bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regional glymphatic abnormality in behavioral variant frontotemporal dementia
Authors: Jiang Deming 
Published: December 2023

AbstractBackgroundThe pattern of glymphatic inflow overlaps with the geographic pattern of behavioral variant frontotemporal dementia (bvFTD). The glymphatic function has not yet been explored in bvFTD. The spatial correlation between regional glymphatic function and bvFTD remain unknown.MethodA total of 60 patients with bvFTD and 61 age‐ and sex‐matched healthy controls (HCs) were selected from two independent cohorts (discovery dataset from Xuanwu Hospital and replication dataset from the Frontotemporal Lobar Degeneration Neuroimaging Initiative study). All participant underwent neuropsychological assessment. Glymphatic measures evaluated from multimodal neuroimaging data, including choroid plexus volume, diffusion along perivascular space (DTI‐ALPS) index, and coupling between blood‐oxygen‐level‐dependent signals and cerebrospinal fluid signals (BOLD‐CSF coupling), were compared between the two groups. To evaluate glymphatic regional function, DTI‐ALPS and BOLD‐CSF coupling were further divided into anterior, middle, and posterior parts. BvFTD‐related metabolic pattern was identified using spatial covariance analysis based on [l8F]‐FDG‐PET.ResultPatients with bvFTD showed higher choroid plexus volume (P < 0.001); middle DTI‐ALPS (P < 0.001); and weaker anterior BOLD‐CSF coupling (P < 0.05) than HCs after controlling for cortical gray matter volume in both datasets. In bvFTD from the discovery dataset, the anterior DTI‐ALPS was negatively associated with the expression of the bvFTD‐related metabolic pattern (r = ‐0.51, P = 0.029) and positively related with regional standardized uptake value ratios of [l8F]‐FDG‐PET in bvFTD‐related brain regions (r = 0.44–0.60, P range: 0.008–0.039). Worse glymphatic function is associated with more severe global cognition decline, disease severity, and neuropsychiatric symptoms. In addition, anterior DTI‐ALPS was higher than posterior DTI‐ALPS (P < 0.001), whereas anterior BOLD‐CSF coupling was lower than posterior BOLD‐CSF coupling (P < 0.001).ConclusionOur findings reveal abnormal glymphatic function, especially in the anterior and middle regions of brain in bvFTD. Regional glymphatic dysfunction may contribute to the pathogenesis of bvFTD.
Persistent financial adversity across adulthood and cognitive ageing: A lifecourse investigation.
Authors: Liu Yiwen , Wels Jacques , James Sarah‐Naomi , Keuss Sarah E , Maddock Jane , Parker Thomas D , Stafford Jean , Schott Jonathan M , Richards Marcus , Patalay Praveetha 
Published: December 2023

AbstractBackgroundCognitive decline in older age has significant health, economic and social consequences and there is evidence that financial adversity might play a role. Financial adversity, for many, is not an acute but a chronic stressor. However, little is known about the effect of persistence exposure to financial adversity across the lifecourse on cognitive ageing.MethodUsing data from the 1946 British birth cohort (N = 2,759) with an embedded neuroimaging study (Insight46; N = 356‐468), we examined the prospective association between financial adversity (low household income, financial hardships; 26‐53 years) and cognitive performance (69 years) and decline (53‐69 years), as well as volumetric measures of brain health (69‐71 years) in older adulthood. Cognitive decline was modelled using latent growth curves, with derived intercepts and slopes used in subsequent regression analyses, adjusted for sex, childhood socioeconomic circumstances (SEC), baseline cognition and internalising symptoms, and educational attainment. Sex, childhood SEC and APOE‐ɛ4 genetic risk were further tested as moderators in regression models using interaction terms. This study has been pre‐registered (https://doi.org/10.17605/OSF.IO/6Y9NV).ResultIncreased exposure to financial adversity showed dose‐response associations with slower verbal memory decline and lower processing speed and verbal memory at 69 years (Table 1). Each increased period of exposure to low household income or financial hardships was associated with a 0.11 and 0.08 standard deviation (SD) decrease in processing speed, and a 0.32 and 0.22 SD decrease in verbal memory at 69 years, respectively. Males persistently exposed to financial hardships showed slower processing speed decline but increased brain atrophy compared to females. Those whose fathers were in unskilled profession or unemployed in childhood, and who also persistently experienced low income themselves showed greater brain atrophy (Fig. 1). APOE‐ɛ4 carriers who persistently experienced financial adversity were also at greater risk for brain atrophy (Fig. 2).ConclusionPersistent financial adversity is directly associated with cognitive performance and may be differentially associated with brain atrophy depending on demographic and genetic factors. Reducing the frequency of financial adversity over the lifecourse may improve cognitive performance and protect against genetic susceptibility to brain atrophy and subsequent dementia risk in the ageing population.
3D Reconstruction of human brain post‐mortem photography and integration of dementia histopathology
Authors: Ortega‐Cruz Diana , Bress Kimberly S. , Gazula Harshvardhan , Rabano Alberto , Iglesias Juan Eugenio , Strange Bryan A 
Published: December 2023

AbstractBackgroundIn Alzheimer’s Disease (AD) and other types of dementia, neuropathological assessment serves as ground truth for diagnosis and validation of novel biomarkers. Such assessment commonly implies inspection of a single histological slide per region of interest. Pathology burden quantification, as well as investigation of its spatial distribution, is thus biased by the variability of tissue sampling in routinary neuropathological practice. Numerous efforts have sought to overcome this lack of generalizability using 3D reconstruction of histology, but available approaches rely on dense sectioning and an MRI scan, which may not be attainable by many brain banks.MethodWe present a histology mapping pipeline that uses blockface images of brain hemisphere slices for 3D spatial localization. The slices are first geometrically stacked and coarsely aligned using a probabilistic atlas. Next, deep learning contrast synthesis is employed to obtain a high‐resolution 3D image of the hemisphere with MRI‐like contrast, which is subsequently registered nonlinearly to a standard atlas (MNI). Histological slides are then registered to the corresponding coronal slice within the subject‐specific reconstructed hemisphere. Finally, the registrations are concatenated to deform the histology to the standard space. We show the applicability of this pipeline by analyzing the distribution of tau AD pathology along the longitudinal axis of the hippocampus in 26 patients with no significant co‐pathologies aside from AD.ResultWe took advantage of the inter‐subject spatial variability observed after 3D slide mapping to achieve extensive sampling along the hippocampal long axis. Our results show an anterior‐posterior gradient of tau burden in the hippocampus that is consistent with previous work using ex vivo MRI and dense histological sampling, further supporting the reliability of the pipeline.ConclusionOur pipeline enables studying pathology in 3D using sparse sampling and in absence of a subject‐specific MRI reference. Moreover, given that dissection photography is standard practice in brain banks, our method is widely applicable to any prospective or retrospective human histology dataset.
Prevalence, incidence, and prognostic indicators of Dementia in patients with TIA and Stroke: the Population‐based Rotterdam Study
Authors: Claus Jacqueline Josephine , Box Camiel , Vinke Elisabeth J. , Rosbergen Mathijs T. , Vernooij Meike W , Ikram M. Kamran , Ikram M. Arfan , Wolters Frank J. 
Published: December 2023

AbstractBackgroundRisk of dementia is high after major stroke, but reliable estimates of dementia by stroke severity, accounting for competing risk of mortality, in a population‐based setting are scarce. In this study, we aimed to determine risk and prognostic indicators of dementia before and after TIA and stroke.MethodWe included all individuals with first‐ever TIA or stroke from the population‐based Rotterdam Study, between 2002‐2018, and matched those on age (+/‐3 years) and sex, using an incidence density sampling approach. We determined prevalence of pre‐event dementia by event severity (TIA vs. minor stroke [NIHSS≤3] vs. major stroke [NIHSS>3]). Similarly, we determined risk of dementia at 1‐,5‐ and 10‐year post‐event using the subdistribution hazards (SDH) cumulative incidence function (CIF), and explored prognostic indicators of dementia.ResultAmong 1352 participants with first‐ever TIA or stroke (mean age: 79.4 (9.5) years, 59.7% women), 466 had TIA, 392 minor stroke, 494 major stroke. Prevalence of pre‐event dementia was higher among patients with major stroke (90/494; 18.2%) than among those with minor stroke (29/392; 7.3%), TIA (37/466; 7.9%). During 10‐year follow‐up, dementia occurred in 784 of 4703 participants without pre‐event dementia or reference participants. Compared to TIA patients, dementia risk was higher after major stroke (HR 2.17; 95% CI 1.53–3.07) and minor stroke (HR 1.63; 95% CI 1.17–2.26). Dementia risk was associated with male sex (SDH‐ratio 1.23; 95% CI 1.04–1.45), age (per 1‐year increase: 1.07; 1.06–1.08), higher education (0.61; 0.44–0.86), diabetes mellitus (1.29; 1.06–1.56), atrial fibrillation (1.40; 1.14–.71), and premorbid cognition (MMSE≤24, 2.39; 1.87–3.05). Among 417 patients with available pre‐event brain MRI, white matter hyperintensity burden (per 1‐% increase of proportion of total brain volume: 1.24; 95% CI 1.07–1.45) and presence of microbleeds (2.14; 1.18–3.86) were indicators of post‐stroke dementia.ConclusionDementia incidence after TIA and stroke is increased in patients with major stroke and to a lesser extent minor stroke, but not TIA. Event severity in combination with clinical and imaging indicators may hold potential for the prediction of cognitive decline after stroke.
Early Cognitive Screening is recommended for the Population with Higher Blood Pressure Variation: A Cross‐sectional Study from a Blood Pressure Management Cohort in Hong Kong
Authors: Jia Pingping , Chan Aaron TC , Yiu Karen KL , Yu Ruby , Tsoi Kelvin KF 
Published: December 2023

AbstractBackgroundCognitive impairment was shown to be associated with blood pressure (BP) and blood pressure variability (BPV), but the association with BPV is still uncertain in Chinese. This study explored whether BPV is associated with cognitive impairment among the elderly in Hong Kong.MethodParticipants in a community‐based cohort for regular BP measurements with health surveys were randomly invited to have a cognitive assessment with a shortened validated version of MoCA. Different thresholds of mild cognitive impairment (MCI) were used with reference to the age group and educational background. BPV was defined as standard deviation. K‐means clustering methods were applied to group the standard deviation of BPV into high, medium, and low variations. Logistic and quantile regression models were conducted to explore the association of MCI with systolic or diastolic BPV and a combined BPV classification. Odds ratios (OR) were adjusted for age, gender, educational background social economic status, and other medical histories, including hypertension, hyperlipidemia, diabetes, and stroke.ResultA total of 573 participants with a mean age of 72 years were included. Most participants were females (86%). The median follow‐up times were eight months with a median number of nineteen BP records. Systolic BPV was shown to be associated with a higher risk of MCI (adjusted OR: 1.16; 95% CI: 1.03 to 1.31); whereas diastolic BPV was not significantly associated with MCI (adjusted OR: 1.05; 95% CI: 0.85 to 1.24) (Table 1). In the combined groupings for BPV classifications, participants with high BPV were shown to have around 5 times higher risk of MCI than those with low BPV.ConclusionEarly stage of cognitive impairment was shown to be associated with systolic blood pressure variability in the Hong Kong population. Early cognitive screening for those with high blood pressure variability levels is recommended.
Metabolic Syndrome Score is Associated with Lower Myelin in Cognitively Healthy Adults
Authors: Burzynska Agnieszka Z , Lee Jongho , Colmenares Andrea Mendez , Hiner Grace Z , Thomas Michael L , Choi Joon Yul 
Published: December 2023

AbstractBackgroundMetabolic syndrome (MetS) is a cluster of cardiovascular risk factors, including abdominal obesity, glucose intolerance, elevated blood pressure (BP), and dyslipidemia. MetS is a known risk factor for cognitive dysfunction and dementia (Yaffe et al., 2004. YAMA), and has been linked to brain atrophy and altered WM microstructure measured with diffusion tensor MR (Alfaro et al., 2018, Metabolism). The metabolic cost of myelin maintenance makes WM particularly vulnerable to metabolic dysfunction. Here, we aim to explore the relationships between MetS and myelin, as well as test whether WC‐myelin association (Bouhrara et al., 2021, Int J Obes) is independent from systolic BP.MethodSample included 90 cognitively and neurologically healthy adults (Bookheimer et al., 2019, Neuroimage), aged 20 to 79 (M = 53, SD = 17) with 76% women. Additional exclusion criteria included systolic blood pressure >140, BMI>33, and >2 on modified Hachinski Ischemic Scale. Myelin water imaging was collected using a 3T Siemens Skyra with a 32‐channel coil and 3D‐gradient and spin‐echo (GRASE) sequence (1.9×1.9×4mm, TR = 1000ms, echoes = 32, first echo = 10ms, echo spacing = 10ms). Myelin Water Fraction maps were nonlinearly aligned to FMRIB58_FA using TBSS in FSL. MetS score was calculated as a sum of z‐scored waist circumference (WC), systolic BP, BMI, and self‐reports history of elevated cholesterol and glucose.ResultA linear regression analysis with MWF as the dependent variable, adjusting for sex, race, ethnicity, age, and age2, income and education, indicated that greater MetS score was associated with lower MWF in several regions including the genu corpus callosum, anterior corona radiata, and external capsule. WC was negatively associated with whole WM MWF (B = ‐.265, t(79,9) = ‐2.150, p = 0.035) after controlling for the above covariates and systolic BP.ConclusionAssociations between MetS with myelin content were detected especially in the late‐myelinating regions. This aligns with the development‐to‐degeneration hypothesis of WM aging, with lower oligodendrocyte‐to‐axon ratio as a possible factor contributing to metabolic vulnerability of late‐myelinating tracts. We also replicated the WC‐myelin association, although in fewer regions and with smaller effects sizes. Together, our results suggest that different metabolic syndrome components may exert both additive/synergistic, and independent effects on myelin integrity across adulthood.
“Don’t you recognize me…?”: Insights From Social Media Posts On The Impact of Alzheimer’s Disease On Care Partners
Authors: Frederiksen Kristian Steen , Crawford Rebecca , Hahn‐Pedersen Julie Hviid , Morrison Ross , Jeppesen Rose , Doward Lynda C , Weidner Wendy S 
Published: December 2023

AbstractBackgroundCaring for someone with Alzheimer’s disease (AD) can have a profound impact on care partners’ wellbeing and daily life. We conducted a social media (SM) review to gain insights into how the impact of AD on care partners is described by persons‐living‐with‐AD (PwADs)/care partners/family members.MethodWeb‐based searches identified SM data from 4 sources: YouTube, Alzheimer’s Association, Alzheimer Society of Canada, and Dementia UK. English‐language SM posts uploaded between May 2011‐May 2021 shared by PwADs/care partners/family members were included in the review if posts discussed the impact of AD on care partners. SM data were analyzed thematically.ResultOf 279 SM posts identified, 55 met the review criteria (21 blog posts, 21 videos, 13 comments). The 55 posts were shared by 70 contributors (4 PwADs and 66 PwAD care partners/family members) who discussed self‐reported/observed impacts of AD on care partners and family members. Notable areas affected included psychological and emotional well‐being (n = 53, 75.7%); a profound theme raised was the emotional distress and sadness (n = 24; 34.3%) associated with the care partners’ experience of ‘living bereavement’; i.e., the gradual psychological receding of a loved one prior to their passing. Care partner emotional distress was also exacerbated by the PwAD’s AD‐related symptoms such as altered behaviour and memory loss. Contributors also reported impacts on care partner, overall health‐related‐quality‐of‐life (n = 27, 38.6%), daily life (n = 9, 12.9%), work and employment (n = 8, 11.4%) and physical health (n = 5, 7.1%). Prioritisation of patient care had long‐term consequences for care partners such as diminished personal wellbeing, family and personal sacrifices including loss of employment and unanticipated financial burden.ConclusionSM research provides a unique approach to explore the experiences and challenges associated with caring for someone with AD potentially not captured through traditional research methods. Insights from SM data emphasized the burden of ‘living bereavement’ for care partners and the subsequent need for improved coping strategies/interventions to enable care partners to better manage this phenomenon. The care partners’ candid posts provided valuable insights on the psychological, social, and financial impairments associated with becoming a care partner, which require further investigation.
A multi‐omics approach to investigate the synapse dysfunction in Alzheimer’s disease
Authors: Kumar Subodh 
Published: December 2023

AbstractBackgroundSynapse dysfunction is an early event for Alzheimer’s disease (AD) progression. Synapse dysfunctions are caused by multiple cellular and pathologic factors such as Amyloid beta, p‐tau, inflammation and aging. However, exact molecular mechanism of synapse dysfunction is largely unknown in AD. Therefore, to understand the molecular basis of synapse dysfunction in AD, we conducted a high throughput multi‐omics analysis of synaptosome fraction in AD and cognitively normal postmortem brain samples.MethodSynaptosomes were extracted from healthy control (HC) postmortem brain (n = 14) and AD postmortem brains (n = 27). Next, we performed miRNAs and mRNAs HiSeq analysis on synaptosomal RNAs. We also used HC (n = 10) and AD (n = 10) synaptosome samples for mass spectroscopy proteomic analysis. We conducted the synaptosomal miRNAs and mRNA sequencing and mass spec analysis on the same groups of samples. Further, we conducted a high throughput multi‐comics analysis to understand the molecular interaction of deregulated synapse miRNAs, mRNAs and proteins at AD synapse.ResultMiRNA HiSeq analysis showed the significant deregulation of several miRNAs in synaptosome fraction in AD vs HC. Our study also identified the several novel potential candidate miRNAs those were deregulated in AD vs HC synaptosomes. Similarly, several protein coding genes and novel transcript were also found to be deregulated in AD vs HC synaptosomes. Further, mass spec analysis showed significant deregulation of several synaptic proteins in AD vs HC synaptosomes. Further, to understand the molecular interaction of synapse miRNAs‐mRNA‐proteins and their deregulation in AD, we conducted high throughput multi‐Omics analysis. Study revealed the involvement of omics targets in several biological process and molecular function such as signal transduction, protein binding, GABAergic synapse and synaptic vesicle cycle etc.ConclusionOur study unveiled the synapse centered novel omics candidates those could be potential therapeutic targets for synapse dysfunction in AD.
Mclena‐1: A Phase II Clinical Trial for the Assessment of Safety, Tolerability, and Efficacy of Lenalidomide in Patients with Mild Cognitive Impairment Due to Alzheimer’s Disease; Interim progress
Authors: Decourt Boris , Wilson Jeffrey , Dumitrescu Liliana , Ritter Aaron , Sabbagh Marwan 
Published: December 2023

AbstractBackgroundAccumulating evidence indicates that inflammation mediated by tumor necrosis factor alpha (TNF alpha), interleukins (e.g. IL‐1 beta, IL‐2, and IL‐6), and chemokines (e.g. IL‐8), is prominent in Alzheimer’s disease (AD) patients. These data suggest that systemic inflammation plays a crucial role in the cause and effects of AD neuropathology. Thus, we propose that modulating systemic inflammation via a pleiotropic immunomodulator is a putative therapeutic intervention if administered at a proper time window during the course of the disease.MethodThis is a Phase II, proof‐of mechanism, placebo‐controlled clinical study on amnestic mild cognitive impairment (aMCI) male and female subjects administered 10 mg/day the immunomodulator, anti‐cancer agent lenalidomide for 12 months on a 1:1 ratio (15 placebo + 15 drug‐treated subjects total) followed by a 6 months washout period. Amyloid loads is measured by FBP PET. The primary endpoints are cognition measured via a large battery cognitive tests every 3 months, and comparison of brain amyloid loads (Florbetapir PET imaging) and neurodegeneration (volumetric MRI) pre‐ and post‐drug treatment. The secondary endpoints are safety, which is evaluated through reported adverse events (AEs), clinical laboratory tests (hematology, serum chemistry, and urinalysis), vital signs, physical and neurological examinations, and electrocardiograms. The tertiary and exploratory objectives will assess blood inflammatory markers after lenalidomide vs. placebo administration.ResultsTo date, 15 participants have signed consent, 7 screen failed, 2 withdrew consent and 6 have completed treatment after 12 months. Adverse events occurred as expected in cancer cohorts. No severe AEs have occurred so far. Importantly, assuming a 1:1 randomization in the blinded phase, several participants have received lenalidomide continuously for 12 months without interruption. Though blinded, the completers appeared to be stable.ConclusionIn the current project we aim to investigate lenalidomide as a possible AD therapy. Our study should allow determining whether or not lenalidomide is safe in subjects suffering neurological disorders, and whether it can alter the clinical course of AD. To date, AEs are as expected and the safety and tolerability are manageable. A second trial coined MCLENA 2 will start soon. It will focus on biomarker endpoints (rather than cognition) following treatment for 6 months