bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of physiological glucose levels on SIM‐A9 microglial cell immune response
Authors: Bruno Lucrezia , Mackenzie Francesca Elizabeth , Stolinski Michael 
Published: December 2023

AbstractBackgroundMicroglia play an important role in the early onset of Alzheimer’s disease pathology1. They are responsible for maintaining brain homeostasis, where changes in energy metabolism alter microglial metabolic profile and function2. The majority of cell culture‐based studies have relied on growing microglia under optimal media conditions, not reflecting the brain’s physiological levels of key metabolites. This study aims to define a suitable experimental culture system that reflects the brain’s physiological glucose level, approximately 1mM3, so the effects of altered glucose concentration can be tested.MethodSIM‐A9 mouse immortalised microglial cells were initially grown in DMEM/F‐12 medium (17.5mM glucose) containing 10% FBS and 0.1% Penicillin/Streptomycin (Gibco, UK). After 20 hours cells were re‐seeded in Neurobasal medium containing 1x B‐27 supplement (Gibco, UK) and either 1mM or 5mM glucose and grown for 20 hours. Cell proliferation and viability was assessed over 40 hours using an Incucyte imaging system (Essen BioScience, UK) and Trypan Blue assay. Media glucose concentration, cellular glucose uptake (Promega, UK), microglia activation and metabolic marker expression using qRT‐PCR were measured following stimulation of cells with Lipopolysaccharide (LPS) (2.5ng/ml)ResultMaintaining SIM‐A9 cells in 1mM and 5mM glucose medium showed static proliferation but similar viability over 20 hours compared to growth in DMEM/F12. LPS treatment increased TNFa and IL1b expression in SIM‐A9 cells in all glucose conditions, indicating the cells’ competency to produce a pro‐inflammatory response. No change in pro‐inflammatory activation markers (TNFa, IL1b) was seen after maintenance in 1mM, but in 5mM glucose for 20 hours, compared to LPS treated cells. Media glucose concentration was 0.7mM over 20 hours in 1mM and 1mM in 5mM glucose media. Expression of glucose transporters Glut1 and Glut3 and glycolysis marker PFKFB3 under these glucose conditions was investigated.ConclusionUntil now microglial metabolic studies have not always reflected the physiological concentrations of glucose in the brain. The results show that culturing microglia in 1mM glucose medium does not induce pro‐inflammatory activation, while maintaining minimal cell death and unvaried confluency.References: Yoshiyama Y et al (2007) Neuron 53(3): 337‐351. 2. Bernier L et al(2020) Trends in Neurosci43(11):854‐869. 3. Van de Ven K et al (2012) Diabetes 61
Feasibility of real world end‐points of functional neurophysiology in Alzheimer’s disease dementia
Authors: Rueda‐Delgado Laura M , Buick Alison R , Hardiman Orla , Muhammed Kinan , Nolan Hugh , Rowe James B. , Waninger Shani , Murphy Brian 
Published: December 2023

AbstractBackgroundClinic‐based biomarkers are effective in tracking disease progression in clinical research, but do not scale to support public health needs or large‐scale real‐world studies. Purely digital markers are scalable but lack the objectivity and neurobiological grounding of clinical measures. These first results of a real‐world feasibility study demonstrate that objective measures of a range of domains including EEG (Figure 1) are user‐friendly and suitable for repeated at‐home use by patients and older controls.Method60 patients and 60 matched controls are being recruited for a 1‐year repeated sampling study in the UK. Patients were clinically assessed to have mild Alzheimer’s type dementia. Participants were asked to complete about 30 minutes of behavioral tasks including memory, executive function, affective processing and language, while synchronized EEG was recorded using a self‐applied dry‐sensor headset. This interim data is from an initial 2‐week burst sampling period, for the first half of the cohorts.ResultAdherence was 76% for the dementia group (N = 29, mean age = 75; ADAS = Cog 24.3) and 88% for the control group (N = 36, mean age = 71; ADAS = Cog 7.8). A symbol substitution task (executive function) differentiated strongly between groups (t(53) = 6.9), and correlated highly with a conventional pen‐and‐paper DSST benchmark (rho = 0.79). An associative memory task also patterned strongly with disease status (t(54) = 5.7) and correlated with the Verbal Paired Associates benchmark (rho = 0.76). The grand average P300 ERP, elicited by a gamified 2‐stimulus oddball task, showed characteristic features of sensory and higher cognitive processing (Figure 2). As expected in the patient group, the P300 was reduced and delayed; and the resting‐state EEG theta and alpha power were enhanced and reduced, respectively. Radar plots (Figure 3), illustrate the pattern observed across domains in one representative Alzheimer’s patient and one control. Data from a fronto‐temporal dementia sister study is included for comparison.ConclusionInterim data from this first‐in‐class study suggest that patients with mild Alzheimer’s disease dementia are capable and willing to participate in intensive home‐based functional neurophysiology studies, if technology is designed to be engaging and easy to use. Initial examination of the data aligns with established benchmarks, constituting positive early evidence for construct validity and technical feasibility.
Physical function predicts declarative memory
Authors: Gray Michelle , Jones Megan , Campitelli Anthony , Gills Joshua L. , Paulson Sally , Glenn Jordan M. 
Published: December 2023

AbstractBackgroundNo cure currently exists for Alzheimer’s disease; however, early detection may help create therapies and treatments to slow cognitive decline. The concept of early detection is simple, but is complicated by the inability of primary care physicians to recognize symptoms until late disease manifestation and failure to provide appropriate screening tools for disease detection. Thus, the purpose of the present investigation was to determine predictors of cognitive performance among community‐dwelling older adults.Method63 community‐dwelling older adults (80.0 ± 5.5 years) participated in the present investigation. Declarative memory was used as the measure of cognition. Physical function was measured using the Short Physical Performance Battery (SPPB), dual‐task fast walking time, and sit‐to‐stand velocity. Linear regression analysis was used to predict cognition from physical function. Odds ratios were used to determine the magnitude of influence of physical function on cognitive function. ANOVA was used to determine differences in individual physical function variable between low and high cognitive groups.ResultsThe linear regression model included dual‐task fast 10‐m walking time, sex, education, and SPPB score and accounted for 39% of the variance in cognitive ability (p<.001). The physical function variables accounted for 8.8% and 8.5% of unique variance in cognition, respectively. For participants performing below the 50th percentile for dual‐task fast walking time, there was a 3.6‐fold increase in declarative memory scores (CI: 1.44‐9.35). Similarly, SPPB values indicative of mobility dysfunction was associated with a 3.2‐times increase in cognitive impairment (CI: 1.31‐7.87). Results of the one‐way ANOVA revealed significant differences in SPPB (p = .002), peak sit‐to‐stand velocity (p = .007), and dual‐task fast walking time (p = .001). The high cognitive group had significantly better physical function compared to the lower cognitive group.ConclusionResults from the present investigation support the use of physical function in predicting current declarative memory among a sample of community‐dwelling adults with no diagnosed cognitive impairment. Future research is needed to determine the ability to predict changes in cognition longitudinally.
Six‐Month Consistency of NIH Toolbox Cognition Battery Scores in Healthy Older Black Women with Subjective Cognitive Decline
Authors: Halter Colt M. , Moll Allison C. , Adams Hannah , Hanna Sophie , DiCerbo Loraine M. , Daugherty Ana M. , Woodard John L. , Giordani Bruno , Kavcic Voyko 
Published: December 2023

AbstractBackgroundInterest in the NIH Toolbox Cognition Battery (NIHTB‐CB) for the clinical assessment of older adults is burgeoning. Longitudinal neuropsychological assessments are the most sensitive way to establish cognitive decline and dementia risk of older adults. The psychometric property of measurement invariance is essential to valid interpretations of change. However, few studies have evaluated the stability of NIHTB‐CB scores in a sample of cognitively normal older adults with subjective cognitive decline (SCD). This study aims to analyze measurement consistency of NIHTB‐CB performance over 6 months.Method
N = 29 cognitively normal, older Black adult women (65‐81 years of age) with SCD were administered the NIHTB‐CB at baseline and six‐month follow‐up. Diagnostic status was determined via consensus conference following NACC UDS guidelines. We evaluated the mean change by matched‐pairs t‐tests, and measurement consistency by two‐way mixed effects models of intraclass correlations coefficients and Bland‐Altman plots. Uncorrected standard scores and fully corrected T scores were analyzed from NIHTB‐CB Cognition Composites of Total Cognition, Fluid Cognition, and Crystallized Cognition.ResultThere were no significant mean differences from baseline to follow‐up for corrected and uncorrected Total Cognition Scores. The uncorrected Fluid Score significantly increased by 2.5 points at follow‐up (t(28) = 2.18, p = .04), and the corrected Crystallized Score increased by 1.8 points at follow‐up (t(28) = ‐2.25, p = .03). The uncorrected Crystallized Score and the corrected Fluid Score did not differ across assessments. Consistency for the uncorrected and corrected Total scores was good, (ICC(3,1) = 0.83 and 0.80, respectively). Similarly, consistency for uncorrected and corrected Fluid Scores was also good (ICC(3,1) = 0.77 and 0.78). Consistency was excellent for uncorrected Crystallized Scores (ICC(3,1) = .92), but good for corrected scores (ICC(3,1) = .87). Discrepancy scores (baseline vs follow‐up) derived from uncorrected scores for the three composites were unrelated to age and education. Bland‐Altman plots of uncorrected scores for the Composite Scores were consistent with the ICC analyses, showing good agreement between measures.ConclusionNIHTB‐CB corrected and uncorrected composite scores have good longitudinal psychometric properties in a sample of older Black adult women with SCD, a relatively under‐investigated examinee sample. These findings also suggest that change in fluid or crystallized cognition over six months is unlikely in persons with SCD.
Cross‐Sectional Associations Among Sleep Quality, Hippocampal Volume, and Memory Complaints in the Offspring Study
Authors: Hokett Emily , Lao Patrick J. , Turney Indira C , Chapman Silvia , Osorio Ricardo S , Brickman Adam M. , Palta Priya , Manly Jennifer J. 
Published: December 2023

AbstractBackgroundPoor sleep quality, a modifiable risk factor for dementia, that is prevalent in non‐Hispanic Black and Hispanic adults, is associated with greater memory complaints and smaller hippocampal volumes in predominantly non‐Hispanic White samples. These associations among sleep quality, memory complaints, and hippocampal volumes are understudied in non‐Hispanic Black and Hispanic adults—populations disproportionately affected by poor sleep quality and cognitive performance. The objective of the current study was to examine associations among sleep quality, memory complaints, and hippocampal volumes in a racially and ethnically diverse, community‐based sample. Given sociocultural and environmental differences that affect sleep, brain measures, and cognitive performance, we hypothesize that poorer sleep quality is associated with more memory complaints and smaller hippocampal volumes, especially in Black and Hispanic adults.MethodParticipants included Black, Hispanic, and White adults from the Northern Manhattan community (n = 1175; 56±11 years; 67% women; 14±3 years of education; 17% Non‐Hispanic White; 20% Non‐Hispanic Black; 63% Hispanic). Participants self‐reported their sleep quality with the 9‐item Pittsburgh Sleep Quality Index, which measures average sleep disturbance over the past month. Participants self‐reported experiences with forgetting (e.g., names, faces, directions) with an abbreviated version of the Memory Functioning Questionnaire. In a subsample of participants, hippocampal volumes were measured on T1‐weighted MRI scans with FreeSurfer software. Sleep quality, hippocampal volume, and memory complaints were treated as continuous variables. We ran multivariable regression analyses adjusted for age, education, gender identity, depression severity, and intracranial volume for analyses with hippocampal volume.ResultAcross racial and ethnic groups, poorer sleep quality was associated with more memory complaints (n = 1175, B = ‐0.31, CI: [‐41,‐.22]). These associations were similar when analyses were stratified by racial and ethnic group. Among Hispanic adults, there was a trending association between poorer sleep quality and smaller left hippocampal volumes (n = 246, B = ‐8.94, CI: [‐18.75,0.88]).ConclusionPoorer sleep quality was associated with more memory complaints across racial and ethnic groups and showed a trending association with smaller hippocampal volumes in Hispanic adults. Future studies with larger samples should replicate these findings with longitudinal data to quantify the temporal relationship of sleep quality with memory complaints and structural brain changes.
A systematic evaluation of hippocampal GABA levels in transgenic mouse models of amyloid and tau
Authors: Mensch André Nunes , Carello‐Collar Giovanna , Bellaver Bruna , Ferreira Pamela C.L. , Ramos Vanessa G. , Pascoal Tharick A. , Rosa‐Neto Pedro , Zimmer Eduardo R 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) is characterized by the extracellular accumulation of amyloid‐β (Aβ) plaques and neuronal deposition of tau tangles, mainly in cortical regions and the hippocampus. Beyond these neuropathological hallmarks, it is suggested that neurotransmission dysfunctions, such as in the γ‐aminobutyric acid (GABA)ergic system, contribute to AD pathophysiology. However, the impact of Aβ and tau in the GABAergic system is still unknown. Thus, we aimed to examine GABA levels in the hippocampus of transgenic mouse models of Aβ and tau.MethodWe systematically reviewed the literature following the PRISMA 2020 guidelines. We searched PubMed and Web of Science databases for studies reporting GABA levels in the 3xTg‐AD and 5xFAD mouse models. These models present APP and PSEN1 mutations, but the 3xTg‐AD also harbors the MAPT P310L tau mutation, which is found in frontotemporal dementia.ResultThe search identified 3,576 articles. Six met the inclusion criteria (n = 26 3xTg‐AD and 26 wild‐type (WT); n = 16 5xFAD and 17 WT). The studies reported no significant differences in the levels of GABA in the hippocampus of 3xTg‐AD mice compared to their WT, but GABA levels decreased as a function of age. By contrast, the 5xFAD mouse model presented higher levels of GABA than their WT littermates.ConclusionHere, we show no significant changes in GABA levels in the hippocampus of 3xTg‐AD mice, whereas the levels of GABA were increased in the 5xFAD. Interestingly, the model harboring APP, PSEN1, and MAPT P310L mutations does not present changes in hippocampal levels of GABA. Our results suggest that Aβ alters GABA levels in the hippocampus, which may be an early change in AD. In addition, hippocampal GABAergic changes seem sensitive to different pathological features of AD.
Within and between‐network functional connectivity disruptions in posterior cortical atrophy and dementia with Lewy bodies
Authors: Singh Neha Atulkumar , Goodrich Austin W , Weigand Stephen D. , Graff‐Radford Jonathan , Machulda Mary M. , Carlos Arenn Faye , Lowe Val J. , Jack Clifford R. , Petersen Ronald C. , Boeve Brad F. , Josephs Keith A , Kantarci Kejal , Whitwell Jennifer L 
Published: December 2023

AbstractBackgroundPosterior cortical atrophy (PCA) and dementia with Lewy bodies (DLB) show overlapping patterns of hypometabolism affecting posterior regions of the brain. Both syndromes show disruptions in functional connectivity, but it is unknown how patterns of disruption within and between networks compare between PCA and DLB.MethodThirty amyloid‐positive PCA, 27 amyloid‐positive DLB (DLB+), 24 amyloid‐negative DLB (DLB‐) patients and 30 cognitively normal amyloid‐negative (CN) individuals were recruited at Mayo Clinic, Rochester, MN, and underwent structural and resting state functional MRI. Spatially preprocessed data was analyzed using the CONN functional connectivity toolbox to explore nine networks: visual, sensorimotor, dorsal‐attention, cerebellar, frontoparietal, memory, language, salience, and default mode networks (DMN). Multivariate linear regression models corrected for multiple comparisons and adjusted for age and sex were fit to analyze within‐network connectivity (Fisher’s R‐to‐Z transformations). Between‐network connectivity was assessed with group level difference maps (two‐sample t‐test) corrected for false discovery rate at p<0.05.ResultMultivariate linear regression models showed reduced within‐network connectivity across all DMN components, sensorimotor, and dorsal‐attention networks, with trends for the visual network in PCA compared to CN. Both DLB‐ and DLB+ showed reduced within‐network connectivity for the cerebellar network, with DLB+ showing reduced connectivity in the posterior‐DMN, memory, and salience networks compared to CN. DLB‐ showed increased connectivity in dorsal‐attention and DMN, while DLB+ showing reduced connectivity in the memory network compared to PCA. Between‐network analysis showed an increase in cerebellar‐to‐sensorimotor connectivity in all three groups, with increase in cerebellar‐to‐dorsal‐attention connectivity in DLB‐ and PCA compared to CN. DLB‐ showed a decrease in posterior‐DMN‐to‐sensorimotor connectivity, while PCA showed reduced connectivity between all DMN components and dorsal‐attention‐to‐sensorimotor connectivity compared to CN. There was an increase in connectivity between all DMN components and a reduction in dorsal‐DMN‐to‐sensorimotor connectivity in both DLB‐ and DLB+ compared to PCA.ConclusionPCA was associated with connectivity disruptions across all DMN components, sensorimotor, dorsal‐attention and visual networks, while both DLB groups showed disruptions in cerebellar networks, with DLB+ showing further disruptions in posterior‐DMN, memory and salience networks. These findings suggest that both PCA and DLB have unique brain network disruptions, with amyloid status influencing connectivity in DLB.
Effect of white matter hyperintensities and amyloid on neurodegenerative change and cognitive trajectory in cognitively unimpaired older adults
Authors: Maillard Pauline , Han Ji Won , Sapkota Shraddha , Harvey Danielle J. , Fletcher Evan , Martinez Oliver , Johnson David K , Olichney John M. , Farias Sarah Tomaszewski , Decarli Charles 
Published: December 2023

AbstractBackgroundOverwhelming evidence of association between amyloidosis and neurodegeneration, particularly in the hippocampus, has been reported. However, the recognition of cerebrovascular disease (CVD), the most common comorbidity in elderly patients with dementia2, as a contributor to neurodegeneration process has remained modest. The objective of this study is to investigate the contributions of amyloidosis, as measured by amyloid PET, and CVD, as reflected by white matter hyperintensity (WMH), on neurodegenerative change and how their combination impacts cognitive trajectory in cognitively unimpaired (CU) individuals.Method139 CU participants from the University of California, Davis Alzheimer’s Disease Research Center diversity cohort received at least two cognitive assessments and underwent a PET exam at baseline, and baseline and follow‐up MRI imaging (Table 1). Z‐score measures of DVR19 and SUVR20 values were used as measure of baseline amyloid beta (Aβ) burden. Baseline WMH volume was log‐transformed and regressed against intracranial volume (TCV). Four markers of neurodegeneration were used, including hippocampal volume (regressed against TCV), mean cortical GM thickness and two cognitive‐related signature region of interest (sROI), including episodic memory and executive function. We used structural equation modeling (SEM) analyses (Figure 1) to investigate associations between cognitive performance trajectories (∼6 years), including episodic memory and executive function, and baseline Aβ, baseline WMH and change in the four neurodegeneration markers.ResultSEM analysis revealed significant effects of increased baseline Aβ and greater baseline WMH on accelerated decrease in neurodegeneration marker measures in all models (Figure 2). Increased baseline amyloid and WMH, but not neurodegenerative change measures, were also associated with accelerated decline in episodic memory performance (pvalues<0.05, Figure 2, panels A‐C‐E). Finally, increased baseline Aβ and accelerated decreased in cortical GM and sROI thickness were found to be associated with accelerated decline in executive function (pvalues<0.05, Figure 2, panels B‐D‐F).ConclusionOur findings suggest that both CVD and amyloidosis simultaneously impact neurodegenerative change and that these pathologies are associated with cognitive trajectories, but the dynamics of these trajectory are different for executive and memory, suggesting different early path of vulnerability for these domains and emphasizing the need to thoroughly understand the interaction between amyloidosis, CVD, and neurodegeneration.