bluuebunny/crossref_metadata_2025_split huggingface dataset:
The relationship between traumatic brain injury and the neuropathology of dementia
Authors: McCann Heather , Halliday Glenda M , Shepherd Claire E 
Published: June 2023

AbstractBackgroundClinical studies indicate that traumatic brain injury (TBI) is linked to an increased risk of dementia during life. However, studies involving neuropathologically‐confirmed cases have shown conflicting results. This study was aimed at assessing a large brain bank cohort to identify any association between TBI and the presence of pathologies underlying the most commonly found dementias, Alzheimer’s disease (AD) and Lewy body disease (LBD).Method636 cases were assessed for this study (average age 76.2). Cases with a history of TBI were identified using donor records held at the Sydney Brain Bank. We use the term "TBI” to include a single or multiple TBIs, as well as repetitive mild neurotrauma that may be subconcussive (N = 109). Amyloid plaque and alpha synuclein pathologies were identified by immunohistochemistry. Neurofibrillary tangles were identified using modified Bielschowsky silver staining. Pathology was assessed according to current neuropathological diagnostic criteria. Multivariate regression statistics were used to assess the effect of TBI, age and gender on amyloid plaque (A score), neurofibrillary tangles (B score) and Lewy pathology stages. Multinomial logistic regression was used to examine the effect of TBI on pathological diagnosis.ResultsTBI was not significantly associated with increased amyloid (p = 0.05) or Lewy pathology stages (p = 0.65), however the odds of having a higher neurofibrillary tangle stage increased by 75% in the TBI group (p = 0.009)(Figure 1). Gender was not a significant predictor of amyloid (p = 0.29), neurofibrillary tangle (p = 0.89) or Lewy pathology (p = 0.15). Not unexpectedly, age was a significant predictor of AD pathologies, including amyloid (p = <0.0000001) and neurofibrillary tangle (p = 0.00002) stages, although age was not a significant driver of Lewy body pathology (p = 0.1). There was no association between TBI and overall diagnosis of AD neuropathologic change or LBD (p = 0.12).ConclusionsIn this elderly neurodegenerative cohort, age remains a risk factor for AD, but not LBD pathology. Gender did not have a significant association with these pathologies in this cohort. TBI did not increase the risk of AD but did increase the frequency of neurofibrillary tangles, suggesting that abnormal tau protein accumulation following TBI is an important long‐term consequence that may contribute to poor brain aging and future neurodegeneration.
Introduction of a new synchronization index by correlating Leg Movements and overall activity distinguishes subjects with normal cognitive functioning from those with MCI: Preliminary results
Authors: Conde‐Lara Federico Menéndez , Rodríguez‐Torres Erika E. , Rosales‐Lagarde Alejandra , Cubero‐Rego Lourdes 
Published: June 2023

AbstractBackgroundExploratory data analysis was performed, looking after correlations of Leg Movement (LMs) against the 22 full‐EEG polysomnography during sleep. The EEG signals were recorded with the 19 derivations from the traditional International 10/20 electrode placement, chin electromyography (EMG), and electrooculogram (EOG). Nine subjects were considered: six in the Mild Cognitive Impairment (MCI) group, and three controls (CTRL). In line with the hypothesis about phasic activity reorganizing cerebral processing, lower correlations were expected for MCI, during REM sleep.MethodFor each subject, the first rotation (PC1) of the Principal Component Analysis (PCA) decomposition of the data (22 channels) was generated. This accounts for the direction of the maximal variance. The proportion of variance explained by PC1 was very high (Table 2). In view of this, pairing the LMs and the PC1 time series allowed for reliable comparisons. As expected, there was no linear relation between the LMs and each of the channels: out of 198 pairs (22 for each subject), the maximal correlation coefficient was 0.0194. Therefore, it was natural to look for nonlinear relationships. The metric considered, was the total variation, at 5‐second intervals. The total variation corresponds with the arclength of the graph and is a measure of variability of a time series. For each subject, correlation coefficients were calculated for the total variations for LM versus PC1.ResultThe mean coefficients for the CTRL group were higher than those for the MCI group for all the sleep epochs (Table 1). The difference was highest for REM sleep. In Table 2, the coefficients of the PC1 for each subject and variable (PC1) are presented (variations of one subject, Fig. 1).ConclusionDue to the small size of the sample, it is not possible to draw any actual conclusions. However, anecdotal evidence was found for differences in synchronic activity between groups. This was most notorious for REM sleep, with decreased correlations for the MCI group. It would be of interest to replicate this study with a much larger sample.
A feasibility study of a brief person‐centered dementia training to promote more empowered staffing teams
Authors: Gholizadeh Shadi , Popolizio Elizabeth M. , Wile Michelle , Smith Erica C. 
Published: June 2023

AbstractBackgroundAs a growing number of people with dementia are opting to age at home, the need for well‐trained, dementia‐knowledgeable nonmedical care teams has increased. An important and understudied member of the in‐home care team is the scheduler/staffing coordinator (SC). The SC often identifies an appropriate professional caregiver/care partner (CP) for the person with dementia, liaises between the CP and the client or client’s family, and provides informal coaching to the CP as challenges arise. The objectives were to: 1) develop a brief person‐centered dementia training program for SCs that is tailored to their role and 2) assess SC’s perspectives on the relevance and accessibility of the training.MethodA small group (N = 10) of SCs across three states and two in‐home care companies attended a four‐part dementia training covering 1) dementia types, symptoms, and experience, 2) behavioral and mood expressions of dementia, 3) mobility and approach considerations in dementia, and 4) engagement and person‐centered care for people with dementia. The SCs completed pre‐ and post‐training questions asking about training needs, confidence in coaching CPs and confidence in finding an appropriate client/care partner match. They were also asked to comment on the relevance and accessibility of the training.ResultPrior to training, SCs reported a desire to learn more about triggers in dementia; best practices for communication with CPs that consider cultural, social, and language differences; and tips for helping CPs who are feeling emotionally dysregulated or overwhelmed. There was a wider range of reported confidence in coaching CPs and finding an appropriate match. The SCs overall found the training to be relevant and reported being highly satisfied with the content. Suggestions to improve the training included shortening the training and simplifying the language.ConclusionSCs have a strong interest in increasing their knowledge about dementia, especially in terms of how to 1) best support CPs experiencing care challenges and 2) facilitate optimal client and CP matches. Future research can explore the impact of the training in a larger sample on outcomes including job satisfaction and self‐efficacy, burnout, and overall dementia knowledge as well as matching and coaching behaviors.
Daily heart rate variability biofeedback practice sessions affect plasma Αβ40 and Αβ42 levels in healthy younger and older adults: A randomized clinical trial (N = 108)
Authors: Min Jungwon , Rouanet Jeremy P. , Martini Alessandra Cadete , Nashiro Kaoru , Yoo Hyun Joo , Porat Shai , Cho Christine , Wan Junxiang , Cole Steve W , Head Elizabeth , Nation Daniel A. , Thayer Julian F , Mather Mara 
Published: June 2023

AbstractBackgroundGenetic mutations affecting β‐amyloid (Αβ) production suggest that decreasing Αβ levels in healthy adults could prevent AD. However, evidence for behavioral interventions that decrease Αβ levels is lacking. The current study examined whether heart rate variability (HRV) biofeedback affects plasma Αβ levels. This intervention involves breathing slowly at a pace that maximizes the amplitude of heart rate oscillations. During slow paced breathing, the vagus nerve receives strong signals from stretch receptors in blood vessels and the lungs. These afferent signals stimulate ascending vagus nerve signaling that activate ‘safety’ signaling pathways, suppressing stress and arousal pathways in the brain and body. Experiencing adversity increases production of Aβ and risk of AD. We hypothesized that, in healthy adults, daily sessions involving slow paced breathing during HRV biofeedback could decrease Aβ by suppressing these adversity‐related processes.MethodHealthy adults (N = 54 age 18‐35; N = 54 age 55‐80) practiced HRV biofeedback daily for five weeks. They were randomized to use slow paced breathing and HRV biofeedback to increase heart rate oscillations (Osc+ condition) or to use personalized strategies and HRV biofeedback to try to decrease heart rate oscillations (Osc‐ condition). Pre‐ and post‐intervention plasma Aβ40 and Aβ42 levels were quantified blind to condition. Gene expression analysis of peripheral blood samples of the 54 younger adults using bioinformatics‐based analyses of genome‐wide RNA profiles examined activity of pro‐inflammatory, neuroendocrine, and antiviral transcription control pathways relevant to the conserved transcriptional response to adversity (CTRA). We predicted that reductions in the CTRA across the 5‐week trial would be associated with reduced plasma Aβ.ResultBoth younger and older adults showed significant differences between Osc+ and Osc‐ conditions in change in plasma Aβ40 and Aβ42 levels (Figure 1). The Osc+ condition decreased Αβ while the Osc‐ condition increased Αβ. Individual changes in plasma Aβ from pre‐ to post‐intervention were associated with changes in expression of the CTRA in the predicted direction.ConclusionHRV biofeedback affects plasma Aβ and these effects are associated with changes in expression of genes upregulated during adversity. Future longer‐term studies should test whether reducing plasma Αβ via the Osc+ intervention reduces risk of developing AD.
Comparison of diagnostic routines for suspected Alzheimer’s Disease patients between US‐American and German health care providers
Authors: Menne Felix , Schipke Carola G. 
Published: June 2023

AbstractBackgroundThorough diagnostics are a prerequisite for the optimal treatment of Alzheimer’s Disease. Biomarker‐based diagnostics are now standard within a research framework. On the contrary, data on diagnostic workups applied by physicians in their everyday clinical practice is scarce.MethodTwo surveys were conducted on the diagnostic actions taken by physicians when faced with patients with AD suspicion. The sample consisted of German (n = 500) and American (n = 100) health care providers, both specialists and non‐specialists.ResultGerman specialists more often conduct neuropsychological testing themselves than their American colleagues (p<0.001). Likewise, in German non‐specialists, neuropsychological testing elsewhere is recommended almost twice as often compared to US physicians (p<0.0001). In contrast, US non‐specialists perform lumbar punctures for CSF analysis themselves twelve times more often than their German colleagues (p<0.0001). Furthermore, they are more than three times as likely to recommend CSF analysis elsewhere than German non‐specialists (p<0.0001). Similarly, US non‐specialists significantly more often recommend patients to have a PET scan with a 4.7‐fold difference (p = 0.0007).ConclusionDiagnostic routines for suspected AD patients are in large parts alike between German and US‐American health care providers. However, when it comes to gathering neurobiological evidence through the means of biomarker‐based CSF or PET diagnostics, German doctors significantly less perform and prescribe these measures.
Weight increases and decreases show distinct association with Alzheimer’s Disease in different age and APOE‐ε4 status
Authors: Li Anqi , Du Jing , Cai Yue , Guo Tengfei ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: June 2023

AbstractBackgroundHigh and low body mass index (BMI) may increase the risk of Alzheimer’s disease (AD) in mid‐life (age<65) and late‐life (age≥65) respectively. However, it is still not fully understood about the associations of BMI changes with AD progression as well as how APOE‐ε4 allele modulates their relationships in mid‐life and late‐life. In this study, we aimed to determine how BMI changes and APOE‐ε4 allele relate to longitudinal β‐amyloid (Aβ) accumulation, tau aggregation, neurodegeneration and cognitive decline in mid‐life and late‐life.MethodWe examined 325 cognitively unimpaired and 391 mild cognitive impairment Alzheimer’s Disease Neuroimaging Initiative participants with longitudinal 18F‐florbetapir (FBP) Aβ PET and BMI measurements. Among of them, 486, 707 and 710 had longitudinal 18F‐fluorodeoxyglucos (FDG) PET, adjusted hippocampal volume (aHCV) and memory scores, and 246 participants had follow‐up 18F‐flortaucipir (FTP) tau PET data measured at a median of 5.5 years post baseline FBP scan. We investigated the associations of BMI slopes with longitudinal changes of AD typical summary cortical region FBP PET and FDG PET, aHCV and memory scores, and follow‐up Temporal‐metaROI FTP PET in different Aβ status (Aβ‐ and Aβ+), APOE‐ε4 status (carriers and non‐carriers), age (mid‐life and late‐life).ResultWe found faster BMI decreases accelerated the rates of Aβ accumulation (Fig.1D, standardized β (βstd) = ‐0.29, p = 0.002), hypometabolism (Fig.3D, βstd = 0.24, p = 0.03), hippocampal atrophy (Fig.3H, βstd = 0.29, p = 0.002), and memory decline (Fig.4D, βstd = 0.28, p = 0.005), and induced marginally higher follow‐up tau deposition (Fig.2D, βstd = ‐0.26, p = 0.09) in Aβ+ late‐life APOE‐ε4 non‐carriers but not in APOE‐ε4 carriers. In contrast, BMI increases were related to faster (Fig.1C, βstd = 0.80, p < 0.001) rates of Aβ accumulation in Aβ+ mid‐life APOE‐ε4 carriers but not in APOE‐ε4 non‐carriers.ConclusionThese findings suggest that weight increase in mid‐life APOE‐ε4 carriers and weight loss in late‐life APOE‐ε4 non‐carriers are environmental risk factors of AD, highlighting the importance of tracking BMI data in Aβ+ individuals.
Plasma lipid signature as an indicator of the risk and rate of progression from mild cognitive impairment to Alzheimer’s disease
Authors: Dakterzada Faride , Jové Mariona , Pamplona Reinald , Piñol‐Ripoll Gerard 
Published: June 2023

AbstractBackgroundOur knowledge about the importance of lipids in progression and the rate of progression from Mild Cognitive Impairment (MCI) to AD is limited. Our objective was to determine plasma lipids that could be implicated in the progression or rate of progression from MCI to AD.MethodWe analyzed the plasma lipid profile of MCI patients (N = 90) by liquid chromatography coupled with mass spectrometry. The association of lipids with progression was studied by logistic regression and a Cox regression model was used to assess lipids associated with the speed of progression. We adjusted our analyses for age, sex, CSF core AD biomarkers, APOE4 status, and Mini‐Mental State Examination (MMSE).ResultForty‐seven (52%) MCI patients progressed to AD during follow‐up (58 ± 12.5 months). Regression analysis detected that presence of APOE4 allele and high levels of four lipids – two as risk factors (p = 0.002) and two as protectors (p = 0.002 and p = 0.003)– were associated with progression (AUC 0.972, p < 0.001). The effect of these lipids in separating progressive from non‐progressive patients was significant when compared with the regression model without them (AUC 0.729 vs 0.972, z = 4.595, |z|>2.575, p < 0.01). Seven lipids were associated with the rate of progression, of which two were associated with a shorter time to progression (OR 9.88, 99% CI [3.08 –31.71], p < 0.001 and OR 34.81, CI 99% [4.88 – 248.3], p < 0.001) and five with a longer time to progression (OR 0.34, 99% CI [0.135 – 0.870], p = 0.003; OR 0.164, CI 99% [0.056 – 0.479], p < 0.001; OR 0.153, 99% CI [0.056 – 0.419], p < 0.001; OR 0.148, CI 99% [0.034 – 0.644], p = 0.001; and OR 0.029, 99% CI [0.007 – 0.131], p < 0.001).ConclusionOur results suggest that lipid dysregulation could have an important role in progression and rate of progression from MCI to AD. Our data also indicate that AD lipid alterations could have clinical implications as circulating biomarkers of progression and progression speed.
Possibility of stimulation of cerebral angiogenesis and neurogenesis with transcatheter intracerebral laser photobiomodulation therapy during dementia in patients with Alzheimer’s disease and in patients with distal cerebral atherosclerosis
Authors: Maksimovich Ivan V 
Published: June 2023

AbstractBackgroundThe research is dedicated to stimulation of cerebral angiogenesis and neurogenesis with Transcatheter Intracerebral Laser Photobiomodulation Therapy (PBMT) in patients with dementia during Alzheimer’s disease (AD) and patients with distal forms of cerebral atherosclerosis.Materials & Methods350 patients with dementia were examined.We carried out determination of CDR, Tomography Dementia Rating scale (TDR), MMSE, cerebral CT, MRI, SG, rheoencephalography (REG), cerebral MUGA.48 (13.71%) patients with AD aged 34‐80 (mean age 67.5) were selected: 17 men (35.42%), 31 women (54.58%). According to their dementia severity, the patients were subdivided: preclinical stage (TDR‐0) ‐ 4, mild stage (TDR‐1) ‐ 16, moderately severe stage (TDR‐2) ‐ 21, severe stage (TDR‐3) ‐ 7.302 (86.29%) patients with distal cerebral atherosclerosis aged 58‐81 (mean age 78) were selected: 226 men (74.83%), 76 women (25.17%). According to their dementia severity, the patients were subdivided: mild stage (СDR‐1) ‐ 284 (94.04%), moderately severe stage (СDR‐2) ‐ 18 (5.96%).At hospital, all the patients underwent PBMT.ResultsAll 48 (100%) patients with AD showed improved cerebral microcirculation and 10‐20% increase in the volume of cerebral temporal lobes, which indicates cerebral neurogenesis development and tissue regeneration. The process was accompanied by a decreased level of dementia and restoration of cognitive functions. Consequently, the patients were transferred to milder TDR groups. Depending on the initial dementia severity, the resulting positive effect was observed during 2‐10 years.All 302 (100%) patients with distal cerebral atherosclerosis showed improved cerebral microcirculation and declining cerebral involutional changes, which indicates neurogenesis development and tissue regeneration. The process was accompanied by a decreased dementia level and cognitive functions restoration. The resulting positive effect was observed for over 10 years.ConclusionsDespite differences in the etiology of AD and distal cerebral atherosclerosis, PBMT is an effective treatment for dementia in these diseases. The method improves the blood supply of the brain; it stimulates neurogenesis and tissue structures restoration, which leads to an improvement in mental and cognitive functions. The resulting effect persists for a long time.
Clinical relevance of disrupted topological organization of anatomical connectivity in behavioral variant frontotemporal dementia
Authors: Chu Min , Liu Li , Nie Binbin , Chen Kewei , Wu Liyong 
Published: June 2023

AbstractBackgroundAbnormalities of neurodegenerative disease are not only involved in individual brain regions but also characterized by the alterations of a balance of connectomes. Graph theory is a novel approach to examine the balance of connectomes. However, the clinical relevance of white matter connectome changes in behavioral variant of frontotemporal dementia (bvFTD) is not well understood.MethodsIn this study, we used DTI image data from 24 patients with bvFTD and 28 normal controls to exploratory investigate the clinical relevance of white matter topological alterations.ResultsThe topological organization was disrupted in patients with bvFTD both globally and locally, some of which were correlated with the severity of behavior symptoms reflected as frontal behavior inventory (FBI), clinical statuses including the mini‐mental state examination (MMSE) and frontotemporal lobar degeneration‐clinical dementia rating scale (FTLD‐CDR). Notably, the nodal parameters of the lost hub regions including bilateral dorsolateral superior frontal gyrus, right orbital inferior frontal gyrus, left insula and left anterior cingulate gyrus were associated with the severity of cognitive and behavioral symptoms.ConclusionTopological measures would be a potential marker to explore the disease severity, mapping the large‐scale structural connectome of the brain will help to understand emergent cognitive behaviors in the disease condition of bvFTD.
Molecular activation of gliovascular signaling precedes blood‐brain barrier disruption and neuronal loss in a mouse model of tauopathy
Authors: Komuro Yutaro , Minaeva Olga , Moncaster Juliet A , Hua Ning , Carmichael S. Thomas , Goldstein Lee E , Hinman Jason 
Published: June 2023

AbstractBackgroundIncreasing evidence points to disruption of the blood‐brain barrier (BBB) as an inciting event in the pathogenesis of Alzheimer’s disease. The contribution of tau‐mediated pathways driving blood‐brain dysfunction are comparatively understudied.MethodUsing the P301S mouse model of tauopathy, we employed dynamic contrast enhanced MRI (DCE‐MRI) and quantitative spatial analysis using gadolinium‐based mass spectrometry imaging to demonstrate widespread BBB dysfunction in late stage tauopathy. To identify molecular pathways regulating intercellular signaling between neurons and gliovascular support cells that are dysregulated in advance of BBB disruption, we developed a cell‐specific viral approach for transcriptional profiling of novel pathways within the multicellular environment of the neurovascular unit (NVU) in tauopathy. Viral constructs using cell‐type specific promoters (hSynapsin, GFAP, or PDGFRb) to drive expression of antigen‐tagged ribosomes (TRAP) were used to study variance in spatial and temporal gene expression patterns in NVU cell types in P301S transgenic mice prior to widespread BBB disruption.ResultRegional disruption of BBB integrity involving the hippocampus, lateral temporal, and frontal cortices is prominent in 11 month‐old P301S mice. Cell‐specific profiling of early symptomatic 6 month‐old P301S mice identified a defined gene expression profile antecedent to BBB disruption in NVU cells comprised of 29 shared and 3299 unique genes across all cell types. In this early symptomatic stage of tauopathy, pericytes (1021 genes) and astrocytes (1717 genes) were remarkably more transcriptionally active than neurons (561 genes). Gene ontology analysis indicates that multiple molecular programs driving neuronal differentiation, neurite outgrowth, and synaptogenesis are expressed in gliovascular cells in the prodromal stage.ConclusionThe specific and temporally regulated coordination of pathways in pericytes and astrocytes in advance of BBB dysfunction implicates the neurovascular unit as a potential driver in the development of tauopathy. This suggests a paradigm exists for gliovascular rescue of neurodegeneration and implicates numerous novel perivascular molecular pathways in the pathogenesis of tauopathy and Alzheimer’s disease.