bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gender differences in dementia risk factors and cognitive performance in the recruitment process of a FINGER‐like multidomain trial to prevent cognitive decline, the CITA GO‐ON trial
Authors: Tainta Mikel , Barandiaran Myriam , Ecay Mirian , Iriondo Ane , Estanga Ainara , Altuna Miren , Lopez Carolina , Saldias Jon , Garcia‐Sebastian Maite , Marta Cañada , de Arriba Maria , Reparaz‐Escudero Imanol , Ros Naia , Domper Jara , Mateo‐Abad Maider , Martinez‐Lage Pablo 
Published: January 2025

AbstractBackgroundSex and gender affect Alzheimer’s and Dementia differently. Some studies show that women are diagnosed at a later stage. This represents an essential challenge for healthcare and makes research challenging as gender biases may impact participant selection for clinical trials. We examined recruitment for the CITA GO‐ON trial, a lifestyle intervention trial to prevent cognitive decline.MethodThe CITA GO‐ON study (ClinicalTrials.gov, NCT04840030) is a population‐based randomized clinical trial that aims to evaluate the effectiveness of a multidomain lifestyle intervention in preventing cognitive decline. Participants are older adults (60‐85 years) at high risk of dementia (CAIDE dementia risk score ≥ 6) using the Cognitive Change Index and Fototest and Memory Alteration Test (T@M) screening tools. Interested individuals fill out a REDCap online form that allows pre‐selection (by estimated CAIDE) for an individualized face‐to‐face screening visit to confirm eligibility. The descriptive analysis of the recruited sample and the comparison of dementia risk factors and cognitive tool performance between genders are presented.ResultOver 2500 subjects showed interest in the study by January 2022 through an online pre‐screening questionnaire. Of these, 60.4% were women (mean age, 67.52 years). After completing the online pre‐selection phase and the screening visit (n = 845), the representation of women dropped to 52.7% and 50.5%, respectively. Table 1 shows some preliminary data on the current recruitment process, which will be finished by Q2 2024. Preselected women have a lower mean CAIDE dementia risk score than men (p<0.001). Women also have fewer years of education and are less physically active. Blood pressure is higher in men. Although both sexes similarly report memory complaints, women perform better in cognition screening tools.ConclusionWomen seem to be more interested in initiatives promoting healthy aging. We have observed differences in dementia risk factors between men and women that could be related to sociocultural gender differences in this range of age. As previous studies have shown, in our study women perform better on brief cognitive tests, making them less likely to be selected. This highlights the importance of considering sex and gender for future analysis, trial designs, and recruitment strategies.
Multilevel measures of socioeconomic disparities impact brain health and dementia across the Americas
Authors: Legaz Agustina , Gonzalez‐Gomez Raul , Migeot Joaquín , Escudero Stefanie Danielle Pina , Altschuler Florencia , Ibañez Agustin 
Published: January 2025

AbstractBackgroundSocioeconomic disparities (SED) influence brain health and dementia. Latin America (LA) is characterized by high SED and a disproportionate prevalence of Alzheimer’s disease (AD) and frontotemporal lobe degeneration (FTLD) compared to high‐income populations like the United States (US). However, the impact of SED on brain reserve across neurocognitive pathways related to aging and dementia in LA remains unknown.MethodWe evaluated how SED impact brain volume and functional connectivity in participants with AD, FTLD, and controls from LA (Argentina, Chile, Colombia, Mexico, Peru) and US, triangulating three SED measures: (i) educational attainment (n = 1410), (ii) cross‐culturally harmonized social determinants of health (SDH; n = 2324), and (iii) structural inequality (GINI index; n = 2135). Data were obtained from the Multi‐Partner Consortium to Expand Dementia Research in Latin America [ReDLat], the Alzheimer’s Disease Neuroimaging Initiative [ADNI], and the Laboratory of Neuro Imaging [LONI]. We controlled for multiple potential confounders (e.g., scanner, TIV, age, sex).ResultAcross the three studies, SED was associated with impaired neurocognitive outcomes, especially in LA compared to the US. (i) Lower educational attainment was associated with reduced fronto‐temporo‐posterior brain volume and connectivity across all LA groups (Fig 1; multiple regressions and kruskall‐wallis comparisons, P<0.05 TFCE correction). (ii) Adverse SDH including childhood SDH, discriminated between controls, AD, and FTLD in LA, affecting patients’ cognition, severity, and functionality (Fig 2A‐B; XGBoost binary logistic regression). Also, adverse SDH induced reduced volume and connectivity (VBM and whole‐brain analysis, both P‐FDR<0.05) across LA groups (Fig 2C). Finally, (iii) Higher structural income inequality at both the state/country levels was associated with reduced volume and connectivity in the temporo‐parietal, cingulum‐limbic, and cerebellar regions, with more pronounced effects in LA groups (Fig 3; multiple regressions with grey matter volume [w‐maps, P‐FWE<0.05] and connectivity [wSDM coefficients, P‐Bonf<0.05]).ConclusionFindings suggest that exacerbated SED, observed in more diverse samples from LA, differentially and negatively impact neurocognitive factors in aging and dementia. This aligns with the notion that SED diminish brain and cognitive reserve, amplifying dementia burden. Tailored, local‐sensitive models are required to leverage the impact of SED in brain health and dementia, particularly in underrepresented populations like LA.
Circulating metabolomic profile of the MIND diet and its relation to cognition in middle‐aged and older adults
Authors: Chen Hui , Shen Jie , Tao Yang , Zhang Yaodan , Gao Mengyan , Ma Yuan , Zheng Yan , Zong Geng , Lin Qing , Tong Lusha , Yuan Changzheng 
Published: January 2025

AbstractBackgroundDietary factors are modifiable risk factors for dementia. In particular, the Mediterranean‐DASH Intervention for Neurodegenerative Delay (MIND) diet has been associated with better cognitive function and lower risk of dementia. However, circulating metabolomic characteristics of the MIND diet and its associations with cognitive function remains unclear.MethodIn the current study, 45906 UK Biobank (UKB) participants (mean age: 56.4 years) were separated into a discovery cohort and an internal prospective validation cohort, and 6193 Whitehall II (WHII) study participants (mean age: 56.8 years) constituted an external validation cohort. We identified the metabolites associated with the alternate MIND diet score (aMIND) using linear regression models, and Benjamini‐Hochberg method was applied to control false discovery rate. We constructed a metabolomic signature score of the MIND diet using elastic net model and assessed the potential mediating role of the metabolomic signature in the associations of the aMIND with cognitive outcomes in the two cohorts.ResultThe aMIND showed significant associations with 149 out of 168 (89%) metabolites in the UKB discovery cohort, and 47 of these associations were also replicated in both the internal validation cohort and the external validation cohort, including 38 lipoprotein subclass, 4 fatty acid, 1 cholesterol, 1 inflammation, 2 lipoprotein particle size, and 1 triglyceride measures. The metabolomic signature score based on the selected metabolites was significantly correlated with the aMIND (Pearson’s r = 0.36, 0.31, and 0.27 in the discovery, internal validation and external validation cohort). In the UKB (491 incident dementia cases during a median follow‐up of 11.8 years), but not WHII (169 in 17.8 years), the MIND metabolomic signature score significantly mediated the association of the aMIND and incident dementia by 45%. In the WHII, association between the aMIND and cognitive function was partially mediated by the metabolomic signature (proportion = 19%, P for mediation = 0.039).ConclusionMIND diet was favourably associated with a panel of metabolites, and a MIND diet metabolomic signature score partially mediated the observed associations between MIND diet adherence and incident dementia and cognitive function.
Association between leisure activities and quality of life in older adults with dementia who use day care rehabilitation services
Authors: Kasuya Masashi , Tanaka Naofumi , Wang Yin‐Jung , Ouchi Yoshitaka 
Published: January 2025

AbstractBackgroundDay care services provide not only physical exercise to improve physical function, but also a variety of activities. These activities are expected to enhance leisure activities of users and improve their QOL. However, the relationship between QOL and the presence of leisure activities in day care service users with dementia has not been clarified.MethodParticipants were 76 older adults (47 women, mean age 82 ± 7 years) aged ≥65 receiving day care services with MMSE scores between 10 and 23. They were administered a series of questionnaires on leisure activities and their quality of life was assessed using the Quality of Life in Alzheimer’s Disease (QOL‐AD). Other assessments included the Geriatric Depression Scale‐15 (GDS‐15) and the Apathy Evaluation Scale (AES). The participants were divided into two groups based on whether or not they participated in leisure activities. Age, gender, nursing care level, MMSE score, GDS‐15 score, AES score, and QOL‐AD score were compared between the two groups. A covariance analysis was then conducted with leisure activity participation as the independent variable and QOL‐AD score as the dependent variable.ResultFifty‐seven participants (37 women, age 80 ± 8 years) participated in leisure activities and 19 participants (10 women, age 83 ± 7 years) did not participate in leisure activities. There were no significant differences in age and gender between the two groups. The level of care required was significantly lower in the group with leisure activities than in the group with no leisure activities (p < 0.01), the MMSE score was significantly larger (p < 0.01) and the GDS‐15 score and AES score were significantly smaller (p < 0.05 and p < 0.01 respectively). Analysis of covariance using age, gender and nursing care level as covariates showed that the QOL‐AD score of the group with leisure activities was significantly greater than that of the group with no leisure activities (p<0.05).ConclusionThis study suggests that providing opportunities for leisure activities in day care services to older adults with dementia who do not participate in leisure activities in their daily lives may be beneficial in improving their quality of life.
Evaluation of the Memory Enhancing Activity of Dichloromethane Fraction of the Methanol Extract of Pycnanthus angolensis Stem Bark on Experimental Models of Memory Impairment
Authors: Chinwuba Patrici Eziafa , Ganiyu Bakre Adewale 
Published: January 2025

AbstractBackgroundPycnanthus angolensis (Welw) Warb., Myristicaceae, is used extensively in ethnomedicine. Numerous health benefits have being ascribed to the use of different parts of P. angolensis including its role in cognition enhancement and inflammation. Hence, this study was undertaken to investigate the stem bark of the plant for memory enhancing activity in mice.MethodThe plant material was grinded into powder and extracted by maceration with 80% methanol at room temperature for 48h. This was subsequently fractionated using N‐hexane, Dchloromethane (DCM), and Ethyl acetate. The Dichloromethane (DCM) fraction‐the most potent fraction‐ (25, 50, and 100 mg/kg) was evaluated for memory enhancing activity using the Y maze, Morris Water Maze (MWM) and the Elevated plus maze (EPM), on the D‐galactose plus scopolamine and ketamine induced amnesia model. The antioxidant markers and acetylcholinesterase inhibiting effect of DCM were also evaluatedResultThe results obtained from the behavioural studies indicate that the DCM fraction significantly (p<0.05) increased the alternation behaviour of the mice in the Y maze, decreased the escape latency in the MWM paradigm and decreased the transfer latency (TL) in the EPM. Biochemically, DCM increased Glutathione (GSH), and superoxide dismutase (SOD), but decreased Malondialdehyde (MDA) and acetylcholinesterase (AChE) activity in the brain.ConclusionThe study therefore suggested that the DCM may possess significant memory enhancing activity, which may be due to the reverser of the activity of scopolamine, thereby, enhancing cholinergic transmission. The attenuation of the effect of ketamine by the DCM may possibly result from an increase in NMDA receptor activity.
Prevalence of undiagnosed dementia among older hospitalized patients: variation by social and demographic factors
Authors: Aliberti Márlon Juliano Romero , Avelino‐Silva Thiago J , Covinsky Kenneth E , Suemoto Claudia Kimie ,   CHANGE Study Group
Published: January 2025

AbstractBackgroundThe profound impact of dementia on acute care, compounded by frequent underdiagnosis, is a significant challenge, especially among certain ethnic and minority groups, and remains largely unexplored in hospital settings. We used data from a multicentric study comprising 43 public and private hospitals in five countries to estimate the prevalence of undiagnosed dementia across different sociodemographic measures.MethodThe CHANGE (Creating a Hospital Assessment Network in Geriatrics) Study, an ongoing cohort designed to identify age‐related conditions like dementia, included patients aged ≥65 years admitted to 43 acute hospitals throughout Brazil and four other countries: Angola, Chile, Colombia, and Portugal. Upon admission, participants underwent a comprehensive geriatric assessment. To determine a previous dementia diagnosis, we consulted close family members and reviewed medical records. Trained investigators also administered the Clinical Dementia Rating (CDR) to family informants, referencing the patients’ cognitive status three months before admission to avoid the influence of acute cognitive impairment. Undiagnosed dementia was defined for participants with no clinical history of dementia and a CDR score ≥1. We estimated the prevalence of undiagnosed dementia across different sociodemographic measures and hospital types.ResultIn a sample of 2,452 participants (mean age = 79±9 years; women = 57%; Black or admixed = 42%), 1,032 (42%) presented with preexisting dementia (CDR ≥1), and among these, 448 (43%) had undiagnosed dementia (Table 1). Although no significant difference was found based on sex, undiagnosed dementia was associated with younger age, Black or admixed race/ethnicity, lower education levels, and lower income (Table 2). Moreover, the rate of undiagnosed dementia was more than double in public hospitals (47%) compared to private hospitals (22%), with a p‐value<0.001. Notably, Black patients with less than 8 years of education in public hospitals were significantly more likely to have undiagnosed dementia compared to White patients with higher education admitted to private hospitals, with undiagnosed dementia rates of 53% versus 20%, respectively (p‐value<0.001) (Figure 1).ConclusionFour out of ten older patients with preexisting dementia had not been diagnosed prior to hospital admission, underscoring the urgent need for practical diagnostic approaches to improve care in acute settings, particularly for ethnic and socioeconomic minorities in public hospitals.
Mental and Physical Health Factors Linking Perceived Control to Brain Health
Authors: Palms Jordan D , Morris Emily P. , Sol Ketlyne , Nelson Monica E , Scambray Kiana A. , Zahodne Laura B. 
Published: January 2025

AbstractBackgroundPerceived control is a psychosocial construct thought to reflect one’s beliefs about their ability to influence life outcomes and includes both internal (self‐efficacy, mastery) and external (structural barriers, constraints) subcomponents. While perceived control has been found to relate to numerous health outcomes such as cardiovascular and mental health, less is known about its impact on brain health. A prior study found that behavioral (i.e., physical activity) and biological (i.e., metabolic systems) health factors mediated the relationship between perceived control and memory (Infurna & Gerstorf, 2013). Furthermore, preliminary analyses indicated greater external control was associated with lower cortical thickness. The current study extends this work by evaluating associations between internal (mastery) versus external (constraints) control and brain health, as well as underlying mechanisms.MethodsThe current study included a subsample of older adults aged 55+ from the Michigan Cognitive Aging Project who completed magnetic resonance imaging (N = 120; Agemean = 62.6; female = 53%; non‐Hispanic Black = 30%). Multiple linear regressions examined associations between Mastery and Constraints subscales from the Perceived Control Scale, and brain health outcomes (cortical thickness composite of nine Alzheimer’s disease signature regions, total gray matter volume, total white matter volume, and white matter hypointensity volume). A mediation analysis explored potential mechanisms of association between perceived control and brain health outcomes through physical (number of chronic illnesses) and mental (depressive symptoms) health factors. Covariates included sociodemographics and total intracranial volume.ResultsMastery was not associated with brain health outcomes. Constraints were negatively associated with cortical thickness (total effect b = ‐.02, 95%CI [‐.03,‐.002]) only. Depressive symptoms fully mediated the relationship between constraints and cortical thickness (indirect effect b = ‐.02, 95%CI [‐.03,‐.01]) such that more constraints led to decreased cortical thickness through increased depressive symptoms. No indirect paths through chronic disease burden were found.ConclusionThese findings suggest that environmental constraints may be an upstream determinant of depressive symptoms, which can lead to negative downstream effects on brain health. Treatment approaches to mental and brain health should address structural barriers in addition to individual factors. Future longitudinal and/or intervention work is needed to confirm the direction of effects, which were based on previous theoretical and empirical work.
Allostasis links white matter hyperintensities with age‐related human brain structure and function: evidence from EEG and structural MRI
Authors: O'Byrne Daniel Franco , Laguardia Ana Maria Castro , Delgado Carolina , Campo Cecilia Gonzalez , Ibáñez Agustín , Medel Vicente 
Published: January 2025

AbstractBackgroundThe human brain integrity relies on the synergistic interplay between neural activity and supporting vascular and metabolic processes throughout life. This relationship, ruled by allostatic mechanisms, regulates brain architecture and activity. White matter hyperintensities (WMH) serve as indicators of the vascular impact on brain structure. While the strong association between vascular/metabolic systems and brain structure/function is established, the precise mechanisms linking allostasis to WMH remain elusive. We hypothesized that allostasis influences white matter through neuroinflammatory mechanisms, and WMH mediate neuroinflammatory effects on EEG measures.MethodTo test this hypothesis we conducted a comprehensive analysis on MRI, EEG, and multisystemic data from 196 subjects (20 to 75 years, 69 females) sourced from the LEMON database in Leipzig, Germany. Using the lesion segmentation tool (LST) on SPM12, we automatically identified WMH in fluid‐attenuated inversion recovery (FLAIR) images. FastSurfer was employed to determine the volumes of the bilateral hippocampus (HV) and lateral ventricles (VV), representing proxies for neurodegenerative and neuroinflammatory processes, respectively. Volumetric corrections were applied using total intracranial volume. Furthermore, a regression analysis was conducted to discern and subtract the shared contributions of VH and VV on each other. EEG data underwent spectral analysis for oscillatory (alpha waves) and aperiodic (1/f) components using NeuroDSP and FOOOF, respectively. An allostatic load index (ALI), incorporating lipid profile, inflammation, metabolic factors, and blood pressure, was computed. All measures were age, sex, and education level‐corrected.ResultWe found age differences in every metric of interest, but importantly just ALI, VV and 1/f correlated with WMH number and those effects survived age correction (Figure 1 A and B). VV, but not HV mediates the relationship between ALI and WMH. Also, WMH completely mediate the effects of neuroinflammation over the 1/f (Figure 1 C).ConclusionOur findings reveal that allostasis affects white matter through neuroinflammatory pathways, with WMH serving as crucial mediators of neuroinflammatory impact on EEG measures. This research provides key insights into the intricate interplay of vascular and metabolic factors with brain structure. Identified relationships and mediators open avenues for targeted interventions and personalized treatments in neurodegenerative and neuroinflammatory conditions.
Expected challenges for memory clinics introducing disease modifying treatments in the Nordics
Authors: Gustavsson Anders , Palmqvist Sebastian , Kern Silke , Saarinen Jukka , Jelic Vesna , Ghadbhan Sohad F , Lennhed Björn Strindberg , Jarholm Jonas Alexander , Dun Alexander Rieem , Cooper Alexandra , Ekelund Mats , Ellgren Maria , Fladby Tormod , Nägga Katarina 
Published: January 2025

AbstractBackgroundNew disease modifying treatments (DMTs) offer a new treatment paradigm in mild cognitive impairment (MCI) or mild dementia due to Alzheimer’s disease (AD). This likely requires significant changes in patient management and need for added capacity for diagnosis, treatment and monitoring.MethodWe surveyed eight selected memory clinics in the three largest and two smaller regions of Sweden, plus one in each of Denmark, Finland and Norway on their current practice, number of patients by diagnosis and available resources. Findings were compared to clinic assumptions on a future scenario where eligible patients with MCI or mild dementia due to AD are offered DMT.ResultUp to 3, but most often less than 1, incident patients in 1000 inhabitants per year are seen at surveyed memory clinics, of which on average about 40% have MCI or mild dementia due to AD. This constitutes not more than a few percent of the 10‐30 persons in 1000 inhabitants expected to have AD at this stage in the Nordics today. Most patients get amyloid biomarker confirmation as part of their diagnosis, while there are long wait times for radiology, in particular magnetic resonance imaging.ConclusionMost patients expected to be eligible for DMTs in AD are not referred to memory clinics today, but are managed in primary care or are not presenting with cognitive complaints to health care at all. Therefore, the main challenge is likely not to treat patients already seen at memory clinics, but to manage a potential increase in patients that would benefit from DMTs. New referral patterns and health care seeking behaviors are therefore expected to determine the need for investments in additional capacity to diagnose and treat eligible patients.