bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utilizing 7 Tesla QSM to evaluate the relationship between cerebral small veins and microbleeds in Alzheimer’s Disease
Authors: Ashouri Laya 
Published: January 2025

AbstractBackgroundCerebral microbleeds (CMBs) are small hypointense round lesions that indicate leakage of blood products from cerebral vessels damaged by β‐amyloid‐40 (Aβ) and typically are detected by T2*‐weighted and susceptibility weighted imaging (SWI) on MRI. They are indicators of cerebral small vessel diseases, especially cerebral amyloid angiopathy (CAA), affecting cortical small arteries. Quantitative susceptibility mapping (QSM) is an advanced MRI imaging technique used to quantify the magnetic susceptibility of tissues in the human body. In this study, we utilized the QSM technique to analyze venous structures at ultra‐high resolution in a cohort of patients with AD and age‐matched control subjects using 7T MRI. Our aim is to evaluate the feasibility of using ultra‐high resolution QSM at 7T MRI to find a link between small veins and CMBs in individuals with AD.MethodIn‐vivo human imaging was performed using a 7T MRI scanner and were analyzed by two neuroradiologists. CMBs were defined as hyperintense, round lesions in the QSM images. For verification, their appearance was matched on the SWI images, where CMBs are hypointense and associated with. CMBs with an immediate adjacent to a vein were assessed in the QSM images. They were defined as CMBs with small veins connection.ResultThis high‐resolution 7T neuroimaging study investigated whether a spatial relationship between small veins and CMBs could be detected in a cohort of AD patients. QSM enabled depiction of cerebral CMBs with a direct connection to a vein and their localization. Our data support the notion that CMBs relate anatomically to veins. Understanding the role of vein pathology in CAA and its role in neurodegenerative pathologies might open novel insights in the pathophysiology of AD.ConclusionA key strength of our study lies in the utilization of high‐resolution QSM at 7T MRI. High‐resolution MRI enhances the visibility of small structures, and when maintained at the same resolution, imaging at a higher field MRI increases the signal‐to‐noise ratio. QSM elevates CMB detection sensitivity while facilitating precise visualization of the brain's venous vasculature. Notably, the postprocessing algorithm ensures a high level of specificity for venous blood susceptibilities, minimizing the likelihood of measuring arterioles or slow‐flow small arteries.
Trajectories in Care Among Veterans with Alzheimer’s Disease in the United States
Authors: Palacios Natalia , Xia Weiming , Reisman Joel , Wang Ying , Morin Peter J , Berlowitz Dan , Monfared Amir Abbas Tahami , Zhang Quanwu , Aguilar Byron J. , Zhang Raymond 
Published: January 2025

AbstractObjectiveFew studies have investigated trajectories in care among patients with Alzheimer’s Disease (AD), especially Veterans who experience a unique set of AD risk factors and challenges in access to AD immunotherapy in the Veterans Affairs Healthcare System (VAHS) of the United States.MethodsWe analyzed trajectories in care based on electronic health records (EHR) among Veterans who were assessed for AD based on ICD‐10 coding within the VAHS between Oct 2015 and Jan 2024. Among Veterans with an ICD‐10 code for AD in the VAHS, we examined frequency distributions of clinical visits by physician specialty (primary care, neurologist, geriatrician, psychiatrist, and other specialties) where the initial AD ICD‐10 coding was recorded. Transition to the specialist care or visit to a dementia clinic was calculated during the year after the initial ICD‐10 coding for AD from the initial visit to a primary care physician. Distribution of the transition to specialist care was examined across non‐Hispanic Black, non‐Hispanic White, Hispanic, and other race/ethnicity groups.ResultsA total of 110,836 Veterans were identified by ≥1 ICD‐10 code for AD with a subsample of 71,666 seen by a clinician with known specialty. Mean age was 80.7 years, 97.3% were male, 11.6% non‐Hispanic Black, 8.2% Hispanic, and 70.7% non‐Hispanic White. More than 41% of the initial AD coding was assigned in the primary care physician, 9% in neurologist, 8% geriatrician, and 12% psychiatrist. In the subsample of 71,666 Veterans within one year, 26.4% had a subsequent visit to a neurologist office or Dementia clinic. Among Veterans initially seen in primary care for AD, 31.7% non‐Hispanic Black (p<0.01) and 25.3% Hispanic (p = 0.22), relative to 23.9% non‐Hispanic White, were subsequently visited a neurologist or a dementia clinic.ConclusionsOver 40% more Veterans were initially evaluated for AD by a primary care clinician than by an AD specialist including neurologists, psychiatrists, and geriatricians. Non‐Hispanic Black Veterans were more likely to follow up with a neurologist or at a dementia clinic compared to Hispanic or non‐Hispanic White Veterans during the year after the initial AD assessment. The findings suggest a need for further enhancement of AD care trajectory.
LGI‐1 Encephalitis: A Comprehensive Multidisciplinary Paradigm for Diagnosis and Management
Authors: Tavakoli Emytis , Fishman Keera , Elmi Sarah 
Published: January 2025

AbstractIntroductionLeucine‐rich glioma‐inactivated 1 (LGI‐1) antibody encephalitis is a rare subtype of autoimmune limb encephalitis (ALE), which is marked by rapid neuropsychiatric decline. This report details a comprehensive approach to its diagnosis and management.AssessmentIn this case, a 68‐year‐old man presented with aggressive behaviors, cognitive decline, and seizure‐like episodes. Initial assessments suggested major neurocognitive disorder, with MMSE and MOCA scores of 20 and 17, respectively, indicating cognitive impairment. EEG confirmed episodes of facio‐brachial dystonic seizures. Further evaluation revealed hyponatremia, temporal lobe atrophy on MRI, and LGI1‐antibodies in the CSF.TreatmentInitial treatments included steroids and IVIG, which did not result in significant improvement. However, after receiving two Rituximab trials, improvements in cognitive and behavioural outcomes were observed. Cognitive predictors of poor outcomes included older age, non‐response to initial therapies, and clinical relapses.DiscussionThis case underscores the complex presentation of LGI‐1 encephalitis, emphasizing the importance of thorough diagnostic evaluations and a multimodal treatment approach. The patient’s cognitive and behavioral improvements post‐treatment highlight the significance of timely and targeted interventions in managing this challenging autoimmune encephalitis. Long‐term follow‐up revealed sustained improvements, reinforcing the potential efficacy of a multidisciplinary treatment strategy.
Advanced circadian rhythms in older adults are associated with higher amyloid‐β and tau PET burden and poorer short‐term memory
Authors: Eckhardt Joanna L , Isenberg A. Lisette , Stradford Joy , Aslanyan Vahan , Fenton Laura E. , Monreal Teresa , Pa Judy 
Published: January 2025

AbstractBackgroundSeveral studies link circadian rhythm disturbances to Alzheimer's disease. However, little is known about circadian rhythm involvement with Alzheimer’s pathology in early stages of the disease. The current study investigates the relationship between circadian rhythms, Aβ and tau PET, and short‐term memory, and explores how circadian rhythms vary between age, sex, and APOE4 status.MethodThis research utilizes baseline data from the Lifestyle Enriching Activities for Research in Neuroscience Intervention Trial. Sixty‐eight older adults ages 55‐80 experiencing early cognitive changes wore a GENEActiv accelerometer for ∼30 days. Accelerometer data was processed using the R package GGIR (v3.0‐1), and circadian rhythm measures were extracted using nparACT (v0.8) and ActCR (v0.3.0). Circadian rhythm variables include interdaily stability (IS) (rhythm synchronization), intradaily variability (IV) (fragmentation), and acrotime (peak activity time). Up‐MESOR and Down‐MESOR signify timing of activity increasing above or below mean activity level, respectively, with lower values indicative of advanced (earlier) circadian phase. Participant Aβ and tau SUVr were measured using PET imaging. Short‐term memory is measured with the California Verbal Learning Test‐II Short Delay Free Recall Total Score. Linear regression models were conducted to test associations between circadian rhythms, Aβ, tau, and short‐term memory, and were adjusted for age, sex, APOE4 status, and years of education. Pearson’s correlation was conducted between circadian rhythms and age. Wilcoxon Rank Sum tests were used to assess differences in circadian rhythms between sex and APOE4 status.ResultParticipant demographics are summarized in Table 1. Regression results are summarized in Table 2. Acrotime and Down‐MESOR were associated with Aβ Composite. Acrotime and Up‐MESOR were associated with tau across multiple Braak regions of interest. Notably, IV was significantly associated with Braak stage III/IV. Both acrotime and Up‐MESOR were associated with Short Delay Free Recall Score. Acrotime (r =‐0.25, p=0.04) and Down‐MESOR (r=‐0.26, p=0.04) were moderately correlated with age. IS (W=368, p=0.03) and IV (W=694, p=0.05) differed by sex, and Up‐MESOR differed by APOE4 status (W=599, p=0.03) (Figure 1).ConclusionParticipants with advanced (earlier) circadian rhythms demonstrate higher Aβ and tau PET burden and poorer short‐term memory. Circadian rhythm measures vary with age, sex, and APOE4 status.
Sleep Encephalography‐Based Brain Age Index as a Potential Biomarker for Incident Cognitive Impairment in Community‐Dwelling Older Men
Authors: Sun Haoqi , Milton Sasha , Thomas Robert J , Westover M. Brandon , Stone Katie L , Yaffe Kristine , Leng Yue 
Published: January 2025

AbstractBackgroundIndividuals with dementia frequently exhibit disturbed sleep electroencephalography (EEG) microstructures, including spindles and slow oscillations. We have previously developed a sleep EEG‐based brain age index (BAI), which integrates multiple sleep EEG microstructures and has been associated with prevalent dementia in clinical populations. Here, we aim to determine if BAI is associated with incident cognitive impairment (CI) in a community population of older men, and its discrimination capability as a digital biomarker.MethodThis longitudinal study included men older than 65 years who completed overnight polysomnography (PSG) between 2003 and 2005 and had incident CI followed until 2016, as part of the Osteoporotic Fractures in Men study (MrOS). BAI was based on a model trained on participants without neurological or psychiatric diseases. Incident CI was defined as self‐reported dementia, dementia medication use, Modified Mini‐Mental State Examination (3MS)<80, or a decline in 3MS from baseline to any following visit ≥1.5 standard deviations below the mean. We fit logistic regression to assess the associations between quintiles of BAI and incident CI.ResultThere were 2,609 men without dementia at baseline (mean age [sd] = 76.0 [5.3] years), of whom 416 developed incident CI during a maximum follow‐up of 11 years. After adjustment for demographics, education, baseline cognition, medication use, comorbidities, and lifestyle, the highest quintile of BAI (BAI>+2.3 years) was associated with incident CI with an odds ratio of 1.66 (95% confidence interval 1.17–2.38, p=0.0051) when compared to the lowest quintile (BAI<‐6.7 years). Other quintiles were not significantly associated with incident CI. BAI showed a cross‐validated accuracy of 60%, sensitivity of 66%, specificity of 55%, and area under the receiver operative curve of 61% for incident CI. When looking at the brain age itself, the brain age performed better than chronological age in predicting incident CI, since the model with brain age achieved lower (i.e., better) Bayesian Information Criterion than another model with age, together with other covariates.ConclusionHigher BAI was associated with incident CI in community‐dwelling older men. These results highlight the potential of BAI as a digital biomarker of future CI in older men.
Psychosocial Well‐Being Factors and Adherence as Predictors of a Working Memory Game’s Outcomes in Older Adults
Authors: Andreo Micaela Noelle , Sierra Francisco J , Skolasinska Paulina , Smith Evan T. , Basak Chandramallika 
Published: January 2025

AbstractBackgroundPreventative interventions for cognitive decline are crucial as the number of individuals with Dementia is projected to reach 78 million by 2030. Cognitive Training can be a promising solution for the maintenance and improvement of neurocognitive functioning and has the potential to delay the onset of AD. This study utilizes a home‐based gamified cognitive training, the Bird Watch Game Unity (BWGU), where participants engage aspects of cognitive control to focus on predictable and unpredictable probe‐cue sequences of novel visual stimuli – pictures of birds. This game trains skills such as updating, focus switching, and working memory capacity.MethodFifty‐six healthy older adults (>65 years) played the BWGU for approximately 15.25 hours on average. Adherence is defined as frequency (the average lagged days between sessions) and duration (total hours trained). This study’s purpose is to determine if fluctuations in daily well‐being measures such as sleep, mood, stress, wellness, and busy‐ness influence a participant’s adherence. Predictive relationships between an individual’s psychosocial well‐being to adherence and their game learning outcomes will also be discussed. Autoregressive Integrated Moving Average (ARIMA) models are used to forecast a participant’s training adherence from day‐to‐day, using their previous days’ relationship with well‐being measures. Secondly, the well‐being and adherence measures are used to predict changes in cognition between pre‐ and post‐training visits at the group level via multiple regression. The cognitive battery being compared at pre‐ and post‐ include RAVLT, RBMT, WAIS‐V, and DSST. Lastly, we will explore the relationship between adherence to the BWGU and well‐being measures to determine if the BWGU has a significant impact on older adult’s well‐being, in addition to the cognitive benefits.ResultFor approximately 30% of participants, the ARIMA models of well‐being and adherence predicted daily average scores. For some individuals, well‐being measures were sufficient alone, and for others the addition of adherence improved their model’s prediction of game outcomes.ConclusionOverall, these findings provide valuable insight into psychosocial factors of learning and adherence to cognitive training, which in turn would help determine both who would benefit the most from training, and the necessary changes to improve future cognitive training interventions.
Exploring the Role of Fatty Acid Supplementation in Persons with Alzheimer’s Disease: A Scoping Review
Authors: Basra Mahi , Patel Saajan , Shah Kriya , Caballero Joshua 
Published: January 2025

AbstractBackgroundLipids are key modulators in the pathogenesis of Alzheimer’s disease (AD). Dysregulation of lipid homeostasis may disrupt the blood brain barrier, alter myelination, disturb cellular signaling and cause abnormal processing of the amyloid precursor protein. The purpose of this scoping review was to evaluate fatty acid supplementation in patients with AD.MethodA literature search was completed using PubMed, EMBASE and Medline identifying peer‐reviewed articles published between January 2015 and November 2023. Randomized controlled trials, correlational studies, clinical trials, and case studies were considered, while meta‐analyses, systematic reviews, scoping reviews, animal studies, and non‐English literature were excluded. The search strategy involved key terms such as “Alzheimer,” “Alzheimer’s Disease,” “AD,” “neuroinflammation,” “fatty acids,” “fat,” and “lipids.” The PRISMA guidelines guided the inclusion/exclusion process.ResultOf the 392 articles initially identified, five met inclusion criteria and were evaluated. Omega‐3 polyunsaturated fatty acid (i.e., fish oil), docosahexaenoic/eicosapentaenoic acid (DEA/EPA), medium‐chain triglycerides (MCT), and a combination product made of docosahexaenoic acid (DHA), EPA, uridine monophosphate, choline, phospholipids, selenium, B/C/E vitamins, and folic acid (Souvenaid®) were used in people with AD. A small study using fish oil (0.45 g of EPA with 1 g of DHA) over one year, showed decreased levels of carbonyl groups and hydroperoxides, but clinical effects were not evaluated. A study using DEA/EPA supplementation showed a decrease in fatty acid metabolism products and prevented deterioration in MMSE scores after 6 months. Additionally, the effect of MCT on cognitive ability in 53 patients with mild to moderate AD suggested APOE4‐/‐ patients with mild to moderate AD may have benefited from the MCT intervention with improved cognitive ability (ADAS‐Cog score) compared to placebo. Other studies evaluating Souvenaid® in combination with acetylcholinesterase inhibitors suggested improvements in behavioral tasks, cognitive function, and increase in hippocampal volume.ConclusionPreliminary trials suggested mild improvements in persons with AD with fatty acid supplementation. Souvenaid® and MCTs seem promising, highlighting potential clinical benefits. However, there is a need for additional extensive studies to validate these findings and establish clinical significance in AD.
Integrating Connectomics Constraints in Event‐Based Modeling of Alzheimer's Disease Progression: An Analysis of ADNI PET Data
Authors: Vahdatian Mahdieh , Zhao Yuji , Kurmukov Anvar , Gutman Boris A 
Published: January 2025

AbstractBackgroundAlzheimer's Disease (AD) presents a major health challenge, with complex and variable neurodegenerative progression. Traditional neuroimaging falls short in fully capturing this heterogeneity. Our study addresses this gap by applying an Event‐Based Model (EBM) to Alzheimer's Disease Neuroimaging Initiative (ADNI) Positron Emission Tomography (PET) data, enriched with connectomics data. This innovative approach promises a more individualized understanding of AD progression, combining PET imaging with insights into brain connectivity from connectomics. Our work aims to enhance early diagnosis and personalized treatment strategies in AD research.MethodOur study applied an Event‐Based Model (EBM) to Alzheimer's Disease Neuroimaging Initiative (ADNI) datasets across ADNI1, ADNI2, and ADNI3. We analyzed a diverse cohort including Alzheimer's Disease (AD), Mild Cognitive Impairment (MCI), Late MCI (LMCI), Early MCI (EMCI), and cognitively normal (CN) groups, using Amyloid (AMY), Fluorodeoxyglucose (FDG), and Tau PET scans. The methodology integrated connectomics data and employed Monte Carlo Markov Chain (MCMC) techniques for enhanced modeling precision. This approach provided an in‐depth understanding of AD progression, combining advanced statistical analysis with diverse neuroimaging data.ResultOptimal order of neurodegenerative events ‐ stages of disease progression as measured by changes in metabolic signature (FDG) or Amyloid accumulation ‐ largely followed previously published results. Earliest regions of Amyloid accumulation mirrored the default mode network (Figure 1). Metabolic changes, notably reduction in FDG SUVR, occurred earliest in the same top 10 regions. Also Z‐test statistic (‐4.78): Indicates a significant difference between the average stages of AD and MCI patients, with AD stages being lower than those of MCI.P‐value (∼0.00000177): Implies an extremely low probability that the observed difference in stages occurred by chance, strongly suggesting a true difference between the groups.ConclusionWe have presented a novel connectome‐informed progression model of amyloid‐beta accumulation and metabolic changes in the brain. The model discriminates well between stages of cognitive decline and suggests that amyloid accumulation and metabolic changes both follow a similar early of pattern conditioned on white‐matter connectivity
Evaluating the Effects of LDL Cholesterol Levels on Tau Visualization in [F‐18]flortaucipir PET Scans
Authors: Virdi Jaipal , Silverman Daniel H. 
Published: January 2025

AbstractBackgroundAlzheimer's Disease and other neurodegenerative diseases are characterized by abnormal tau protein accumulation in the brain. PET imaging utilizing the [F‐18]flortaucipir tracer is a widely used method for visualizing such conditions, yet its effectiveness can be compromised by off‐target binding. To shed light on this issue, our study focuses on how elevated cholesterol concentrations of low‐density lipoproteins (LDL) and standard uptake values (SUVR) from corresponding tau‐PET scans may influence the efficacy of [F‐18]flortaucipir.MethodDemographic, metabolic, and imaging data were sourced from the Alzheimer's Disease Neuroimaging Initiative for 56 subjects at varying cognitive statuses (CN, n=24; SMC, n=4; MCI, n=25, and AD, n=3). This included t1‐weighted MRI scans and tau‐PET scans acquired with [F‐18]flortauicipir. Cholesterol levels were calculated using the ratio of cholesterol to total lipids in the LDL. Image processing was conducted using Clinica software, with volumes of interest mapped using SUVR from the Hammers atlas.ResultOur analysis revealed significant correlations between LDL cholesterol levels and radiotracer uptake in the right & left caudate and accumbens nuclei (r=0.45, p=0.00046; r=0.45, p=0.00049; r=0.28, p=0.032, and r=0.26 p=0.05 respectively). When subjects were stratified with respect to the presence (n=27) or absence (n=29) of the APOE4 allele, some interaction was observed for the right caudate nucleus, which became somewhat more tightly correlated to the LDL parameter among those with the ε4 genotype (r=0.53, p=0.003).ConclusionA plausible mechanism explaining the correlations found and [F‐18]flortaucipir off‐targeting binding as a whole may be that oxidized low‐density lipoproteins (oxLDL), which proliferate as concentrations rise, could prompt microglia to transform into lipid‐laden foam cells. These cells could then create hydrophobic pockets that slow the radiotracer washout, with this effect being localized to the basal ganglia. This aligns with other research that has identified heightened oxLDL levels to specifically affect the perivascular spaces in the basal ganglia. Furthermore, our findings are consistent with previous studies that have shown increased microglial inflammation associated with the APOE4 genotype.