bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUVR cut off using Optimal time of the Early‐phase 18F‐florbetaben brain image compared to the 18F‐fluorodeoxyglucose brain image
Authors: Shin HyunJi , Kang Do‐Young 
Published: June 2023

AbstractBackgroundEarly phase amyloid positron emission tomography (PET) imaging is known to correlated with glucose metabolism. However, studies on the optimal time frame and SUVR cut off for early‐phase amyloid PET have not been sufficiently progressed. In this study, the optimal time of early‐phase 18F‐FBB was determined and SUVR cut off was obtained.MethodTo determine the optimal time frame, the correlation between FBB and FDG SUVR of 67 subjects(34, Alzheimer’s disease(AD), 4 mild cognitive impairment(MCI), and 29 health control(HC)) was compared. In this method, 83 brain regions were treated as gray matter masks using an integrated brain map of PMOD 3.6. After obtaining the optimal time of FBB, which has a high correlation compared to FDG, a total of 225 subjects(188 AD, 37 HC) were targeted. SUVR cut off of dual‐phase 18F‐FBB PET of 11 brain regions was obtained. Calculate the composite mean SUVR and regional SUVR using MedCalc.ResultThe highest correlation between early‐phase 18F‐FBB and 18F‐FDG peaked at ‐.8747 at 270‐330s. Considering the minimum time and correlation between image noise and visual analysis, 90 to 330 seconds were set as the optimal time frame(r‐ratio ≥0.875).In the early‐phase FBB, cut off values in the order of HC>AD were valid. The classification accuracy of the composite mean SUVR was 72%(AD 69.15%, HC 86.49%), and the regional area accuracy was 85.78%(AD 93.62%, HC 45.95%). In the delay‐phase FBB, cut off vlaues in the order of AD>HC were valid. The classification accuracy of the composite mean SUVR was 77,33%(AD 72,87%, HC 100%), and the regional area accuracy was 84.89%(AD 86.17%, HC 78.38%). In the early and delay‐phase FBB, the classification accuracy of the composite mean SUVR was 90.67%(AD 92.02%, HC 86.49%), and the regional area accuracy was 88%(AD 98.4%, HC 37.84%).ConclusionIn this study, it is possible to know the optimal time frame of the early‐phase 18F‐FBB showing a high correlation with 18F‐FDG. Composite mean SUVR and regional SUVR cut off of the dual‐phase 18F‐FBB are helpful for visually ambiguous analysis.
Association of sleep duration with cognitive performance and structural brain differences: A large population‐based cross‐sectional study
Authors: Wang Zhiyu , Wang Jiao , Yang Wenzhe , Dove Abigail , Qi Xiuying , Pan Kuan‐Yu , Xu Weili 
Published: June 2023

AbstractBackgroundSleep duration has been linked to dementia risk; however, its association with cognitive functioning in specific domains and the underlying mechanisms remain unclear. We aimed to examine the association of sleep duration with cognitive performance and structural brain differences using magnetic resonance imaging (MRI).MethodsWithin the UK Biobank, 43,255 dementia‐free participants (aged ≥44, 52.0% female) were included. Self‐reported sleep duration (hours/day) was recorded following a structured questionnaire and trichotomized as short (≤5), normal (6‐8), and long (≥9) sleep. Cognitive functioning (including fluid intelligence, pairs matching, reaction time, and numeric memory) was evaluated using a touchscreen test battery. MRI scans were performed, and total and regional brain volumes (including white matter, gray matter, and hippocampus), and white matter hyperintensities (WMH) were measured. Data on lifestyle factors and medical conditions were collected. Data were analyzed using linear regression.ResultsOf all participants, 2092 (4.8%) had short, 38,041 (87.9%) had normal, and 3122 (7.2%) had long sleep. In multi‐adjusted linear regression, compared with normal sleep duration, both short (β: ‐0.14, 95%, CI: ‐0.19 to ‐0.10) and long (β: ‐0.06, 95% CI: ‐0.10 to ‐0.03) sleep were related to poorer performance in fluid intelligence. Long sleep was also associated with poorer numeric memory (β: ‐0.06, 95% CI: ‐0.10 to ‐0.01). In MRI data analyses, compared with normal sleep duration, short sleep was related to a smaller hippocampus volume (β: ‐0.05, 95% CI: ‐0.09 to ‐0.01), while long sleep was associated with smaller total brain (β: ‐4.51, 95% CI: ‐6.82 to ‐2.21), gray matter (β: ‐3.32 95% CI: ‐4.70 to ‐1.94), and hippocampus (β: ‐0.06, 95% CI ‐0.09 to ‐0.02) volumes, but greater WMH (β: 0.05, 95% CI: 0.01 to 0.08), after adjusting for confounders.ConclusionsShort and long sleep durations are associated with poorer cognitive performance in different domains. Short sleep may indicate neurodegeneration, and long sleep may implicate both neurodegenerative and vascular changes in the brain.
BMD‐001, a nanoparticle containing miR‐485‐3p antisense oligonucleotide, blocks Alzheimer's disease progression
Authors: Koh HanSeok , Min Hyun Su , Lim Yu Na , Jang Hannah , Yang Jinhee , Kim Daehoon , Cho HyunJeong , Ryu JinHyeob 
Published: June 2023

AbstractBackgroundAlzheimer’s disease (AD) is a form of dementia characterized by progressive memory decline and cognitive dysfunction, which affects more than 44 million people worldwide. Currently, there is no effective therapy for AD despite its increasing global incidence; thus, effective treatment strategies for AD are urgently needed.MethodIn a previous report, we confirmed that expression of miR‐485‐3p was increased in the brain tissues, CSF, and plasma exosomes of AD patients than in healthy controls. In addition, the therapeutic potential of downregulation of miR‐485‐3p was also shown in 5XFAD AD model mice. Based on this target validation, we developed a nanoparticle containing antisense oligonucleotide (ASO) targeting miR‐485‐3p, named BMD‐001, which has a high CNS‐targeting ability to cross the blood‐brain barrier (BBB). BMD‐001 was injected into 10‐month‐old 5XFAD mice by intravenous injection, once weekly for four weeks. Behavioral tests were performed at 11 months and their brain pathology was examined after 8‐week‐washout at 13 months.ResultTo evaluate in vivo pharmacokinetics of BMD‐001, the plasma levels of Cy5‐labeled ASO encapsulated in the nanoparticle were measured after intravenous injection along with a naked ASO without formulation of nanoparticle. The half‐life of the ASO in the nanoparticle was 93 min while that of the naked ASO was only 43 sec. Furthermore, we also observed that the brain accumulation of the fluorescent ASO in the nanoparticle was 64‐fold higher than the naked ASO and was maintained up to 16 hours, as monitored by in vivo imaging. After BMD‐001 injection, miR‐485‐3p expression was decreased in the brain tissue. We found that BMD‐001 enhanced Aβ clearance via phagocytosis of Aβ in vitro and in vivo. Furthermore, BMD‐001 reduced Aβ plaques, tau pathology, inflammasome, neuroinflammation, and cognitive decline in the 5XFAD mice.ConclusionCollectively, our findings suggest that BMD‐001 is delivered to the brain through the efficient BBB penetration. Furthermore, BMD‐001 can be a promising candidate for treatment of AD pathology and cognitive decline, establishing a new paradigm in the AD field.
Multimorbidity patterns in people with Alzheimer’s disease
Authors: Chi Nai‐Ching , Lozier Patrick , Street Nick , Buckwalter Kathleen , Gardner Sue , Rakel Barbara , Perkhounkova Yelena , Hein Maria 
Published: June 2023

AbstractBackgroundMultimorbidity is highly impactful for older adults, especially when it co‐occurs with Alzheimer’s disease (AD). However, scarce evidence is available about comorbid conditions co‐occurring with AD. We aimed to identify the most prevalent comorbid conditions and examine the common multimorbidity patterns in patients with AD.MethodUsing electronic health records of a university hospital, we extracted data from 2,646 older adults with AD (ICD‐10) using Calderón‐Larrañaga’s inventory of chronic conditions. Leverage correlation was performed to detect multimorbidity patterns.ResultAD patients had on average 13 comorbid conditions and 50% of them had at least 10 comorbid conditions co‐occurring with AD. Hypertension (51.7%), lipoprotein metabolism disorders and other lipidemia (35%), depression (33.9%), general mental disorders (31.96%), sleep disorders (26%), urinary disorders (25.3%), anemia (24.6%), joint disorders (23.19%), chronic kidney disease (21.25%), and other functional intestinal disorders (20.66%) were the top 10 prevalent comorbid conditions. The common multimorbidity patterns were “disorders of lipoprotein metabolism and other lipidemia” and “hypertension” (frequency [n = 747, 30%]; leverage:0.09), followed by “hypertension” and “hypertensive kidney disease” (frequency [n = 189, 8%]; leverage:0.06), “presence of cardiac and vascular implants and grafts” and “disorders of lipoprotein metabolism and other lipidemias” (frequency [n = 181,7%; leverage:0.05), and “Type 2 diabetes” and “hypertension (frequency [n = 181,7%; leverage:0.05).”ConclusionOur results align with prior studies that cardiovascular disease, diabetes, osteoarthritis, and depression are common conditions in people with AD. These findings might support future studies investigating the mechanisms linking multimorbidity to AD, which ultimately can guide preventive actions and comprehensive approaches for managing these co‐occurring conditions.
Associations between hippocampal subfield volume and cognitive performance
Authors: Tan Jaclyn , Lim Mervyn Jun Rui , Chen Christopher , Hilal Saima 
Published: June 2023

AbstractBackgroundIt is well demonstrated that hippocampal atrophy is associated with cognitive impairment. Existing studies have associated smaller hippocampal volumes with dementia, and hippocampal volume reduction has been established as a biomarker for the conversion of mild cognitive impairment to Alzheimer’s Disease. Although some studies have examined correlations between hippocampal subfield volumes and cognitive domains such as memory, further research is needed to clarify the associations between the volume of each subfield and the various cognitive domains. So far a few studies have been conducted among Asian populations. A more specific understanding of these relationships is crucial given the functional and histological differences in the subfields and their distinct patterns of atrophy, which imply that the hippocampal subfields may affect cognition differentially. This study aimed to investigate the associations between the volumes of 12 hippocampal subfields on cognitive performance in a Singaporean sample.Method448 patients at a memory clinic in Singapore (97 with no cognitive impairment, 177 with CIND, and 174 with dementia) underwent magnetic resonance imaging (MRI) and a neuropsychological assessment. MRI was processed through free surfer (v.6.1) to extract volumes of 12 hippocampal subfields—the tail, subiculum, presubiculum, parasubiculum, CA1, CA3, CA4, fimbria, fissure, molecular layer, the molecular and granule cell layers of the of the dentate gyrus (GCMLDG), and the hippocampus‐amygdala transition area (HATA). Cognition was assessed using NINDS–Canadian Stroke Network harmonization neuropsychological battery.ResultGlobal cognition was associated with the subiculum, presubiculum, CA1, CA3, CA4, molecular layer, and GCMLDG (all p‐values < .0005). Except for the fissure, all hippocampal subfields were associated with visuospatial skills (all p‐values < .05) and memory (all p‐values < .035). The fimbria was associated with the most cognitive domains, including executive dysfunction (p = .011), language (p = .006), visuomotor function (p = .003), visuospatial skills (p < .001), and memory (p < .001).ConclusionThe current study builds on existing research on the associations between hippocampal subfield volumes and cognitive dysfunction. Longitudinal studies are required to investigate the volumetric reduction of hippocampal subfields as a biomarker of cognitive decline.
Evaluation of salivary levels of beta amyloid in patients with Alzheimer’s disease
Authors: Santos Gustavo , Pardi Paulo , Vale Francisco , Fazan Valeria 
Published: June 2023

AbstractBackgroundSalivary analysis of amyloid beta protein levels in Alzheimer’s disease patients and research participants without Alzheimer’s disease.MethodThis is a case‐control study carried out in patients with a diagnosis of probable AD and cognitively healthy patients without AD. There were 3 groups, totaling 76 people: group 1 with AD; Group 2 without AD (under 59 years old) and group 3 without AD (over 60 years old). Ethics committee opinion n° 3,130,636. Salivary analysis of Ab‐40 and Ab‐42 performed by the ELISA method.ResultOur investigations for salivary AB42 showed slightly higher levels in male and female AD patients compared to healthy ones. The general AB42 group for AD was superior to the general group of healthy ones, demonstrating the feasibility of using saliva as a diagnostic element for AD.ConclusionAmyloid beta protein in fractions 40 and 42 amino acids (Ab1‐40 and Ab1‐42) were expressed in higher concentrations in AD patients and reduced in healthy ones, strengthening the hypothesis of the use of this fluid as an adjuvant in the diagnosis of Alzheimer’s Disease.
Racial/ethnic and sexual orientation disparities in adverse childhood experiences, marijuana use and subjective cognitive decline: A mediational approach
Authors: Brown Monique J 
Published: June 2023

AbstractBackgroundAdverse childhood experiences (ACEs) have been shown to be positively associated with substance use and abuse, and have also been linked to subjective cognitive decline (SCD). However, studies examining potential pathways between ACEs and SCD are lacking. In addition, this relationship and related pathways may differ by race/ethnicity and sexual orientation. The aim of this study was to determine the mediational role of marijuana use in the association between ACEs and SCD. The secondary aim was to determine the potential disparities by race/ethnicity and sexual orientation.MethodData were obtained from the 2019 Behavioral Risk Factor Surveillance System (N = 14,248). Path analysis was used to determine the mediating role of marijuana use between ACEs and SCD. Overall analyses adjusted for gender, age, income, education, employment and race/ethnicity. Stratified path analyses by race/ethnicity and sexual orientation were also conducted.ResultOverall, there was a direct association between ACEs and marijuana use (B = 0.102, p = <0.001), marijuana use and cognitive decline (B = 0.119, p<0.001); and between ACEs and cognitive decline (B = 0.047, p<0.001). There was an indirect association where marijuana use mediated the association between ACEs and SCD (B = 0.005, p<0.001). Stratified analyses by race/ethnicity found that marijuana use mediated the association between ACEs and SCD among White (B = 0.003, p<0.001), but not Black, Other or Hispanic respondents. Stratified analyses by sexual orientation found that marijuana use mediated the association between ACEs and SCD among heterosexual (B = 0.002, p = 0.006) but not LGBT respondents.ConclusionDisparities by race and sexual orientation existed in the mediating pathway of ACEs and SCD. Intervention programs addressing early trauma and cognitive function should consider these disparities. Future research should examine additional pathways between ACEs and SCD, especially for racial/ethnic and sexual minority populations.
LTD‐inducing low frequency stimulation enhances p‐Tau181 and p‐Tau217 in an age‐dependent manner in live rats
Authors: Hu Neng‐Wei , Zhang Yangyang , Yang Yin , Hu Zhengtao , Zhu Manyi , Qin Shuangying , Rowan Michael J 
Published: June 2023

AbstractBackgroundThe progressive cognitive decline in Alzheimer’s disease (AD) patients correlates with the extent of tau pathology, in particular tau hyperphosphorylation, which is strongly age‐associated. Although elevation of phosphorylated tau (p‐Tau) on residues Thr181 (p‐Tau181), Thr217 (p‐Tau217), and Thr231 (p‐Tau231) in cerebrospinal fluid or blood are recently proposed to be particularly sensitive markers of early Alzheimer’s disease (AD), the generation of p‐Tau during brain activity is poorly understood. A major form of synaptic plasticity, long‐term depression (LTD), has recently been linked to the enhancement of tau phosphorylation. It is still unknown whether the expression levels of p‐Tau181, p‐Tau217, and p‐Tau231 can be enhanced by physiological LTD induction.MethodYoung adult (2‐3‐months) and aged (17‐18‐months) male Sprague Dawley rats were used in all experiments. Prior to the surgery, animals were anesthetized with urethane (1.5‐1.6 g/kg, i.p.). Field excitatory postsynaptic potentials (EPSPs) were recorded from the stratum radiatum in the CA1 area of left or right hippocampus in response to stimulation of the Schaffer collateral‐commissural pathway. LTD was induced using 1 Hz low frequency stimulation (LFS) consisting of 900 pulses (0.2 ms duration). The rats were sacrificed 30 min post‐LFS. The expression levels of p‐Tau181, p‐Tau217, p‐Tau231, p‐Tau202/205, p‐Tau396, and total tau were analyzed using western blotting and immunofluorescent staining.ResultHere we show that LFS, used to induce LTD, enhances p‐Tau181 and p‐Tau217 in an age‐dependent manner in the hippocampus of live rats. In contrast, phosphorylation at residues Thr231, Ser202/Thr205, and Ser396 is less sensitive to LFS. Further, blocking either NMDARs or mGluR5 strongly inhibits the elevation of both p‐Tau181 and p‐Tau217. Finally, targeting ageing with a small molecule cognitive enhancer ISRIB (trans‐isomer) prevents the increase of both p‐Tau181 and p‐Tau217 by LFS in aged rats.ConclusionOur data provide an in vivo means to uncover brain plasticity‐related cellular and molecular processes of tau phosphorylation in health and ageing conditions.
Supporting the caregiver through the continuum of care
Authors: Renzulli Brenda , Bakkali Leen 
Published: June 2023

AbstractBackgroundCaring for Dementia patients is taxing, affecting the caregiver emotionally, physically and financially. Often this results in strained relationships and health issues for the caregiver who becomes known as the ‘invisible patient’.MethodThe Bridgeport Hospital Center for Geriatrics multidisciplinary team engages with our patients and their caregivers in a variety of locations and methods.We provide a number of educational opportunities, assist in goal setting and in long term planning. We offer LCSW counseling, support groups, and focus on giving a voice to the caregiver through a variety of means.ResultThese engagements have helped our patients and their families as they navigate this difficult journey. Families report through surveys lessened burden, they report being ‘heard’ and being grateful for the 24/7 support.ConclusionWe found that our multidisciplinary approach and seeing patients and their caregivers at different points within the of the medical system improves outcomes. Both patient and caregiver satisfaction is improved and stress/burden are decreased.
Clinically relevant and explainable feature extraction from remote monitoring data for the prediction of urinary tract infections
Authors: Capstick Alexander , Palermo Francesca , Li Honglin , Barnaghi Payam , Wingfield David , Kolanko Magdalena A , Sharp David J 
Published: June 2023

AbstractBackgroundA frequent cause for hospitalisation in people living with dementia (PLWD) is urinary tract infections (UTIs) (Dufour et al., 2015). Early detection aids in avoiding unplanned hospitalisations and machine learning and connected sensors enable development of risk analysis models based on in‐home monitoring data. This work makes use of data from the ongoing Minder study at the UK Dementia Research Institute, including in‐door movement, appliance use, physiology, sleep, and environmental information. Previous work (Li et al., 2020) shows complex models can achieve high accuracy when detecting UTIs, but interpretability and generalisability remain an open issue. This work evaluates how clinically interpretable features and simple models perform.MethodThe engineered features reflect visible symptoms of UTIs in older adults and are daily aggregated and pre‐processed information from PLWD’s homes containing passive sensors. 14 activity, sleep and physiological features were engineered relating to bathroom visits, entropy rate, physiological readings, and sleep behaviour. Raw data consisted of frequencies of the activity sensor firings. Their use in predicting cases of UTIs was compared by evaluating multilayer perceptron models on labelled data (643 negatives and 311 positives, from 39 PLWD), using 5‐fold cross‐validation (80%/20% train/test split), with 5 repeats. Prior to training and testing, the data was z‐normalised using unlabelled data. When evaluating, recall is most essential because reducing false positive rates is crucial in our setting.ResultThe highest performing model achieved the best accuracy, recall, precision and F1 score (85.6%, 69.9%, 81.5%, 74.8%) on combinations of engineered and raw features; though not significantly higher than with raw features alone (83.2%, 63.5%, 80.5%, 70.8%). Full results can be seen in the attached figure.ConclusionOur engineered features do not significantly improve results but add interpretability and generalisability to predictions. The models' hidden layers have a high capacity for learning patterns in the raw data, however, may not be clinically interpretable and we hypothesise that engineered features improve generalisation. Engineered features are homogeneous across the cohort and new data, and so create a way of representing the data which is not single device dependent. To verify this, we will continue our data collection and will conduct further experiments.