bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amyloid‐associated hyperconnectivity drives tau spreading across connected brain regions in Alzheimer’s disease
Authors: Roemer Sebastian Niclas , Wagner Fabian , Evangelista Lisa , Rauchmann Boris‐Stephan , Dehsarvi Amir , Steward Anna , Dewenter Anna , Biel Davina , Zhu Zeyu , Pescoller Julia , Gross Mattes , Perneczky Robert , Malpetti Maura , Ewers Michael , Schöll Michael , Dichgans Martin , Höglinger Günter , Brendel Matthias , Jäkel Sarah , Franzmeier Nicolai 
Published: January 2025

AbstractBackgroundIn Alzheimer’s disease, Aβ triggers tau spreading which drives neurodegeneration and cognitive decline. However, the mechanistic link between Aβ and tau remains unclear, which hinders therapeutic efforts to attenuate Aβ‐related tau accumulation. Preclinical research could show that tau spreads across connected neurons in an activity‐dependent manner, and Aβ was shown to trigger neuronal hyperactivity and hyperconnectivity. Therefore, we hypothesized that Aβ induces neuronal hyperactivity and hyperconnectivity, thereby promoting tau spreading from initial epicenters across connected brain regions.MethodsFrom ADNI, we included 140 Aβ‐positive subjects across the AD spectrum plus 69 Aβ‐negative controls, all with baseline amyloid‐PET, 3T resting‐state fMRI and longitudinal Flortaucipir tau‐PET data. For validation, we included cross‐sectional tau‐PET, amyloid‐PET and resting‐state fMRI data of 345 preclinical AD patients from A4. PET and fMRI data were parceled into 200 cortical ROIs, ROI‐wise longitudinal tau‐PET change rates were computed using linear mixed models. Resting‐state fMRI connectivity was computed across the 200 ROIs. Subject‐specific tau epicenters were defined as 5% of ROIs with highest baseline tau‐PET. Further, we included post‐mortem brain tissue from 5 AD patients vs. 4 controls stained for Aβ and c‐Fos, i.e. a marker of ante‐mortem neuronal activity.ResultsIn the AD spectrum cohort, we confirmed that Aβ induces hyperconnectivity of temporal lobe tau epicenters (Figure 1) to posterior brain regions that are highly vulnerable to tau accumulation in AD (Figure 2A‐C). This was fully replicated in the validation cohort of preclinical AD patients with low cortical tau‐PET, suggesting that the emergence of Aβ‐related hyperconnectivity precedes neocortical tau spreading (Figure 2D). Supporting that Aβ‐associated fMRI‐based hyperconnectivity may mirror neuronal hyperactivity, we found that neurons in AD post‐mortem tissue expressed higher levels of c‐Fos compared to controls, i.e. a Calcium‐sensitive marker of ante‐mortem neuronal activity (Figure 3). Lastly, using longitudinal tau‐PET, we confirmed that Aβ‐related connectivity increases of the tau epicenters to posterior brain regions mediated the effect of Aβ on tau accumulation and triggered faster tau spreading (Figure 4).ConclusionsOur translational results suggest that Aβ promotes tau spreading via increasing neuronal activity and connectivity. Therefore, Aβ‐associated neuronal hyperexcitability may be a promising target for attenuating tau spreading in AD.
Synaptic loss pattern is associated with functional connectivity in Alzheimer’s disease
Authors: Luan Ying , Wang Weiyi , Huang Qi , Guan Yihui , Li Binyin , Schöll Michael , Franzmeier Nicolai , Xie Fang 
Published: January 2025

AbstractBackgroundSynaptic loss is identified as a strong correlate of cognitive impairment in Alzheimer’s disease (AD). Pathological tau can induce direct toxicity to synapse and spread trans‐synaptically across connected neurons. Recent neuroimaging evidence revealed that tau pathology propagates along interconnected brain regions throughout macroscale brain networks. However, whether synaptic loss propagates in AD follows a similar vein is unclear.MethodSeventy‐six amyloid‐positive (Aβ+) subjects across AD spectrum and 48 cognitively normal (CN) Aβ‐ controls characterized by cross‐sectional [18F]florbetapir amyloid‐PET were included in the current study. The density of synaptic vesicle glycoprotein 2A (SV2A) was measured by [18F]SynVesT‐1 PET. A normative template of functional connectome distance across 200 neocortical regions of interest (ROIs) was generated using resting‐state fMRI data from 1000 subjects of the Human Connectome Project. We assessed the association between synaptic loss and functional connectivity by correlating the cross‐subject inter‐regional covariance with the normative functional connectivity template. In a next step, we tested whether the functional distance to synaptic loss epicenter (i.e., top 10% ROIs with greatest synaptic loss) is associated with synaptic loss in connected regions at both group‐ and subject‐level.ResultAmong Aβ+ subjects, inter‐regional covariance of SV2A‐PET‐assessed synaptic loss was associated with inter‐regional functional connectivity (Figure 1), suggesting that higher functional connectivity may facilitate the propagation of synaptic loss. At both group‐ and subject‐level, we found that shorter functional distance to synaptic loss epicenters is associated with greater levels of synaptic loss in connected regions (Figure 2).ConclusionWe found that inter‐regional functional connectivity is associated with greater synaptic loss in AD, suggesting that synaptic loss may systematically propagate along brain connections.
Aging, musical rhythm, and functional connectivity in the brain
Authors: Colverson Aaron , Chen Yu , Williamson John B. , Cohen Ronald A. , Rankin Katherine P. ,   UCSF, Memory and Aging Center
Published: January 2025

AbstractBackgroundAging associates with decreased functional connectivity between brain regions linked to musical rhythm perception. Producing rhythmic music may result in strengthened functional connectivity of these regions, but more evidence is needed to support intervention design. Currently, few studies directly contrast younger and older adults’ rhythmic music performance to understand brain‐behavior relationships. We used task‐based functional magnetic resonance imaging to examine aging‐related differences in connectivity among brain regions associated with perceiving and performing increasingly complex musical rhythms.MethodParticipants (younger = 14, ages 18‐35; older = 14, ages 55‐79) completed one imaging run, sequentially tapping along to simple (paced and unpaced metronome, and unsyncopated) and complex (syncopated) musical rhythms on a response box. Simple rhythms maintained metric regularity, whereas complex rhythms deviated from the main pulse. Behavioral performance measures included overall timing error for the unsyncopated and syncopated conditions, and averaged standard deviation from mean error for paced and unpaced metronome. We ran seed‐to‐voxel analyses of known brain correlates (cortical and subcortical) of musical rhythm, contrasting effects of rhythm performance from each seed to examine functional connectivity.ResultYounger adults performed better than older during simple (paced metronome (F(1,26) = 20, p<0.001) and unsyncopated (F(1,26) = 13.2, p = 0.001)) rhythms, with a similar nonsignificant trend for complex rhythms (syncopated: F(1,26) = 3.77, p = 0.063). Seeding from the right cerebellar lobule VI, contrasting difference in performance during syncopated and unsyncopated blocks, a significant negative correlation was found with right pre‐ and post‐central gyri and right superior parietal lobule (cluster‐level, FDR corrected p<0.05, voxel threshold p<0.001). Applying the same contrasts while seeding from the left putamen yielded a significant negative correlation with the right cerebellum Crus I&II.ConclusionOlder adults performed simple musical rhythms less accurately than younger, and trended toward poorer accuracy in performing complex rhythms. During perception and performance of more complex musical rhythms, greater activation was found in circuits connecting the cerebellum (pattern abstraction) to parietal (timing representation) and basal ganglia (discrepancy monitoring) regions. Though we found no age difference, larger studies may be better powered to discriminate age‐related neural patterns. Studies investigating how music‐making interventions strengthen these circuits may provide avenues for improving cognition in aging adults and possibly individuals with neurodegenerative disease.
Myelin water imaging with clinically feasible scan time: The accelerated BMC‐mcDESPOT (aBMC‐mcDESPOT) method
Authors: Bae Jonghyun , Gong Zhaoyuan , Guo Alex , Laporte John P , Faulkner Mary E , Bouhrara Mustapha 
Published: January 2025

AbstractBackgroundIn 2016, we introduced the Bayesian Monte Carlo analysis of multicomponent‐driven equilibrium observation of T1 and T2 (BMC‐mcDESPOT) MRI method for myelin water fraction (MWF) mapping, a surrogate of myelin content. While BMC‐mcDESPOT has been extensively applied to study brain aging, dementias, and risk factors influencing myelination, it still requires a lengthy acquisition time (∼17 min) which hampers its integration in clinical studies and trials. In this study, we aim to accelerate the BMC‐mcDESPOT method for whole brain, high‐resolution, MWF mapping within clinically feasible scan time of ∼6 min.MethodData AcquisitionReference data (ref‐BMC, no‐acceleration): Two subjects underwent the BMC‐mcDESPOT protocol consisting of SPGR and bSSFP images at 10 different FAs. For assessing reproducibility, three sets of fully‐sampled datasets were collected without any under‐sampling (total acquisition time =17 min).Compressed sensing acceleration (cs‐BMC): Three sets of accelerated scans were acquired using compressed sensing (CS) with an acceleration factor of ∼2 (9 min) (Figure 1(a)).Image domain acceleration (du‐BMC): The undersampling in the data domain was retrospectively performed on the bSSFP images by selecting only 2 optimal images instead of the full 10 images (12 min) (Figure 1(b)).Combined accelerations (aBMC): The above two acceleration methods were combined and resulted in an acquisition time of ∼6min. (Figure 1(c))Data ProcessingWe estimated MWF maps from the different undersampling methods described above. The accuracy was evaluated between the MWF from the reference and those from each undersampled dataset. The reproducibility was measured with the coefficient of variations (CoV) across different measurements for each sampling method. We also performed Bland‐Altman analysis to quantify bias and limits of agreement (LOA).ResultFigure 2 shows a representative slice of MWF estimates from different sampling methods. The different acceleration methods showed similar regional patterns, with relatively low errors (du‐BMC/cs‐BMC/aBMC=10.8/9.8/13.7%) and CoV (ref‐BMC/du‐BMC/cs‐BMC/aBMC=9.0/14.3/10.7/15.3%). While a slight bias in the derived MWF values was observed (Figure 3), the LOA for aBMC was under 5% in white matter.ConclusionaBMC‐mcDESPOT is a practical MRI method for accurate determination of MWF within 6 min, offering unique opportunities to further integrate myelin imaging in clinical studies and trials.
ECT‐AD: Baseline Demographics of a Novel Therapeutic Intervention for Severe Agitation and Aggression in Dementia
Authors: Forester Brent P. , Merrill Julia G. , Hermida Adriana P. , Lapid Maria I. , Mueller Martina , Nykamp Louis J. , Patrick Regan E. , Mattingly Jefferson , Seiner Steve J. , Petrides Georgios 
Published: January 2025

AbstractBackgroundEffect and Safety of Electroconvulsive Therapy plus Usual Care for the Acute Management of Severe Agitation in Dementia (ECT‐AD) is a multi‐site NIA‐funded FDA‐regulated pioneering clinical trial to investigate the effectiveness of electroconvulsive therapy (ECT) in treating severe and treatment‐refractory agitation and aggression among individuals with advanced dementia, a condition that has a profound negative impact on patient quality of life and caregiver burden. Here we present baseline demographics of the patient population in this ongoing trial.MethodTo date we have enrolled 18 participants, with a mean age of 74.1 years, where majority are male (61.1%). The racial composition is predominantly White (94.4%), with Asian representation (5.6%, 1/18), and with 11.1% (2/18) identifying as Hispanic or Latino. Dementia subtypes in our cohort include Alzheimer’s disease (AD, 77.8%), vascular dementia (VaD, 16.7%, 3/18), and frontotemporal dementia (FTD, 5.6%, 1/18).ResultBaseline assessments reveal severe cognitive and functional impairment, as indicated by a mean Mini‐Mental State Examination (MMSE) score of 4.0, Barthel Index (BI) score of 52.2, and SIB‐8 score of 2.9, all consistent with advanced stages of dementia. High mean total scores on the Cohen‐Mansfield Agitation Inventory (CMAI, 75.8), Neuropsychiatric Inventory (NPI) agitation (15.1) and aggression (9.2) scales, and Pittsburgh Agitation Scale (PAS, 7.8), reflect the severe levels of agitation and aggression in our participants.ConclusionThese baseline demographic and clinical data underscore the profound impact of advanced dementia, highlighting the need for innovative treatment approaches like ECT. The ECT‐AD trial offers a critical step towards understanding and improving the management of agitation in dementia, with implications that could enhance current clinical care practices.
Whispered Struggles in the Workplace: A Scoping Review of Cognitive and Interpersonal Challenges and Organizational Strategies for Employees living with Dementia
Authors: Jindal Shruti , Pit Sabrina , Hamiduzzaman Mohammad 
Published: January 2025

AbstractBackgroundDementia, including its younger‐onset variant, increasingly challenges diverse workplaces, affecting both employees living with dementia and their employers. With a growing global trend of individuals extending their working years, it becomes crucial to understand the specific challenges and implications for those with dementia within various employment contexts. This review delves into the cognitive, interpersonal, and organizational challenges faced by employees living with dementia across a broad range of workplaces, reflecting the evolving dynamics of today’s work environment.MethodIn this scoping review, we employed Arksey and O’Malley’s framework, using a structured approach to explore the intersection of dementia and employment. Our methodology, shaped by the PRISMA‐P guidelines, involved a systematic search in PubMed and PsycINFO for studies published from 2000 onwards. We utilized a comprehensive set of search terms and Boolean operators, focusing on the experiences and challenges faced by employees living with dementia. This included assessing workplace adjustments, organizational support strategies, and employee well‐being. The selection criteria were defined to include studies that specifically addressed cognitive and interpersonal challenges in the workplace, avoiding broader dementia‐related topics to maintain focus on our research objectives.ResultThe review systematically identified key areas of concern and gaps in the current literature regarding dementia in the workplace. It underlined the necessity for workplace adjustments, including flexible hours and modified job responsibilities, to support employees with dementia. The role of organizations in facilitating appropriate workplace accommodations and support strategies, such as supportive supervision and access to tailored occupational health services, was also a significant finding. More importantly, this scoping review identified critical questions for future investigation, including the efficacy of current workplace adjustments, the role of policy in shaping organizational support, and the long‐term impact of such accommodations on both the employee with dementia and workplace dynamics.ConclusionThis review underscores the need for comprehensive workplace strategies and policy reforms to support employees with dementia, highlighting the critical role of organizational support and flexibility.
Underlying mechanisms for altered reactivity of posterior cortical electroencephalographic alpha rhythms in DLB and PDD
Authors: Lizio Roberta , Percio Claudio Del , Noce Giuseppe , Lopez Susanna , Jakhar Dharmendra , Carpi Matteo , Arnaldi Dario , Güntekin Bahar , Yener Görsev , Ferri Raffaele , Frisoni Giovanni B. , Babiloni Claudio 
Published: January 2025

AbstractBackgroundThe amplitude of resting‐state electroencephalographic (rsEEG) rhythms is a promising neurophysiological biomarker to investigate the abnormalities of oscillatory neurophysiological thalamocortical mechanisms related to the general cortical arousal and vigilance in wakefulness in patients with dementia due to neurodegenerative diseases as Alzheimer’s disease (ADD), Parkinson’s disease (PDD) and Lewy Body disease (DLB). Here, we tested the hypothesis that the reactivity of posterior rsEEG alpha (about 8‐12 Hz) rhythms during the transition from eyes‐closed to ‐open condition may be lower in PDD patients than in DLB patients.MethodsA Eurasian database provided clinical‐demographic‐rsEEG datasets in 35 ADD patients, 65 PDD patients, 30 DLB patients, and 25 matched cognitively unimpaired (Healthy) persons. The rsEEG rhythms were investigated at individual delta, theta, and alpha frequency bands, as well as fixed beta (14‐30 Hz) and gamma (30‐40 Hz) bands. The eLORETA freeware was used to estimate cortical rsEEG sources.ResultsResults showed substantial (i.e., greater than ‐10%) reduction (reactivity) in the posterior alpha source activities from the eyes‐closed to the eyes‐open condition in 88% of the Healthy seniors, 53% of ADD patients, 53% of the DLB patients, and only 37% of the PDD patients (Figure 1). In these alpha‐reactive participants, there was lower reactivity in the posterior alpha source activities in the three neurodegenerative (i.e., ADD, PDD, and DLB) groups than in the Healthy group. Furthermore, the reduction of the occipital alpha reactivity was stronger in the PDD and DLB groups than in the ADD group. Finally, the reduction of the parietal alpha reactivity was stronger in the PDD group than in the ADD and DLB groups (Figure 2).ConclusionThese results suggest that ADD, PDD, and DLB patients may be characterized by very poor reactivity in the posterior cortical mechanisms desynchronizing rsEEG alpha rhythms in relation to increased vigilance levels as an interesting neurophysiological biomarker. This biomarker may be used as a primary endpoint for interventions with drugs or brain electromagnetic stimulations to improve vigilance regulation and quality of life in neurodegenerative patients, allowing them to follow TV programs and interactions in their social environment.
Ultra‐widefield retinal and choroidal vascular architecture in mild cognitive impairment and normal cognition
Authors: Joseph Suzanna , Haystead Alice , Robbins Cason B , Threlfall Adam , MacGillivray Tom , Stinnett Sandra , Grewal Dilraj S , Fekrat Sharon ,   iMIND research group
Published: January 2025

AbstractBackgroundMild cognitive impairment (MCI) is currently a clinical diagnosis characterized by decline in memory and daily cognitive function from baseline. Exploratory studies using optical coherence tomography angiography have reported alterations in the retinal capillary plexus vessel density and attenuation of the retinal nerve fiber layer, but these results appear to be mixed. We used ultra‐widefield (UWF) imaging to evaluate retinal and choroidal vasculature and structure in individuals with mild cognitive impairment (MCI) compared to controls with normal cognition.MethodA cross‐sectional comparison of patients with MCI compared to cognitively normal controls. Scanning laser ophthalmoscopy (SLO) (California, Optos Inc, Marlborough, MA) was used to obtain UWF fundus color images. Images were analyzed with the Vasculature Assessment Platform for Images of the Retina (VAMPIRE) software. Measured metrics included vessel width gradient, vessel width intercept, large vessel choroidal vascular density, vessel tortuosity, and vessel fractal dimension.Result131 eyes of 82 MCI patients and 231 eyes of 133 cognitively normal participants were analyzed. Both retinal artery and vein width gradients were less negative in MCI vs. controls, demonstrating decreased rates of vessel thinning towards the periphery (p < 0.001, p = 0.027). Retinal artery and vein width intercepts, a metric that extrapolates vessel width at the center of the optic disc, were smaller in MCI patients vs controls (p < 0.001, p = 0.017). The large vessel choroidal vascular density was greater in MCI patients vs controls (p = 0.025).ConclusionWhen compared to controls with normal cognition, MCI patients had overall thinner retinal vasculature manifested in both the retinal arteries and veins. Furthermore, in MCI, these thinner arteries and veins attenuated at a lower rate when traveling towards the periphery, when compared to controls, perhaps because they were already more attenuated posteriorly. MCI patients also had increased choroidal vascular density.
Correlation between ERP and CSF biomarkers in Mild Cognitive Impairment and Dementia patients in a general neurological clinic population
Authors: Levy Igor 
Published: January 2025

AbstractBackgroundWe have recently reported on the use of Event‐Related Potentials (ERP) biomarkers to separate Amyloid PET positive vs Amyloid PET negative patients with mild cognitive impairment (MCI) and dementia.A large body of evidence shows that low levels of beta amyloid and increased tau in the CSF are highly correlated with Alzheimer’s pathology in the brain. We investigated the correlation between amyloid and tau in the CSF, and ERP responses in patients with MCI and dementia.MethodPatients with MCI and Dementia in a general neurological outpatient clinic underwent ERP testing. CSF analyses for Amyloid and TAU were also performed, and the results correlated with the output from the ERP test. When CSF studies were indeterminate, readings for brain amyloid brain load were obtained through PET analysis as part of the IDEAS (Imaging Dementia ‐Evidence for Amyloid Scanning) study when feasibleResultData will be presented at the conference with correlation between ERP markers and CSF amyloid and tau levels in patients with MCI and dementia.ConclusionStudy results will provide valuable insights into the use of ERPs in a general neurological population with Alzheimer’s disease and cognitive impairment.