bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma insulin is an early biomarker of amyloid‐β pathology in Alzheimer’s disease
Authors: Chen Yuhan , Wang Zhibo , Mao Zhiqi 
Published: January 2025

AbstractBackgroundEvidence suggests that type 2 diabetes (T2D) is an independent risk factor for Alzheimer's disease (AD), sharing similar pathophysiological traits like impaired insulin signaling. However, how plasma insulin changes with AD key pathologies and its diagnostics value remain unclear.MethodA total of 304 participants were included in the Alzheimer’s Disease Neuroimaging Initiative (ADNI), assessing plasma insulin and cerebrospinal fluid (CSF) AD pathology. We explored the cross‐sectional and longitudinal associations between plasma insulin and AD pathology and compared their associations across different AD clinical and pathological stages. We also explored the potential diagnostic value of plasma insulin on AD pathology using the receiver operating characteristic (ROC) curves.ResultIn the non‐demented group, A+ participants (e.g., as reflected by CSF Aβ42) exhibited significantly reduced plasma insulin levels compared to non‐demented A‐ participants (P < 0.001). Furthermore, A+T‐ participants (e.g., as reflected by CSF Aβ42 and CSF p‐tau181) had lower plasma insulin levels than A‐T‐ participants in the non‐dementia group (P = 0.002). No significant differences were observed in the dementia group (Figure 1). In addition, a notable positive correlation was found between plasma insulin levels and CSF Aβ42 (P < 0.001) in all participants. When stratified by clinical status and pathological status, this association only existed in the A‐ group (P = 0.002) and the non‐demented group (P < 0.001) (Figure 2). Moreover, plasma insulin at baseline was significantly associated with longitudinal changes in CSF Aβ42 (P = 0.02), while baseline CSF Aβ42 was not associated with longitudinal changes in plasma insulin (Figure 3). Regarding the diagnostical value, plasma insulin alone demonstrated acceptable accuracy in distinguishing A+ from A‐ individuals in the whole participants (area under the curve [AUC]=0.61) and more prominent in the non‐dementia group (AUC = 0.65) than in the dementia group (AUC = 0.52). When added age, sex, and APOE ε4 status were as predictors, the AUC of plasma insulin reached 0.8 in the whole participants.ConclusionThese findings pinpoint the association between plasma insulin and early Aβ pathology in the early stages of AD, suggesting that plasma insulin can serve as an early biomarker of Aβ pathology.
Patients with Controlled and Uncontrolled Type 2 Diabetes: Systemic Oxidative Stress and Systemic Inflammation as Predictors of Peripheral and Central Neuropathy
Authors: Oo Thura Tun , Skarr Max , Mon Yee Yee , Htwe Kyi Kyi 
Published: January 2025

AbstractBackgroundDiabetes mellitus increases the risk of cognitive decline and neuronal degeneration. In diabetes, persistently elevated blood sugar levels cause not only the generation of reactive oxygen species (ROS), but also systemic inflammation (1). This raises an intriguing question: do patients with controlled or uncontrolled diabetes exhibit similar levels of oxidative stress and systemic inflammation as reliable predictors of peripheral neuropathy and cognitive decline?MethodIn 2019, 150 participants with diabetes mellitus who had been diagnosed for more than 5 years were voluntarily enrolled. Blood was obtained to measure systemic oxidative stress and inflammation. Vibrometer and Mini‐Mental State Examination (MMSE) were used to assess peripheral and central neuropathy, respectively. The association with peripheral and central neuropathy was evaluated using multivariate logistic regression analyses.ResultUsing HbA1C (6.5%) targets for categorization, 60% of participants were controlled diabetes patients and 40% were uncontrolled patients. The plasma malondialdehyde level was significantly higher in patients with uncontrolled diabetes than patients with controlled diabetes (63% Vs. 23%, P < 0.05). The C‐reactive protein (CRP) level significantly higher in patients with uncontrolled diabetes than patients with controlled diabetes (70% Vs. 35%, P < 0.05). In patients with uncontrolled diabetes, there was a correlation between the level of plasma malondialdehyde and sensory neuropathy as well as cognitive decline (r = 0.774, P < 0.05 and r = 0.734, P < 0.05, respectively), whereas we found the correlation between the level of CRP and sensory neuropathy as well as cognitive decline (r = 0.873, P < 0.05 and r = 0.688, P < 0.05, respectively). Both sensory neuropathy and cognitive decline were uncorrelated with the level of plasma malondialdehyde in patients with controlled diabetes, and neither was there a correlation with the level of CRP.ConclusionThis study demonstrated that systemic oxidative stress and systemic inflammation are reliable clinical predictors of peripheral and central neuropathy in uncontrolled diabetes, but not in controlled diabetes.
Multivariate sleep health and cognitive functions in healthy older adults: results from partial least square correlation analysis
Authors: Qin Shuo , Ng Eric Kwun Kei , Soon ChunSiong , Chua XinYu , Zhou Juan Helen , Koh Woon‐Puay , Chee Michael Wei‐Liang 
Published: January 2025

AbstractBackgroundPast studies examining sleep‐cognition relationships mostly employed univariate approaches, which are subject to problems such as multicollinearity and multiple comparisons. Further, results from small sample univariate analyses are difficult to compare, precluding the identification of the aspects of sleep health associated with a particular cognitive domain(s). The current study used a multivariate approach to identify key sleep metrics and cognitive domains that contribute to the maximum sleep‐cognition covariance in healthy older adults. From the reduced list of sleep metrics and cognitive domains, novel associations between different aspects of sleep health and cognitive domains can be uncovered.MethodThe current study is part of the ongoing SG70: Toward Healthy Longevity in Singapore study, which aims to comprehensively assess factors that affect aging health in over 1000 Singaporean older adults. From the SG70 study, 440 healthy older adults wore an Oura Ring (OuraHealth OY) for 14‐30 days. Twenty‐three metrics encompassing 4 major aspects of objective sleep health: duration, timing, regularity, and continuity were extracted (Figure 1). Cognition was assessed using a comprehensive battery that encompassed 7 domains. The overall covariance between sleep and cognition was examined by a partial least square correlation (PLSC) analysis. Sleep metrics and cognitive domains that contributed significantly to significant PLSC components were identified by bootstrapping.ResultPLSC analysis identified a component that explained 68% of covariance between sleep and cognition matrices (r=0.17, p<0.001). Bootstrapping tests further identified 10 sleep continuity and regularity metrics and 4 corresponding cognitive domains that contributed significantly to the observed covariance (Figure 2). Post‐hoc univariate analyses showed that sleep continuity metrics correlated with speed of processing, while sleep regularity metrics correlated with verbal memory, visual‐spatial ability, executive functions, and speed of processing (Figure 3).ConclusionOur results suggest that sleep continuity and regularity may be more sensitive markers of impairments across multiple cognitive domains in healthy aging compared to sleep duration and timing. In addition, they support the utility of multivariate analyses in uncovering significant association patterns between sleep and cognition.
“Strengthening Dementia Care: Advancing Through ADI Accreditation for Excellence and Acknowledgment”
Authors: Utomo Amalia Fonk , Aguilar Diego 
Published: January 2025

AbstractBackgroundThe ADI Accreditation Programme, launched in December 2020, aims to support all Alzheimer and dementia associations and other organizations, in improving care for people living with dementia. By providing a standards‐based approach to knowledge and skills, ADI establishes benchmarks that program providers must adhere to. Successful completion of an evaluation allows carers, trainers & program providers to earn ADI Accreditation, indicating that they have reached the required global standard for their training and learning activities, including culturally appropriate context to improve care quality. This program is open to ADI members, and organizations including universities & training colleges.ActivitiesOur Global Review Panel (GRP) Members consists of multi‐discipline, cultural and regional experts in the global dementia field. Successful completion of an evaluation process: initial application, evaluation report, virtual/in‐person or hybrid visit from our GRP Members, the program/providers can earn it.The first provider accredited was Kiang Wu Nursing College (KWNC) of Macau on January 25, 2021. The project involved discussions on external‐internal governance, trainers‐program committees, students, graduates & other stakeholders. A 3‐day virtual visit to KWNC in September, including evaluation, involved carers, trainers, students & collaboration with other organizations and people living with dementia, followed by a final review by the GRP in October‐November.Silverado Memory Care became the first program to be accredited for their Dementia Care Program on December 22, 2022. In‐person visits took place on August 16‐17 2022. University of Bradford UK, became the first university in Europe to be accredited their Centre for Dementia Applied Science on December 22, 2022. In‐person visit took place on June 20‐21 June 2023. Wicking Dementia Research & Education Centre University of Tasmania, received their accreditation after virtual visit on 29‐30 August 2023. All process involving trainers, stakeholders, associates & staff in 2024 Dementia Australia is currently on the process along with new potentials.ResultsKWNC Macau, Silverado, University of Bradford & University of Tasmania received ADI Accreditation. Throughout the program, there has been an increase in awareness and understanding of the importance of high‐quality culturally contextualized carer training achieved.
Caregivers’ perception of ageing, perceived health and strain in caregiving – The preliminary cross culture analysis
Authors: Lai Frank HY , Siu Andrew Man‐hong , Hai Eddie Yip‐kuen , Whittington Stephanie , Lai Cynthia Yuen‐yi , Chan Wallace Chi‐ho , Yip Ben Chi‐bun 
Published: January 2025

AbstractBackgroundUnderstanding how caregivers perceive their own aging process is essential for addressing their well‐being and the quality of care they provide. This study aimed at exploring the relationship between caregivers’ self‐perception of ageing in relation to their strain experienced in caregiving, and their perceived physical and mental health symptoms. Moreover, to examine if the strain experience and perceived health condition were key predictors to their self‐perception of ageing. Additionally, to analyze how demographic variables, such as gender and cultural background, would impose influence on self‐perception of ageingMethodA questionnaire was developed in collect data on the variables, including self‐perceptions of ageing (SPA), caregivers' perceived strain (PS), caregivers physical health symptoms (PHS), and mental health symptoms (MHS).Result60 spousal caregivers, 33 male and 27 female with (24 Western, 24 Asian, and 12 Black Asian) participated in a cross‐sectional survey. There was a strong negative correlation between the self‐perception of ageing and caregivers’ strain (r = −.55, p < .001), physical symptoms (r = −.67, p < .001), and mental health symptoms (r = −.36, p < .001). Results of multiple regression analysis showed that caregivers’ strain, physical symptoms, and mental health are good predictors of self‐perception of ageing, and the regression equation account for a significant proportion of variance in self‐perception of ageing (R2 = .56, Adjusted R2 = .53).ConclusionCultural background imposes influence on self‐perception of ageing, and there are significant interactions between gender and cultural background. Post‐hoc multiple comparisons using Bonferroni tests showed that Western had significantly higher self‐perception of ageing scores than the other two culture groups, while the differences between Asian or Black Asian group are significant.
Alzheimer diseases CSF biomarkers correlate with systemic biomarkers in a cohort of Hispanics
Authors: Villarreal Alcibiades E , Oviedo Diana C , Carreira Maria B , Rangel Giselle , Araujo Pahola , de Roux Ricardo Williams , Balaguer Rainier Rodríguez , Díaz Marilisa , Novarro‐Escudero Nelson , Tamayo David Alberto Anguizola , Villarreal Julio , Dondis David , Benzadon Aron , Britton Gabrielle B 
Published: January 2025

AbstractBackgroundWe are conducting a biomarker‐based study to describe the demographic and biomarker profiles of Panamanians. The objective of this report is to present the main findings on CSF, genetic and serological biomarkers’ distribution and their association with cognition in a cohort of elderly people in Panama.MethodInformed consent was applied to all participants, demographic data, medical history, and neuropsychological and functional status were collected, and non‐fasting blood samples were obtained. We performed a cross‐sectional analysis of aged individuals for blood and CSF biomarkers and Apolipoprotein E (ApoE) expression (N=45). The following measures were obtained: MMSE, Global Deterioration Scale, and Geriatric Depression Scale 30‐item version. The following biomarkers in CSF were analyzed: Ab1–42, T‐tau and P‐tau181.ResultWe performed group comparisons and analyzed in‐group correlations between blood‐based and CSF biomarkers. Group differences across three CFS profile categories (normal, plausible AD, and AD) were calculated using ANOVA. The Innotest Amyloid Tau Index (IATI) was used to assign 45 biochemical CSF profiles into: normal CSF profile (n=19), plausible AD profile (n=18) and AD profile (n=8). Groups did not differ with respect to age, sex, or education level. AD group expressed at least one copy of the allele 4 of ApoE significantly more than normal and plausible AD profile groups (p=0.017 and 0.035, respectively). Significant correlation between IL‐18 and Ab1–42 was observed in normal group, and no correlations were found between blood and CSF markers in plausible AD group. The greatest number of significant correlations was found in AD group: B2M, CRP, Eotaxin3, PPY, SAA, TARC correlated with P‐tau181; IL‐10, IL‐7 with Ab1–42; and FVII with T‐tau.ConclusionIn this analysis we observed a strong correlation of systemic biomarkers with CSF profiles (IATI profiles), mainly in the Alzheimer's disease group. Blood‐based biomarkers might facilitate diagnosis and clinical design in the future, but further validation is required.
Unravelling excitation/inhibition imbalance in early and familial Alzheimer's Disease
Authors: van Nifterick Anne M 
Published: January 2025

AbstractBackgroundAn early disruption in excitation‐inhibition (E‐I) balance is believed to underlie abnormal local and global network dynamics in Alzheimer’s disease (AD). While prior studies proposed that changes in E‐I balance may underlie the established slowing of oscillatory activity and changes in functional connectivity in symptomatic AD, the specific alterations occurring in the presymptomatic stage of AD remain poorly understood. This study aims to identify local and global spectral power and functional connectivity changes in individuals with familial AD before the onset of clinical symptoms.MethodResting‐state magnetoencephalography (MEG) recordings were conducted in a unique cohort of cognitively unimpaired individuals carrying autosomal dominant mutations in the APP and PSEN1 genes (n = 11), leading to early‐onset AD. Each mutation carrier was demographically matched with three cognitively healthy subjects (HCs) without mutations and with available MEG. We compared source‐level whole‐brain average and regional spectral power and volume‐conduction corrected functional connectivity measures across different frequency bands. Hub vulnerability was assessed using the hub disruption index. Significant MEG measures were correlated with age, estimated years before symptom onset (EYBSO), and cognitive performance.ResultCognitively normal mutation carriers exhibited signatures of oscillatory slowing, characterized by a widespread higher relative power in the theta band (4‐8 Hz) and a lower parieto‐temporal‐occipital peak frequency compared to HCs. Additionally, they presented frequency‐ and degree‐dependent functional connectivity changes: higher phase‐based functional connectivity in the theta band in initial low‐degree regions (as determined by weighted degree in HCs), but lower global amplitude‐based functional connectivity in the alpha (8‐13 Hz) and beta (13‐30 Hz) bands compared to HCs, most strongly in initial high‐degree regions. No correlations between MEG measures and age, EYBSO, or cognitive indices were found after correction for multiple comparisons.ConclusionNeurophysiological changes occur before the onset of cognitive symptoms in individuals carrying mutations in the APP or PSEN1 genes. These changes include oscillatory slowing and frequency‐ and degree‐dependent functional connectivity alterations, mirroring alterations observed in clinical stages of AD and suggesting an early E‐I imbalance. These findings contribute to a comprehensive understanding of presymptomatic pathophysiological alterations in AD.
Validation of diffusivity along the perivascular space as a biomarker for vascular cognitive impairment and dementia
Authors: Liu Xiaodan , Barisano Giuseppe , Maillard Pauline , Arvind Caprihan , Cen Steven , Shao Xingfeng , Jann Kay , Ringman John M , Lu Hanzhang , Arfanakis Konstantinos , Decarli Charles , Gold Brian T , Satizabal Clandia L. , Fadaee Elyas , Habes Mohamad , Stables Lara , Singh Herpreet , van der Kouwe Andre J. , Schwab Kristin , Helmer Karl G , Greenberg Steven M. , Wang Danny JJ ,   MarkVCID Consortium
Published: January 2025

AbstractBackgroundTo validate the index of diffusivity along the perivascular space (ALPS index) as a biomarker for vascular cognitive impairment and dementia (VCID).MethodThe participants and MRI data used in this study were acquired as part of the MarkVCID consortium, which consisted of seven sites. A total of 578 participants (72.5±7.2 years old, 232 Male) who received baseline and follow‐up cognitive evaluations (Montreal Cognitive Assessment (MoCA), Principal Component Analysis derived General Cognitive Function (GCF_PCA), and composite score of Executive Function (EFC)) and MRI examinations were included in this study. The diffusion tensor imaging (DTI) data were processed by using an in‐house automatic processing pipeline with FMRIB Software Library 6.0.6. The mean free water (mFW) and peak width of skeletonized mean diffusivity (PSMD) were computed in the white matter (WM). The ALPS index was defined as the average of bilateral ALPS indices which were calculated by the ratio of mean of x‐axis diffusivity in the projection fibers (Dxxproj) and x‐axis diffusivity in the association fibers (Dxxassoc) to the mean of y‐axis diffusivity in the projection fibers (Dyyproj) and z‐axis diffusivity in the association fibers (Dzzassoc). The WM hyperintensity volumes (WMHV) were calculated on FLAIR images and normalized by intracranial volume (ICV). Univariate correlation (Pearson or Spearman) was used to examine the associations between imaging markers (ALPS index, mFW, PSMD, and WMHV). Linear regression models were used to evaluate the associations of baseline ALPS index with baseline and longitudinal changes of cognitive outcomes, regressing out three types of covariates: 1) age, sex, and education, 2) added vascular risk factors (VRFs), including diabetes, hypertension and smoking, 3) further added mFW, PSMD and WMHV. SAS 9.4 software was used for all statistical analyses, and P<0.05 was regarded as statistical significance.ResultThe baseline ALPS index was significantly correlated with existing biomarkers of cerebral small vessel disease (cSVD)‐related VCID, i.e., mFW and WMHV (P<0.01) (Figure 1), and baseline cognitive performances, i.e., MoCA total score, GCF_PCA score, and EFC score (P<0.05) after adjusting for the demographics, VRFs, and existing biomarkers (Figure 2).Conclusionthe ALPS index is an independent contributor to the cognitive decline in cSVD.
Potentially modifiable risk factors for dementia putting the evidence together: Total population attributable fraction
Authors: Livingston Gill , Huntley Jonathan D , Liu Kathy Y , Gonzalez Sergi Costafreda , Selbaek Geir , Alladi Suvarna , Ames David , Banerjee Sube , Burns Alistair , Brayne Carol , Fox Nick C , Ferri Cleusa P , Gitlin Laura N. , Howard Robert J , Kales Helen C , Kivimaki Mika , Larson Eric B , Nakasujja Noeline , Rockwood Kenneth , Samus Quincy M , Shirai Kokoro , Singh‐Manoux Archana , Schneider Lon S. S. , Walsh Sebastian , Yao Yao , Sommerlad Andrew , Mukadam Naaheed 
Published: January 2025

AbstractBackgroundOur authors from around the world met to summarise the available knowledge, decide which potentially modifiable risk factors for dementia have compelling evidence and create the most comprehensive analysis to date for potentially modifiable risk factors to inform policy, give individuals the opportunity to control their risks and generate research.MethodWe incorporated all risk factors for which we judged there was strong enough evidence. We used the largest recent worldwide meta‐analyses for risk factor prevalence and relative risk and if not available the best data. We performed new meta‐analyses for depression and hearing loss relative risks.We used all 37,000 participants aged ≥ 45 years from HUNT, Norwegian longitudinal population‐based study, to estimate communalities (risk factors clustering) as people frequently have multiple risk factors. Four principal components explained 51% of total risk factors variance. We then calculated weighted population attributable fraction (PAF) estimates.ResultWe will present each potentially modifiable dementia risk factor’s prevalence, communality, relative risk, unweighted and weighted PAFs and our new lifecourse infographic.ConclusionOur results give hope suggesting many dementias can be prevented or delayed. Many risk factors are linked to deprivation, for example, where people live and exposure to air pollution, or finding affordable healthy food within walking distance and having the resources and skills to prepare it. We have more evidence that longer exposure to a risk has more effect, for example in diabetes, and that risks have more effect in otherwise vulnerable people, for example air pollution. Thus, it is important to redouble efforts to treat existing conditions in communities and people with multiple risks where approaches beyond individual treatment or behaviour change have potentially larger impact. While association is not causation, the effect on cognition of multicomponent, hearing aid and hypertensions RCTs, and naturalistic changes with reduction in air pollution, cigarette smoking, social contact, hearing and vision corrections and work cognitive stimulation, continue to suggest causal relationships with dementia. Socially disadvantaged groups in all countries are more at risk and should be prioritised for intervention. There is more evidence that risks are also modifiable for people at increased genetic risk.