bluuebunny/crossref_metadata_2025_split huggingface dataset:
Classic biomarkers in exercise research for brain health promotion: From cells to communities
Authors: Barha Cindy K 
Published: January 2025

AbstractThere is growing recognition that exercise is a potent stimulus for improving cognitive and brain function in both humans and rodents. While the mechanisms underlying the effect of exercise on cognition are very likely multifactorial, it is clear that the secretion and function of several classical factors are involved. Work done in rodents implicates several growth factors, including BDNF, IGF‐1, and VEGF, in the ability of exercise to induce neuroplastic changes within key brain regions associated with learning and memory. However, confirming these growth factors as mediators of exercise efficacy in human trials has been less successful. This is likely related to several things, including a disconnect between human and rodent exercise studies in terms of design and analysis. We suggest that biological sex alone and in interaction with important genetic polymorphisms implicated in cognitive decline as vital moderating factors that must be considered in the search for exercise biomarkers.A sex difference exists in exercise efficacy for cognition, with older females showing greater benefits for executive functions than older males. The ε4 variant of the apolipoprotein E (APOE) gene moderates the effect of exercise on cognition; although the direction of the relationship is unclear. Biological sex may interact with the APOE gene to further moderate exercise effects on cognition. Our work indicates that biological sex interacts with APOE4 status to moderate exercise effects on the brain in both humans and rodents. Additionally, the BDNFval66met polymorphism also influences exercise efficacy for promoting cognition and neuroplasticity in a sex‐dependent manner. How these polymorphisms impact classic exercise biomarkers in males and females are important avenues of research. Work in rodents indicates that systemic/central sex hormones are further involved in the effect of exercise; though which hormones and to what extent is still unclear. There is an overall paucity of studies in humans that have investigated the role of different sex hormones in mediating the cognitive‐response to exercise in the context of aging. A greater appreciation of tissue‐specific effects of exercise on sex hormone production and growth factors and the synergistic interaction between biological sex and genetics, will help move this field forward.
Aerobic exercise and Alzheimer’s disease blood‐based biomarkers
Authors: Erickson Kirk I. 
Published: January 2025

AbstractA greater amount of physical activity is associated with a reduced risk of developing dementia, including Alzheimer’s disease. Engaging in physical activity affects several pathways that are associated with memory impairments including hippocampal integrity, resting state networks, and metabolic function. Further, exercise interventions are effective at improving various measures of brain health in late adulthood that overlap with the cognitive functions that these brain regions support. Yet, there remains a poor understanding of the mechanisms that link physical activity and exercise behaviors to improvements in brain health outcomes and reduced risk of developing dementia. There is also significant heterogeneity in this literature that could likely be explained by factors that moderate the impact of exercise on brain health. In this presentation we will discuss recent research on exercise and brain health in late adulthood and will discuss the evidence for several levels of mechanisms and moderators of these effects including examining the impact of exercise interventions on Alzheimer’s disease blood‐based biomarkers. Preliminary results will be described from a multi‐site, 12‐month, 3x per week supervised, moderate‐intensity, Phase III randomized clinical trial of aerobic exercise in 648 cognitively normal adults between 65‐80 years of age. Blood samples were taken before and after the completion of the intervention as well as a comprehensive cognitive battery and PET amyloid. The results from this aerobic exercise intervention will be discussed including the impact of the intervention on cognitive performance and the role that changes in Alzheimer’s disease blood‐based biomarkers play in relation to functional outcomes. Overall, physical activity and exercise behaviors are important modifiable lifestyles that carry significant consequences for learning, memory, and Alzheimer’s disease risk in late adulthood.
Preference Assessment in Dementia Care: Systematic Literature Reivew
Authors: Lim Hyejeen , Choe Young Min , Hwang Jaeuk , Choi Soo‐Hee , Kim Seong Jae , Lee Jung Hie , Woo Jong Inn , Seo Eun Hyun 
Published: January 2025

AbstractBackgroundBoosting shared decision‐making (SDM) for individuals with dementia is a critical aspect of patient‐centered care. This collaborative approach respects the autonomy and dignity of patients, even when they face challenges in communication or decision‐making due to their medical condition. Understanding patients’ values and preferences may be central to a successful SDM process. The aim of this study is to review various preference evaluation methods used for individuals with dementia in clinical settings, and to suggest the most effective and feasible tools for accurately measuring values and preferences.MethodsWe strictly followed an updated guideline for the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) (Page et al., 2021). A systematic review was conducted through a search of three online databases (PubMed, Web of Science, Cochrane) and included studies about patient preferences published in English between 2000 and 2023. This review included studies that used a quantitative approach including surveys and structured interviews to gather data on the preferences of individuals with dementia and cognitive impairment. Specific inclusion and exclusion criteria are shown in Figure 1.ResultsAfter identification of 268 studies, twenty studies were finally eligible for review (Figure 1). Five categories of preference evaluations were generated from the review: (a) values and preferences in decision‐making (n = 6), (b) treatment goals (n = 2), (c) discrete choice experiments for preferences (n = 3), (d) diagnosis disclosure and communication (n = 5), (e) advanced care planning (n = 4). Most of the studies demonstrated substantial reliability and validity in their assessment methods for individuals with dementia.ConclusionsOur findings suggested that individuals with dementia can reliably express their values and preferences about treatment that they currently receive or will need in the future. Moreover, our review highlighted the need for flexible and adaptable assessment to accommodate each patient’s unique circumstances. The utilization of tools with the autonomy preference index, clearly defined treatment goals, and transparent diagnosis disclosure, seem to be critical for fostering effective SDM process.
Effect of Occupational Toxin Exposure on the risk of dementia; Results of the Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD)
Authors: Kim Hak Hyeon , van der Bent Yvonne , Kim Tae Hui , Kwak Kyung Phil , Kim Bong Jo , Kim Shin Gyeom , Kim Jeong Lan , Moon Seok Woo , Park Joon Hyuk , Ryu Seung‐Ho , Yoon Jong Chul , Lee Dong Young , Lee Dong Woo , Lee Seok Bum , Lee Jung Jae , Jhoo Jin Hyeong , Han Ji Won , Kim Ki Woong 
Published: January 2025

AbstractBackgroundThe global increase in the aging population has led to a corresponding rise in dementia cases. This study explores the potential link between occupational toxin exposure and the incidence of dementia, aiming to identify high‐risk populations.MethodWe analyzed data from 2,485 male participants aged 60 and over in the Korean Longitudinal Study on Cognitive Ageing and Dementia (KLOSCAD). Participants were categorized into no or very low, low and high toxin exposure risk groups based on their lifetime occupation according to the International Standard Classification of Occupations classification. Exposure to the specific hazard type, including carcinogens, skin sensitizers, airway sensitizers, mutagenic substances, reprotoxic agents and biological hazards were identified in relation to their lifetime occupation. We conducted multinomial logistic regression analysis, adjusting for occupation‐related factors, APOE genotype, age, education, health status and lifestyle behaviors, to investigate the relationship between the levels of toxin exposure risk, specific toxin types, and the incidence of mild cognitive impairment (MCI), Alzheimer’s disease (AD) dementia and other dementia.ResultCompared to the no or very low toxin exposure risk group, participants in the low toxin risk exposure group (odds ratio (OR) 2.24, 95% CI 1.08 – 43.64) and high toxin risk exposure group (OR 2.97, 95% CI 1.31 – 6.74) showed a significantly increased risk of AD dementia. Exposure to carcinogens, skin sensitisers, reprotoxic agents and biological hazards showed a significant association with the risk of incident AD dementia. Among toxin types, skin sensitizers presented the highest OR of 5.48 (95% CI 1.29‐23.31) in multivariable model. No significant associations were found with MCI and other dementia.ConclusionHigher risk of lifetime occupational toxin exposure may be associated with an increased risk of AD dementia, showing consistent results across various toxin types, underscoring the need for heightened attention to toxin exposure in AD dementia prevention.
Contrast of Early Phase Amyloid PET
Authors: Kameyama Masashi , Sakata Muneyuki , Ishibashi Kenji , Tago Tetsuro , Kamitaka Yuto , Toyohara Jun , Ishii Kenji 
Published: January 2025

AbstractBackgroundThe method of obtaining pseudo‐cerebral blood flow images from the initial minutes of amyloid PET scans has been proposed. This technique proves to be highly valuable as it not only indicates the presence of amyloid accumulation but also reveals sites of neurodegeneration. However, the obtained early images represent the K1 image rather than cerebral blood flow. Consequently, the contrast in early images from amyloid PET tracers is thought to be compromised when compared to cerebral blood flow images.MethodTo enhance the contrast in early images obtained from amyloid PET tracers and thereby improve diagnostic accuracy, we developed a method for contrast recovery and established a methodology for determining the parameter involved in achieving this contrast recovery, drawing insights from a thorough literature review. Additionally, we conducted a comparative analysis involving PiB's early images and FDG, investigating their respective contributions.ResultOur study demonstrated a strong correlation between FDG and early images of PiB, with relatively inconspicuous underestimations in high‐blood‐flow regions.ConclusionWhile we theoretically established a method to recover the contrast in early images, our findings suggest that amyloid PET tracers may exhibit a higher permeability‐surface area product than anticipated. This observation raises the possibility that, without correction, these tracers might inherently provide sufficient contrast.
From Plan To Impact – expediting progress towards targets of the WHO Global Action Plan on Dementia
Authors: Barbarino Paola , Aguilar Diego , Arthurton Lewis , Lynch Chris 
Published: January 2025

AbstractBackgroundIn 2017, all 194 Member States of the World Health Organization (WHO) unanimously adopted the Global Action Plan on the public health response to dementia 2017‐2025, the primary aim being for countries to implement National Dementia Plans (NDP). However, as outlined in Alzheimer’s Disease International’s (ADI) recent From Plan to Impact report, WHO Member States have been far too slow to act ‐ falling far short of the 146 countries target. In response, ADI launched the #WhatsYourPlan campaign, in collaboration with ADI Members, with the single‐minded aim of galvanising governments to act on their 2017 commitment.MethodStrategizing and working with ADI Members, official communications were sent to relevant ministries to enquire as to the status of the NDP, and to request a formal meeting. For Ministries where a response was not obtained, subsequent letters were sent to elicit a response. ADI has also, in some instances, sought advice and utilised WHO regional and national offices, and other multilateral bodies and stakeholders, to help follow up with Ministries of Health for those that have been willing to engage.Results52 ADI members and thus 52 countries, joined the campaign. In total from the onset of the campaign, 205 official communications were shared with Member States, resulting in a total of 29 high‐level meetings. In total 20 Member States committed to developing an NDP, just over a third of all participating ADI Members and over half of the number of plans already in existence in WHO Member StatesConclusionsThough progress on the GAP has been slow, ADI’s successful #WhatsYourPlan campaign demonstrates that collaborative efforts between governments and stakeholders can make a tangible impact on policy development and implementation of NDPs. The fight for a better world for people living with dementia is ongoing, and it is crucial to utilise all available means to transform this vision into reality. As such, ADI is calling for an urgent extension of the Global Action Plan until 2029 with current progress putting people living with dementia and their caregivers are at a severe disadvantage.
Characterizing brain structures associated with subjective cognitive decline and mild cognitive impairment: a population‐based study
Authors: Chen Ziwei , Xie Qianqian , Wang Jiafeng , Zhang Huisi , Li Chunyan , Cong Lin , wang yongxiang , Song Lin , Du Yifeng , Qiu Chengxuan 
Published: January 2025

AbstractBackgroundThe structural brain alterations for subjective cognitive decline (SCD) and mild cognitive impairment (MCI) are poorly defined. We sought to characterize grey matter volume (GMV) and cortical thickness associated with SCD and MCI among rural‐dwelling older adults in China.MethodThis population‐based cross‐sectional study included 1072 dementia‐free participants derived from the brain MRI substudy of MIND‐China in 2018‐2020. We defined MCI following the Petersen’s criteria, and SCD as the self‐reported AD8 questionnaire score ≥2. Data were analyzed using voxel‐based morphometry (VBM), surface‐based morphometry analysis (SBM), and logistic regression models.ResultSCD was defined in 243 individuals and MCI in 246 individuals. VBM analyses revealed a significant reduction in GMV among people with MCI compared to normal controls (NC) in several brain regions, such as bilateral temporal lobes and bilateral precuneus (P<0.05). There were no significant differences in GMV between SCD and NC (P<0.05). The ROI‐wise SBM analyses revealed that SCD was significantly associated with cortical thinning in the right paracentral sulcus, left caudal middle frontal gyrus, and entorhinal cortex (P<0.05) and that MCI was significantly associated with cortical atrophy in the left caudal middle frontal gyrus, temporal lobe, frontal lobe, and parietal lobe (P<0.05).ConclusionThe structural brain altercations are characterized by reduced GMV mainly in the bilateral temporal lobe and bilateral precuneus, and thinner cortical thickness in the temporal lobe, frontal lobe, and parietal lobe for MCI, and by cortical thinning in the right paracentral sulcus, left caudal middle frontal gyrus, and entorhinal cortex for SCD.
The Associations of Physical Activity from Midlife to Late Life with Incident Dementia: The Health and Retirement Study, 1996‐2020
Authors: Zhang Yanan , Yang Chih‐Hsiang , Merchant Anwar T , Wei Jingkai 
Published: January 2025

AbstractBackgroundWhile physical activity is found to be associated with a lower risk of dementia in numerous studies, less is known whether this association varies over time. We aim to examine the potential time‐varying associations of physical activity with risk of dementia from midlife to late life.MethodParticipants aged 54 to 64 years of the Health Retirement Study (HRS) in 1996 were included. Physical activity was measured using self‐report questionnaires. Physically active was defined as having vigorous activity ≥3 times a week during 1996‐2002, and as having vigorous activity >1 time a week during 2004‐2020. Ascertainment of dementia was based on the Langa‐Weir Classification of Cognitive Function (range 0‐27), which included immediate and delayed recall items, the serial 7s, and backward counting. A score <6 was considered having dementia. Participants were followed up until the occurrence of dementia, death/lost to follow‐up, or the last interview in 2020, whichever came first.A time‐varying effect logistic regression was fit to examine the trend of the association between physical activity and dementia across ages. Regression covariates includes time‐invariant variables (age at baseline, sex, race/ethnicity, and education) and time‐variant variables [BMI (Kg/m2), current smoking status (Yes/No), number of days/week drinks, hypertension (Yes/No), diabetes (Yes/No), cardiovascular diseases (Yes if reporting any of heart problems or stroke), and cancers (Yes/No)]. Missing values were imputed by the values from the previous interview. To check the impact of revised definitions of physical activity, a sensitivity analysis was also conducted.ResultA total of 7,001 participants were included in the analysis. During an average follow‐up period of 15.1±7.8 years, 736 cases of dementia occurred. Being physically active in midlife was associated with a lower risk of dementia. The association was not static and became attenuated with aging, and no significant association was observed after the age of 75.ConclusionThe association of physical activity with incident dementia attenuated throughout the progress of aging. While the possibility of reverse causality needs to be further explored, our results may suggest that physical activity may be initiated at an earlier stage of life for risk reduction of dementia.
Education and Midlife Cognitive Functioning: Evidence from the High School and Beyond Cohort
Authors: Warren John Robert , Grodsky Eric , Muller Chandra , Manly Jennifer J. , Brickman Adam M. 
Published: January 2025

AbstractBackgroundEducation is associated with cognitive functioning and risk of Alzheimer’s Disease and related dementias (ADRD). However, researchers rarely consider anything about education other than highest degree completion. Do schools’ social and academic contexts and students’ other (non‐attainment) schooling outcomes independently predict cognitive outcomes? If so, this opens the possibility of manipulating educational policies and practices to improve long term cognitive well‐being.MethodThis study included a nationally representative sample of 12,530 Americans followed prospectively from high school through age ∼60 as part of the High School and Beyond cohort study. OLS regression models estimated associations between various aspects of education ─ including schools’ social and academic contexts; students’ grades, test scores, and course taking; and degree attainment ─ and multiple dimensions of cognition, before and after adjustment for confounders.ResultEducational attainment predicts cognitive functioning at age ∼60. However, the social and academic contexts of schools and other measures of students’ educational performance predict cognition at least as well—even after adjusting for attainment.ConclusionEducation is more than just how far in school people go, and degree attainment is not the only ─ or perhaps even the primary ─ thing about education that has long run consequences for cognitive functioning and ADRD risk. Advancing our understanding of how and why education shapes cognitive functioning and ADRD risk requires analyses of data with nuanced information about schools, schooling, and student performance.
Validation of a binding site on the SORLA‐retromer complex that augments endosomal recycling: Implications for a novel class of AD drugs
Authors: Merchant Kalpana M. , Andersen Olav M. , Lefker Bruce , Withka Jane , Small Scott A. , Petsko Gregory A. , Klein Joel , Armstrong Rob 
Published: January 2025

AbstractBackgroundGenetic studies have established that loss of function SORL1 gene variants are associated with Alzheimer’s disease (AD). SORL1 encodes an endosomal trafficking receptor, SORLA, which regulates endosomal protein recycling through its interaction with the retromer core complex (consisting of VPS26, VPS35 and VPS29). Deficits in the levels and function of the SORLA‐retromer complex are thought to underlie AD. We set out to identify and validate potential small molecule binding sites on the SORLA‐retromer complex that may restore endosomal recycling and lead to disease‐modifying therapies for AD.MethodWe engineered HEK293 stable cell lines expressing a SORL1 reporter construct to monitor shedding and production of soluble SORLA (sSORLA), as indicators of endosomal recycling activity. In parallel, we synthesized cell‐permeant derivatives (R8 and TAT‐conjugations) of a retromer stabilizing cyclic peptide, RT‐L4 (Chen et al., Sci Adv, 2021), and its analogs, M10 and M7, that bind to the VPS26‐VPS35 interface in vitro at range of potencies. These peptides and several controls were tested for their ability to augment the shedding of SORLA in the cell media. Cell viability was assessed using CellTiter‐Glo and DRAQ7 staining.ResultUsing a Homogenous Time‐Resolved Fluorescence (HTRF) binding assay, we confirmed that the cell‐permeant derivatives of RT‐L4, M10 and M7 bind to the retromer heterotrimer at affinities similar to the parent cyclic peptides. Treatment of HEK293 cells with cell‐permeant derivatives of these peptides, but not unmodified peptides and controls, increased sSORLA levels in the media at potencies that correlated with their binding affinity for the VPS26‐VPS35 interface. These effects were seen at concentrations that did not produce significant cell toxicity monitored by two different methods.ConclusionThese data validate the VPS26‐VPS35 interface as a target for small molecules to enhance SORLA‐retromer‐mediated recycling. The results provided a compelling rationale to conduct a high throughput screen to discover and develop a novel class of AD drugs.