bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Graph‐Theoretic Approach for fMRI Time‐Series Classification into Healthy and MCI
Authors: Acharya Ameiy , Sinha Neelam 
Published: January 2025

AbstractBackgroundMild Cognitive Impairment (MCI), a transitional stage between healthy aging and Alzheimer's disease, offers a critical intervention window (Vega and Newhouse, 2014). Diagnosing MCI proves challenging due to subtle neurodegenerative changes. Our study employs graph representations of fMRI time‐series, emphasizing connectivity between brain regions (Stam and Reijneveld, 2007). Utilizing the Dosenbach‐160 ROI atlas and extracting eigenvalues and eigenvectors, we apply machine learning for classification.MethodEach subject contributes fMRI data from six networks, with each network comprising 187 timestamps and varying numbers of Regions of Interest (ROIs). For every network of each subject, we segment the timestamps into 11‐time interval batches, generating 17 graphs to encapsulate the subject's representation within a network. The principle guiding our approach is that similar eigenvalues reflect similar graphs. Construction of partial correlation graphs involves deriving precision matrices, where ROIs become graph nodes, and partial correlations form edge weights. Transforming these graphs into adjacency, degree, and Laplacian matrices, we further apply eigen‐decomposition on the Laplacian matrix to extract eigenvalues and eigenvectors. The eigenvectors corresponding to the largest absolute eigenvalue serve as features for SVM and Logistic Regression classification.ResultIn our balanced dataset of 100 subjects (50 healthy, 50 MCI) sourced from publicly available ADNI database, SVM achieves accuracies of 80.39% (DMN), 76.86% (Cerebellum), 85.69% (Cingulo‐opercular), 76.27% (Fronto‐parietal), 72.94% (Occipital), and 90.20% (Sensorimotor). Logistic Regression yields accuracies ranging from 71.18% to 86.27%. Notably, the Sensorimotor, Cingulo‐Opercular and DMN networks display distinctive connectivity alterations in MCI, reflecting the versatility and generalizability as well as the medical correctness of our approach. These findings underscore the method's robust ability to discern intricate brain connectivity patterns and contribute to potential clinical relevance for early neurodegenerative disorder diagnosis and interventionConclusionOur study showcases the effectiveness of a graph‐theoretic approach in capturing the intricate connectivity dynamics of fMRI time‐series data across multiple networks. By representing each subject within a network through graphs, we unveil the subtleties of MCI pathology. The derived insights not only contribute to enhanced diagnostic precision but also shed light on the intricate relationships within brain networks.
Planning Ahead with Care: A Randomized Clinical Trial of a Video Intervention to Improve Caregiver Knowledge of Severe Dementia and Medical Care Decisions
Authors: Brandt Katherine , Quimby Megan , Wong Bonnie , Quintiliani Lisa M. , Marchesano Amy , Goldstein Alexa , Celaj Gent , Howe Inola , Krahn Erin , O’Chander Raseeka , Krivensky Samantha , Paasche‐Orlow Michael K. , Volandes Angelo , Dickerson Brad C 
Published: January 2025

AbstractBackgroundCaregivers of individuals living with dementia frequently make medical decisions for care recipients, often without a clear understanding of those needs. Educational tools are needed to guide caregivers about when and how to raise the topic of advance care planning (ACP).MethodCaregivers of individuals living with dementia (N = 130) were randomized into control (N = 64) (ACP verbal educational script) or intervention (N = 66) (ACP verbal educational script and video) groups. Both groups completed online surveys and participated in online interviews. The educational intervention was performed at baseline with pre‐ and post‐intervention assessments. Baseline, three‐ and six‐month interviews assessed severe dementia and medical care knowledge quantitatively (true/false questions) and qualitatively (open‐ended questions). Decisional conflict (Decisional Conflict Scale) and decisions for comfort care (open‐ended questions) were also examined.ResultAcross the entire sample, severe dementia and medical care knowledge increased immediately after the educational intervention. Although the groups did not differ in severe dementia or medical care knowledge (all p values n.s.), the video intervention group demonstrated increased confidence in knowledge about both topics (p<0.05). Post‐intervention, participants’ confidence in severe dementia knowledge and medical care knowledge were higher in the video intervention group vs. control group (p<0.05). Chi‐square analysis indicated that decision for comfort care did not differ between groups (p>0.196). There was no difference between groups in total decisional conflict score or in any of the 5 subscores, pre‐ or post‐intervention (all p values n.s.). However, across all participants there was a decrease in total decisional conflict score and in each subscore pre‐ to post‐intervention (all p values < .001).ConclusionCaregivers of individuals living with dementia benefit from education about the stage of severe dementia and medical care decisions that may need to be made. Analysis is ongoing for three‐ and six‐month follow‐up sessions.
Automated word class and person usage metrics as markers of Alzheimer’s and frontotemporal dementia
Authors: da Cunha Pamela Lopes , Ruiz Fabian , Ferrante Franco Javier , Sterpin Lucas , Ibañez Agustin , Slachevsky Andrea , Matallana Diana , Martinez Angela , Hesse Eugenia , Garcia Adolfo M 
Published: January 2025

AbstractBackgroundDementia impacts the way individuals perceive and describe everyday events. Alzheimer's disease (AD) notably affects processing of entities manifested by nouns, while behavioral variant frontotemporal dementia (bvFTD) often presents a detached, third‐person perspective. Yet, the potential of natural language processing tools (NLP) to detect these variations in spontaneous speech remains explored. To tackle this gap, we analyzed both patterns via automated discourse‐level metrics in individuals with AD and bvFTD, contrasting them with healthy controls (HCs).MethodsPersons with AD (n = 21), bvFTD (n = 21), as well as HCs (n = 21), narrated a typical day of their lives. We analyzed the frequency of nouns and verbs, along with first‐ or third‐person usage, via part‐of‐speech and morphological tagging, respectively. Inferential statistics and machine learning were used to examine whether these features were useful for discriminating patients from HCs at both the group and the subject level. We further evaluated whether such features correlated with cognitive symptom severity, as captured through the Montreal Cognitive Assessment (MoCA).ResultsCompared with HCs, AD (but not bvFTD) patients exhibited a lower proportion of nouns, without differences in verb ratio. Conversely, persons with bvFTD (but not those with AD) had a greater proportion of third‐person markers and a reduced proportion of first‐person markers. Machine learning analyses showed that these features robustly identified individuals within each group (AUCs = 0.75). No linguistic feature was significantly correlated with MoCA scores in either patient group.ConclusionsSpontaneous daily narratives offer distinct markers for AD and bvFTD, detectable through automated analysis. Focusing on specific linguistic attributes relevant to each type of dementia not only aids in understanding but also enhances diagnosis and tracking of these conditions. Overall, our findings attest to the relevance of NLP tools as a viable, cost‐effective means to identify scalable dementia markers.
Comparing overall medical costs of operative versus nonoperative treatment for femoral neck fractures among Alzheimer’s disease patients: a retrospective cohort study
Authors: Yang Yijiong 
Published: January 2025

AbstractBackgroundAddressing femoral neck fractures resulting from ground‐level falls in older adults with Alzheimer’s disease (AD) involves a personalized treatment plan, leading to a substantial economic burden on the healthcare system. The debate surrounding the advantages and disadvantages of surgical interventions versus non‐operative approaches for femoral neck fractures in older individuals with AD remains a topic of active discussion.MethodIn this retrospective cohort study, the total medical expenses associated with operative and non‐operative therapies were compared while adjusting for patients' demographics and baseline health conditions. The study included Optum beneficiaries diagnosed with Alzheimer’s disease (AD) who filed an initial claim for femoral neck fracture between January 1, 2012, and December 31, 2017. Generalized linear regression with a gamma distribution and log link was performed to compare the adjusted overall medical costs between treatment groups controlling for patients’ demographic characteristics (age, gender, race, residential region), insurance type, and baseline health status.ResultA total of 4,157 AD patients with femoral neck fracture was identified. This included 1,508 cases undergoing internal fixation, 2,334 cases of arthroplasty surgery, and 315 cases of non‐operative treatment. Among them, 59.8% were female (n = 2,487), and the median age was 81 years. The adjusted average total medical costs for arthroplasty and internal fixation were $207,392 and $170,210, which were higher than average total cost for non‐operative group (mean = $63,041). Arthroplasty treatments exhibited overall medical costs 2.56 times higher (95% CI: 2.288 – 2.875) than those of non‐operative treatment, while internal fixation’s overall costs were 2.33 times higher (95% CI: 2.067 – 2.628) than non‐operative treatment. Comorbidities such as history of fall, sarcopenia/muscle weakness, abnormal weight loss, depression, and fatigue had a significant influence on the overall medical cost. Patients with history of fall had an estimated 1.22 times higher medical cost compared with those without history of fall.ConclusionThe operative treatment groups exhibited higher overall medical costs. The overall costs encompassed not only the direct medical costs associated with surgery but also post‐surgery rehabilitation expenses in nursing homes or home health settings.
Amyloid burden and APOE modify sex differences in estimated meta‐temporal region tau onset age
Authors: Heston Margo B. , Cody Karly , Teague Jordan P , Chavez Elena Ruiz De , Morse Jacob , Deming Yuetiva , Engelman Corinne D. , Chappell Richard J , Langhough Rebecca E. , Gleason Carey E. , Clark Lindsay R. , Zuelsdorff Megan L. , Betthauser Tobey J. 
Published: January 2025

AbstractBackgroundRecent advances in Alzheimer’s disease (AD) temporal biomarker modeling have revealed considerable heterogeneity in age at amyloid onset, and recently we and others identified sex and APOE differences in tau onset age and subsequent dementia development. Here we assessed whether amyloid burden, APOE‐ε4 dose, and sex interact to predict estimated T+ onset age (ETOA).MethodsAlzheimer’s Disease Neuroimaging Initiative participants (N=911, Table 1) underwent serial PET imaging to quantify global cortical amyloid ([18F]Florbetapir SUVR50‐70, [18F]Florbetaben SUVR90‐110) and meta‐temporal tau ([18F]Flortaucipir SUVR80‐100) burden. Cortical amyloid SUVRs were harmonized using linear transformation to Centiloids (CL). Sampled iterative local approximation (SILA) was used to model ETOA and, separately, to estimate amyloid CL burden at ETOA. Kaplan‐Meier survival curves and Cox regression were used to test CL*APOE‐ε4*sex interaction effects on ETOA. Event time was ETOA for T+ individuals and age at last tau PET scan (right censored) for T‐ individuals who could become T+.ResultsWe observed a significant CL*APOE‐ε4*sex interaction on ETOA (p=0.013, Table 2). APOE‐ε4 was associated with earlier ETOA in a dose‐dependent manner and effects were greater in females compared to males. ETOA differences between sexes and across APOE‐ε4 were attenuated at higher amyloid burden, largely due to the increased presence of T+ across all APOE‐ε4 statuses and both sexes (Figure 1). Main effects also revealed that higher cortical amyloid burden at ETOA was associated with earlier ETOA and greater T+ risk, as was greater APOE‐ε4 dose (Table 2).ConclusionsThese results suggest that amyloid burden, APOE‐ε4, and sex may influence when temporal tau deposition becomes abnormal. Smaller sample size among APOE‐ε4 carriers, and especially ε4 homozygotes, limits the estimates in this cohort. Future extensions of this work will expand to a multicohort sample, to attempt replication of these findings and to investigate how these factors and their interaction predict time from amyloid and tau onset to dementia.
Capacity for Alzheimer’s Disease confirmatory testing in the US ‐ current situation and simulations for future increase
Authors: Roth Sophie , Yan Jessie T. , Patru Maria‐Magdalena , Mattke Soeren , Ortsäter Gustaf , Gustavsson Anders 
Published: January 2025

AbstractBackgroundRecent advances in Alzheimer’s Disease (AD) disease modifying therapies (DMTs) emphasize the need of an early, timely and accurate diagnosis to initiate treatment and improve patient outcomes. Clinicians must confirm amyloid pathology through cerebrospinal fluid (CSF) testing or amyloid positron emission tomography (PET) scan to qualify patients. As a result, the demand for confirmatory CSF or imaging biomarker testing is predicted to rise significantly.MethodWe developed a model to analyze diagnostic capacity for patients with mild cognitive impairment (MCI) seeking care in the US. We assessed amyloid PET and CSF testing from a payer’s perspective over 5 years. It was assumed that CSF testing is constrained by the number of lumbar puncture procedures rather than laboratory capacity. Of all currently available PET capacity per year, about 5% is used for AD diagnosis; this is assumed to increase approximately 7% per year. We compare four scenarios: 1) currently observed CSF (about 3.5%) and amyloid PET (< 1%) usage based on Medicare data; 2) increasing CSF use to meet the increasing demand for confirmatory testing, while PET remains as in scenario 1; 3) 100% amyloid PET 4) 100% CSF usage.ResultCurrent usage of CSF and amyloid PET testing (scenario 1) cannot meet the increasing demand for AD confirmatory testing: Assuming 50% of patients with MCI seek care annually, there would be an excess demand of about 10 times in year 1. Increasing CSF usage in scenario 2 would lead to timely diagnosis of up to 55% of beta amyloid positive patients in 5 years, of which 45% is attributed to CSF testing and the remaining to PET use. The more extreme scenarios 3 and 4 of 100% use of either PET or CSF, result in <1% patients and 12.6% patients being diagnosed in year 1, respectively.ConclusionIncreasing CSF use and capacity could meet the demand for confirmatory testing the quickest, reduce wait times and increase the number of timely diagnosed patients, especially during the time where more amyloid PET capacity is being instituted. Efforts to increase CSF usage and capacity could positively impact patient outcomes.
Association of metabolic syndrome with brain imaging and cognitive function in UK Biobank
Authors: Qureshi Danial , Topiwala Anya G , Al‐Abid Md Shehab Uddin , Allen Naomi , Kuzma Elzbieta , Littlejohns Thomas J 
Published: January 2025

AbstractBackgroundMetabolic syndrome (MetS) has been previously associated with an increased risk of developing dementia. Exploring links between MetS, neuroimaging and cognitive function measures can offer insights into whether MetS adversely affects brain health prior to dementia onset. We sought to examine the association of MetS with brain structure and cognition.MethodsParticipants were selected from the UK Biobank multi‐modal imaging study (2014‐ongoing). MetS was defined as the presence of ≥3 of the following components: elevated waist circumference, triglycerides, blood pressure, HbA1c, or reduced HDL‐cholesterol. Neuroimaging outcomes included total brain, grey/white matter, white matter hyperintensity (WMH) and hippocampal volume from T1/T2‐weighted magnetic resonance imaging (MRI), and cognitive tests measuring executive function, reasoning, memory, and processing speed. Cross‐sectional associations were assessed using linear regression adjusted for age, sex, ethnicity, education, socioeconomic status, household income, smoking status, alcohol intake, physical activity, APOE‐ε4 carrier status, and assessment centre. Neuroimaging analyses were further adjusted for imaging‐related confounders (head size, head position, head motion).ResultsAmong 32,864 dementia‐free participants, 9,484 (29%) had MetS. MetS was significantly associated with lower total brain volume (β:‐0.06, 95%CI: ‐0.08, ‐0.04), grey matter volume (β: ‐0.09, 95%CI: ‐0.11, ‐0.07), hippocampal volume (left = β: ‐0.02, 95%CI: ‐0.05, ‐0.00; right = β: ‐0.03, 95%CI: ‐0.05, 0.00), and greater WMH volume (β: 0.10, 95%CI: 0.08, 0.12). MetS participants performed significantly worse on cognitive tests of working memory (β: ‐0.11, 95%CI: ‐0.14, ‐0.08), verbal declarative memory (β: ‐0.10, 95%CI: ‐0.12, ‐0.07), processing speed (β: ‐0.09, 95%CI: ‐0.12, ‐0.06), verbal and numerical reasoning (β: ‐0.06, 95%CI: ‐0.08, ‐0.03), executive function (β: 0.05, 95%CI: 0.02, 0.07), and non‐verbal reasoning (β: ‐0.04, 95%CI: ‐0.06, ‐0.01). We observed dose‐response relationships, with an increasing number of MetS components being associated with lower brain volume, greater WMH volume, and poorer cognitive function across all tests.ConclusionMetS was associated with lower brain volume, greater vascular pathology, and poorer performance across multiple domains of cognitive function. These findings demonstrate that MetS is related to poorer brain health in dementia‐free individuals and could represent a novel risk factor for future development of dementia.
A Feasibility Study of Brain‐WISE: A Group‐Based, Person‐Centered Dementia Risk Reduction Program
Authors: Cohen Matthew L. , Van Buren Kimberly , Myers Mindy J , Ellison James M , Martens Christopher R. , Lanzi Alyssa M 
Published: January 2025

AbstractBackgroundReducing risk of dementia requires a person to have accessible information about health and risk factors, person‐centered health goals, and self‐efficacy. Here, we test the feasibility of a new risk reduction program called Brain Wellness Information, Support, and Empowerment (Brain‐WISE). Its unique features are that it (1) is aligned with a theoretical model of behavior change, (2) is relatively brief (six 90‐min sessions), (3) is conducted with groups of people who have pre‐existing community; (4) includes individual and group activities and person‐centered health goals; and (5) is conducted with speech‐language therapists.MethodsWe conducted two waves of a single‐arm pilot study with 49 older adults (aged 64‐93) to iteratively refine the program and evaluate its feasibility (adherence, acceptability, and pilot efficacy). Each of the six treatment sessions included a group lecture on brain health topics interspersed with individual and group activities. Brain health topics included (1) normal and abnormal cognitive aging and management of chronic conditions; (2) physical activity; (3) MIND Diet; (4) hearing, cognitive, and social health; (5) preventative use of cognitive aids and strategies; and (6) stress management and sleep. Adherence was measured with attendance. Acceptability was measured with bespoke questionnaires. Patient‐reported outcome measures were administered before and 1 week after treatment to assess changes in intermediate psychological outcomes (e.g., self‐efficacy) and ultimate behavioral outcomes (e.g., physical activity).ResultsBetween Waves 1 and 2 we modified lecture content and activity materials, and selected different outcome measures. Attendance in Waves 1 and 2 was 97% and 93.4%, respectively. In each domain of acceptability (lecture content, lecture delivery, and activities), session‐specific mean responses on a 5‐point scale ranged from 4.1 to 4.7. In Waves 1 and 2, 92.3% and 90% of participants agreed or strongly agreed that the program was worthwhile. After Wave 2, pre‐post dementia knowledge increased, MIND diet scores improved, exercise increased, and perceived barriers to lifestyle change decreased. Self‐efficacy did not change.ConclusionsThe Brain‐WISE program is a feasible dementia risk reduction program for community‐dwelling older adults. Based on these findings, a full‐scale RCT to evaluate its efficacy is warranted.
Disentangling Molecular Links Underlying the Heart‐to‐Brain Connection in Older Adults
Authors: VandeBunte Anna M. , Saloner Rowan , Paolillo Emily W. , Ehrenberg Alexander J. , Cadwallader Claire J. , Chen Coty , Wyss‐Coray Tony , Rojas Julio C. , Chan Brandon , Lago Argentina Lario , Bennett David A. , Kramer Joel H. , Casaletto Kaitlin B. 
Published: January 2025

AbstractBackgroundCardiovascular disease (CVD) is among the strongest modifiable risk factors for dementia. However, vascular health is multifaceted, and its neurobiological underpinnings are unclear. A recent study (Williams et al. 2022) leveraged blood proteomics and machine learning to identify a novel group of 27 proteins that robustly predicted 4‐year likelihood of myocardial infarction, stroke, heart failure, or death. We examined whether these CVD‐related blood proteins also relate to brain health outcomes in older adults across three study cohorts.MethodDiscovery cohort included 84 older adults from the UCSF Memory and Aging Center (57% female; 79% clinically normal; 21% mild cognitive impairment [MCI] due to Alzheimer’s disease [AD]) with plasma assayed for the 27 CVD‐related proteins (SomaScan) and plasma neurofilament light (NfL, Simoa). Participants completed brain MRI and neuropsychological evaluations. Separate regression models related each CVD protein to each brain health outcome (NfL, total gray matter volume, global cognition), adjusting for age, sex, BMI, and TIV and education, as appropriate. CVD proteins that reached significance in the discovery cohort were validated in an independent in‐vivo cohort with plasma SomaScan and all three brain outcomes (Stanford ADRC; n=40, 25% AD) and an autopsy cohort with brain tissue protein quantification (Selected Reaction Monitoring) and cognitive data (Rush ADC; n=1103, 40% AD) via parallel regression models.ResultIn the discovery cohort, three CVD‐related plasma protein levels individually associated with global cognition (JAM2, PTPRJ, NCAM1, ps<0.03) and four proteins associated with plasma NfL (PTPRJ, GOLM1, SPON1, LRP11, ps<0.02). Only ADAMTS13 associated with total gray matter volume (p<0.01). In validation analyses, higher abundance of plasma SPON1 related to higher plasma NfL (β=0.38, p=0.02 [Stanford]), and higher abundance of SPON1 in brain tissue related to poorer cognition (β=‐0.13, p<0.0001 [Rush]). Brain tissue SPON1 also significantly differed across clinical diagnostic groups (normal≤ AD/MCI<AD dementia; f=4.71, p=0.0009).ConclusionWe demonstrate overlap in proteins associated with CVD risk and brain aging. Cross‐validation analyses in plasma and postmortem brain tissue highlight increased SPON1 as a robust predictor of worse neurobehavioral outcomes. SPON1 is an extracellular matrix protein involved in both smooth muscle and nervous tissue growth, and may represent a common link between heart health and brain health.