bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peripheral immunity is associated with the risk of incident dementia
Authors: Zhang Ya‐Ru 
Published: June 2023

AbstractBackgroundCentral immunity components especially microglia in dementia have been well studied and corresponding immunotherapy gradually caught the attention. However, few studies focused on peripheral immunity and dementia.MethodTo address the issue, we examined the longitudinal association between incident dementia and peripheral immunity markers encompassing immune cell counts, and their derived ratios including neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), systemic immune‐inflammation index (SII) and lymphocyte‐to‐monocyte ratio (LMR), utilizing data of 361653 participants from the UK Biobank (UKB).ResultDuring a median follow‐up of 8.99 years, 4239 participants developed dementia. The results revealed that increased innate immunity markers were associated with higher dementia risk (per SD increment hazard ratio [HR]; 95% confidence interval [CI] 1.14; 1.09‐1.19 for neutrophils, 1.16; 1.11‐1.20 for NLR and 1.11; 1.07‐1.16 for SII), while increased adaptive immunity markers were associated with lower dementia risk (0.93; 0.90‐0.97 for lymphocytes and 0.94; 0.90‐0.98 for LMR).ConclusionOur study pinpoints the differential role of innate and adaptive immunity in dementia incidence, which may provide some new perspectives in etiology and therapy of dementia.
Study the potential of PS23 probiotics in Alzheimer’s disease model mice
Authors: Chang Ching‐Hwa , Shih Jui‐Hsin , Tsai Ying‐Chieh , Hsieh Hsiu‐Mei 
Published: June 2023

AbstractBackgroundAlzheimer’s disease (AD) is the most common form of dementia that affects memory, thinking, and behaviors. Studies have proved that there is a bidirectional communication in the gut‐brain axis. Recently, increasing evidence indicate the association between gut dysbiosis and AD, and studies show that probiotics can affect gut dysbiosis through the gut‐brain axis. Lactobacillus paracasei PS23 is a probiotic isolated from healthy human feces, and several studies suggest it can ameliorate cognitive decline, aging progression, and depression. Whether PS23 show effect on AD remains to be explored.MethodWe applied the PS23 one week before and four weeks after the Aβ injection into the mouse hippocampal CA1 region. A series of behavior tasks were performed to analyze the cognition and anxiety of mice. We also investigated whether probiotic PS23 changed the gut microbiota composition and gene expression in mouse hippocampus.ResultPS23 showed a tendency in improving the short‐term memory and spatial learning ability of an Aβ‐injected acute AD model mice. In addition, synapse protection and anti‐inflammation were observed after PS‐23 treatment. The gut microbiota composition showed some bacteria strains were different after Aβ injection and oral administration of PS23. How the alteration in microbiota associates with AD is under characterization. In addition, the alteration in hippocampal gene expression profile will be used to further elucidate the molecular mechanism of PS23 in the AD model mice.ConclusionResults of this project suggest that PS23 might have benefit in improving the short‐term memory and spatial learning of an Aβ‐injected acute AD model mice through anti‐inflammation, which could provide some options in the strategy for AD prevention or therapy.
Chronic glial activation causes cholinergic cell loss in the basal forebrain during pathological aging
Authors: Gamage Rashmi Vasundhara , Childs Ryan , Hornas Gintara , Wagnon Ingrid Marguerite , Niedermayer Garry , Muench Gerald Wolfgang , Gyengesi Erika 
Published: June 2023

AbstractBackgroundNeuroinflammation, described by chronic glial reactivation lead to gradual neurodegeneration during pathological aging, contributing to disorders like Alzheimer’s disease (AD). Cholinergic cell loss in the basal forebrain (BF) including the medial septum (MS) is associated with AD; however the underlying mechanism is still unknown. Hence, this study investigated the effects of aging and chronic neuroinflammation on the MS cholinergic cell numbers and morphology.MethodAged, 12 and 24 months WT and GFAP‐IL6 mice (presenting IL‐6 overexpression under the GFAP promoter, resulting in chronic glial activation) were used. Immunohistochemistry combined with unbiased stereology and 3D morphology analysis were used to estimate the number and morphology of Iba1+ microglia and ChAT+ cholinergic cells in the MS. Transcriptomic analysis of the MS was performed using qPCR.ResultStereological estimation of MS microglia number displayed a significant 25% increase in GFAP‐IL6 mice compared to control WT (12M). A significant 30% increase was obtained for GFAP‐IL6 (24M) mice compared to control (24M). Furthermore, a significant 23% increase in microglia was described for GFAP‐IL6 (24M) compared to the GFAP‐IL6 (12M) mice. A significant 28% and 38% decrease in microglial 3D surface area, and volume respectively were observed between WT and GFAP‐IL (12M) mice, as well as 26% and 34% decrease respectively between WT (12M) and (24M), resembling reactive microglial morphology. Meanwhile, cholinergic cell number displayed a significant 31% decrease in GFAP‐IL6 (12M) mice compared to WT (12M). While a significant 30% decrease was displayed in GFAP‐IL6 (24M) mice compared to WT (24M) mice. There was a tendency for the cholinergic cell number to decrease with ageing among control and GFAP‐IL6 cohorts. Cholinergic cell morphology displayed significant 58% and 67% reduction in the 3D dendritic field surface area, and volume respectively between WT (12M) and GFAP‐IL (12M) mice, as well as 41% and 46% decrease respectively between WT (12M) and (24M), displaying patterns like neuronal degeneration.ConclusionThese findings demonstrate a significant impact of both aging and chronic glial activation alone on cholinergic cell number and morphology in the MS, resembling the cholinergic cell loss in AD, which can exacerbate throughout ageing leading to neurodegenerative impairments.
A comprehensive array of gray matter labels for the MIITRA atlas: Interoperability with complementary atlases
Authors: Niaz Mohammad Rakeen , Ridwan Abdur Raquib , Wu Yingjuan , Zhang Shengwei , Bennett David A , Arfanakis Konstantinos 
Published: June 2023

AbstractBackgroundA comprehensive array of gyral‐based,cytoarchitecture‐based,and functional connectivity‐based gray matter labels were constructed in the Multichannel Illinois Institute of Technology & Rush university Aging (MIITRA) atlas space in order to enhance the functionality of the atlas and its interoperability with complementary atlases.MethodT1w images from the 400 older adults included in the construction of the MIITRA atlas (50%male;64.9‐98.9 years of age) were processed with Freesurfer’s standard recon‐all pipeline. The Freesurfer outputs for all images were manually edited. Parcellations from Yeo,Desikan‐Killiany,HCP‐MMP,Brainnetome,Brodmann,Destrieux,Campbell,Flechsig,Mindboggle,Kleist,Smith,and EconomoCT atlases were projected onto the surface of each image and then converted to volumetric labels. The T1w images were also nonlinearly registered using ANTs‐SyN to the MNI152‐6thgen,MNI‐Colin,and the MNI‐2009b templates, and volumetric labels from Harvard‐Oxford,Julich,AAL3,Buckner,CoBrALab,CAREN,Striatum‐subdivision and Hippocampal‐subfields atlases were warped to the space of each image. The ANTs‐derived transformations applied on individual T1w images to build the MIITRA T1w template were used to map the corresponding gray matter labels from raw space to exact physical locations in the final MIITRA space. The performance of the MIITRA gray matter labels in segmentation of the gray matter of a separate group of 100 older adult individuals was evaluated in terms of label overlap, geometry, and dissimilarity when comparing the MIITRA labels warped to each individual’s space, to the respective reference labels from the source atlases.ResultExamples of the gray matter labels in MIITRA space are shown in Figure1. The measures of overlap between the warped and reference labels for each set of labels were generally high, with an average Dice coefficient of 0.78±0.3, average Jaccard coefficient of 0.59±0.27(Fig.2), sensitivity of 0.74±0.1, and specificity of 0.86±0.35(Fig.3). The label geometry showed a high correlation both in terms of the average volume of each label(correlation coefficient = 0.997,p‐value<10−10) and in terms of the average surface area of each label(correlation coefficient = 0.991,p‐value<10−10)(Fig.4). The values of dissimilarity were low, with an average volume error of 0.38±0.2(Fig.5).ConclusionThe gray matter labels in the MIITRA, in combination with the high‐resolution T1w template of the atlas, allowed segmentation of the gray matter of older adults that is in good agreement with the reference labels from the source atlases.
The effects of cognitive and physical exercise interventions on cognition in Huntington’s disease: A systematic review
Authors: Huynh Katharine , Nategh Leila , Jamadar Sharna , Georgiou‐Karistianis Nellie , Lampit Amit 
Published: June 2023

AbstractBackgroundCognitive and physical exercise interventions demonstrate efficacy in improving cognition in several populations but have not been reviewed in Huntington’s disease (HD). This systematic review aims to examine the effects of cognitive and physical interventions in HD.MethodElectronic databases (MEDLINE, EMBASE, PsycINFO, CENTRAL) were searched from inception through till 10 May 2021 for interventional studies of cognitive or physical exercise interventions in HD, with any control or no control. Clinical trial registries, theses databases and organisational websites were additionally searched. The primary outcome was change on objective measures of cognition. Additional outcomes included change in psychosocial, functional and neuroimaging outcomes. Risk of bias for each outcome domain was assessed independently by two reviewers using the Cochrane RoB 2 and ROBINS‐I tools. As studies reported multiple eligible outcomes in cognitive and psychosocial domains, composite effect sizes were calculated as standardized mean differences (Hedges’ g) with 95% CI.ResultFifteen studies (three cognitive, five physical, seven multidomain interventions) were included. There were five randomized controlled trials, two non‐randomized controlled trials and eight single arm studies. Most studies were therefore considered at serious risk of bias due to confounding. Interventions that included cognitive training (alone or combined with exercise) tended to report larger cognitive effect sizes, whereas studies of physical exercise (alone or combined with cognitive rehabilitation or stimulation) reported negligible benefits. Studies of multidomain interventions had larger effects on psychosocial functioning. Functional outcomes were only available from studies of multidomain interventions, which had negligible benefits. Across interventions, structural brain changes were reported in cortical and subcortical regions, but regions of interest and analyses were heterogeneous. No studies reported functional brain changes.ConclusionOur review indicates that cognitive training may benefit cognition in HD, while multidomain interventions may improve psychosocial function. Cognitive and physical interventions may promote structural brain changes, but functional brain changes are unclear. Larger randomised controlled trials are required to confirm the effects of cognitive or physical interventions in HD.
Associations of lifespan cognitive reserve with mild cognitive impairment and dementia among older adults with low literacy: A population‐based cohort study
Authors: Li Yuanjing , Ren Yifei , Cong Lin , Hou Tingting , Song Lin , Wang Mingqi , Wang Xiang , Shi Lin , Dekhtyar Serhiy , Wang Yongxiang , Du Yifeng , Qiu Chengxuan 
Published: June 2023

AbstractBackgroundEducational attainment in early life represents a major contributor to cognitive reserve (CR). High CR capacity derived from lifespan enriching factors could delay cognitive decline. We sought to investigate the longitudinal associations of CR capacity with mild cognitive impairment (MCI) and dementia among older adults with no or low literacy.MethodThis population‐based cohort study included 2141 rural participants (age≥60 years; 59.5% women; 84.8% illiteracy or elementary school) in the Shandong Yanggu Study of Aging and Dementia who were free of dementia at baseline (August‐December 2014) and who undertook follow‐up examinations in March‐September 2018. CR capacity was estimated by integrating early‐life education attainment, adulthood occupation and marital status, and late‐life physical activity and social support, and categorized into low, intermediate, and high levels using tertiles. MCI and amnestic MCI were defined according to the Petersen’s criteria that integrated clinical assessment with neuropsychological tests. Dementia and Alzheimer’s disease (AD) were diagnosed according to the DSM‐IV and NIA‐AA criteria, respectively. Data were analyzed using the structural equation and Cox proportional‐hazards models.ResultDuring an average of 3.7 (SD = 0.4) years of follow‐up, 102 of the 2141 dementia‐free participants were diagnosed with dementia, including 75 with AD. Compared to the low CR level, intermediate and high CR levels were associated with multi‐adjusted hazards ratios (HRs) (95% confidence intervals [CIs]) of 0.59 (0.37–0.94) and 0.47 (0.26–0.85) for dementia and 0.53 (0.31–0.92) and 0.38 (0.17–0.83) for AD, respectively. In addition, out of the 1727 MCI‐free participants at baseline, 330 developed MCI at follow‐up, including 270 with aMCI. Intermediate and high CR levels (vs. low) were associated with multi‐adjusted HRs (95% CIs) of 0.70 (0.53–0.92) and 0.60 (0.45–0.81) for MCI and 0.65 (0.48–0.87) and 0.58 (0.42–0.79) for amnestic MCI, respectively.ConclusionIn Chinese rural elderly, high CR capacity is associated with reduced risks of MCI, amnestic MCI, dementia, and AD. This suggests that the effect of CR capacity in delaying the onset of MCI and dementia exists even among rural older adults with no or very low literacy.
Association between amyloid, tau and cerebral small vessel disease
Authors: Cai Yuan , Liu Wanting , Fan Xiang , Wu Kuan‐Jung , Shi Lin , Au Lisa Wing Chi , Lam Bonnie Y.K. , Abrigo Jill , Mok Vincent C.T. , Ko Ho 
Published: June 2023

AbstractBackgroundControversy exists with respect to the etiological role of cerebral small vessel disease (CSVD) in Alzheimer’s disease (AD). We thus evaluated the association between white matter hyperintensity (WMH), an MRI marker of CSVD, with brain amyloid β (Aβ) and tau burden and their plasma markers among subjects with varying severity levels of cognitive impairment.MethodsWe recruited 84 subjects from the CU‐SEEDS (The Chinese University of Hong Kong‐Screening for Early AlzhEimer’s DiseaSe) study who were stroke‐free and had varying severity levels of cognitive impairment: 10 healthy controls [HC], 32 with subjective cognitive decline [SCD], 26 with mild cognitive impairment [MCI] and 16 with dementia. All subjects underwent structural MRI, 11C‐ PIB, and 18F‐T807 positron emission tomography (PET), to measure WMH volume, and pathological Aβ deposition (A+) and tau burden (T+), respectively. WMH volume was quantified by automatic segmentation using AccuBrain® IV 1.1. Plasma levels of Aβ40, Aβ42, total tau (t‐tau), phosphorylated tau at 181 (p‐tau181) and neurofilament light chain (NfL) were measured by Single Molecule Array (SiMoA) assays among 71 subjects.ResultsThe mean age of the subjects was 67.5. 34 (40.8%) were male. No significant associations were found between WMH volume and global 11C‐PIB or 18F‐T807 standardized uptake value ratio (SUVR) on PET. Interestingly, we found that increasing WMH volume significantly correlated with higher plasma p‐tau181 level (β = 0.10; 95% C.I.: 0.012 – 0.188; P = 0.03). There were no associations between WMH volume and plasma Aβ40, Aβ42, t‐tau or NfL levels.ConclusionBrain WMH volume was associated with plasma p‐tau181 level but not with PET tau positivity in the brain. Our results suggest that CSVD burden may contribute to elevated plasma phosphorylated tau in AD, and such change may precede PET‐detectable elevated tau burden in the brain.
Longitudinal brain atrophy rates in presymptomatic genetic frontotemporal dementia
Authors: Poos Jackie M. , Grandpierre Leonie D.M. , van der Ende Emma L. , Panman Jessica L. , Papma Janne M. , Seelaar Harro , van den Berg Esther , van ’t Klooster Ronald , Bron Esther E , Steketee Rebecca M.E. , Vernooij Meike W , Pijnenburg Yolande A.L. , van Swieten John C. , Rombouts Serge A.R.B. , Jiskoot Lize C. 
Published: June 2023

AbstractBackgroundIn light of upcoming clinical trials for genetic frontotemporal dementia (FTD), it is important to identify at what age brain atrophy rates start to accelerate and deviate from normal aging effects to find the optimal starting point for treatment. We aimed to investigate longitudinal brain atrophy rates in the presymptomatic stage of genetic FTD, using normative brain volumetry software.Method34 GRN, eight MAPT, and 14 C9orf72 presymptomatic mutation carriers underwent longitudinal volumetric T1‐weighted MRI of the brain with a one‐ to two‐year interval (mean number of scans = 3.5, SD = 1.6). Images were automatically analyzed with Quantib® ND which consisted of volume measurements (CSF and grey + white matter) of lobes (left, right, and combined), cerebellum, and hippocampus. All volumes were compared to reference centile curves based on a large population‐derived sample of non‐demented individuals (n = 4951). Mixed‐effects models were fitted to analyze atrophy rates of the different gene groups as a function of age, and were corrected for sex, head coil, and scanner software version.ResultAtrophy rates of the total brain, frontal lobe, and temporal lobe differed between gene groups (all p<0.002). GRN mutation carriers declined faster than the reference centile curves for all brain areas, though relative volumes remained between 5th and 75th percentile between the ages of 45 – 70. In MAPT mutation carriers, frontal lobe volume was already at the 5th percentile at age 45, and showed further decline between the ages 50‐60. Temporal lobe volume started in the 50th percentile at age 45, but showed fastest decline over time compared to other brain structures. Frontal, temporal, parietal and cerebellar volume already started below the 5th percentile compared to the reference centile curves at age 45 for C9orf72 mutation carriers, but there was minimal decline over time until the age of 60.ConclusionWe provide evidence for longitudinal brain atrophy in the presymptomatic stage of genetic FTD. The affected brain areas and the age after which atrophy rates start to accelerate and diverge from normal aging slopes differed between gene groups. These results highlight the value of normative volumetry software for disease‐tracking and staging biomarkers in genetic FTD.
Associations of patient‐specific resting state variability with CSF and clinical biomarkers: Data from Alzheimer’s disease clinical trials
Authors: Gobbi Susanna , Scelsi Marzia A. , Delmar Paul , Bittner Tobias , Klein Gregory , Magon Stefano 
Published: June 2023

AbstractBackgroundChanges of brain functional connectivity assessed using MRI in patients with Alzheimer’s disease (AD) have been previously reported. However, factors contributing to the variability among patients have not been sufficiently investigated. Here, we investigated the association of patient‐specific resting state parameters with CSF markers and clinical measures.MethodWe analyzed the baseline rs‐fMRI of 158 patients (87 female, age 50‐89) with mild AD collected in the Marguerite RoAD trial of gantenerumab in mild AD (NCT02051608) and 132 cognitively unimpaired adults (88 female, age 56‐90) from ADNI. We investigated the within‐ and between‐subjects’ variability in five brain networks (Sensory Motor, Cerebellar, Visual, Default Mode and Cognitive Control), inferred from the two groups using a Bayesian probabilistic model (PROFUMO, Harrison‐Smith‐2015; Harrison‐Woolrich‐2020). We computed spatial maps, BOLD amplitude changes, and spatial (temporal) functional connectivity between‐ and within‐networks for each subject. Those metrics were compared between groups using T‐tests. In AD patients we used linear models to investigate associations of the extracted metrics with CSF markers (Amyloid Beta 42, p‐Tau217, pTAU/Abeta 1‐42 ratio and Neurogranin) and cognitive scores (ADAS‐Cog 13, MMSE and ADCS‐ADL), while controlling for age, sex and MRI‐scanner type. All results were corrected for multiplicity using FDR.ResultOn average the signal amplitude was lower in the Cognitive Control and the Sensory Motor (p < 0.0001) networks in AD patients compared to cognitively unimpaired adults. Interestingly, in AD patients the lower amplitude observed in the cognitive control network was associated with cognitive decline (β = 0.02, p = 0.01). Moreover, significant associations were observed in AD patients between lower signal amplitude and higher CSF levels of ABeta 42 (β = ‐0.02, p = 0.036) and cognitive decline (β = 0.02, p = 0.008) (Fig.2). AD group showed on average reduced functional connectivity compared to the healthy one. Furthermore, the within‐AD patients’ analysis showed weak between‐ and strong within‐networks connectivity (T‐test, q < 0.05, Fig.1).ConclusionIn patients with mild AD, the signal amplitude and connectivity in the cognitive control and DMN networks were associated with both CSF level of ABeta42 and cognitive scores.