bluuebunny/crossref_metadata_2025_split huggingface dataset:
MIND‐China in 2018‐2023: Multimodal interventions in rural communities
Authors: Qiu Chengxuan 
Published: January 2025

AbstractBackgroundWorldwide, ∽40% of dementia cases are preventable by interventions to target major modifiable risk factors. In the multimodal interventions to delay dementia and disability in rural China (MIND‐China), we aim to test the effect of multimodal intervention programs on maintaining cognitive and physical function among rural‐dwelling older adults and discuss about challenges and opportunities for a multidomain intervention study in a rural population.MethodMIND‐China targets people who are aged 60‐79 years and living in rural communities (52 villages) in Shandong. The study tested two intervention programs: The vascular intervention included treatment of hypertension, diabetes, and dyslipidemia; the multimodal intervention included vascular interventions plus non‐pharmacological intervention (e.g., group exercise, personalized leisure activities, and cognitive training). The control group received regular primary care. Baseline assessments and recruitment for interventions were performed in 2018‐2019. Follow‐up assessments were conducted in 2021 and 2023. The primary outcome is the composite cognitive z‐score from a neuropsychological test battery. Secondary outcomes are physical function, dementia, cardiovascular events, and mortality. Measures were taken to overcome barriers for study participation and to achieve high rate of participating interventions and follow‐up assessments.ResultAt baseline (March‐September 2018), 5765 persons (74.9% of all eligible persons; age ≥60 years; 57.2% women; 40.6% illiteracy; and 88.3% farmers) were recruited. In 2019, recruitment for interventions was performed aiming to recruiting 3000 participants who were aged 60‐79 years and free of dementia and disability. The cluster(village)‐based randomization method was used to assign participants into three groups. The intervention programs were organized by local coordinators and village doctors, even during COVID‐19 pandemic, whenever possible. Follow‐up assessments for intervention participants were conducted in 2021 and 2023. The interventions ended in October‐November 2023. The assessments and diagnosis of outcomes and data cleaning are ongoing. Factors associated with participation in and adherence to the interventions and follow‐up assessment are being analyzed.ConclusionMIND‐China successfully recruited a large sample of participants for a multimodal intervention in rural communities. The project is expected to clarify whether the personalized culture‐sensitive multimodal interventions may help maintain cognitive and physical function among rural elderly populations in China.
Proteomic Signature of The Cerebrospinal Fluid (CSF) in Preclinical and prodromal AD: A key role for adhesion proteins
Authors: Neal Reem M. , Yang zhiyi , Hajjar Ihab 
Published: January 2025

AbstractBackgroundAlzheimer's Disease (AD) proteomic studies have focused on understanding the pathophysiology of AD during the late stages of AD. However, recent studies have suggested that the preclinical stage of AD represents a golden window for intervention. Yet, little is known about the influence of the cerebrospinal fluid (CSF) molecular environment on the mechanisms underlying the pathogenesis of AD during the preclinical stage.MethodWe performed targeted proteomics using Olink® platform that measured 276 proteins related to neuronal injury, endothelial function, and cardiometabolic pathways in samples from 354 participants recruited for the BSHARP study. Advanced bioinformatic pipeline for data reduction, protein‐protein interaction networks, and module development were used. Resultant Hub proteins that are associated with various clinical phenotypes and biological traits such as levels of CSF AD biomarkers (Aβ42, Tau, and pTau) and the Aβ42/Tau Ratio (TAR) were identified. We then ran the list of Hub proteins through the STRING database to identify critical proteins and performed a pathway enrichment analysis to understand their role in AD.ResultWe compared CSF and plasma proteomic profiles between participants who have normal cognitive function and those who have based on TAR status. As a result, we identified critical proteins that are associated with AD clinical phenotypes and levels of CSF AD biomarkers such as Aβ42, Tau, and pTau (all p‐values <0.05). We also found a significant difference in levels of 6 of the critical genes based on TAR status (HGF, ICAM1, VCAM1, NRP1, NRP2, SCARB2, CCL3). Pathway enrichment of the critical proteins using Gene Ontology (GO) Biological Process identified a series of pathways related to cell adhesion, inflammation, and endothelial function as well as response to Amyloid (all p‐value <0.05) pathways which are known to be related to AD.ConclusionOur findings reveal that adhesion and endothelial‐related pathways are highly associated with AD phenotypes, especially in the preclinical stage. This suggests a possible proteomic signature in the CSF of individuals with preclinical AD that is driven by adhesion molecules and contributes to the pathogenesis of AD. Future studies investigating this contribution might provide insight into the molecular mechanisms underlying AD.
Real‐world utilization of diagnostic tests for mild cognitive impairment, Alzheimer’s disease, and other dementias in Medicare fee‐for‐service beneficiaries
Authors: Yan Jessie T. , Dillon Allison , Meng Tong , Ramesh Viviktha , Sabbagh Marwan N. , Roth Sophie 
Published: January 2025

AbstractBackgroundUse of neuroimaging [e.g. magnetic resonance imaging (MRI), positron emission tomography (PET), or computed tomography (CT) scan], cerebrospinal fluid (CSF), and blood biomarker tests can contribute to a more accurate and earlier diagnosis of Alzheimer’s disease (AD). This study aimed to examine real‐world utilization of existing diagnostic tests for mild cognitive impairment (MCI), AD, or other dementias in a large US elderly population.MethodUsing data from the Medicare 100% Research Identifiable files, this retrospective observational study included Medicare fee‐for‐service beneficiaries ≥ 67 years old and newly diagnosed with MCI, AD, or other dementias between 2015 and 2020. The study index date was the first disease diagnosis date. Descriptive analyses were conducted to examine the use of MRI, CT, PET, CSF, and any blood tests within 1 year before the index date in the overall study group and by three cohorts (MCI, AD, and other dementia). To understand test utilization patterns over time, test rates were also stratified by index year.ResultThe final study sample consisted of 653,420 patients (9.1% MCI, 30.3% AD, and 60.6% other dementias). Overall, during the 1 year before the index date, 71.9% had at least one blood test, 53.9% had any neuroimaging test, 46.4% had CT, 17.7% had MRI, 0.7% had PET, and 2.2% had CSF. Across cohorts, the other dementia cohort had the highest utilization of any neuroimaging test (56.2% vs. 51.4% in AD vs. 46.9% in MCI). The MCI cohort had the highest utilization of CSF (3.5% vs. 2.2% in other dementias vs.1.8% in AD). The use of these diagnostic tests increased slightly from 2015 to 2020 (see Figure 1).ConclusionIn the six years prior to the availability of disease‐modifying therapies (DMTs), blood tests, MRI and CT were the predominant diagnostic tests, while the use of CSF and PET was very infrequent. Despite the modest increasing trends, substantial improvements are needed in the use of confirmatory tests, especially PET and CSF which will be necessary for increased utilization of new DMTs.
Digital Clock Assessment in South Asian Setting: Insights from the P‐CARRS study
Authors: Jagannathan Ram , Mohan Deepa , Komal Rani , Kondal Dimple , Subramani Poongothai , Pai Rima , Ali Mohammed K , Mohan Sailesh , Alladi Suvarna , Tandon Nikhil , Prabhakaran Dorairaj , Mohan V , Levey Allan I. , KM Venkat Narayan , Goldstein Felicia 
Published: January 2025

AbstractBackgroundDetection of presymptomatic individuals or those with subtle cognitive changes in midlife may prevent or slow the course of Alzheimer's Disease by identifying candidates for disease‐modifying treatments. Utilizing newer delivery approaches involving digital measures shows promise for cognitive phenotyping, early detection, ease of administration, and scoring, particularly in low‐resource settings. However, the feasibility of these approaches, along with their association with demographics and their effectiveness in detecting fine‐grained aspects of cognitive performance in low‐resource settings, remains unclear. We conducted a pilot study evaluating digital cognitive screening using an iPad‐administered clock drawing test in a diverse South Asian population residing in India.MethodsIndividuals ≥ 50 years old (median: 61.0 years; range: 50‐89 years; female: 56%; education: up to primary schooling: 8%; high school to secondary: 65%; graduation and above: 27.4%) nested within the ongoing population‐based longitudinal Precision‐CARRS study representing socio‐demographically and linguistically diverse adults from Delhi and Chennai in India (n=300; 150/site) were studied. Participants were administered the FDA‐approved, iPad‐based clock drawing test using a commercially available Linus Health Digital Clock (DCTclock) screening tool. The DCTclock summary score, ranging from 0 to 100, was derived through AI analytics and provided various features, including drawing efficiency, information processing, simple motor skills, and visuospatial reasoning. Performance on the traditionally administered paper/pencil version of the Mini‐Cog test incorporating clock drawing and three‐item recall was used to classify participants as cognitively impaired (0‐2 points) or intact (3‐5 points).ResultsDCTclock was administered in ∼3‐4 minutes, and only 0.7% of clocks were unanalyzable due to missing components. Older age and lower education (p<0.0001) were associated with worse DCTclock summary scores. There were no sex differences in performance (p=0.90). Compared to those cognitively intact based on the Mini‐Cog scores (n=252), the impaired group (n=48) performed significantly worse on the DCTclock summary score and spatial reasoning components (Table).ConclusionScreening for cognitive status using digital clock measurement is highly feasible and takes a short amount of time to administer in low‐resource settings. The DCTclock provides fine‐grained measures of performance not available on traditional paper/pencil measures, which may prove sensitive to early detection of cognitive impairment.
Insights From A Super Seniors Population: Plasma Biomarkers Increase In Magnitude And Variability With Age
Authors: Cooper Jennifer G , Stukas Sophie K , Ghodsi Mohammad , Leach Stephen , Brooks‐Wilson Angela , Wellington Cheryl L 
Published: January 2025

AbstractBackgroundPlasma biomarkers such as neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and phosphorylated tau‐181 (p‐tau‐181) have been thoroughly investigated in Alzheimer’s disease and other dementias. However, further investigations into how biological variables can influence biomarker concentrations in both normative and cognitively resilient populations will be important for more robust interpretations of biomarker levels. This study investigates how ageing modifies plasma biomarkers in a normative, epidemiologically representative Canadian population and in cognitively healthy seniors over 80 years old.MethodBiomarkers were analysed on the Quanterix Simoa HD‐X analyzer using Neurology 4‐plex E and p‐tau‐181 assays. N=900 Canadian Health Measures Survey plasma specimens were analyzed as a normative population. Using smoothed quantile regression, the 5th, 50th and 95th percentiles from ages 3‐79 years were determined. The percentiles from 50, 60, and 70 years old were extracted here for analysis. N=480 plasma specimens were analyzed from cognitively healthy Super Seniors Study participants with a median age of 88 years old (IQR= 87‐90y), who had never been diagnosed with dementia, cancer, diabetes, cardiovascular or major pulmonary disease.ResultIn the normative population, between 50 to 70 years old, median concentrations increased by 88% for NfL, 79% for GFAP, and 38% for p‐tau‐181. When compared to 50‐year‐olds in the normative population, the median biomarker concentration in Super Seniors were also higher; 3.4 times for NfL, 3.3 times for GFAP, and 2.2 times for p‐tau‐181. The variability of plasma biomarkers, measured as the range between the 5th and 95th percentiles, also increased with age. Compared to 50 years old, the ranges at age 70 were 2.8 times larger for NfL, 2.2 times larger for GFAP, and 1.5 times larger for p‐tau‐181; While the ranges observed in Super Seniors, compared to 50 years old, were 5.3 times larger for NfL, 3.4 times larger for GFAP, and 2.8 times larger for p‐tau‐181.ConclusionCognitively healthy seniors over 80 years have higher and more variable plasma biomarker concentrations than a normative 50‐year‐olds. These data indicate that age, regardless of cognitive status, modifies biomarker concentrations over the age of 80 years.
Age‐Related Structural and Vascular Changes in the Choroid Plexus: Insights from the HCP Dataset
Authors: Sun Zhe , Li Chenyang , Wisniewski Thomas , Ge Yulin 
Published: January 2025

AbstractBackgroundThe choroid plexus (ChP) plays a vital role in CSF production and waste clearance. While existing imaging studies have established connections between ChP volume changes and age‐related neurodegenerative diseases, a comprehensive investigation into the microstructural and vascular changes associated with aging remains insufficient. This study aims to explore ChP changes in normal aging using diffusion and perfusion MRI in the HCP‐Aging dataset to enhance our understanding of age‐related microstructural and vascular changes in the ChP.MethodOur analysis included 641 healthy participants (age: 36‐90 years; mean±SD = 60±16 years; 282 males) with the following MRI parameters: (1) T1 MPRAGE for ChP segmentation[1]; (2) Diffusion MRI for quantification of mean diffusivity (MD); (3) PCASL MRI for quantification of cerebral blood flow (CBF) and arterial transit time (ATT). The ChP mask was co‐registered with MD, CBF, and ATT maps to extract corresponding values. Pearson's correlation and one‐way ANOVA were used for age effects and perfusion property comparisons among gray matter (GM), white matter (WM), and ChP, respectively.ResultChP imaging revealed increased volume, increased MD, and decreased CBF across different age groups (Figure 1). Figure 2 demonstrated a positive correlation between ChP volume and age (r = 0.31, p<0.0001), while ChP CBF declined with age (r = ‐0.41, p<0.0001) and MD positively correlated with age (r = 0.56, p<0.0001). Adjusting for age and sex, ChP CBF negatively correlated with volume (r = ‐0.26, p < 0.0001). One‐way ANOVA analyses indicated significant differences in CBF and ATT among ChP, GM, and WM (p<0.0001 for all comparisons), with ChP exihbiting the highest CBF and shortest ATT (Figure 3).ConclusionIn addition to volume changes, we found significant age‐related diffusion and perfusion changes in the ChP in this large dataset. The decline in CBF and the increase in MD with aging suggest vascular degeneration and compensatory dystrophic hyperplasia of surrounding tissues of ChP. These findings in normal aging set a crucial normative reference for future studies on cognitive impairment in abnormal aging processesReferences: 1. Tadayon, E., et al. J Alzheimers Dis (2020).
Short‐term Sirolimus Treatment Increases Cerebral Blood Flow in Asymptomatic APOE4 Females Determined by 3T MRI
Authors: Neher Caitlin M. , Khegai Oleksandr , Overschmidt Jessica , Cassani Joanne , Xing Xin , Flemister Abeoseh , Green Stefan J. , Kurt Mehmet , Beversdorf David Q. , Xu Feng , Grinstead John W. , Balchandani Priti , Altes Talissa A. , Lin Ai‐Ling 
Published: January 2025

AbstractBackgroundApolipoprotein ε4 allele (APOE4) is the strongest genetic risk factor for late‐onset Alzheimer’s disease (AD) with females having higher risk than males. Compared with non‐carriers, cognitively normal, middle‐aged APOE4 carriers have lower cerebral blood flow (CBF) decades before clinical symptoms appear. Early intervention to protect CBF would be critical for APOE4 carriers to mitigate AD progression. We have shown in APOE4 mice that Rapamycin (a.k.a. Sirolimus), a FDA‐approved mTOR‐inhibitor, can restore CBF. Here, in the first human study, our goal is to determine whether the findings translate to human APOE4 carriers by measuring CBF with MRI.MethodThe study was performed at the University of Missouri. Low dose Sirolimus (1 mg/day) was given for 4 weeks to two middle‐aged, cognitively normal APOE4 females (45‐65 yrs; MOCA>28). APOE status was determined by oral swabs. 3T MRI‐based pseudo‐continuous arterial spin‐labeled (PCASL, 1.7x1.7x4mm resolution) images were acquired at four time‐points: baseline (pre‐treatment), 2nd and 4th week into treatment, and washout (2 weeks post‐treatment). PCASL data was processed with FSL BASIL toolbox and regionally analyzed using FreeSurfer segmentation of T1‐weighted images.ResultAverage values of CBF (ml/100g/min) increased in all areas of investigation. When compared to baseline values, we observed an average 34.8±2.1% increase in washout CBF in the cortex across subjects (Figure 1). Within the cortex, there was an average increase of 41.5±8.9, 28.2±6.2, 37.4±1.7, and 33.1±0.3% in the frontal, parietal, temporal and occipital lobes, respectively. White matter CBF showed a similar trend, increasing by 33.7±4.9% across subjects from baseline to washout (Figure 2). Smaller AD‐associated regions were evaluated and also showed CBF improvement: the entorhinal cortex showed a 25.1±4.3% increase, while the hippocampus and amygdala showed a 21.4±1.1 and 23.6±9.8% increase, respectively (Figure 3). No side effects were observed, and no changes in blood glucose and HbAc1 levels were found in the participants.ConclusionShort‐term Sirolimus treatment can effectively increase CBF for asymptomatic APOE4 females, who have the highest risk for AD. Future work will include APOE4 males, increase the sample size and compare CBF with non‐carriers (e.g., APOE3/APOE2). Restoration of CBF may pave a way to mitigate or prevent AD developments for APOE4 carriers.
Perivascular space enlargement and cerebrovascular and Alzheimer’s diseases
Authors: Moyano Jose Bernal , Menze Inga , Yakupov Renat , Kaya Pinar , Aki Cagla , Pfister Malte , Geisendörfer Jonas , Peters Oliver , Priller Josef , Schneider Anja , Fließbach Klaus , Wiltfang Jens , Buerger Katharina , Perneczky Robert , Teipel Stefan , Laske Christoph , Spottke Annika , Heneka Michael T. , Wagner Michael , Ramirez Alfredo , Wolfsgruber Steffen , Kleineidam Luca , Jessen Frank , Schreiber Stefanie , Düzel Emrah , Ziegler Gabriel 
Published: January 2025

AbstractBackgroundPerivascular spaces (PVS) can become large enough to be visible in magnetic resonance imaging (MRI). The exact aetiology of PVS enlargement in humans remains, however, elusive and under continuous debate [1‐5]. Here, we tracked PVS volumes longitudinally over three years in 525 individuals along AD syndromal cognitive stages, namely cognitively unimpaired (CU), mild cognitive impairment (MCI), and Alzheimer’s disease (AD), to pinpoint conditions related to PVS enlargement.MethodWe studied centrum semiovale (CSO) and basal ganglia (BG) PVS computationally over three to four annual visits in 525 DELCODE participants (CU/MCI/AD 417/72/36; 49.52% female, mean age 70.85 (SD 5.78)) [6]. We segmented PVS using a multimodal Hessian‐based filtering method [7] leveraging T1w and FLAIR imaging, which we validated against clinical visual ratings. We used linear mixed‐effect modelling to study temporal PVS volume changes. First, we tested whether PVS volumes increased over follow‐ups in CU. Second, we explored whether longitudinal PVS enlargement was associated across ROIs, and predicted by individual white matter hyperintensities (WMH), Amyloid and Tau positivity status at baseline in the entire cohort. We adjusted all analyses by age, sex, years of education, and total intracranial volume.ResultWe observed PVS volume increase over follow‐ups in healthy ageing with a significant individual difference of change (Figure 1; BG: B=0.06 [95%‐CI 0.04‐0.08], p<0.001; CSO: B=0.06 [95%‐CI 0.04‐0.09], p<0.001). PVS enlargement in BG was associated with that in CSO (ρ=0.17, pFDR<0.001). Participants with greater baseline WMH volumes tended to have faster BG‐PVS enlargement (ρ=0.05, pFDR=0.06). Participants with both Amyloid and Tau positive tended to have faster CSO‐PVS enlargement than those with neither (Figure 2; Χ²(2)=5.07, p=0.079, η²=0.014).ConclusionGiven our findings, ageing is a primary driver of PVS enlargement. Associations between PVS and WMH underline shared cerebrovascular mechanisms. Detrimental cycles driven by neurotoxic waste accumulation might also contribute to PVS enlargement. Further research is needed to disentangle pathological cascades, their concurrent dynamics, and their unique contribution to disease progression.References10.1016/j.neurobiolaging.2022.01.00610.18632/oncotarget.1772410.1002/ana.2647510.1161/STROKEAHA.117.01752610.1016/j.clineuro.2019.05.00210.1186/s13195‐017‐0314‐210.1007/BFb0056195
Training of formal caregivers in geriatric mental health and dementia care: Experiences and challenges from the Indian context
Authors: Sivakumar Palanimuthu Thangaraju 
Published: January 2025

AbstractThe population of older adults in India is projected to increase from the current estimate of 150 million to 350 million by the year 2050. The prevalence of older adults with mental health problems including dementia is also increasing rapidly. The socio‐cultural changes in the joint family system have necessitated the increasing requirement of formal caregivers for supporting the care of older adults in home as well as residential care institutions. Home care services providing caregiver assistance, day care, old age homes, residential care institutions for persons with mental illness or dementia are available predominantly in major cities. However, there is a huge variability in the profile of formal caregivers ranging from those with no training to qualified nurses as caregivers depending on the affordability. The need for training of formal caregivers in geriatric mental health and dementia care is acknowledged by most of the the stakeholders in the care of older adults. However, there are no minimum standards of training for the formal caregivers. The lack of trained caregivers has contributed to the increase of elder abuse, higher stress, and burnout for the caregivers with adverse impact on the quality of care of older adults. This presentation will summarize the experience and challenges related to the implementation of the training of formal caregivers in geriatric mental health and dementia care. The training initiatives for the formal caregivers conducted by the Government and Non‐Governmental organizations ranges from brief sensitization program for half a day to formal certificate course for 3 months. Most of the training programs are focused on the basic aspects of geriatric care with inadequate component of practical training. High rates of discontinuation and change of jobs, poor working conditions, lack of motivation among the caregivers and employers, lack of mandatory requirement of training are some of the important challenges limiting the progress in ensuring trained formal caregivers.