bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurofilament light and cognition in community-dwelling non-Hispanic Blacks
Authors: Abdullah Lubnaa , Zhang Fan , Hall James , O’Bryant Sid 
Published: November 2024

Background No large-scale characterizations of neurofilament light chain (NfL) and cognitive outcomes have been conducted in community-dwelling non-Hispanic Blacks. Objective This study aims to enhance the application of blood biomarkers, in particular NfL, to ethno-racially diverse communities. We assess the association of NfL with cognitive outcomes, hypothesizing that NfL can identify cognitive changes regardless of diagnostic category. Methods Baseline data were analyzed among n = 283 non-Hispanic Blacks (NHB) from the multi-ethnic Health and Aging Brain Study- Health Disparities (HABS-HD). Plasma NfL was measured on the Simoa platform. Linear regression models were conducted, covarying for age, gender, and education. Results The majority of study participants (72%) were cognitively unimpaired (CU), with 21% having mild cognitive impairment (MCI), and 6.7% with Alzheimer's disease (AD). In adjusted models among the entire sample, significant associations existed between NfL and Trails A ( p < 0.0001), Trails B ( p < 0.0001), phonemic (FAS) and semantic (Animals) fluency ( p = 0.03), and Symbol Digit Substitution ( p < 0.001). When separated by diagnostic classification, significant associations were removed for functions involving executive functions for all diagnostic groups. Higher levels of NfL were positively associated with cognitive diagnosis, older age, and less education. Conclusions Plasma NfL levels are significantly associated with measures of executive functioning, which elucidate NfL as a non-specific marker of neurodegeneration associated with efficiency of brain functions involving attention, processing, and generativity. NfL may be a sensitive measure for the detection of alterations in cognitive processing before the onset of phenotypic functional changes of neurodegeneration.
Regional differences in glucose metabolic decline and tau deposition in the Alzheimer's continuum brain
Authors: Ishii Kazunari , Yamada Takahiro , Hanaoka Kohei , Kaida Hayato , Kojita Yasuyuki , Kono Atsushi , Hanada Kazushi , Saigoh Kazumasa , Sakuta Shizuka , Hashimoto Mamoru , Kato Takashi , Nakamura Akinori ,   for BATON Study Group
Published: November 2024

Background: Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β and tau proteins, leading to neurofibrillary tangles. A biomarker-based diagnostic method called the ATN system categorizes AD pathology into amyloid-β (A), tau (T), and neurodegeneration (N). The relationship between regional tau deposition and reduced glucose metabolism in the preclinical AD stage is not well understood. Objective: We presented voxel-by-voxel metabolic/tau deposition ratio (MTR) images to investigate the effects of tau deposition on metabolism in AD brains on a stage-by-stage basis. Methods: We selected 174 subjects who underwent 3D-MRI, FDG-PET, amyloid PET, and tau PET scans. MTR images were created by normalizing FDG-PET toMK6240 PET images. Voxel-wise comparisons among 63 cognitively normal amyloid-negative (CNA) subjects, 49 subjects with AD dementia (ADD), 23 subjects with mild cognitive impairment due to AD (MCA), and 39 preclinical AD (PRC) subjects were conducted. Results: There was reduced glucose metabolism in ADD and MCA groups compared to CNA, predominantly in parietotemporal areas. Tau deposition was observed in wider areas in ADD and restricted to the medial temporal lobes in MCA. MTR exhibited significant reductions in broader regions in ADD and MCA, indicating simultaneous glucose metabolism decrease and tau deposition. At the MCA and PRC stages, glucose metabolism impairment and tau deposition were shown in separate regions by FDG PET and tau PET, respectively, while MTR images showed impairment in both regions. Conclusions: Our findings suggest that MTR imaging provides insights into AD pathophysiology by simultaneously assessing glucose metabolism and tau deposition. In the early stage of the AD continuum (MCA and PRC), metabolic decline and tau deposition occur independently in different brain regions.
Structural white matter connectivity differences independent of gray matter loss in mild cognitive impairment with neuropsychiatric symptoms: Early indicators of Alzheimer's disease using network-based statistics
Authors: Pajavand Amir Mohammad , Grothe Michel J , De Schotten Michel Thiebaut , Giorgi Filippo Sean , Vergallo Andrea , Hampel Harald ,   for the Alzheimer's Disease Neuroimaging Initiative
Published: November 2024

Background Depression and circadian rhythm disruptions are non-cognitive neuropsychiatric symptoms (NPS) that can appear at any stage of the Alzheimer's disease (AD) continuum. Evidence suggests that NPS are linked to AD pathophysiology and hippocampal dysfunction. Objective To examine structural white matter (WM) connectivity and its association with gray matter (GM) atrophy and to identify specific AD-related neural networks linked to NPS in individuals with mild cognitive impairment (MCI). Methods Ninety-six older adults participants were divided into three groups based on the Global Depression Scale, Neuropsychiatric Inventory, Clinical Dementia Rating, and Mini-Mental Status Examination. Twelve individuals with MCI and NPS (MCI+) and 49 without NPS (MCI-) were classified, along with 35 age and gender-matched healthy individuals. Voxel-based morphometry and tract-based spatial statistics were employed to identify structural and microstructural alterations. Network-based statistics analyzed structural WM connectivity differences between MCI groups and healthy controls. Results Significant structural WM connectivity and GM loss were exclusively observed in MCI+ individuals compared to controls. The hippocampus, amygdala, and sensory cortex showed GM atrophy (p < 0.05), while the thalamus, pallidum, putamen, caudate, hippocampus, and sensory and frontal cortices exhibited structural WM connectivity loss (p < 0.01). These data indicate early limbic system involvement even without GM atrophy. Conclusions Structural WM connectivity loss within the Papez circuit may precede and potentially predict GM atrophy in the temporal lobe of individuals with MCI+. These findings highlight the importance of investigating structural WM alterations in the prodromal phase of AD, which may inform diagnostic and therapeutic strategies in early AD.
Effect of ceftriaxone on the glutamate-glutamine cycle and seizure susceptibility of Tg2576 mouse model of Alzheimer's disease
Authors: Dejakaisaya Hattapark , Lin Runxuan , Harutyunyan Anna , Chan Jianxiong , Kwan Patrick , Jones Nigel C 
Published: November 2024

Background Individuals with Alzheimer's disease (AD) have a heightened risk of epilepsy. However, the underlying mechanisms are not well-understood. Objective We aimed to elucidate the role of the glutamate-glutamine cycle in this mechanism and test the effect of ceftriaxone, a glutamate transporter-1 (GLT-1) enhancer, on seizure susceptibility in the Tg2576 mouse model of AD. Methods First, we assessed expression levels of key proteins in the glutamate-glutamine cycle in Tg2576 ( n = 7) and wild-type littermates ( n = 7), and subsequently in the kindling model of epilepsy ( n = 6) and sham ( n = 6). Then, kindling susceptibility was assessed in three groups: 200 mg/kg ceftriaxone-treated Tg2576 (Tg-Ceft, n = 9); saline-treated Tg2576 (Tg-Sal, n = 9); and saline-treated wild-type (WT-Sal, n = 15). Mice were treated for seven days before kindling, and seizure susceptibility compared between groups. Results Protein levels of GLT-1 ( p = 0.0093) and glutamine synthetase ( p = 0.0016) were reduced in cortex of Tg2576 mice, compared to WT. Kindling increased GLT-1 (cortex: p < 0.0001, hippocampus: p = 0.0075), and glutaminase (cortex: p = 0.0044) protein levels, compared to sham. Both Tg-Ceft and WT-Sal displayed Class IV seizures in response to the first stimulation ( p > 0.99), while Tg-Sal displayed Class V seizure ( p = 0.0212 versus WT-Sal). Seizure susceptibility of Tg-Ceft was not different from Tg-Sal ( p > 0.05), and kindling rates did not differ between groups. Conclusions Disruptions to key components of the glutamate-glutamine cycle are observed in models of AD and epilepsy. However, increasing GLT-1 through ceftriaxone treatment did not influence seizure susceptibility in Tg2576 mice, suggesting this is not an effective strategy to lower seizure susceptibility in AD, or a higher dosage is needed.
Genetic variants for Alzheimer's disease and comorbid conditions
Authors: Pan Minmin , Lai Dongbing , Unverzagt Frederick , Apostolova Liana , Hendrie Hugh C , Saykin Andrew , Foroud Tatiana , Gao Sujuan 
Published: November 2024

Background Alzheimer's disease and related dementias (ADRD) frequently co-occur with comorbidities such as diabetes and cardiovascular diseases in elderly populations. Objective Utilize a life-course approach to identify genetic variants that are associated with the co-occurrence of ADRD and another comorbid condition. Methods Research data from African American participants of the Indianapolis-Ibadan Dementia Project (IIDP) linked with electronic medical record (EMR) data and genome-wide association study (GWAS) data were utilized. The age of onset for ADRD was obtained from longitudinal follow-up of the IIDP study. Age of onset for comorbid conditions was obtained from EMR. The analysis included 1177 African Americans, among whom 174 were diagnosed with ADRD. A semi-parametric marginal bivariate survival model was used to examine the influence of single nucleotide polymorphisms (SNPs) on dual time-to-event outcomes while adjusting for sex, years of education, and the first principal component of GWAS data. Results Targeted analysis of 20 SNPs that were reported to be associated with ADRD revealed that six were significantly associated with dual-disease outcomes, specifically congestive heart failure and cancer. In addition, eight novel SNPs were identified for associations with both ADRD and a comorbid condition. Conclusions Using a bivariate survival model approach, we identified genetic variants associated not only with ADRD, but also with comorbid conditions. Our utilization of dual-disease models represents a novel analytic strategy for uncovering shared genetic variants for multiple disease phenotypes.
Primary cortical cell tri-culture to study effects of amyloid-β on microglia function and neuroinflammatory response
Authors: Kim Hyehyun , Le Bryan , Goshi Noah , Zhu Kan , Grodzki Ana Cristina , Lein Pamela J , Zhao Min , Seker Erkin 
Published: November 2024

Background Microglia play a critical role in neurodegenerative disorders, such as Alzheimer's disease, where alterations in microglial function may result in pathogenic amyloid-β (Aβ) accumulation, chronic neuroinflammation, and deleterious effects on neuronal function. However, studying these complex factors in vivo, where numerous confounding processes exist, is challenging, and until recently, in vitro models have not allowed sustained culture of critical cell types in the same culture. Objective We employed a rat primary tri-culture (neurons, astrocytes, and microglia) model and compared it to co-culture (neurons and astrocytes) and mono-culture (microglia) to study microglial function (i.e., motility and Aβ clearance) and proteomic response to exogenous Aβ. Methods The cultures were exposed to fluorescently-labeled Aβ (FITC-Aβ) particles for varying durations. Epifluorescence microscopy images were analyzed to quantify the number of FITC-Aβ particles and assess cytomorphological features. Cytokine profiles from conditioned media were obtained. Live-cell imaging was employed to extract microglia motility parameters. Results FITC-Aβ particles were more effectively cleared in the tri-culture compared to the co-culture. This was attributed to microglia engulfing FITC-Aβ particles, as confirmed via epifluorescence and confocal microscopy. FITC-Aβ treatment significantly increased microglia size, but had no significant effect on neuronal surface coverage or astrocyte size. Upon FITC-Aβ treatment, there was a significant increase in proinflammatory cytokines in tri-culture, but not in co-culture. Aβ treatment altered microglia motility evident as a swarming-like motion. Conclusions The results suggest that neuron-astrocyte-microglia interactions influence microglia function and highlight the utility of the tri-culture model for studies of neuroinflammation, neurodegeneration, and cell-cell communication.
Mild behavioral impairment in people with mild cognitive impairment: Are the two conditions related?
Authors: Scheuermann Julia-Sophia , Graessel Elmar , Kratzer André , Scheerbaum Petra 
Published: November 2024

Background Mild cognitive impairment (MCI) and mild behavioral impairment (MBI) are both considered potential prodromal stages of dementia, especially Alzheimer's disease. Previous literature has lacked specific information about MBI in individuals with MCI and associations of several aspects of both, MBI and MCI. Objective Our aim was to investigate whether associations exist between aspects of MBI and aspects of cognitive performance in certain dimensions of the Montreal Cognitive Assessment (MoCA). Methods We used baseline data from the double-blind randomized controlled intervention MCI-CCT-study. Current cognitive performance of individuals with MCI was measured with the MoCA. MBI was assessed with the MBI Shortscale (MBI short), which was administered through a self-report interview. Associations were assessed with Pearson correlations. Sensitivity analyses were conducted for gender and cognition. Group differences were examined with independent samples t-tests or Welch test. Significant correlations were considered in binary logistic regressions under control of covariates. Results There was no significant correlation between the current MoCA and MBI short scores in the total sample or in the gender-related analysis. Using dichotomized cognitive performance, significant correlations between MCI and MBI were revealed for individuals with lower MoCA scores. On the task level, several significant associations were identified between MoCA dimensions and MBI dimensions in the total sample and in the sensitivity analyses, also under control of covariates. Conclusions Our findings support the hypothesis that with increasing cognitive decline, the association between MCI and MBI becomes stronger. Furthermore, a certain cut-off on the MoCA must be reached to identify a correlation.
Investigating the efficacy of ergothioneine to delay cognitive decline in mild cognitively impaired subjects: A pilot study
Authors: Yau Yu Fung , Cheah Irwin K , Mahendran Rathi , Tang Richard MY , Chua Ru Yuan , Goh Rachel ES , Feng Lei , Li Jialiang , Kua Ee Heok , Chen Christopher , Halliwell Barry 
Published: November 2024

Background Dementia, particularly Alzheimer's disease, is a major healthcare challenge in ageing societies. Objective This study aimed to investigate the efficacy and safety of a dietary compound, ergothioneine, in delaying cognitive decline in older individuals. Methods Nineteen subjects aged 60 or above with mild cognitive impairment were recruited for this double-blinded, randomized, and placebo-controlled study (ClinicalTrials.gov identifier: NCT03641404, registration date: 19/08/2018). Subjects received either ergothioneine (25 mg per capsule) or a placebo, taken 3 times a week for one year. The whole blood profile, markers of renal and liver functions, neurocognitive performance, plasma levels of ergothioneine and its metabolites, and plasma biomarkers related to neurodegeneration were measured across the study. Results Ergothioneine intake did not alter clinical safety markers (blood counts, kidney and liver function) throughout the study, further validating its safety for human consumption. Subjects receiving ergothioneine demonstrated improved performance in assessment of learning ability and stabilized plasma levels of neurofilament light chain, compared with the placebo group, which saw no improvement in cognitive assessments and a significant increase in neurofilament light chain levels. Conclusions Prolonged intake of ergothioneine showed no toxicity in elderly people. Enhanced Rey Auditory Verbal Learning Test performance and stabilized neurofilament light chain levels suggest improvements in memory and learning abilities and a deceleration of neuronal damage, respectively. Our results add to existing data that ergothioneine is safe for extended consumption and may hold the potential to delay cognitive decline in elderly adults.
Benefits of nostalgic landmarks for people living with Alzheimer's disease
Authors: Oliver Alice , Wildschut Tim , Redhead Edward S , Parker Matthew O , Sharif Saif , Wood Antony P , Sedikides Constantine , Cheston Richard 
Published: November 2024

Background Emerging literature shows that nostalgia induced by autobiographical reflection and music confers psychological benefits to people living with dementia. Objective Our objective was to test the potential benefits of nostalgic landmarks for people living with Alzheimer's disease. Methods We displayed the landmarks as wall-mounted pictures within a virtual environment. In Experiment 1, we developed the nostalgia manipulation by using pictures associated with the decade during which participants lived most of their childhood. To examine the effectiveness, tolerability, and safety of this pictorial nostalgia induction, we conducted the experiment with 172 healthy adults. In Experiment 2, we recruited 20 participants living with Alzheimer's disease who experienced mild to moderate cognitive impairments. We further personalized the pictorial nostalgia induction by interviewing them about fond memories from their past and generating images corresponding to these events. We hypothesized that navigating a virtual environment with wall-mounted nostalgic (compared to control) pictures would confer psychological benefits. Results The nostalgic (versus control) pictures evoked higher levels of momentary nostalgia; the manipulation was successful (Experiments 1 and 2). Compared to control pictures, nostalgic pictures significantly increased self-reported positive (but not negative) affect, self-esteem, self-continuity, social connectedness, and meaning in life (Experiments 1 and 2). Participants in the nostalgia condition (compared to controls) evinced better picture recognition, but not improved spatial memory (Experiment 2). Conclusions Our findings demonstrate that nostalgic landmarks confer psychological benefits and enhance picture recognition among people living with Alzheimer's disease. This work has real-world applications for dementia-friendly design and therapy-related practices.
Reactions of clinical neuropsychologists to the Alzheimer's Association workgroup's draft diagnostic and staging criteria for Alzheimer's disease
Authors: Kiselica Andrew M , Atkins Kelly J , Han S Duke , Diaz-Orueta Unai , Gogniat Marissa A , Blanco-Campal Alberto , Hermann Greta ,   Contributing Neuropsychologists, Duff Kevin 
Published: November 2024

Background An Alzheimer's Association (AA) workgroup published criteria for the diagnosis and staging of Alzheimer's disease (AD). To date, there have not been empirical investigations of professionals’ opinions regarding the AA criteria for AD. Objective Our goal was to survey clinical neuropsychologists with expertise in dementia about these criteria. Methods Participants were recruited from a professional interest group of neuropsychologists focused on dementia. They rated their agreement with 15 statements about the AA draft criteria for AD prior to publication of the final version. The 15 statements were rated on a 4-point Likert scale ranging from 1 = Strongly Disagree to 4 = Strongly Agree. Results Sixty-one respondents provided analyzable data. When all 15 statements were coded such that higher values suggested more concern about the recommendations, the mean rating was 3.12 ( SD = 0.36), suggesting that overall respondents had modest concerns about the recommendations. The statements that yielded the most concern focused on barriers to the implementation of the recommendations, including a lack of healthcare resources and costs of biomarker testing. Conversely, participants were equivocal about the criteria being a positive step forward and had mixed opinions about the applicability of these criteria to diverse groups. Conclusions Opinions of neuropsychologists suggest the need for important revisions or additions to the AA criteria for AD, including a clearer statement of purpose and more guidance on practical implementation.
Association of the ascending aortic length with acute type A aortic dissection: A retrospective cohort study
Authors: Korpela Tarmo , Salomaa Elina , Kauhanen Petteri , Selander Tuomas , Hedman Marja , Husso Annastiina 
Published: November 2024

Background and Aims: To investigate whether, alongside aortic dilatation, ascending aortic (AA) elongation is associated with the increased risk for aortic dissection. Methods: This retrospective study included patients treated for Stanford type A aortic dissection (n = 102) in Kuopio University Hospital between 2009 and 2022, patients with AA dilatation (maximal diameter > 40 mm) (n = 134), and healthy controls (n = 191). AA length and dimensions were measured from aortic computed tomography angiography (CTA) images. AA length was defined as the distance between the aortic annulus and the origin of the brachiocephalic trunk. Results: After adjusting the AA length to the patients’ age, height, body surface area (BSA), sex, and maximal diameter, the dissected aortas were 14 mm longer than in the healthy controls and 5 mm longer than in the dilated non-dissected aortas (p < 0.001). The dilated non-dissected aortas were 8 mm longer than in the healthy controls (p < 0.001). In the dissection cohort, 25/102 (25%) patients had maximal AA diameter < 55 mm and 16/102 (16%) patients had maximal AA diameter ⩾ 55 mm together with AA length > 110 mm. By combining 110 mm AA length and < 55 mm diameter, 58% of the dissection patients would have been identified instead of using solely AA diameter ⩾ 55 mm as a cut-off criterion, based on which only 33% patients met the indication for elective surgery. Conclusion: AA length seemed to have an association with acute type A dissection, and therefore, it could be an additional tool in identifying patients who may benefit from preventive aortic surgery. [Formula: see text]
Association between carpal tunnel syndrome and shoulder pain: a case–control study
Authors: Akrivos Vasileios S , Koutalos Antonios A , Varitimidis Sokratis E 
Published: November 2024

We investigated the prevalence of shoulder pain around the scapular spine in patients with carpal tunnel syndrome and in the general population. In those with carpal tunnel syndrome, 63% reported shoulder pain, against 5% in the control group. Level of evidence: III