bluuebunny/crossref_metadata_2025_split huggingface dataset:
Canada’s Enhanced Dementia Surveillance Initiative: Improving national dementia measures to inform public health actions
Authors: Shaver Larry C , Marion Danielle , Pelletier Catherine 
Published: January 2025

AbstractBackgroundThe Enhanced Dementia Surveillance Initiative (EDSI), led by the Public Health Agency of Canada (PHAC), supports the implementation of Canada’s first national dementia strategy. To improve the national monitoring of dementia and its health impacts, the EDSI projects focused on priority data gaps: dementia by cause, progression stages and impacts; socio‐demographic characteristics, risk and protective factors; and caregivers.MethodPHAC collaborated on 15 projects with multiple stakeholders (universities/research institutions, health organizations, and federal/provincial government departments). Each employed novel methods and data sources in the Canadian public health surveillance context. Existing and linked health administrative data, electronic medical records (EMR), various primary data collections, and longitudinal cohorts were leveraged to apply new approaches addressing the listed data gaps.ResultProjects enabled various surveillance advancements in dementia health measures; examples are presented under four categories.1. By leveraging existing databases with new linkages, algorithm validation and data visualization techniques, projects were able to better identify and characterize (clinical and sociodemographic characteristics) people living with dementia and their caregivers.2. By enhancing linked health administrative data for national surveillance, new methods to report on dementia in long term care and dementia comorbidities were developed, and health care costs across dementia progression stages were calculated.3. By developing new conceptual and data models, it was possible to enhance the understanding of the dementia national data landscape. The impact of selected factors on dementia risk in the population was also estimated, and dementia patients’ trajectories across care settings were described.4. By applying a health equity lens, progress was made towards an improved monitoring of dementia in diverse populations, such as Indigenous communities and individuals experiencing homelessness.ConclusionThrough a knowledge synthesis of the results and findings from the EDSI projects, PHAC aims to identify and integrate best practices for national dementia surveillance. The expected long‐term outcome of this initiative is to contribute to more robust evidence on dementia in Canada to help inform related public health actions.
Modeling Early Detection and Geographic Variation in Health System Capacity for Alzheimer’s Disease‐Modifying Therapies
Authors: Liu Jodi L. , Baker Lawrence , Chen Annie , Wang Jessie , Girosi Federico 
Published: January 2025

AbstractBackgroundThe widespread availability of effective disease‐modifying therapies would be a breakthrough in slowing the progression of early Alzheimer’s disease (AD) to later stages of dementia. The purpose of this study is to explore how primary care capacity, variation in patient care‐seeking, and geographic variation in capacity can affect the delivery of AD‐modifying therapies.MethodWe used a county‐level simulation model to assess patient demand and provider supply for the delivery of AD‐modifying therapies. The model simulates the progression of people aged 50 and older through a clinical pathway and through disease states (normal cognitive, mild cognitive impairment, and Alzheimer’s dementia), and compares patient demand to the health care system capacity for detection, diagnosis, and treatment. We developed an interactive, web‐based tool that allows users to adjust key parameters and explore their effects on results.ResultCare models that enable primary care practitioners to diagnose and evaluate patients for treatment eligibility would make the biggest impact on reducing wait times for dementia specialists and increasing the number of people treated from 2025 through 2044. Improved triage of patients using blood‐based biomarker tests in primary care settings could further reduce caseloads for specialists. The estimated wait times and number of patients treated are sensitive to patient uptake of brief cognitive assessments. There is substantial geographic variation in health care system capacity across the US to detect, diagnose, and treat early AD. Estimated average wait times can be three times longer in rural areas compared to urban areas. States with long wait times include Alaska, Arkansas, Idaho, Mississippi, Montana, Nevada, Oklahoma, and Wyoming.ConclusionWidespread delivery of AD‐modifying therapies will require a combination of strategies to communicate the value of detection and treatment to patients, integrate PCPs into the detection and diagnosis pathway, and address capacity disparities across the United States. Further work is needed to evaluate how primary care‐led models of care can widely and effectively evaluate and manage treatment for people with early AD, as well as how technological advancements, such as improved biomarkers and computerized testing, can be integrated into workflows to better serve people living with AD.
Estimating preclinical amyloid positivity in the community: a case study transporting estimates from ADNI to ARIC
Authors: Stapp Emma K , Mayeda Elizabeth Rose , Stuart Elizabeth A , Gottesman Rebecca F. , Wong Dean F. , Mosley Thomas H. , Griswold Michael E. , Glymour M. Maria , Zimmerman Scott C , Power Melinda C 
Published: January 2025

AbstractBackgroundEstimates of the prevalence of preclinical amyloid positivity in the US general population are of great interest to the field, but difficult to measure and thus unavailable in representative studies. A statistical approach from causal inference, ‘transport’, may allow for improved generalizability of findings from a sample of persons from one population to another. We aimed to explore the feasibility and validity of extending results from a deeply‐phenotyped convenience sample, the Alzheimer’s Disease Neuroimaging Initiative (ADNI), to a representative target sample, the Atherosclerosis Risk in Communities Study PET Amyloid Imaging Study (ARIC‐PET) — with “proof of concept” defined by the performance of the transport estimator in recovering the observed prevalence of amyloid positivity in ARIC‐PET.MethodEligible ARIC‐PET and ADNI participants were either white or Black and had normal cognition or mild cognitive impairment. Amyloid positivity was defined using study‐specific cutoffs for standardized uptake value ratio (SUVR). Probability of selection into ADNI (vs. into ARIC‐PET), given harmonized sociodemographic and clinical covariates, was estimated using gradient boosted trees (GBM). The resulting study participation probability scores were used to transport the prevalence of amyloid positivity from ADNI to ARIC using inverse odds of sampling weights. Estimates of amyloid positivity prevalence derived from ADNI and from transporting from ADNI to ARIC‐PET were compared to the observed prevalence in ARIC‐PET, overall and by age, sex, race, education, and APOE e4 status.ResultTransported prevalences substantially underestimated observed prevalences of amyloid positivity in most groups, with the exception of white, non‐Hispanic individuals and persons with at least one APOE e4 allele, where prevalence was slightly overestimated. Prevalence of preclinical amyloid positivity based on transporting ADNI was further from the prevalence in ARIC‐PET than the raw prevalence of amyloid positivity in ADNI except for white, non‐Hispanic individuals and those with mild cognitive impairment.ConclusionTransport estimators rely on adequately modeling the selection process. Available data may be insufficient to capture selection biases into deeply‐phenotyped convenience samples, particularly for groups who are under‐represented in research. Transport estimators will have greatest utility when applied to samples derived from known sampling strategies, and with increased diversity in dementia research.
Housing characteristics by living arrangement of older adults with cognitive impairment in the United States
Authors: Okoye Safiyyah , Gitlin Laura N. 
Published: January 2025

AbstractBackgroundThe home environment is where daily activities are performed and older adults with and without cognitive impairment spend most of their time. While home safety is a priority for healthcare providers, there is limited understanding of housing characteristics of older adults with cognitive impairment in the United States and whether they differ for those who live alone or with others.MethodsWe draw on data collected from N = 968 community‐living older adults with cognitive impairment who responded to the 2022 National Health and Aging Trends Study, a population‐based national survey that comprehensively assesses characteristics of older adults (≥65 years) and their households in a two‐hour in‐home interview. Housing characteristics reported by self/proxy response were: building type, own or rent, home modifications, and whether living in subsidized housing. Housing characteristics directly observed by interviewers were: home disorder (e.g., flooring problems, pests); home disrepair (e.g., missing siding, broken steps); and street disorder (e.g., litter, graffiti, vacant houses). Cognitive status was measured by a composite measure.ResultsWe found that 26.0% (n = 261) of our sample lived alone, 46.4% (n = 373) lived with a spouse, and 27.6% (n = 334) lived with others (non‐spouse). The prevalence of some housing characteristics differed between the three groups. For example, renting was most prevalent among those who lived with others (non‐spouses); 67.1% vs 48.4% if lived alone and 20.9% if lived with a spouse. Living in an apartment or mobile home (vs house) was more prevalent for those who lived alone (27.1% vs. 15.4% if lived with others (non‐spouse) and 13.5% if lived with a spouse). Other characteristics were similar across groups: approximately 45% (n = 437) of the overall sample lived in a home with internal disorder, 24% (n = 187) in a home with external disrepair, and 20% (n = 202) on a street where disorder was noted (rates did not statistically significantly differ between groups).ConclusionsAlthough the distribution of some housing characteristics differed by living arrangement, 25‐50% in all groups were observed to have housing challenges such as disrepair and disorder. As housing conditions can have significant health consequences and prompt relocation, attention to housing should be part of routine dementia care.
Lifespan cardiometabolic exposures are associated with midlife white matter microstructure: The Bogalusa Heart Study
Authors: Dugan Reagan T , Ramakrishnapillai Sreekrishna , Amant Julia St , Murray Kori , McKlveen Kevin , Naseri Maryam , Madden Kaitlyn , Bazzano Lydia , Carmichael Owen T. 
Published: January 2025

AbstractBackgroundCompartment model analysis of diffusion MRI data provides unique information on the microstructural properties of white matter in the brain. However, studies relating compartment model microstructural measures to longitudinal cardiometabolic health data are rare.MethodIn this study, 130 cognitively healthy participants in the Bogalusa Heart Study (age 55.4 ± 4.5) completed high angular resolution diffusion MRI scans. Neurite orientation dispersion and density imaging (NODDI) and diffusion tensor analysis were performed, and values of neurite density, orientation dispersion, free water fraction, fractional anisotropy, and mean diffusivity were measured in ROIs of highly organized and diffuse white matter. Multiple linear regression models were used to relate the white matter microstructure metrics to demographics and cardiometabolic risk factors.ResultOrganized tracts showed significantly greater NDI, and FWF, and significantly lower ODI, than the diffuse white matter. In organized white matter greater age was associated with greater FWF and lesser NDI, women had lower FWF than men, and African Americans had greater ODI than whites. Worse cardiometabolic measures and brain health were generally associated with lesser NDI. Greater blood pressure in pre‐adulthood was associated with lesser NDI. Within the diffuse white matter, greater age was associated with greater FWF, women had lesser FWF than men, and African Americans had lesser NDI and greater ODI than whites. Worse cardiometabolic measures and brain health were generally associated with greater FWF.ConclusionIn a racially diverse, cognitively healthy, middle‐aged community cohort sample, summary measures from diffusion tensor and compartment model analyses of multi‐shell diffusion MRI data were associated cardiometabolic risk factors from youth to midlife as well as demographic factors.
Incretin receptor agonists rapidly and markedly attenuate multi‐cause insulin resistance in the hippocampal formation from MCI and AD dementia cases
Authors: Talbot Konrad 
Published: January 2025

AbstractBackgroundOnly about 50% of the variance in cognitive decline occurring during Alzheimer’s pathogenesis is attributable to standard AD biomarkers (cerebrocortical Aβ, pathological tau, and atrophy) (Tosun et al., Alzheimer’s Dement. 18: 1370, 2022). Other factors contributing to such decline include brain insulin resistance (BIR). Levels of its biomarker, pathological IRS‐1 pS616 (insulin receptor substrate‐1 phosphorylated at S616), accounts for as much as 47% of the variance in episodic memory scores in an elderly population we studied (Talbot et al., JCI 122: 1316, 2012). To better understand BIR in Alzheimer’s disease (AD), its proximal causes, and if incretin receptor agonists (IRAs) can reduce BIR, we extended our earlier ex vivo work on the hippocampal formation (HF) of non‐cognitively impaired (NCI) and AD dementia (ADd) cases to non‐amnestic MCI (naMCI) and amnestic MCI (aMCI) casesMethodDiverse brain banks donated fresh frozen HF tissue from NCI, naMCI, aMCI, and ADd cases (n = 10 per diagnostic group) who were age‐ and ‐sex matched whites with no history of diabetes and low postmortem intervals (m ± SD = 6.75 ± 2.2 h). Using our ex vivo stimulation protocol (Talbot et al., 2012), tissue sections were tested for insulin‐induced phosphorylation of insulin signaling and regulating enzymes after 30 min incubations in 0, 1, or 10 nM insulin with or without 30 min preincubation in 100 nM of liraglutide activating GLP‐1 (glucagon‐like peptide‐1) receptors, [D‐Ala2]‐GIP activating GIP (gastric inhibitory peptide) receptors, or Peptide 19, a dual IRA activating both GLP‐1 and GIP receptors. Statistical significance was defined as p < 0.05.ResultHF responsiveness to 1 and 10 nM insulin was significantly reduced in both the MCI and ADd samples. Pretreatment with each of the IRAs tested virtually restored normal insulin responsiveness in both MCI groups even though the proximal cause of insulin resistance in naMCI differed from aMCI and ADd. Only the dual IRA, however, significantly increased insulin responsiveness in ADd samples.ConclusionIRAs reaching brain neurons can virtually eliminate hippocampal insulin resistance in naMCI and aMCI cases, but significantly reducing such resistance in ADd cases appears to require a dual IRA.
Usefulness of Safinamide in Lewy Body Dementia
Authors: Oliveros‐Cid Antonio , Moreno Lisbed Rondon , Martinez Esther Sierrra , Beltran Pablo Navarro , Miguel Nicolas Fayed , Lopez Maria Angeles Cid , Salvador Fernando Jarauta , Oliveros‐Juste Antonio 
Published: January 2025

AbstractBackgroundThe therapeutic management of dementia with Lewy bodies (LBD) is a challenge given the high sensitivity to drugs in this disease. This is particularly sensitive with regard to the management of parkinsonism. In particular, treatment of motor symptoms with levodopa or dopaminergic agonists poses a risk of worsening cognitive and behavioral symptoms. Safinamide is a drug with several mechanisms of action (dopaminergic and non‐dopaminergic), authorized to treat idiopathic Parkinson’s disease, complementary to levodopa alone or in combination with other antiparkinsonian drugs, in patients with fluctuations. The scarce literature on the use of safinamide in MCI shows benefits with few side effects.MethodWe present 4 cases of patients with Dementia with Lewy Bodies (DLB) evaluated in our clinics, where safinamide improved motor symptoms without worsening cognitive or behavioral symptoms. MDS‐UPDRS (I, II, III, IV), RBDSQ, CGI‐S, CGI‐C, SEADL, PGI‐S, PGI‐C, MDS‐NMS, MoCA, CDT, RBANS were performed before and after at least 3 months of Safinamide therapy.ResultThe study included 3 males and 1 female aged between 63 and 78 years, diagnosed with DLB 1 to 4 years before starting Safinamide treatment. The most evident parkinsonian symptoms were axial rigidity, antecollis, camptocormia, simple and complex motor fluctuations, and freezing of gait. All of them exhibited fluctuations in both motor and cognitive evolution, with characteristic cognitive decline and visual hallucinations. All had previously received treatment with L‐dopa and were on acetylcholinesterase inhibitor therapy. UPDRS‐III scores ranged from 24 to 43 points. Initial safinamide dose: 50 mg/24 h. Final safinamide dose: 100 mg/24 h. Mean improvement in UPDRS: 17%.ConclusionIn these 4 isolated cases, we observe that safinamide treatment improved axial and appendicular rigidity without worsening cognitive or behavioral symptoms. It could be considered as a safe and effective option in DLB, even in patients with insufficient improvement with L‐dopa, and without clinically significant interactions with acetylcholinesterase inhibitors. Further extensive studies would be necessary to confirm this preliminary observation.
Social vulnerability and cognitive functioning among older adults in the United States National Health and Nutrition Examination Survey
Authors: Arboleda‐Merino Laura C , Walker Erika , Fansler Samuel D , Park Sung Kyun , Bakulski Kelly M. 
Published: January 2025

AbstractBackgroundNumerous social factors, including socioeconomic status, education, and healthcare access, influence health outcomes in older adults. Despite the potential clinical utility of assessing social vulnerability, it is not routinely evaluated in clinical assessments of older adults. This study aims to investigate the association between cognitive decline and a comprehensive social vulnerability index, defined as an index comprising many social factors such as income, education, and housing tenure.MethodThe study used data from the US National Health and Nutrition Examination Survey (NHANES) 1999‐2002 and 2011‐2014 cross‐sectional cycles. Cognition was assessed using the Digit Symbol Substitution Test (DSST, scores 0‐117) among participants 60+ years of age. Social vulnerability was assessed using a modified Social Vulnerability Index (SVI) based on components such as race/ethnicity, household income, education, health insurance, employment, housing tenure, and food security, with scores indicating the degree of social vulnerability ranging from 0 (least vulnerable) to 7 (most vulnerable). Associations of social vulnerability with cognitive function (adjusted for sex, age, and NHANES cycle) were analyzed by generalized linear models.ResultParticipants with complete cognition and demographic measures (n = 5,272) were of mean age 70.5 years, 51.1% female, 68.0% had completed high school or above, and 55.0% were non‐Hispanic White. The mean DSST score was 43.3 (SD = 18.1), and 24.8% had low cognitive performance (lowest 25th percentile; DSST<31). The mean SVI was 2.55 (SD = 1.67). In adjusted analyses, each additional social deficit—a one unit increase in the Social Vulnerability Index—was associated with almost 6 points lower DSST score (β: ‐5.97; 95% Confidence interval (CI): ‐6.20, ‐5.74; p <0.0001).ConclusionOur results suggest that increasing social vulnerability, defined by using a social vulnerability index incorporating many social factors, is associated with lower cognitive functioning among older adults. The results suggest the need for further investigation into the relationship between social vulnerability and cognition, with a focus on exploring potential interventions to mitigate its impact.
The Multiple Neurovascular Pathologies in Older Adults Living with and without Peripheral Insulin Resistance
Authors: Mehta Rupal I. , Capuano Ana W. , Biswas Roshni , Bennett David A. , Arvanitakis Zoe 
Published: January 2025

AbstractBackgroundThe overall odds and permutations of neurovascular pathologies (NVP) in older adults living with diabetes or peripheral insulin resistance (PIR) have not been comprehensively investigated. Moreover, specific biological mechanisms linking apolipoprotein E (ApoE) genotype, NVP, and Alzheimer’s disease (AD) remain unclear. Here, we examine the odds and permutations of NVP in older adults with PIR in relation to those without.Materials and MethodThis study evaluated older adults who were followed in longitudinal studies of aging and underwent autopsy. Annual clinical evaluations included data to classify PIR status by history, direct medication inspection, and/or blood hemoglobin A1C level (≥6.5%). Neuropathological examinations were systematically performed upon death and included evaluation for NVP and AD pathology. Logistic regression models were used to analyze the association of PIR with the presence of moderate to severe NVP as well as NVP permutations, respectively, in persons with or without ApoE ε2 or ε4 allele and/or AD.ResultA total of 1997 older adults (404 with PIR) were studied. Participants died at mean age of 89 years (SD = 6.81 years). Overall, persons with PIR had higher odds of chronic macroinfarcts (odds ratio (OR), 1.33 [95% CI, 1.08–1.65]) and chronic microinfarcts (OR, 1.37 [95% CI, 1.10‐1.71]) but exhibited lower odds of CAA (OR, 0.74 [95% CI, 0.59–0.92]). Analysis of NVP permutations revealed that single pathologies (with absence of others) were most common, followed by combined microinfarcts plus macroinfarcts. Persons with PIR had higher odds of microinfarcts alone (OR, 1.56 [95% CI, 1.02–2.37]), macroinfarcts alone (OR, 1.54 [95% CI, 1.01‐2.35]), and combined microinfarcts with macroinfarcts (OR, 2.02 [95% CI, 1.21‐3.35]). However, the odds of microinfarcts were not significantly higher in persons with PIR when controlling for the presence of ApoE ε2 allele, and only the presence of both types of infarcts together was significantly higher in PIR after controlling for the presence of ApoE ε4 allele with or without AD.ConclusionThis study examined multiple NVP in persons with and without PIR. It shows that older adults living with PIR, relative to those without, have higher odds of microinfarcts and macroinfarcts in the absence of CAA, atherosclerosis and arteriolosclerosis.