bluuebunny/crossref_metadata_2025_split huggingface dataset:
Current epidemiological and experimental evidence relating the chemical exposome to Alzheimer’s disease
Authors: Lefèvre‐Arbogast Sophie , Chaker Jade , Mercier Fabien , Barouki Robert , Coumoul Xavier , Miller Gary W , David Arthur , Samieri Cécilia 
Published: January 2025

AbstractThis critical overview aims to provide one of the most comprehensive synthesis of epidemiological and experimental evidence relating the chemical exposome to Alzheimer’s Disease (AD). We have focused on chemical pollutants that mostly result from anthropic activities and involved in toxicology pathways, including pesticides, organic solvents, metals, combustion air pollutants, dioxins, flame retardants, fluorosurfactants, plastic components and food/cosmetic additives. In total, we have reviewed over 120 epidemiological studies examining the link between chemical exposures and the risk of AD or cognitive impairment in older adults, along with more than 250 experimental studies assessing the impact of chemical exposures on neurodegeneration‐related pathways.The predominant emphasis in epidemiological research has been on pesticides, metals, solvents and combustion air pollutants. The most consistently observed associations with AD/cognitive impairment involve occupational exposure to pesticides and exposure to fine particulate matter. Less is known about the impact of lower levels of pesticide exposure in the general population, with emerging evidence supported by a few studies. Conversely, in the general population, there is growing evidence of the role of air pollution, especially increased exposure to fine particulate matters, in AD. Regarding metals and solvents, associations with AD have been suggested in several case‐control or cross‐sectional studies but the overall weight of evidence remains low. In experimental studies, pesticides and metals have also been the most extensively investigated and predominantly implicated in the disruption of neurotransmission, oxidative stress and mitochondrial dysfunction; some pesticides might also specifically target amyloid‐β aggregation.Finally, our comprehensive literature review highlights a gap in knowledge concerning the influence of many chemical exposures on AD, especially the most recent pesticide families as well as synthetic additive chemicals considered as ubiquitous. Yet, some of these chemicals have been incriminated in neurodevelopmental defects, and there exists suggestive, albeit still limited, evidence of their involvement in neurodegeneration‐related pathways, such as neurotransmission disruption, supporting the need for further research efforts.
Toxicological evaluation of environmental chemicals associated with AD identified using an exposomic framework
Authors: Kalia Vrinda 
Published: January 2025

AbstractExposure to environmental chemicals has been associated with Alzheimer’s disease (AD); however, most studies have used a targeted approach to study this relationship. While targeted approaches have been critical to understand mechanisms, they do not reflect real world exposures where an individual is exposed to multiple chemicals at the same time. Exposomics provides the opportunity to use an ‐omics level approach to understand the environmental drivers of disease by measuring the burden of multiple chemicals at the same time. Using an exposomic approach, we found a metabolite of the legacy pesticide DDT to be associated with AD in an observational study. We then investigated whether DDT can exacerbate AD‐related pathology using a transgenic strain of the nematode model Caenorhabditis elegans (worm) that expresses a mutant tau protein fragment that is prone to aggregation.Exposure to 3µM DDT resulted in internal levels of 0.5 pg (SD: 0.01) p, p’‐DDT per worm and 0.1 pg (SD: 0.01) of its metabolite p, p’‐DDE. We found that exposure DDT significantly restricted growth in the transgenic strain more than it does in wildtype worms. Further, DDT significantly lowered mitochondrial respiration rates in both strains. High‐resolution mass spectrometry‐based metabolomics (HRMS) analysis using the whole worm showed reduced levels of several amino acids and an increase in adenosylselenohomocysteine in DDT exposed worms. DDT exposure in the transgenic strain significantly increased the amount of time spent curling. The curling phenotype has been previously associated with mitochondrial dysfunction. Our data suggest that low level exposure to DDT likely exacerbates the mitochondrial inhibitory effects of aggregating tau protein in C. elegans.We are investigating the relationship between persistent organic pollutants and age‐related cognitive decline in the Reference Ability Neural Network study. This study, conducted in healthy volunteers, allows us to consider the relationship between exposure and poor cognitive function without confounding by underlying disease. We plan to investigate the potential mechanism through which these chemicals affect neuronal health while considering them as a mixture using C. elegans. Recent advancements in predictive toxicology provide a starting point to consider the appropriate health and functional end points that should be investigated.
Research gaps and unmet challenges to study the impact of chemicals on neurodegenerative diseases
Authors: Samieri Cécilia , Lefèvre‐Arbogast Sophie , Chaker Jade , Mercier Fabien , Barouki Robert , Coumoul Xavier , Miller Gary W , David Arthur 
Published: January 2025

AbstractChemicals are ubiquitous in modern life. More than 100,000 chemicals are currently used worldwide, and the production continues to increase. Measuring with accuracy all the components of the chemical exposome represents a tremendous challenge which has been only very partly met so far, and gaps in science remain multiple. For example, there is a need for a comprehensive understanding of the chemical exposome’s impact on the brain, emphasizing the integration of various exposure routes and an expanded list of emerging concern chemicals. Biomonitoring, a relatively recent approach, has begun linking internal exposure to neurological impacts, shedding light on the potential neurotoxicity of non‐persistent pesticides like neonicotinoids and pyrethroids. Research should explore overlooked ubiquitous chemicals, such as flame retardants, fluorosurfactants, plasticizers, and food additives, and overlooked pathways such as neurovascular dysfunction or the impact on non‐neuronal cells.Furthermore, analytical challenges posed by exposomic studies are specifically important, since the chemical space is highly variable, dynamic and diverse in concentration levels (with ultra‐trace substances). Chemical exposures are multiple and potential additive or synergistic effects of chemicals, within mixtures, likely underlie the impact of the chemical exposome on the brain. Capturing the depth and breadth of that chemical exposome necessitates cutting‐edge molecular markers. The development of high throughput omics‐based molecular approaches has allowed simultaneous analysis of thousands of individual biological entities at a large scale – a technological revolution which has enabled the development of exposomics. High‐resolution mass spectrometry (HRMS)‐based methods applied to various matrices, allows to uncover unknown elements of the internal chemical exposome associated with neurodegenerative diseases.This presentation will discuss all the promises that new technologies combined with omics‐based methodologies could provide to uncover unknown chemical signatures associated to neurodegenerative diseases.
Sleep health, cognitive function, and self‐management skills in middle‐aged adults
Authors: Kim Minjee , Yeh Fangyu , Zheng Pauline , Kwasny Mary , Yoshino‐Benavente Julia , Curtis Laura M , Bailey Stacy C , Bonham Morgan , Sun Britney , Luu Han Q , Cecil Patrick , Agyare Prophecy , Zee Phyllis C , Wolf Michael S 
Published: January 2025

AbstractBackgroundPoor sleep health has been associated with worse cognitive and health outcomes in older adults. Less is known about this relationship in midlife. Thus, we aimed to investigate the relationship between self‐reported sleep health, cognitive function, and performance on common health tasks among middle‐aged adults, as sleep may be a modifiable target to address later life risk of cognitive decline.MethodEnglish‐speaking adults aged 35‐64 were recruited from an academic general internal medicine practice and federally qualified health centers in the greater Chicagoland area. Multidimensional sleep health (regularity, satisfaction, alertness, timing, efficiency, and duration) was measured by the RU‐SATED questionnaire. Global cognitive function was measured using the Montreal Cognitive Assessment (MoCA); age‐ and education‐adjusted Z‐scores were calculated. Cognitive impairment was defined as MoCA Z‐score lower than one standard deviation below population mean. Performance on common health tasks (e.g. comprehension of print health material, recall of spoken instructions, dosing medications, recall of multimedia education) were assessed using the Comprehensive Health Activities Scale (CHAS). We examined the association between sleep health, cognitive impairment, and health task performance using univariate and multivariable logistic regression. Covariates, selected a priori, included age, sex, number of chronic conditions, and depressive symptoms.ResultA total of 310 participants (mean age 51.2 ± 8.1; 66% female; 39% non‐Hispanic Black, 32% non‐Hispanic White, 21% Hispanic; 54% with 2+ chronic conditions) were included in analyses. The median sleep health score was 8 (interquartile range: 6‐10) and cognitive impairment was found in 11.3%. Poorer sleep health was significantly associated with cognitive impairment after adjusting for a priori covariates (adjusted odds ratio, 0.98; 95% CI, 0.96‐0.99; P = 0.007). Both poorer sleep health (ß, 1.11; 95% CI, 0.22‐1.99; P = 0.014) and cognitive impairment (ß, ‐27.7; CI, (‐34.3)‐(‐21.1); P<0.001) were independently associated with poorer performance on health tasks, after adjusting for a priori covariates.ConclusionPoorer self‐reported sleep health in midlife was associated with a greater likelihood of cognitive impairment, whereas both poorer sleep health and cognitive impairment were associated with lower self‐management abilities to navigate healthcare. Future studies should examine whether sleep‐targeted intervention in midlife can mitigate cognitive later‐life decline and poorer health outcomes.
Dietary intervention, biomarkers of brain pathology and neurodegeneration, and cognition: The MIND Trial Study
Authors: Dhana Klodian , Rajan Kumar B , Aggarwal Neelum T. , Arfanakis Konstantions , Carey Vince J , Sacks Frank , Barnes Lisa L. 
Published: January 2025

AbstractBackgroundPlasma levels of phosphorylated tau (pTau‐181), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) as biomarkers of brain pathology and neurodegeneration have been associated with cognition and Alzheimer’s dementia. Whether a dietary intervention modifies these relationships by potentially promoting cognitive reserve is unknown. We conducted a posthoc analysis of the MIND trial to investigate whether dietary intervention modifies the association of longitudinal changes in pTau‐181, NfL, and GFAP with cognition during 3 years of follow‐up.MethodMIND trial was a 3‐year, two‐site, randomized controlled clinical trial comparing the MIND diet with a usual diet on cognitive changes among 604 older participants (65 to 85 years) with a family history of dementia but without cognitive impairment, overweight, and with suboptimal diets at enrollment. pTau‐181, NfL, and GFAP were measured in plasma from blood collected after an overnight fast. Relative change in biomarkers (i.e., %change) from baseline to Year 3 were computed [(year 3 ‐ baseline)/baseline)*100]. Global cognition was derived from a standardized 12‐test cognitive battery. We included 508 individuals with biomarkers and cognitive assessments at the baseline and year 3.ResultChanges in pTau‐181 and NfL were associated with global cognition. One SD increase in %change of pTau‐181 was associated with 0.049 SD units lower in cognition at year 3 ($∖beta$ ‐0.049; 95%CI ‐0.081 to ‐0.016). For NfL, cognition was 0.044 SD units lower at year 3 (β ‐0.044; 95%CI 0.076 to ‐0.012). The strength of these associations differed by the dietary arm (p for interaction = 0.063), such that effects were attenuated in the MIND diet arm and more robust in the control arm. Specifically, pTau‐181 in the MIND diet group was ‐0.027 (p = 0.264), and in the control group, ‐0.076 (p = 0.001). For NfL, these estimates were ‐0.022 (p = 0.263) and ‐0.087 (p = 0.002) in the MIND and control diet arms, respectively.ConclusionLevels of biomarkers reflecting neurodegeneration increase with age, and we showed that the greater increase was associated with lower cognitive scores. Among individuals with greater changes in biomarkers, MIND diet intervention attenuated the association with cognition, suggesting that the MIND diet may promote cognitive reserve in older adults.
Expanding Clinical Services to Hispanic/Latinx Dementia and Caregiver Populations in Central Virginia
Authors: Tlatenchi Antonio A Martinez , Sabino Yenifer A Valera , Rossetti M. Agustina 
Published: January 2025

AbstractBackgroundHispanic/Latinx older adults have increased risk of developing Alzheimer’s disease, poor access to timely and quality dementia care, as well as limited access to caregiver support and interventions. We addressed these structural barriers at a local level in central Virginia in order to improve disparities in risk, early detection, and care.MethodSystematic expansion of services was undertaken by establishing a Spanish neuropsychological clinic, providing personalized scheduling services by providers to ensure appropriate follow‐up after referral is received, engaging in dementia specific community talks through a broader health system initiative (UVA Latinx Health Initiative), and facilitating dementia care coordination services for caregivers.ResultThe expansion of services has resulted in increased care to the Spanish‐speaking population with minimal wait‐time from time of referral to neuropsychological services and assignment of a care coordinator. Additionally, community talks resulted in increased awareness of services in the local area.ConclusionThese efforts have addressed well documented barriers of the Latinx community including timely and adequate access to dementia specific care for patients and their caregivers.
Creating Inclusive Research Through a Culturally Aware Data Collection Site
Authors: Salazar Hector , Lingler Jennifer H , Simó Carola A. Ferrer , Carter Fabu P. , Bester James , Floyd Lytonia , SmithBA Tracy , Dupaty Annik , Gleason Carey E. 
Published: January 2025

AbstractBackgroundEthnic and racial diversity in clinical research is critical for developing generalizable treatments and caregiving strategies. Barriers to participation among persons from underrepresented groups (URG) are systemic in clinical research. To increase URG research participation, we designed a community‐based data collection site where study participants complete full research visits.MethodFor an Alzheimer’s disease study, we established the first community‐based data collection site in Madison, WI, forging connections with Black community leaders and campus outreach staff. The site is proximal to diverse neighborhoods, public transportation, and is a hub for multi‐ethnic businesses. We rent space in the South Madison Partnership Office, an established community outreach center. This has allowed us to cultivate a consistent presence in the Black community, which evolved into a full data‐collection site. Staff include research specialists, community liaisons, nurse practitioners, and clinicians who are culturally‐aware and members of the Black community. The site is decorated with art from local Black and Indigenous artists, and food served is from a local Black‐owned business.ResultWe established proof of concept by successfully launching a fully‐equipped research site in the community, used for memory testing, biometric readings, blood draws, and one‐on‐one conversations with clinicians. Initial comments suggest participants prefer this comfortable, familiar setting over that of a hospital setting.ConclusionResearchers can use culturally‐aware and convenient data collection sites. Our site prioritizes the needs of participants toward the goal of achieving representation of racialized groups in research. This model has potential for broad implementation across aging and biomedical research.
Community Involvement: From Presentations to Participation
Authors: Tang Tara , Lavoie Athena , Brunson Gregory A 
Published: January 2025

AbstractBackgroundBuilding a foundation of trust is the first step to establishing a relationship with the community that transcends any enrollment period. The Memory and Aging Program (MAP) Outreach Team formed in 2016 and has grown to a core of four team members in 2022, all focused on educating the public about Alzheimer’s Disease and Related Disorders (ADRD) and sharing opportunities to participate in research. This team explores different approaches to improve the access underrepresented populations (URPs) have to research and share some of their takeaways from community events.MethodThe team specializes in building trust and two‐way communication with community partners. In 2023 MAP held ∼ 200 outreach events and presentations, 115 in underrepresented communities, where individuals were invited to join our prevention registry, and offered opportunities to learn about pathways to research participation. Health fairs held at community centers focused on the overall health of the BIPOC community and partnered with other organizations for health screenings, food and music. ApoE “swab parties” provided education and a low burden pathway to participate in research at cultural venues, alumni events and conferences. They offered time to meet MAP people in a warm environment to facilitate genuine conversations.ResultIn combination with events and social media campaigns, the prevention registry has grown to over 5,300 enrollees, 16% of which are representative of URPs. Our swab parties generated 335 biospecimens, 7% enrolled in studies. The 2023 health fairs were attended by approximately 230 individuals with approximately 11% enrolling in our prevention registry. We established 20 new community connections and saw a 76% increase in URP events since 2022.ConclusionIt’s imperative researchers continue to refine best practices in diversity recruitment and enrollment to foster trust between URPs and investigators. Authentic connections are best made by hosting frequent events that focus on the community’s overall health and located in settings where people feel comfortable. We’re optimistic in 2024 with plans to translate our registry into Spanish, acquire a sprinter van to bring memory screens and blood draws to community events, and offer more studies in Spanish with an increase in bilingual staff.
Non‐traditional Dementia Caregivers: Does a more distant relation diminish burden?
Authors: Leggett Amanda N. , Troost Jonathan , Tsuker Sophia , Miner Jennifer A. , Carlozzi Noelle E. 
Published: January 2025

AbstractBackgroundExamination of family caregiving and the stress process has focused on a “primary” caregiver (e.g., spouse, adult child) at the exclusion of other members of the caregiving network. Yet “non‐traditional” (e.g., grandchild, friend) caregivers are increasingly providing substantial caregiving support. This study explores whether non‐traditional dementia caregivers vary from traditional caregivers in terms of caregiving approaches and outcomes.MethodParticipants included 200 family caregivers (n = 156 traditional and n = 54 non‐traditional) for a person living with dementia from the Style Measure Study. Descriptive statistics and t‐tests were run to examine differences between traditional and non‐traditional caregivers. Linear regressions were run adjusting for caregiver demographics and the care context with caregiver type predicting use of dementia management strategies (criticism, encouragement, active management), Neuro‐QOL measures of caregiver strain, caregiver‐specific anxiety, feeling trapped, and positive affect, PROMIS measures of sleep‐related impairment, fatigue and pain intensity, and caregiver readiness.ResultNon‐traditional caregivers were significantly younger, more likely to be Black, had higher levels of financial difficulty, had provided care for less time, and reported significantly greater pain intensity and significantly lower levels of caregiver readiness. In adjusted linear regressions however, caregiver type only predicted use of active management care strategies; traditional caregivers used more active management than non‐traditional caregivers (B = ‐2.24, p<.05).ConclusionNon‐traditional caregivers are notably distinct from their traditional counterparts demographically, yet non‐traditional status generally did not predict differences in caregiving outcomes. Future research should prioritize inclusion of diverse caregivers to represent the broader caregiver population and recognize that their care needs are just as extensive as traditional caregivers.
External Validation of Dementia Prediction Models in Black or African American and White Older Adults: A Population‐Based Study in the United States
Authors: Dhana Klodian , Beck Todd , Liu Xiaoran , Dhana Anisa , Ng Ted K.S. , Desai Pankaja , Evans Denis A , Rajan Kumar B 
Published: January 2025

AbstractBackgroundIdentifying people at high risk of dementia allows for timely intervention, potentially slowing cognitive decline and delaying the onset of dementia. We externally validated commonly used risk predictions model for Alzheimer’s dementia in Black American and white older adults.MethodThe study included 2,130 participants with 1,159 Black American and 971 white participants without dementia at baseline from the Chicago Health and Aging Project (CHAP). Based on a recent systematic review and a comparative analysis, four prediction models were selected, including Cardiovascular Risk Factors, Ageing and Dementia (CAIDE), Dementia Risk Score (DRS), Brief Dementia Screening Indicator (BDSI), and Australian National University AD Risk Index (ANU‐ADRI). Using reported scores (i.e., points or beta estimates) from each model, we computed the predicted risk of dementia. The clinical diagnosis of dementia was based on the criteria of the joint working group of NINCDS and ADRDA for probable Alzheimer’s disease. The performance of each prediction model was assessed by the C‐statistic (discrimination ability) and calibration plots (comparing observed vs. expected dementia probabilities).ResultDuring 18 years of follow‐up, 275 (23.7%) Black and 167 (17.2%) white older adults developed incident dementia. Of the prediction models evaluated, BDSI had the highest discriminant value for dementia risk with c‐statistics of 0.79 (95%CI 0.74‐0.84) in Black and 0.77 (95%CI 0.70‐0.85) in white individuals. The c‐statistics for ANU‐ADRI were 0.78 (95%CI 0.74‐0.83) in Black and 0.75 (95%CI 0.70‐0.81) in white participants. CAIDE had a lower discriminating power, 0.55 (95%CI 0.51‐0.58) and 0.53 (95%CI 0.48‐0.57), respectively, in Black and white individuals. DRS performed better among individuals aged 65‐79 (c‐statistics: 0.75 in black and 0.66 in white individuals) than 80‐95 (c‐statistics: 0.61 in black and 0.55 in white individuals). The calibration plots showed that prediction models (i.e., DRS and CAIDE) significantly underestimated (i.e., 10 times lower) the risk of Alzheimer’s in both Black and white study participants.ConclusionThe prediction model assessed in this study underestimated the risk of Alzheimer’s in both Black and white individuals. This underscores the necessity for developing models specific to race to predict the risk of Alzheimer’s dementia more accurately in the population.