bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of multivitamin‐mineral supplementation on change in cognitive function in the COSMOS Clinical subcohort and meta‐analysis of COSMOS cognition studies
Authors: Vyas Chirag M. , Rist Pamela M. , Sesso Howard D. , Manson JoAnn E. , Okereke Olivia I. 
Published: December 2023

AbstractBackgroundFew randomized clinical trials (RCTs) have investigated the effect of multivitamin‐mineral supplementation (MVM) on cognitive change among community‐dwelling older adults and effects remain untested using detailed in‐person, gold‐standard neuropsychological assessments; thus, we tested the effect of daily MVM vs. placebo on cognitive function among older adults enrolled in the in‐clinic component of COSMOS (COcoa Supplement and Multivitamin Outcomes Study). Furthermore, we conducted a meta‐analysis of the findings from the three COSMOS cognition studies: COSMOS‐Clinic (n = 603 for the detailed in‐person cognitive assessments), COSMOS‐Mind (n = 2262 for telephonic‐based cognitive assessments); and COSMOS‐Web (n = 3562 for computer‐based cognitive assessments) to provide a robust evaluation of the effects of MVM on cognition.MethodsCOSMOS is a 2×2 factorial RCT of cocoa extract supplements (Mars Edge; containing 500 mg/day flavanols) and/or MVM (Haleon, as Centrum Silver) for cardiovascular and cancer prevention. In COSMOS‐Clinic, n = 573 of n = 603 COSMOS‐Clinic participants completed all cognitive tests at baseline; n = 492 completed all cognitive tests at both baseline and 2‐year follow‐up. The primary outcome was global cognitive score [averaging z‐scores of 11 tests: general cognition (the Modified Mini‐Mental State), episodic memory (Consortium to Establish a Registry for Alzheimer’s Disease [CERAD] word list learning and delayed recall tests; East Boston Memory Test immediate and delayed recall trials), CERAD word list recognition, and executive function/attention (two fluency tests; Trail Making Tests A and B; digit span backwards)]. Episodic memory and executive function/attention were examined separately. Finally, we used random‐effects models to meta‐analyze the findings of three COSMOS cognition studies.ResultsIn COSMOS‐Clinic, we observed a signal for effect of MVM vs. placebo on improvement in global cognition over two years (mean difference = 0.06, 95% confidence interval [CI]: ‐0.003, 0.12). MVM vs. placebo led to significant improvement in episodic memory (mean difference = 0.11, 95% CI: 0.001, 0.23) but not in executive function/attention (mean difference = 0.04, 95% CI: ‐0.04, 0.11). The meta‐analysis of three COSMOS studies showed significant benefits of MVM on global cognition and episodic memory (will be presented in detail).ConclusionDaily MVM compared to placebo showed improvement in global cognition and episodic memory over 2 years among community‐dwelling older adults.
Masseter muscle volume measured by MRI correlated with cognitive function in a memory clinic
Authors: Muranaka Michiho , Tatewaki Yasuko , Thyreau Benjamin , Sakamoto Maya , Takano Yumi , Yamamoto Shuzo , Tomita Naoki , Nakase Taizen , Taki Yasuyuki 
Published: December 2023

AbstractBackground“Oral frailty” which indicates a decline in oral function, has been focused on the fact that it can also affect cognitive function in the elderly population. Although Several studies have been attempted for establishing the utility of the cross‐sectional area or volume of masticatory muscles as objective indices reflecting oral frailty, no report has examined the relationship between masticatory muscles volume and cognitive function in detail. In this study, we aimed to clarify the relationship between size of masseter muscle, one of major masticatory muscles, and cognitive function in the elderly.MethodA total of 349 subjects (mean age 77.3 +/‐ 9.2 years, 126 males and 223 females, 58 with subjective cognitive impairment, 88 with mild cognitive impairment, and 203 with dementia), who visited the Memory clinic of Tohoku University Hospital with a chief complaint of forgetfulness by March 2018 were included. Using 3D T1‐weighted images acquired on a 3‐Tesla MRI system, the bilateral masseter muscle cross‐sectional area was automatically calculated for all subjects using a custom deep‐learning image‐processing model trained on a subset of subjects to identify the relevant muscles and consistent section. Then, partial correlations with the MMSE score were conducted, adjusting for age and gender.ResultThe mean left and right masseter muscle cross‐sectional area are 399.3±84.7mm2 in subjective cognitive impairment, 387.9±106.5 mm2 in mild cognitive impairment, and 355.1±88.4 mm2 in dementia, respectively (p < 0.01). Adjusted for age and sex, they showed a significant correlation with MMSE (R = 0.151, p < 0.01). For post‐hoc stratified analysis, there was a significant correlation between mean masseter muscle cross‐sectional area and MMSE with female patients (R = 0.049, p < 0.05), whereas no correlation with male patients after adjusted age (R = 0.025, p > 0.05).ConclusionOur result revealed that the masseter muscle cross‐sectional area obtained from MRI may be related to cognitive function in the patients with complaint of forgetfulness. Therefore the masticatory function may reflect cognitive function in the elderly who are vulnerable in their memory, and the cross‐sectional area of masseter muscle based on MRI could be a potential indicator for predicting dementia risk.
The role of fibrinogen in neurodegeneration during a neuroinflammatory disease
Authors: Sulimai Nurul , Brown Jason , Lominadze David 
Published: December 2023

AbstractBackgroundFibrinogen is not only a marker of inflammation, but also a cause of inflammatory responses. We previously showed that when elevated during traumatic brain injury (TBI), fibrinogen increased cerebrovascular permeability mainly via caveolar transcytosis and, after extravasation and deposition in vasculo‐astrocyte interface, it activated astrocytes causing neurodegeneration that was associated with memory reduction.MethodTo define the possible mechanisms of fibrinogen‐induced activation of neurons, primary mouse brain cortical neurons from C57BL/6 mice were plated in poly‐d‐lysine‐ and laminin‐coated cell culture plates. Cells were treated for 1 hour with fibrinogen (0.5 or 1 mg/mL) in the presence or absence of a nuclear factor‐κB (NF‐kB) blocker, caffeic acid phenethyl ester (CAPE), or media alone (control). All groups contained hirudin to prevent the conversion of fibrinogen to fibrin. Levels of interleukin‐6 (IL‐6) and chemokine (C‐C motif) ligand 2 (CCL2) were assessed by qRT‐PCR. NF‐kB activity was measured in neuronal nuclear protein and cell extracts by the TransAMTM NF‐kB p65 protein assay and Western blot (WB). In parallel, using a cortical contusion injury (CCI), a mouse model of mild‐to‐moderate TBI was created in C576J mice. NF‐kB was detected with immunocytochemistry in cultured cells and brain samples collected 14 days after CCI. The specific association of fibrinogen with its neuronal receptors intercellular adhesion molecule‐1 (ICAM‐1) and cellular prion protein (PrPC) was assessed with a proximity ligation assay in cells.ResultFibrinogen specifically bound to neurons via its receptors ICAM‐1 and PrPC and increased NF‐kB levels. Fibrinogen caused upregulation of pro‐inflammatory cytokines IL‐6 and CCL2 mRNA. ELISA and WB NF‐kB p65 analysis demonstrated increased DNA binding by p65 and protein expression in fibrinogen‐treated neurons compared to that in control and CAPE groups. Fibrinogen caused translocation of NF‐kB p65 to the nucleus.ConclusionResults suggest that a specific interaction of fibrinogen with neurons results in neuroinflammation through activation of NF‐kB.
Day hospital for psychogeriatric patients: implementation of best practice
Authors: Bassitt Debora Pastore , Buchain Patricia Cardoso , Alves Tania Correa de Toledo Ferraz , Filho Geraldo Busatto 
Published: December 2023

AbstractBackgroundPsychogeriatric day hospitals best practices deliver integrated patient and family centered care by multidisciplinary teams, providing a safer transition between acute psychogeriatric units to rehabilitation services and outpatients clinical care. This reduces inpatient length of stay and rehospitalization rates, favoring a successful daily routine care at home. We implemented in 2022 an elderly day hospital service at the Institute of Psychiatry USP Medical School, Brazil. This case report illustrates how day hospitals can contribute to a better clinical outcome.Case report64 year‐old male patient with bipolar disorder (BD), recurrent readmissions in our psychogeriatric unit due to either complications from bipolar disorder or clinical conditions and family burden (2020 for 90 days due to rapid cycling BD and 2021 to treat clinical conditions 4 days). When he was at home his family reported increased burden and difficulty in daily care. They asked for readmissions in this period .The cognitive impairment and functional decline were associated with neuroprogression in BD.The lack of adequate treatment worsened psychiatric, cognitive symptoms and the capacity to maintain his activities of daily living (ADL).In 2022 he was admitted due to behavior symptoms (irritability and aggressivity) in our inpatient unit for 19 days. Transitioned to day hospital, he attended activities for two months, twice a week. The intervention provided cognitive and functional stimulation, caregivers training and psychoeducation. It was performed in groups and individually (patient and family).We observed improvement in cognition, basic daily life activities and social support. Admission and transition to outpatient care were CGI‐04‐04, MMSE 20‐23 and Katz 02‐04. We observed reduction in family burden and management of psychiatric and behavior symptoms.ConclusionPatient and family needs were identified and cared for, and we achieved an improved health outcome by creating a safe transition, reducing length of stay and preventing readmission. This present intervention demonstrates a clinical example of the coordinated approach in order to provide transitional care and enable rehabilitation (cognition, basic daily life and bipolar symptoms).The benefits of the patient‐ family centered care provides consistent recovery and decreased length of hospital stay and risk of readmission.
The interplay between White Matter Hyperintensities and regional β‐Amyloid on Defaults Mode Network
Authors: Ali Doaa , Bahrani Ahmed A , Khouli Riham H El , Gold Brian T. , Jiang Yang , Zachariou Valentinos , Wilcock Donna M. , Jicha Gregory A 
Published: December 2023

AbstractBackgroundCerebral small vessel ischemic disease (SVID) has been suggested to contribute to the pathogenesis of Alzheimer’s disease (AD). Yet, the mechanistic role of SVID in potentially contributing to AD pathology is unclear. The main objective of this study was to test the hypothesis that axonal SVID influences amyloid β (Aβ) levels within connected default mode network (DMN) tracts and cortical regions in cognitively unimpaired older adults.MethodRegional Standard Uptake Value ratios (SUVr) from Aβ‐PET, and white matter hyperintensity (WMH) volumes from 3D MRI FLAIR images were analyzed across a sample of 72 clinically‐unimpaired (Mini‐Mental State Examination (MMSE) ≥ 26), aged participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI3). The association of WMH volumes in major fiber tracts projecting from cortical DMN regions and Aβ‐PET SUVr in the connected cortical DMN regions were analyzed using linear regression models adjusted for age, sex, ApoE and total brain volumes.ResultThe regression analyses demonstrate that increased WMH volumes in the superior longitudinal fasciculus (SLF) was associated with increased regional SUVr in the inferior parietal lobule (IPL) (p = 0.011).ConclusionThe findings suggest that the relation between Aβ parietal cortex is partially driven by SVID in downstream axonal pathways in pAD. The biological relationships and interplay between Aβ and white matter microstructure alterations that precede overt WMH development across the continuum of AD progression warrants further study.
Serum biomarkers indicate sex differences in response to pathology inhibition in aged mice with tau pathology
Authors: Chowdhury Anisuzzaman , Collins Jessica M , Perry Sharn , Breadmore Michael , Shigdar Sarah , King Anna E 
Published: December 2023

AbstractBackgroundThe failure of some clinical trials using drugs that remove brain amyloid to prevent progression of dementia suggest that neurodegenerative disease may not progress in a linear fashion and threshold levels of one pathology may initiate alterations that are unable to be reversed upon removal of the initiating pathological process. We used the inducible Tg4510 mouse tauopathy model to determine whether neurodegeneration could be halted following removal of transgene expression in mice aged to 18 monthsMethodPathology was induced in mice from 8 weeks until 18 months of age (n = 20 equal male/female; both tau transgenic and non‐transgenic) by removal of doxycycline (dox) diet. Dox diet was returned to half the animals from 18‐23 months to inhibit pathology. Levels of serum Nfl were measured using SIMOA assay throughout disease progression and p‐tau181 along with other serum biomarkers were measured at endpoint. Immunohistochemical assays were performed to quantitate numbers of neurons (NeuN) and tau load (PHF‐tau) in hippocampus.ResultSerum Nfl increased over aging in all mice and was significantly higher in tau transgenics relative to non‐transgenics at 18 months (p<0.05). Between 18 and 23 months, the rate of serum Nfl increase was significantly(p<0.05) reduced in male transgenic mice on dox compared to female transgenic mice, so that by 23 months levels were not different from non‐transgenic mice. Similarly, the numbers of neurons in the hippocampus of male mice on dox at 23 months was significantly higher than their female counterparts (p<0.05). When looking at levels of serum p‐tau181 at 23 months, there was significantly (p<0.05) higher levels in male mice on dox than female miceConclusionThese data suggest that aged female mice have ongoing neurodegeneration following removal of pathology induction that is similar to mice with continued pathology induction. The differences in serum p‐tau‐181 may indicate that female mice fail to clear pathological tau from the brain. Further studies will examine the relationship between histopathology and blood biomarkers and determine whether female mice on dox have a higher tau pathology load than their male counterparts.
Trajectories of white matter degeneration in frontotemporal dementia: new insights using fixel‐based analysis
Authors: Landin‐Romero Ramon , Quang Halle , Matis Sophie , D'Souza Arkiev , Calamante Fernando , Piguet Olivier 
Published: December 2023

AbstractBackgroundThe three clinical presentations of frontotemporal dementia (FTD), behavioral‐variant FTD (bvFTD), progressive non‐fluent aphasia (PNFA), and semantic dementia (SD), are caused by abnormal aggregation of protein pathologies and progressive brain atrophy that precede the emergence of clinical symptoms. Neuropathology shows a ‘prion‐like’ propagation along white matter pathways before aggregating in the neuronal cell bodies of the grey matter. The in‐vivo mapping of upstream white matter trajectories of degeneration can improve disease staging and understanding of disease mechanisms in FTD, but longitudinal white matter studies are rare due to methodological challenges. Here, we develop a novel neuroimaging approach to map white matter changes in FTD using fixel‐based analysis (FBA), a new diffusion weighted imaging technique.MethodSixty FTD patients (23 bvFTD, 15 PNFA and 22 SD) were matched with 30 heathy controls. Participants underwent a comprehensive annual clinical assessment and high‐resolution multimodal MRI (median 2 years; range 1‐6 years). Time‐varying changes in white matter fibre density and cross‐section were computed with MRtrix3, FreeSurfer 7.1.1 and Spatiotemporal Linear Mixed Effects models.ResultAll FTD syndromes showed more extensive white matter changes at baseline than previously reported. In bvFTD, atrophy extended posteriorly over time, encroaching in tracts connecting subcortical and motor‐associations regions (Fig 1). In PNFA, baseline left‐lateralized atrophy extended anteriorly and inferiorly and into the contralateral hemisphere, eventually mirroring patterns of atrophy at presentation (Fig 2). In SD, the focal left temporal baseline atrophy extended posteriorly and laterally along the inferior and superior longitudinal fasculi, and involving the right hemisphere with disease progression (Fig 3).ConclusionThe FBA approach enabled the identification of new white matter bundles in FTD, with syndrome‐specific effects and improved biological interpretability compared to traditional tensor imaging methods. Our method can be extended beyond FTD to other neurodegenerative disorders to inform better models of disease staging and provide useful targets for patient stratification and monitoring in trials of disease‐monitoring interventions.
Impact of multidomain lifestyle intervention on white matter integrity: theSUPERBRAIN exploratory sub‐study
Authors: Moon So Young , Kim Sohui , Hong Chang Hyung , Park Yoo Kyoung , Na Hae Ri , Song Hong‐Sun , Park Hee Kyung , Lee Jong‐Min , Jeong Jee Hyang , Choi Seong Hye 
Published: December 2023

AbstractBackgroundIn the SoUth Korean study to PrEvent cognitive impaiRment and protect BRAIN health through lifestyle intervention in at‐risk elderly people (SUPERBRAIN), we evaluated the impact of a 24‐week facility‐based multidomain intervention (FMI) and home‐based MI (HMI) on white matter integrity.MethodTotally, 152 participants, aged 60‐79 years without dementia, were randomly assigned to the FMI, HMI, or control groups. Among them, 55 participants (20 FMI, 19 HMI, and 16 controls) underwent brain MRI at baseline and 24 weeks. The dtifit tool was used to fit the diffusion tensor model and computed diffusion scalar maps for fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). Individual FA, MD, AD, and RD at baseline were compared among groups using one‐way analyses of covariance (ANCOVA) with age, sex, years of education, and imaging site effects added as covariates of no interest. In addition, to compare changes in the FA, MD, AD, and RD from baseline to the study endpoint, we used two statistical analyses. First, ROI‐wise paired t‐tests were used to analyze longitudinal changes in white matter integrity for control and intervention group. The statistical significance level was set at bonferroni corrected p‐value < 0.05. And then, significant brain image measures in previous paired t‐test were compared between each group pair (FMI vs. control; HMI vs. control; FMI+HMI vs. control) using ANCOVA with changes as dependent variables and age, sex, education, and site as covariates.ResultThe FA, MD, AD, and RD at each ROI at the baseline were not different among groups after bonferroni correction. In cingulum regions, the FA and AD were increased and the MD and AD were decreased significantly in the intervention group. The AD in right uncinate fasciculus was also increased in intervention group. Finally, among the significant regions in paired t‐test, compared with the control group, the FMI, HMI, and intervention group yielded significantly more beneficial effects on the AD of the cingulum regionsConclusionThe change of white matter integrity in the intervention group suggests that multidomain lifestyle intervention may be beneficial through structural neuroplastic changes in highly complex tract.
Associations between neighborhood environment and computerized cognitive performance among older Black adults
Authors: Allan Alexa C , Gamaldo Alyssa A. , Thorpe Roland J. , Roberts Jennifer D , Evans Michele K , Zonderman Alan B 
Published: December 2023

AbstractBackgroundStudies have suggested that neighborhood quality is associated with health outcomes beyond individuals’ socioeconomic characteristics (Kind & Buckingham, 2018; Ludwig et al., 2011). Limited research has explored how subjective neighborhood quality is associated with cognitive functioning, particularly among socioeconomically diverse Black adults. The current study examined the cross‐sectional association between perceived neighborhood characteristics and cognitive functioning among Black adults.MethodThis study included 1,079 community‐dwelling, socioeconomically diverse Black adults (Mage = 56.64, SDage = 9.14; 59% female) from wave 4 of the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study. Neighborhood quality was assessed using three scales about built environment disorder (e.g., litter, graffiti, and crime), social cohesion (e.g., close‐knit neighborhood, neighbors can be trusted), and social control (e.g., neighbors take action for children disrespecting adults). Cognitive functioning was assessed using the computerized Joggle battery. Multivariable linear regression analyses were conducted with each cognitive measure as the outcome measure. Models were adjusted for age, sex, education, reading literacy, poverty status, and depressive symptoms.ResultIn the adjusted models, higher built environment disorder was associated with slower performance (p < .05) on an attention and visual orientation measure and fewer correct responses (p’s < .05) on attention, executive function, and speed measures. High social cohesion was associated with faster performance (p < .05) on attention, visual orientation, executive function, and speed measures. Additionally, high social cohesion was associated with greater numbers of correct responses (p < .05) on an attention and executive function measure. Interestingly, high social control was associated with slower performance on executive function. Significant interactions were observed between neighborhood quality and covariates. For example, higher perceived social cohesion was associated with slower average reaction time on memory and attention, particularly for individuals with higher depression total scores. In contrast, higher perceived social cohesion was associated with faster average reaction time on executive functioning, particularly for men.ConclusionThese findings underscore the importance of environmental characteristics for cognitive performance among Black adults. Further, these findings support the continued assessment of contextual factors as mechanisms or avenues for understanding how to improve cognitive functioning.