolling >50% who identify as Black, African American, or Hispanic. Employing a semi‐structured interview approach, the focus group guide consists of 5 lead questions and follow‐up probes, aiming to explore participants' experiences in receiving amyloid PET results and to characterize their post‐disclosure information and support needs. Verbatim transcripts of focus group recordings will be analyzed using thematic analyses.

Result

Preliminary findings from initial focus groups with Black, African American and Hispanic participants and families will provide perspectives on decision‐making, expectations, and post‐disclosure experiences. This study is anticipated to yield novel insights into patient and family preferences for receiving high stakes ADRD diagnostic information and to identify potential gaps in current support mechanisms.

Conclusion

The results from this focus group investigation will contribute to a more comprehensive understanding of the information and support needs of culturally diverse families post‐ADRD diagnosis. Ultimately, this study seeks to inform culturally responsive care practices and will be disseminated to AD Research Centers and dementia experts, fostering the enhancement of best practices for biomarker disclosure and dementia‐related education.
Investigating the Relevance of Genetic Variation at Post‐Translational Modification Sites in the Polygenic Risk Model for Alzheimer’s disease‐associated Phenotypes
Authors: Paço Samantha LG , Pereira Felipe Luiz , Andrews Shea J , Grinberg Lea T. , Naslavsky Michel Satya
Published: January 2025

Background

The outcomes of extensive Genome‐Wide Association Study (GWAS) data in Polygenic Risk Score (PRS) studies exhibit varying odds ratios (ORs), ranging from 1.13 (Bellenguez) to 1.34 (Kunkle). These diverse outcomes stem from inherent limitations within the tool, including SNP selection criteria, rare variant exclusion, the absence of biological information integration, and considerations for diverse populations.

Overcoming PRS limitations and enhancing efficiency requires strategic integration of genetic loci annotations with post‐translational modifications (PTMs), impacting AD‐related processes and genes (NFT, PSEN1, PSEN2, APP).

Furthermore, the inclusion of diverse populations, specifically working with admixed populations like the Brazilian dataset, is essential for a nuanced understanding of these factors. This approach is critical for a comprehensive application of PRS in advancing our understanding of Alzheimer’s disease.

Consequently, The main goal is to evaluate PTM impact on Alzheimer’s disease phenotypes using Polygenic Risk Score models in Brazilian and European populations.

Method

The initial outcomes of the project involve the establishment of the PTMflex Annotator. This annotator seamlessly integrates the PTMnet and PhosphoSitePlus datasets with functional protein information from the NCBI platform. Serving as a unified tool, it facilitates efficient access and exploration of PTM sites and types. Users can input parameters such as genomic position, Ref seq transcript, or protein ID for precise inquiry.

The whole‐genome sequence datasets from the European Population (ADNI) and the Brazilian Population (ABraOM) will be integrated into the PTMflex Annotator for PTM extraction and verification. Subsequent tasks include logistic regression to determine PTM weights for each variant and calculating the total PTMs feature of each sample. The project concludes with a comprehensive PRS enrichment analysis, assessing the combined impact of PTMs and the PRS model through PLINK software, utilizing PGS003957 ‐ Kunkle (12,002 Variants) and PGS003953 ‐ Bellenguez (1,937 Variants) as base dataset.

Result

The ongoing phases of the project include applying target data into the PTMflex Annotator.

Conclusion

Anticipating discernible differences in the influence of PTMs within the prediction model across the two populations, the comprehensive whole‐genome sequence dataset is expected to identify rare variants linked to PTMs that could impact the Alzheimer’s disease phenotype.
Simian varicella virus infection in rhesus macaques is associated with amyloid deposition in multiple organs and arteries and production of an amyloidogenic state
Authors: Mahalingam Ravi , Bubak Andrew N. , Bustillos Amalia , Feia Brittany , Das Arpita , de Haro Eileen , Doyle‐Meyers Lara , Looper Jayme , Niemeyer Christy S. , Restrepo Diego , Nagel Maria A. , Traina‐Dorge Vicki
Published: January 2025

Background

Varicella zoster virus (VZV) is latent in ganglionic neurons in >90% of the world population and reactivates to produce herpes zoster in older adults. Zoster increases dementia risk, of which Alzheimer’s disease (AD) is the most common. However, a critical barrier in studying the mechanisms by which VZV contributes to dementia is that VZV is an exclusively human virus. Simian varicella virus (SVV) is the non‐human primate homolog of VZV that produces the same clinical spectrum of disease from varicella to latency to zoster. Thus, we used the SVV infection model in vivo to examine how infection may recapitulate AD pathology, specifically the induction of amyloidogenic peptides and amyloid deposition, thereby accelerating disease progression.

Method

Rhesus macaques were infected with SVV such that they developed varicella, established virus latency, then developed zoster following immune suppression; serum, tissues, and arteries were harvested across timepoints. Blood was examined for the presence of SVV DNA by PCR from pre‐inoculation to zoster. Serum was analyzed by ELISAs and Thio‐T assays (following an amylin spike) for the presence of amyloidogenic peptides and an amyloid‐promoting environment, respectively. Various tissues and arteries in the periphery and central nervous system were examined by immunohistochemistry for SVV antigen and amyloid.

Results

At the height of SVV viremia, increased amylin was seen and an amyloidogenic environment was induced in serum compared to pre‐inoculation and viremia resolution. SVV antigen co‐localized with amyloid in the periphery (pancreas, GI tract, temporal artery, olfactory epithelium and bulb) and amyloid was found in central nervous system (cerebral arteries).

Conclusion

Varicella infection may accelerate AD progression, in part through increasing the amyloid burden. In particular, the presence of amyloid in cerebral arteries in infected monkeys further support the role of varicella infection in the cerebrovascular disease (including cerebral amyloid angiopathy) seen in AD brains.
Effects of Different Intensity Exergame Balance Training on Balance and Cognition in Patients with MCI
Authors: Saeed Aruba , Amjad Imran
Published: January 2025

Integrating balance and cognitive training of varied intensities through exergame balance training may offer a distinct approach to enhancing balance and cognitive abilities in patients with mild cognitive impairment. The objective is to determine the relationship and effects of exergame balance training of different intensities on balance and cognition in patients with mild cognitive impairment (MCI). In this four‐arm parallel design Randomized Clinical Trial, ninety‐seven participants with mild cognitive impairments MoCA (18‐24), between the ages of 50 and 75 years, participated in novel exergame balance training. They were randomly assigned to one of four exergame balance training groups (mild, moderate, high, and control). All participants received twenty‐four sessions including forty minutes/sessions three times/week. The MoCA and BDNF were used to assess cognition, time up and go test (TUG), TUG dual task for functional mobility, Gait speed normal and fast for dynamic stability at baseline, after the 4th and 8th week. The correlation between cognition and balance was determined by spearman’s correlation. The mixed model analysis of covariance while fixing the baseline values as a covariate was used to determine interaction effects between interventions and time. Post hoc analysis was performed to investigate the findings between different complexity levels and the control group, and repeated measure ANOVA to determine within group differences.

There was a strong relationship between MoCA and TUG, TUG dual task with (rs = 0.41), (rs = 0.43) respectively and moderate relationship between MoCA and slow and Fast gait speed (rs = 0.15), (rs = 0.24) respectively of high intensity group. A significant interaction effect of group and time was observed for MoCA, TUG (1,3) = 19.34, <0.001, η2 = 0.217, TUG dual task (1,3) = 21.24, <0.001, η2 = 0.233, gait speed fast tests (1,3) = 11.889, 0.001, η2 = 0.151. Post‐hoc analysis at different intensities demonstrated a significant difference between mild, moderate and high complexity groups with the control group for MoCA, TUG, TUG dual task, Gait speed normal and fast (p<0.01).

The results indicate that exergame balance training of mild, moderate and high complexity influence the balance and cognition abilities differently with the improvement in the high intensity to a greater extent.
(In)Equity in Alzheimer’s Clinical Trials: A Long Road Ahead?
Authors: de Souza Ana Cláudia , Borelli Wyllians Vendramini , Rosa‐Neto Pedro
Published: January 2025

Background

Dementia is a complex condition that affects individuals in various ways around the world, with a particularly high prevalence and incidence in low‐ to middle‐income countries. However, the majority of clinical trials on immunomodulators in Alzheimer’s disease have predominantly been conducted in specific geographic regions and populations. Our objective is to assess the diversity and inclusiveness of the participant samples in terminated phase 2 or 3 clinical trials for anti‐amyloid therapies.

Method

We performed a systematic review for completed and terminated phase 2 or 3 clinical trials for Alzheimer’s disease in ClinicalTrials.gov with results published. We also searched for MEDLINE using “((anti‐amyloid) AND (alzheimer disease[MeSH Terms])) AND (therapy[MeSH Terms] OR (drug) OR (trial))”. We selected only trials using anti‐amyloid therapies regardless of the disease stage (Figure 1. Flowchart). We included all studies that provided sociodemographic characteristics of the sample studied. Variables collected were gender, race, countries where the trial was conducted, and mean years of education.

Result

A total of 16055 individuals over 12 trials were evaluated in this work (ENGAGE, EMERGE, GRADUATE I and II, CLARITY‐AD, A4, EXPEDITION3, ELN115727, CREAD and CREAD 2, TRAILBLAZER‐ALZ 1 and 2). Gender was similarly distributed among studies (8911 females, 55.5%). Participants included were mostly white individuals (13664, 85.1%), with a minority of asian individuals (1259, 7.8%), and black individuals (202, 1.2%). Ethnic origins were demonstrated in 8 studies and only 774 (4.8%) individuals self‐reported as being hispanic. Studies were conducted in 164 countries taken altogether, but included only 25 (15.2%) low‐ and middle‐income countries.

Conclusion

Clinical trials using anti‐amyloid drugs have failed to represent the majority of individuals living with AD‐related cognitive impairment on a global scale. It ultimately increases the disparities presented in the diagnosis and treatment of individuals with dementia. Ideally, anti‐amyloid trials should incorporate the epidemiology of individuals with dementia worldwide. These observations underscore the urgent need for coordinated efforts involving scientists, societies, local governments, and industry to prioritize equity as a central goal in science.
Variation in Survival After Dementia Diagnosis by Sex, Race/Ethnicity, and Geography
Authors: Lopez Maria J. , Lin Haiqun , Zafar Anum , Kim Hyosin , Xia Weiyi , Montaner Olga F Jarrín
Published: January 2025

Background

Dramatically varying estimates of survival time following an initial diagnosis of Alzheimer’s disease and other dementias have been reported across different studies. The prevalence of dementia increases with age while survival time decreases with increasing age at diagnosis. This study aimed to investigate how survival time after a diagnosis of dementia varies by sex, race/ethnicity, and age at time of diagnosis.

Method

A retrospective analysis of the Centers for Medicare & Medicaid Services Chronic Conditions Warehouse 100% Master Beneficiary Summary File was conducted for Medicare beneficiaries aged 50 and older who died in 2019 and had a dementia diagnosis date (n = 884,548). Survival time in years and associations with sex, race/ethnicity, age at diagnosis, clinical and sociodemographic factors, and state of residence were investigated. Descriptive statistics, generalized gamma regression survival‐time models, and Kitagawa‐Blinder‐Oaxaca decomposition of racial/ethnic differences were conducted.

Result

Among the 2019 Medicare decedents with dementia, the median survival time in years was shorter for American Indian/Alaska Native (AIAN) (2.7, IQR 0.8‐6.0) and White (2.9, IQR 0.8‐6.3) beneficiaries, and longer for Black (3.4, IQR 0.9‐7.4), Asian American/Pacific Islander (AAPI) (3.6, IQR 1.1‐7.8), and Hispanic (3.8, IQR 1.1‐8.5) older adults. Median survival time also varied by sex and age at dementia diagnosis. Hispanic and AAPI females diagnosed with dementia before age 80 had a median survival time exceeding 6 years after a dementia diagnosis. Median survival time also varied by geographical region and was notably longest for female Hispanic decedents in Puerto Rico (9.0, IQR 2.5‐14.7). Using the Kitagawa‐Blinder‐Oaxaca modeling decomposition approach, clinical and sociodemographic predictors fully explained the difference in survival time between White, Black, and AIAN individuals; however, more than half of the difference in longer survival time for Hispanic and AAPI individuals was unexplained.

Conclusion

Hispanic and AAPI older adults live significantly longer after receiving a diagnosis of dementia compared to White, Black, and AIAN older adults. Unexplained differences may be associated with cultural factors, family and social support systems, healthcare access and utilization, environmental factors, and differences in diagnosis rates and timing of diagnosis.
Construction of the Cognitive Function Trajectory File
Authors: Zafar Anum , Lin Haiqun , Kim Hyosin , Xia Weiyi , Lopez Maria J. , Montaner Olga F Jarrín
Published: January 2025

Background

Characterizing changes in cognitive function during the last years of life is vital for providing appropriate care, supporting quality of life, and planning for future demands on our medical and social resources. The aim of this project was to construct a cognitive function trajectory file spanning the last five years of life to better understand common patterns of cognitive aging.

Method

The analytic cohort included 2019 Medicare decedents, aged 50 or older at death, with five years of continuous enrollment before death (n = 1,952,408). We extracted and harmonized cognitive function data elements from Medicare fee‐for‐service claims, encounter file, assessment, and Medicaid data during 2014‐2019. The data elements used for harmonization included ICD‐9 and ICD‐10 codes, the Brief Interview for Mental Status, and other cognitive function assessment items. We created a four‐category indicator for cognitive function: no impairment, memory loss, mild cognitive impairment (MCI), and dementia/severe cognitive impairment. Similar to our approach to creating the care trajectory file, the cognitive function trajectory file was expanded at day‐level and then collapsed quarterly (3‐month) basis for the last five years of life (20 quarters). We employed a thorough carry‐forward method to address gaps in information.

Result

Using the information from combined assessment and claims, at death 69% of individuals aged 90 and older had dementia and 13% had MCI, and among individuals age 80‐89, 56% had dementia and 14% had MCI. Females had greater cognitive impairment at death (56% dementia, 14.4% MCI) compared to males (44.5% dementia, 15% MCI). Cognitive function at the end of life was similar across racial and ethnic groups: White (50.4% dementia, 15.1% MCI); Black (52.3% dementia, 14.7% MCI); Hispanic (51.43% dementia, 12.1% MCI); Asian American/Pacific Islander (AAPI) (52.7% dementia, 13.1% MCI); American Indian/Alaska Native (43.6% dementia, 15.2% MCI).

Conclusion

The successful construction of this analytic file allows for the exploration of varying patterns of cognitive functional decline and their multi‐level predictors including individual, community, societal, and environmental factors. This approach can also be applied in research for development of new dementia care strategies and risk‐ and protective factors associated with cognitive decline.
Health Services Use and End‐of‐Life Outcomes Among People with Dementia and Multiple Chronic Conditions
Authors: Kim Hyosin , Lin Haiqun , Zafar Anum , Lopez Maria J. , Xia Weiyi , Montaner Olga F Jarrín
Published: January 2025

Background

Individuals with dementia often have one or more chronic conditions, and the disease burden and care experience may differ based on the plurality of chronic conditions. We aim to describe the individual characteristics, health care use, and place of death for individuals with dementia and multiple comorbidities.

Method

A retrospective cohort of individuals who died in 2019 with dementia, and were continuously enrolled in Medicare for at least three years. We constructed a database summarizing health services utilization during the last three years of life and end‐of‐life outcomes by harmonizing inpatient and hospice claims, and assessment data from post‐acute and long‐term care settings. Individuals were categorized by number of comorbidities. Bivariate association analyses were performed to assess the statistical differences in the variables of interest by comorbidity levels.

Result

Beneficiaries with dementia (n = 933,618) had a median of seven additional comorbidities [IQR 5‐8]. Fifteen percent had three or fewer comorbidities. Those with four or more comorbidities were significantly more likely to be hospitalized (85% vs. 67%), admitted to a nursing home (66% vs. 51%), and use home health care (56% vs. 49%) during the last three years of life compared to those with fewer comorbidities. Inpatient death without hospice (29% vs. 18%) was higher among those with four or more comorbidities compared to those with fewer comorbidities. A greater use of hospice was observed within beneficiaries with three or less comorbidities in addition to dementia (71% vs. 62%).

Conclusion

Individuals with dementia and more than four additional chronic conditions used more health care services in both inpatient and home care settings, while they underutilized hospice services at the time of death compared to those with fewer chronic conditions. Policies aimed at enhancing access to home‐ and community‐based services for individuals with dementia and multiple comorbidities have the potential to enhance end‐of‐life care experiences and contribute to care quality for people living with dementia and support for their family caregivers.
Association between the social exposome and vascular brain injury in brain bank donors
Authors: Keller Sarah A. , Powell W. Ryan , Buckingham William R. , DeWitt Amanda , Bendlin Barbara B. , Kind Amy J.H.
Published: January 2025

Background

The social exposome, all social‐environmental exposures accumulated over the life course, could partially explain Alzheimer’s disease and other dementias (ADRD) disparities. Measurement and linkage of life course social exposome metrics to biological samples may inform opportunities for intervention. While there is increasing emphasis on the life course social exposome in ADRD research, there is little consensus on its measurement. Vascular brain injury (VBI) is a measure of changes in the cerebral blood vessels associated with increased risk of ADRD, but the extent to which social exposures are associated with VBI is unknown.

Method

We evaluated the association between life course social exposome measures and the VBI burden acrosstwo Alzheimer’s Disease Research Center (ADRC) brain banks. Geocoded life course donor addresses were linked to time‐concordant national Area Deprivation Index (ADI) rankings, with greater ADI denoting greater county‐level disadvantage. Life course social exposome was examined separately as 1, a cumulative measure of the number of years spent above the population median life course ADI, and 2, the change in ADI from youth to adulthood. The outcome was the presence of any of four VBI indicators: infarcts, microinfarcts, hemorrhages, and white matter rarefaction. The association of life course social exposome to VBI burden was evaluated via logistic regression adjusting for sex and age at death.

Result

This sample contained 740 donors from two brain banks. The population median ADI was 7.08 (IQR, 5.5) and the mean number of years spent above this threshold was 19.95 (SD, 20.89). More years living in a county above the population median was associated with increased VBI burden (OR, 1.04, 95% CI, 1.03‐1.05). A median ADI which increased (OR, 3.67, 95% CI, 3.65‐3.70) or remained stably high between youth and adulthood (OR, 3.08, 95% CI, 3.01‐3.14) resulted in increased odds of VBI burden.

Conclusion

This study shows promise for clarifying the relationship between the social exposome and ADRD brain pathology post‐mortem. We found associations between higher life course ADI (greater disadvantage) and VBI burden. Identifying dosages and timing of life course exposures critical for development of VBI allows for future intervention to reduce disparities in ADRD.
Public data tracing: A novel method for retrospectively collecting occupational data for brain bank research donors
Authors: Otte Rachel C. , Etter Lauren , Surovell Elliot I. , Lim Sarah , Pfaff Aly , DeWitt Amanda , Sharrow Jessica , Salamat Shahriar , Zuelsdorff Megan L. , Rissman Robert A. , Bendlin Barbara B. , Kind Amy J.H. , Powell W. Ryan
Published: January 2025

Background

Working conditions and contexts may influence the development of Alzheimer’s Disease and related dementias (ADRD), exposing individuals to modifiable risk factors across their life. Measurement of ADRD pathology at autopsy provides a gold standard outcome for evaluating the effects of lifetime exposures, but approaches to quantify ante‐mortem work exposures are limited. Here we describe a new method to retrospectively capture occupational histories by systematically extracting occupational information using archival public records— i.e., public data tracing—and provide preliminary feasibility for ongoing data collection for two ADRC brain bank cohorts.

Methods

Our sample includes individuals donating to two ADRC brain banks between 1986‐2018 who had residential histories previously constructed and are part of ongoing efforts to build occupational histories (n = 651 of a planned 1154). They had a mean age at death of 81.7 (SD = 10.3) years, were 51.9% (n = 338) female, and had a median year of birth = 1926 and median year of death = 2012. Quantifying occupational exposure entails systematic searches of archival collections available in‐person and online (e.g., Ancestry.com) to locate records (Figure 1). Two researchers independently verified the identity and content of public records using the Genealogical Proof Standard. Data collection occurred from June‐December 2023.

Results

We identified an average of 10.7 (SE = 0.28) records with occupational information per donor with an average 1.29 (SE = 0.02) hours spent extracting and validating each donor’s occupational history. The most common public record types included: federal censuses (≥1 record for 70.5% of donors), city directories (70.2%), obituaries (62.6%), newspapers (58.3%), yearbooks (40.1%), military records (27.7%), marriage records (6.9%), and voter registrations (6.2%), which varied by time (Figure 2). In addition, we found the number of public records varied by sex, with more records containing occupational information identified for males (14.2 average records) compared to females (7.2).

Conclusions

Preliminary findings suggest that applying public data tracing methods to collect occupational information is feasible. There are both limitations and opportunities, particularly as public record availability seems to vary by time (both calendar and lifecourse) and donor sex. This new method quantifies occupational exposures over the lifecourse, creating new opportunities to study the relationship between work and ADRD brain health.
Neighborhood racial income inequality and ADRD risk
Authors: Zahodne Laura B. , Sol Ketlyne , Scambray Kiana A. , Lee Ji Hyun , Palms Jordan D , Morris Emily P. , Taylor Lauren , Ku Vivian , Lesniak Mary , Melendez Robert , Elliott Michael R , Clarke Philippa
Published: January 2025

Background

Neighborhood conditions and their racial patterning represent under‐studied factors that could contribute to racial disparities in dementia risk. Neighborhood socioeconomic status (SES) has been linked to dementia, but the racial distribution of SES within a neighborhood may also matter for dementia risk.

Method

Individual‐level data from 460 (47% Black, 46% White, 7% other) older adults from the Michigan Cognitive Aging Project (Table 1) were linked to census tract‐level data from the National Neighborhood Data Archive. Neighborhood SES was operationalized as composite measures of neighborhood disadvantage and neighborhood affluence. Neighborhood racial income inequality was operationalized as the ratio of median incomes for White versus Black residents. Generalized estimating equations accounting for geographic clustering examined associations between neighborhood factors and performance on a comprehensive neuropsychological battery, adjusting for individual‐level (age, gender, race/ethnicity, education, income) and neighborhood‐level (population density, proportion of Black residents) covariates.

Result

Neighborhood racial income inequality was uniquely associated with worse cognitive health across multiple domains (Table 2, Figure 1), and these associations did not differ by participant racial identity. Neighborhood disadvantage was only associated with worse cognitive health among Black participants (p’s < .007).

Conclusion

Both overall neighborhood SES and racial inequities in the distribution of economic resources within neighborhoods are associated with dementia risk independent of individual‐level SES and other characteristics of the neighborhood. Findings highlight potential negative cognitive impacts of structural racism on a community that may be universal. Racial differences in both the level of neighborhood disadvantage and the strength of its associations with cognitive health (i.e., differential impact) likely contribute to racial inequalities in dementia. Future work should characterize mechanisms underlying these effects, as well as develop and test policies and interventions to improve neighborhood conditions and dismantle structural racism in order to promote health equity.
Social Engagement is associated with better cognition in Quilombola Communities: Insights for Engaging underserved Brazilian Populations in Alzheimer’s Disease Research
Authors: Simon Sharon Sanz , Cappi Carolina , Junior João de Deus Cabral , Alves Gilberto Sousa , de Oliveira Bruno Luciano Carneiro Alves
Published: January 2025

Background

Quilombos are settlements founded by descendants of runaway slaves in Brazil, typically located in remote rural areas. Quilombola communities typically present poor basic sanitation and health, high levels of illiteracy, and limited access to social and health services, especially among older adults. Therefore, the Quilombola population is socially vulnerable and likely to present an increased risk for dementia, although underrepresented in aging/dementia research. Future research is needed to map dementia risk factors in this population. The present study aims to investigate the association between cognition and socio‐cultural engagement, potentially protective for dementia.

Method

This study is part of the Population Survey of the Living Conditions and Health Status of Older Persons Living in Quilombola Communities in the Baixada Maranhense (IQUIBEq) project, a cross‐sectional household survey conducted in 11 Quilombola communities in Maranhão (Brazil). The study comprised 221 older adults (60‐104 years), selected in partnership with local social services and community health workers. Participants completed a health survey and a cognitive screening (Mini‐Mental State Examination). Demographics, cardiovascular risk factors (waist‐to‐hip ratio and BMI), cognitive performance, and social engagement were described. Regression analysis examined the association between social engagement and cognition. Our models controlled for age, sex, race, education, family income, and cardiovascular risk factors. We also examined if sex and age moderated the association observed.

Result

Higher social engagement is associated with better cognition (p <.001) above and beyond demographics and cardiovascular risk factors. We observed the social activities that mostly drove our results were attending community meetings (e.g., community movements or resident associations) and attending religious/faith services. Moreover, age and sex did not moderate the association between social engagement and cognition.

Conclusion

Social engagement may be a key aspect of cognitive/brain health in the Quilombola population, a group that faces poor life conditions. Social engagement may not only provide social/emotional support among the community members but can facilitate access to basic needs (e.g., housing, sanitation). Other potential mechanisms are the cognitive stimulation present in social interactions and the effects of spiritual/faith/religious engagement. Although the results are limited by the cross‐sectional design and survival bias, they may inform public health strategies in underserved populations.
Natives Engages in Alzheimer’s Research (NEAR)
Authors: Bogic Marija
Published: January 2025

Background

The Native Hawaiian/Pacific Islander (NHPI) and American Indian/Alaska Native (AI/AN) populations are rapidly aging but there is limited data on Alzheimer’s disease and related dementias (ADRD). Despite the high prevalence of ADRD risk factors, the healthcare systems serving these communities are inadequately equipped to address the economic and social impact of ADRD. NEAR aims to reduce ADRD‐related health disparities by collaborating with a wide network of community and academic partners to gain a better understanding of the disease, implement interventions, and mitigate its impact on these communities.

Method

NEAR is the only P01 focusing on AI/ANs or NHPIs and ADRD‐related health disparities since the NIA began documenting P01s in 1984. Based at Washington State University, NEAR includes collaborators from the University of Miami, Brigham Young University, University of Hawai`i, University of Washington, University of Minnesota, and University of Colorado, along with 35 community partners. The program consists of 3 culturally‐informed projects, supported by an Administrative Core, Recruitment and Engagement Core, Biospecimen Core, and Research Methods Core. Notably, NEAR involves 12 AI/AN or NHPI scientists and all Projects and Cores are led by a Native researcher. Indians Transforming Alzheimer’s Care Training is a group‐randomized trial to improve ADRD diagnosis and care for AI/AN elders through culturally‐informed provider training. ‘IKE Kupuna is a randomized controlled trial testing the effectiveness of Hula in preventing cognitive decline in NHPI elders. Cognition After Obstructive Sleep Apnea Treatment Among Native American People is an observational study that screens for obstructive sleep apnea and cognitive impairment on 2 reservations, followed by a trial of motivational interviewing to improve adherence to sleep apnea treatment and improve or preserve cognitive function.

Result

There are no results since this is a grant abstract.

Conclusion

The decentralized model and collaboration with a diverse group of AI/AN and NHPI scientists, along with world‐class ADRD experts, has enabled NEAR to create unique scientific resources and a large network of academic and community partnerships. This integrated effort holds great promise for improving the diagnosis and quality of ADRD care while advancing the scientific field.