bluuebunny/crossref_metadata_2025_split huggingface dataset:
Caregivers of people with Alzheimer’s Disease in Puerto Rico 2021 ‐ 2022: A panoramic view of their epidemiological profile, health status and quality of life
Authors: Cabrera Alex , Felici Marcos E. , Cartagena Marianne 
Published: January 2025

AbstractBackgroundAlzheimer’s Disease (AD) is the fourth leading cause of death in Puerto Rico (PR), with an estimated prevalence of 14%. Caregivers are an essential part in the management and care of people with AD. Providing care for a person with Alzheimer can change over time and can become a challenge for the caregivers. For this reason, self‐care is one of the most important things that a caregiver must do. The main objective of this research is to perform an epidemiological profile of caregivers for people with Alzheimer in PR and analyze the health status and quality of life variables collected by the PR Behavioral Risk Factor Surveillance System (PRBRFSS).MethodA descriptive cross‐sectional study was carried out using the PRBRFSS data for 2021‐2022. Univariate analysis was performed to obtain an epidemiological profile of caregivers for people with Alzheimer in Puerto Rico, as well as to analyze health status and quality of life variables.ResultFor 2021‐2022, according to the PRBRFSS, a total of 318,924 people in Puerto Rico identified themselves as caregivers. Among these, 16.9% reported being a caregiver of a person with Alzheimer. Approximately 23.0% of the caregivers for people with AD were in the 55‐64 age group, 63.9% were women, 41.4% were married, 70.6% had education above high school, and 47.2% had an annual income of $25,000 or more. In terms of health and quality of life, 23.1% reported having bad or poor health, 23.6% reported having depression, and 60.7% reported at least one comorbidity. Likewise, 24.4% reported difficulty seeing, 23.1% walking or ascending stairs, 18.6% concentrating or remembering, 11.0% performing tasks alone, 8.0% hearing, and 6.5% dressing or taking a bath.ConclusionCaregiving for a person with Alzheimer becomes more challenging over time due to the evolution of symptoms and the level of care needed. For this reason, caregivers need to maintain good health and reduce the risk of burnout. This research demonstrates the importance of continuing to create programs and support groups for caregivers of people with Alzheimer to encourage self‐care and improve their health and quality of life.
Relation Between Markers of Systemic Inflammation, White Matter Lesions, and Cognitive Performance in Late Adulthood
Authors: Jain Shivangi , Lesnovskaya Alina , Wan Lu , Molina‐Hidalgo Cristina , Huang Haiqing , Marsland Anna , Grove George , Oberlin Lauren , Kang Chaeryon , Kramer Arthur , Hillman Charles , McAuley Edward , Burns Jeffrey M , Vidoni Eric D , Sutton Brad , Erickson Kirk I. 
Published: January 2025

AbstractBackgroundAging is associated with heightened systemic inflammation, decline in selective aspects of cognition, and an increase in white matter lesions (WMLs). Both WMLs and systemic inflammation have been related to cognition. However, it is not clear how they interdependently relate to cognitive aging. In this study we examined whether WMLs mediate the relation between markers of systemic inflammation and cognition in late adulthood.MethodBaseline data from the randomized clinical trial “Investigating Gains in Neurocognition in an Intervention Trial of Exercise” (IGNITE) were used, which included 598 healthy older adults (mean age=69.9±3.75 years). Interleukin 6 (IL‐6) and Tumor Necrosis Factor Alpha (TNF‐α) were included as markers of systemic inflammation. A confirmatory factor analysis of cognitive performance resulted in factors measuring episodic memory (EM), processing speed (PS), working memory (WM), attentional control (AC), and visuospatial function (VF). WML volumes were computed from FLAIR and T1 scans using UBO detector. Mediation models were run with age, sex, years of education, and study site included as covariates.ResultHigher levels of IL‐6 were associated with more WMLs (b = 0.12, p < 0.001) as well as lower scores on all cognitive factors (all p < 0.03). In contrast, higher levels of TNF‐ α were associated with more WMLs (b = 0.10, p < 0.05) but not with any of the cognitive measures (all p > 0.3). More WMLs were associated with poorer PS, WM, AC, and VF (all p < 0.03), but not EM (all p > 0.05). Further, associations between IL‐6 and measures of PS, WM, AC, and VF were statistically mediated by WMLs (all b = ‐0.01, all p < 0.05).ConclusionThese findings suggest that markers of systemic inflammation might lead to poorer cognitive performance by impacting WMLs. The differences between IL‐6 and TNF‐α with cognition highlight the need for more research to understand how different cytokine pathways relate to cognition. Our results are important for building a mechanistic framework to understand the interplay between inflammation, WMLs, and cognition and could inform the development of targeted interventions focusing on regulating cytokines to support brain health and cognitive aging.
Performance of a new instrument designed to assess medication use in cognitive impairment and dementia: A cross‐sectional analysis
Authors: Sharma Rishabh , Lee Linda , Chang Feng , Patel Tejal 
Published: January 2025

AbstractBackgroundThe Medication Review in Cognitive Impairment and Dementia (MedRevCiD) checklist is a new tool designed to assist health care professionals in optimizing medication use in individuals with Mild Cognitive Impairment (MCI) or dementia. It consists of 6 domains, each of which addresses a specific medication use issue such as medication management and adherence. The primary objective of this study was to compare the mean number of drug‐related problems (DRPs) identified with MedRevCiD Checklist to the Medication Appropriateness Index (MAI) in older adults attending a primary care‐based memory clinic.MethodsA cross‐sectional analysis was conducted at a Multi‐speciality Interprofessional Team‐based (MINT) memory clinic. A medication review was conducted by applying the MAI initially, followed by application of the MedRevCiD checklist to assess medication use and to identify DRPs for participants enrolled in the study. The Wilcoxon signed‐rank test was used to determine if a significant difference exists in the average number of DRPs per person as identified through MedRevCiD compared to MAI.ResultsA total of 44 participants with a mean age of 80.2 ± 6.2 years enrolled in the study. Of the participants, 45.5% (20/44) were female, 36.4% (16/44) had mild cognitive impairment, 20.5% (9/44) had mixed dementia and 11.4% (5/44) had vascular dementia. Participants had an average of 6.7 ± 3.4 comorbidities, most commonly hypertension (63.6%, 28/44), hyperlipidemia (31.8%, 14/44), chronic kidney disease (27.2%, 12/44) and obstructive sleep apnea (25%, 11/44). Participants were taking a median of 7.5 medications (interquartile range 6) per person. A total of 134 DRPs were identified with the use of the MedRevCiD as compared with 81 with the use of the MAI (mean 3.05 ± 4.0 with MedRevCiD vs 1.84 ± 2.9 with MAI; p<0.001). Over 50% of the DRPs identified with the MedRevCiD fell within Domain 6 which focuses on optimizing medication use, while the majority of the DRPs identified from the MAI were focused on drug/disease interactions.ConclusionFindings provide insight into the frequency of DRPs among older adults with MCI or dementia. The MedRevCiD checklist proved to be a valuable tool with heightened ability in detecting DRPs in this population.
Characterising subpopulations of patients with Alzheimer’s disease dementia who have high healthcare utilisation and costs
Authors: Edwards Sophie , Trepel Dominic , Ritchie Craig W , Hahn‐Pedersen Julie Hviid , Chan Mei Sum , Bray Benjamin D , Clark Alice , Wichmann Christian Ahmad , Evans Marc 
Published: January 2025

AbstractBackgroundHow and why healthcare utilisation and costs vary between patients with Alzheimer’s disease dementia (ADD) is not well understood but is important in ensuring that efforts to improve the diagnosis and treatment of ADD are prioritised effectively. We aimed to investigate variation in healthcare resource utilisation (HCRU) among patients with ADD in England and identify the clinical and demographic factors which characterise subpopulations with the highest HCRU.MethodThis was a retrospective cohort study using Discover, a linked electronic health record database of 2.8 million residents in London, England. We identified individuals with ADD using diagnostic codes and estimated HCRU and total healthcare costs over up to 9 years of follow up (2010‐2019). Individuals included in the 2019 cross‐section were stratified into cost quintiles, and K‐medoids clustering was used to identify subpopulations with high costs.ResultWe identified 18,116 individuals with ADD between 2010 and 2019 (Table 1). Costs in the highest HCRU cost quintile in 2019 accounted for 56% of all healthcare costs in the ADD population, were approximately 20 times higher than the lowest cost quintile (£13,665 vs. £678 per patient per year [ppy]) and were largely attributed to hospital admissions (Figure 1). Individuals in the higher cost populations tended to be older, male, have a higher comorbidity burden and a lower median survival than those in the lower cost populations. The three groups with the highest costs identified by the cluster analysis had substantial comorbidity burden, with more than 65% of individuals having four or more comorbidities (Figure 2). The most common comorbidities were cardiometabolic diseases, chronic kidney disease, and frailty. The costs in the highest cost cluster were more than double the cluster with lowest costs (£6,355 vs. £3,160 ppy).ConclusionHealthcare utilisation and costs in individuals with ADD vary widely, with a large proportion of costs being attributable to a minority of patients with multiple comorbidities, particularly cardiometabolic diseases and frailty. Health systems should focus on patients with clinical profiles associated with high costs in efforts to improve the timely diagnosis and treatment of ADD and mitigate the financial costs of ADD on patients, health systems, and society.
Social Support, Isolation, and Cognitive Health among LGBTQ+ Older Adults in the United States
Authors: Lampe Nik M. , McKay Tara 
Published: January 2025

AbstractBackgroundLack of social support and social isolation are risk factors for poor cognitive health. Lesbian, gay, bisexual, transgender, and queer (LGBTQ) older adults consistently report higher levels of isolation and less social support in population studies. In this study, we test the effects of support for LGBTQ+ identity and feelings of social isolation on subjective cognitive health in a cohort of LGBTQ+ older Americans.MethodWe use Wave 1 data from the Vanderbilt University Social Networks, Aging, and Policy Study (VUSNAPS). VUSNAPS recruited 1,256 LGBTQ+ adults aged 50+ in four US states between 2020‐2021. Subjective cognitive problems were measured using a 15‐item scale capturing problems with memory, cognition, and functioning. Chi‐square tests and logistic and Poisson regressions were used to test associations between levels of support from family, coworkers, neighbors, and number of days feeling isolated in the last 7 days with the number of cognitive difficulties reported and reporting >4 cognitive difficulties. Analyses control for gender, race, education, employment status, personal income, age, and married/partnered status.ResultAbout 11% of respondents reported having >4 cognitive difficulties. Compared to respondents reporting <4 cognitive difficulties, respondents reporting >4 cognitive problems were more likely to be bisexual (16.8 vs 10.6%, p<.05), report personal income lower than US median personal income (16.2% vs 7.5%, p<.001), and be working less than full time (13.6 vs 7.3%, p<.001). Respondents with LGBTQ+ supportive families and coworkers reported significantly fewer cognitive problems (IRR = 0.698, p<.001; IRR = 0.846, p<0.1), and those with supportive families were 43.2% less likely to report >4 cognitive problems (p<.01). Presence of unsupportive families, coworkers, neighbors, and friends were significantly correlated with feelings of social isolation (p<.01 for each). One third of respondents (35.0%) reported feeling isolated ≥4 of the last 7 days. Respondents who reported feeling isolated ≥4 days were two‐and‐a‐half times more likely to report ≥4 cognitive problems (OR = 2.67; p<.001).ConclusionWe find associations between subjective cognitive health and LGBTQ‐specific social support in a large sample of older LGBTQ+ adults. Availability of social support and risk of social isolation should be assessed when administering cognitive screenings for LGBTQ+ older patients.
Multivariate genomic analyses of frailty reveal the unique importance of cognitive and multimorbidity pathways for aging‐related health outcomes
Authors: Foote Isabelle F , Flint Jonny P , Fisk John D , Karakach Tobias K , Rutenberg Andrew , Martin Nicholas G , Lupton Michelle K , Cox Simon R , Luciano Michelle , Rockwood Kenneth , Grotzinger Andrew D 
Published: January 2025

AbstractBackgroundFrailty is a complex clinical state that is associated with poorer health outcomes and increased dementia risk in older adults. It is routinely measured using the Frailty Index, which is a proportional score based on the number of ‘deficits’ that an individual has. Whilst such measures are useful for risk assessment, the aggregation of highly heterogeneous deficit profiles in genetic studies may obscure important insights into the underlying biology of frailty.MethodWe used Genomic Structural Equation Modelling to model shared genetic signal between 30 deficits from the Frailty Index using summary data from genome‐wide association studies (GWAS). This involved conducting a multivariate GWAS to identify genomic risk loci associated with each of the latent frailty factors in our model. We used polygenic risk scores (PRS) to test the predictive accuracy of the latent factors for detecting frailty status in 3 external cohort studies. Finally, we tested the genetic correlation between our latent frailty factors and >50 aging‐related outcomes, including dementia.ResultThe genetic architecture of the frailty deficits was best captured by a general factor influencing all 30 deficits, plus 6 additional latent factors representing genetic overlap between distinct subsets of deficits that were uncorrelated with the general factor. These 6 factors can be broadly described as reflecting pathways linked to social isolation, unhealthy lifestyle, multimorbidity, metabolic/respiratory status, cognition, and disability. GWAS conducted to measure the effects of individual genetic variants on these frailty factors identified 408 genomic risk loci. Our PRS analyses demonstrated consistent evidence that shared genetic pathways between frailty deficits linked to multimorbidity and cognition, but unique of the general frailty factor, are particularly important for predicting frailty status. Genetic correlation analyses further highlighted a significant genetic association between frailty pathways linked to cognition and Alzheimer’s disease (rg = 0.32, SE = 0.07, p = 5.58×10−06).ConclusionOur findings provide novel insights into the characterization of general and specific pathways within the frailty state at the genetic level. We demonstrate how refining our knowledge of frailty, particularly in relation to multimorbidity and cognitive impairment, may help to stratify frail individuals at increased risk of developing dementia or other adverse health outcomes.
Risk factors for subjective and objective cognitive decline in sexual minority older adults
Authors: Manca Riccardo , Flatt Jason D. , Venneri Annalena 
Published: January 2025

AbstractBackgroundSexual minority older adults (SMOAs) report subjective cognitive decline (SCD) more than heterosexual older adults (HOAs). Inconsistent findings have emerged about the risk of cognitive decline in SMOAs. This study aimed to compare the impact of multiple psycho‐social risk factors on both objectively assessed and subjectively reported cognitive decline between HOAs and SMOAs.MethodTwo samples of self‐identified HOAs (n = 4180) and SMOAs (n = 92) who completed Waves 8 and 9 of the English Longitudinal Study of Ageing were selected. Reliable change indices for episodic and semantic memory were created to assess longitudinal cognitive changes. SCD was self‐assessed for both memory and general cognition. Mental and cardiovascular health, marital status, loneliness, and socio‐economic status (SES) were investigated as risk factors for cognitive decline. The effect of each risk factor and their interaction effects with sexual orientation on memory changes and SCD were tested, respectively, with general linear and logistic regression models. Age, education, and sex were included as covariates. A sensitivity analysis was carried out in a sub‐sample (n = 92, per group) matched for demographics.ResultCognitive changes and rates of SCD were similar between SMOAs and HOAs. All risk factors, apart from marital status, were associated SCD risk, while only SES was associated with decline in episodic memory (β = .01, p = .038). A SES×sexual orientation interaction was found for semantic memory (β = ‐.06, p = .042); among those in the lowest quintile, SMOAs had better semantic memory preservation over time than HOAs. A sensitivity analysis found among those in the highest quintile, SMOAs had worse semantic memory decline than HOAs.ConclusionSCD was associated with a multitude of risk factors, in line with previous evidence of SCD as a heterogeneous construct. This was similar between SMOAs and HOAs. Longitudinal changes in semantic memory were, instead, differentially impacted by SES in the groups. Sensitivity analysis confirmed a potential lack of protective effect in SMOAs, although the groups did not differ for SES. These findings may be interpreted within the framework of material deprivation, which is more likely among SMOAs and may contribute to their cognitive decline more severely than in HOAs.
Comparison of tau‐PET tracers for in vivo Braak staging: the HEAD Study
Authors: Macedo Arthur C. , Therriault Joseph , Rahmouni Nesrine , Servaes Stijn , Wang Yi‐Ting , Tissot Cécile , Lussier Firoza Z , Arias Jaime Fernandez , Socualaya Kely Monica Quispialaya , Hosseini Seyyed Ali , Ferreira Pamela C.L. , Bellaver Bruna , Ferrari‐Souza João Pedro , Aguzzoli Cristiano Schaffer , Povala Guilherme , Pascual Belen , Gordon Brian A. , Lowe Val J. , Oh Hwamee , soleimani‐meigooni David N. , Baker Suzanne L. , Pascoal Tharick Ali , Rosa‐Neto Pedro 
Published: January 2025

AbstractBackgroundTau‐PET tracers allow for in vivo Braak staging of individuals in the Alzheimer’s disease (AD) continuum. The impact of tracers’ characteristics for Braak staging using tau‐PET remains unclear. Therefore, we performed a head‐to‐head comparison of Braak staging using first‐ and second‐generation tau‐PET tracers.MethodWe assessed 51 cognitively unimpaired (CU) and 49 cognitively impaired participants (mean [SD] age 69.4 [7.5] years) with at least two tau‐PET ligands ([18F]MK6240, [18F]AV1451, and/or [18F]RO948) at McGill University, as part of the HEAD study. We calculated standardized uptake value ratios (SUVR) in Braak‐like regions of interest (ROI) for each ligand and investigated their association using Spearman’s correlation. Thresholds defined the presence of tauopathy in each Braak ROI, which was used to assign a Braak stage to each participant. Finally, we assessed the agreement between the Braak staging provided by each tracer, both for the traditional (using separate Braak stages – 0, I, II, III, IV, V, and VI) and simplified (using joint Braak stages – 0, I‐II, III‐IV, and V‐VI) frameworks.ResultIn all Braak ROIs, we found positive correlations between the SUVR values of the three tracers (Figure 1). The strongest correlation was between [18F]MK6240 and [18F]RO948 in Braak II (r=0.94), and the weakest between [18F]AV1451 and [18F]RO948 in VI (r=0.51). Inter‐tracer agreement regarding the latest stage of abnormality was substantial or nearly perfect between pairs of tracers but moderate between the three tracers (Figure 2A). The simplified framework presented greater agreement compared to traditional Braak staging, except between [18F]MK6240 and [18F]RO948. At the ROI level, the lowest agreements were observed for Braak II and I‐II, when [18F]MK6240 and [18F]RO948 were compared to [18F]AV1451 (Figure 2B‐C). [18F]AV1451 had the highest probability of overestimating the Braak stage assigned by [18F]MK6240 and by [18F]RO948, especially at earlier stages (Figure 3).ConclusionThe ligands presented moderate to nearly perfect agreement for in vivo staging of AD severity. Off‐target binding of [18F]AV1451 to the choroid plexus might explain disagreements at early stages. Overall, slight improvements in agreements were achieved with the simplified framework, as observed in histopathological staging.
DTI and DKI differences in the fornix microstructure associated with sleep apnea in cognitively normal patients
Authors: Figueredo Luisa F , Chen Jenny , Parekh Ankit , Bubu Omonigho M , Fieremans Els , Osorio Ricardo 
Published: January 2025

AbstractBackgroundObstructive sleep apnea (OSA) is a complex and heterogeneous condition associated with chronic physiological and neuropsychological disturbances (1–4). One notable neuropsychological effect observed in OSA patients is memory impairment (2,5). Additionally, some reports suggest that OSA may be associated with Alzheimer’s Disease (AD) (4). Memory consolidation is regulated through a cohesive network of structures, including the hippocampus, fornix, anterior thalamus, and mammillary bodies (6). Diminished mammillary body and hippocampal volume have been described in OSA patients compared to normal subjects, suggesting potential circuit changes (2). This study aims to comprehensively evaluate the effects of OSA on the fornix microstructure in cognitively normal patients, measured by DTI and DKI variables.MethodsOne‐night polysomnography, neurocognitive assessment, and brain diffusion MRI (dMRI) with DTI (Diffusion Tensor Imaging)/DKI (Diffusion Kurtosis Imaging) protocol were performed in 145 individuals with a mean age of 65 [61‐70] and a mean Mini‐Mental‐Score (MMSE) of 29 [28‐30]. OSA measurements included the Apnea‐Hypopnea Index (AHI) and variables related to sleep duration and fragmentation. Microstructural properties of white matter tracts (DTI. DKI (8–10)) were estimated after preprocessing dMRI using DESIGNER pipeline (https://arxiv.org/abs/2305.14445).ResultsA correlation matrix between AHI3% and AHI4% revealed positive correlations with Axial Kurtosis (AK) and axial diffusion (ADi), and negative correlations with Mean Diffusivity (MD) and Mean Kurtosis (MK). Figure 1C‐1D illustrates a significant difference between patients with and without OSA. Associations between AHI3% and AHI4% and log Fornix FA, MD, RD, ADi, MK, RK, AK, De″, De⊥ and Da were tested while adjusting for age, sex, hypertension, APOe4, BMI, and N1%, N3%. Unadjusted linear regression models appear in Figure 2, where only AK (Figure 2D), and MK (Figure 2F) showed statistical significance. Finally, multivariable‐adjusted models for AHI3% revealed a significant association with AK and MD only (Table 1).ConclusionOSA may be associated with microstructural changes in the fornix in cognitively normal patients, particularly in those with severe OSA. This study might contribute as a baseline for future works that include progression to AD.