bluuebunny/crossref_metadata_2025_split huggingface dataset:
LEADing Advance care conversations: Development of an intervention platform
Authors: Dassel Kara B , Nachtweih Emily , Supiano Katherine P , Utz Rebecca , Iacob Eli 
Published: June 2023

AbstractBackgroundThe LEAD Guide (
Life‐Planning in Early Alzheimer’s Disease; Dassel et al., 2019) addresses changes in cognition and goals of care along the Alzheimer’s disease and related dementias (ADRD) continuum and anticipates the need for surrogate decision‐makers upon loss of the care recipient’s decisional abilities.MethodWe developed a preliminary interactive version of the LEAD Guide, which serves as the foundation of a self‐administered intervention designed to promote and guide community‐based ADRD dyads through a dementia‐focused ACP process. The intervention model includes the LEAD Guide, along with education/information about ACP in the context of ADRD, and interactive instructions. We developed the LEAD Intervention using an iterative design process, which relied on feedback from a 11‐member community advisory board comprised of a clinical dementia specialist, the Director and Program Manager from the State Chapter of the Alzheimer’s Association, and community‐based ADRD dyads. We used Qualtrics, a web‐based survey platform, to simulate the basic functionality and flow of the interactive web‐delivered intervention we envisioned. We then conducted extensive beta‐testing with our community advisory board through written surveys and focus groups.ResultIn general, users were enthusiastic about the LEAD Intervention and appreciated the opportunity to engage in meaningful guided ACP with their family member. Recommended revisions fell into two categories: technological (adding a progress bar, reducing the number of items per page, adding back arrows, reducing text and using more graphics/figures, closed‐captioning, video‐facilitated instructions) and personalization (using piped text that integrates participants’ names into survey items to increase a personal feel, and creating downloadable copies of participants’ LEAD Guide responses).ConclusionThe process of creating a feasible, acceptable, and efficacious intervention requires input from ADRD experts as well as community‐based caregivers and persons with mild ADRD. The iterative process that our research team engaged in with our community advisory board members provided invaluable information on how to create and revise a web‐based ACP intervention platform for community‐based ADRD dyads. We are currently enrolling 60 ADRD dyads in the revised web‐based intervention, with the goal of exploring the impact on relationship quality, decision‐making self‐efficacy, and ACP congruence within participant dyads.
Altered transposable elements expression and gene networks remodeling precede disruptions in sleep/wake cycles in a tauopathy mouse model of AD
Authors: de Evsikova Caralina Marin , Evsikov Alexei 
Published: June 2023

AbstractBackgroundAlzheimer’s Disease (AD) is an widespread neurodegenerative disorder, common in elder and Veterans communities, culminating in dementia with non‐cognitive behavioral and metabolic symptoms, such as hyperactivity and altered sleep/wake patterns. In demented patients, sleep/wake cycle disruptions facilitate weight loss, which is associated with adverse outcomes like accelerated AD progression and higher institutionalization. Tg4510 mice, which express a P301L mutant variant of human tau, develop both cognitive and non‐cognitive symptoms. Several mouse models of tau deposition, including Tg4510 mice, also have negative energy balance. To identify early factors affecting AD, we measured locomotor, sleep/wake patterns in vivo, and analyzed RNA‐seq data from Tg4510 mice to identify gene and transposable elements (TE) expression changes involved in behavioral derangements in AD.MethodLocomotor activity, sleep and wake intervals and patterns were measured using in vivo metabolic cages for two weeks over 24 hr and day and night cycles from Tg4510 mice (n = 5‐7) vs. controls (n = 7‐10) before and after the onset of tauopathy (at 2 and 7 months of age respectively). In additional experiments, we analyzed RNA‐seq from hippocampi of Tg4510 mice (n = 5) vs. controls (n = 6). Using our established TTESA bioinformatics pipeline, reads were aligned to reference genome and expression of genes or TEs was measured with featureCounts. Pathway enrichment analysis using Visual Annotation Display was used to discover common functional and disease pathways using Gene Ontology, Protein Ontology, and Mammalian Phenotype Ontology.ResultWe observed altered locomotor and sleep patterns during the night phase starting in young Tg4510 vs. controls. TTESA results detected the majority of significantly differentially expressed TEs were retrotransposons (70%), which consisted mainly of long terminal repeats (LTRs; 70%) and some LINE retroelements (30%) and SINEs (<8%) in transgenic mice. VLaD pathway analysis revealed several biological processes upregulated in transgenic mice, including non‐cognitive behavioral pathways were downregulated, such as the regulation of circadian sleep/wake cycle with changes in the expression levels of Per2, Per3 (p<0.0001).ConclusionEarly dysregulation of TEs may be involved in rewiring gene expression networks underlying behavioral changes in wake and sleep cycles and other circadian patterns of behavior in this humanized mouse model of AD.
The effects of different knee osteoarthritis criteria on trail‐making test times in an elderly Malaysian cohort
Authors: Tan Guo Jeng G , Tan Maw Pin 
Published: June 2023

AbstractBackgroundKnee osteoarthritis (KOA) is a common cause of morbidity among older people with its prevalence expected to increase with population ageing. The relationship between KOA and cognitive performance, however, is not well understood despite both conditions sharing common risk factors including age and metabolic syndrome. We evaluated the cognitive performance of individuals with and without KOA to evaluate this relationship.MethodData is from the Promoting Independence in our Seniors with Arthritis (PISA) study, which is comprised older adults with and without KOA recruited from an urban tertiary hospital and its catchment population. Basic demographics, physical and psychosocial characteristics were recorded. Cognitive performance was determined using the Trail‐Making Test (TMT). KOA was defined using the American College of Rheumatology (ACR) criteria, presence of knee pain, self‐reported physician diagnosis (SRPD), and the Kellgren‐Lawrence’s (KL) radiographic criteria. Multiple linear regression models were created and bootstrapping was used for Kellgren‐Lawrence in view of the smaller sample who had radiographic investigations.ResultTwo‐hundred and thirty participants, mean (SD) age of 66.93 (7.12) years, were recruited. KOA was present in 120 (58.0%), 94 (40.9%), 85 (39.9%), and 33 (57.9%) according to ACR, knee pain, SRPD and KL criteria respectively. TMT‐A scores were variably influenced by age, gender, years of education, grip strength, functional reach and presence of metabolic syndrome using the four KOA criteria. TMT‐B scores were influenced by age, gender, years of education, grip strength and depression scores differentially using the four KOA criteria. No significant associated was observed between KOA and TMT‐A or TMT‐B scores after adjustment for the potential confounders above.ConclusionKnee OA was not associated with differences in cognitive performance evaluated with TMT which is a cognitive screening tool which mainly evaluates attention, working memory and executive function. The presence of KOA did not influence TMT performance in this study, which suggests that KOA does not affect the above cognitive domains regardless of criteria for diagnosis. This suggests that cognitive impairment and KOA do not share common pathological processes despite the presence of common risk factors.
Nanoparticle based intranasal drug delivery system of some herbal medicinal plants for Alzheimer’s disease
Authors: Singh Manisha 
Published: June 2023

AbstractBackgroundDiseases of the Central Nervous System (CNS) such as epilepsy, schizophrenia, meningitis, migraine, Parkinson’s disease and Alzheimer’s disease require delivery of the drug to the brain for effective treatment but it remains problematic area to deal with, as the central nervous system (CNS) is isolated from the whole body by the blood–brain barrier (BBB). This tight physiological barrier limits the drug diffusion towards the brain parenchyma and is considered as the bottleneck in brain drug development. Now this can be circumvented by intraventricular or intracerebral administration. Intra Nasal delivery thus attributes to non‐invasive, essentially painless, high vascularity and the permeability of the nasal mucosa, which aids the drug in bypassing the aforementioned processes of degradation. Now the increasing realization of the side effects of allopathic medicines, coupled with the growing awareness about the medicinal benefits as well as therapeutic effect of herbal products is pushing up the demand for herbal extracts and herbal‐based supplements worldwide.MethodIn this study we designed a natural compound based Nanoformulations for drug delivery via nasal route to treat Alzheimer’s conditionResultAfter various preliminary studies we prepared standard extract loaded Nanoformulations with their particle size between the range 80 – 290nm and sustained release kinetics profile. Further, the toxicity analysis (morphological, cell viability, cytotoxicity assays) of these nanoformulations was performed on RPMI2650 (Human nasal septum) and NB41A3 (Mouse hippocampus) cell lines based on the route and site of drug delivery. Lastly, in vivo experiments were performed with AD (cognitive impairment) induced mice model. There was seemingly, a significant decrease in anti ß amyloid antibody positive neurons in case of optimised nanoformulations in comparison to the galantamine. It was also found to have reduced lesions caused due to the amyloid aggregation reflecting a noted improvement in dispersing and reducing the lesions in the hippocampal tissues.ConclusionIn conclusion, the present study demonstrates that the developed nanoformulations have potential therapeutic effects on improving the pathological state of AD, and might be taken further as a promising candidate for clinical research to evaluate its efficacy in humans.
Carotid pulse wave velocity measured using a fast single‐slice oblique‐sagittal phase‐contrast MRI is associated with cognitive impairment
Authors: Tang Jianing , Pahlavian Soroush Heidari , Joe Elizabeth B , Chui Helena C , Yan Lirong 
Published: June 2023

AbstractBackgroundArterial stiffness is one of the earliest markers of vascular dysfunction1. Elevated arterial stiffness leads to the transmission of excessive pulsations into the downstream microvasculature, which may be linked to cognitive impairment in aged individuals. Pulse wave velocity (PWV) is an established surrogate of arterial stiffness. To date, PWV measurement at carotid arteries or above has been still limited. Previous work has introduced a fast MRI method to measure carotid PWV (cPWV) using single‐slice oblique‐sagittal phase‐contrast MRI (OS PC‐MRI)3. In this study, we evaluated the association between cPWV and cognitive impairment in an aged group.MethodThe MRI experiments were conducted on Siemens Prisma 3T MRI scanner. A 2min TOF MRI was performed to localize carotid arteries including CCA and ICA. The 3D MR angiogram was reformatted to determine an oblique slice to maximally cover both CCA and ICA (Figure 1a). A single‐slice retrospectively gated 2D OS PC‐MRI with a single in‐plane velocity encoding (CCA to ICA) (Venc = 80cm/s, temporal resolution = 14.22ms) was performed to simultaneously acquire blood velocity waveforms at each location along the CCA‐ICA segment. cPWV was calculated as the inverse slope of the line fitted to the transit time versus distance along the vessel (Figure 1b). 15 elderly participants (age: 71.4 ± 8.5 years) were enrolled in this study. Each participant underwent cognitive assessments including CDR and 13 out of 15 were conducted the MoCA.ResultThere was a significant difference (p = 0.0496) in cPWV between the participants with normal cognition (CDR = 0) and cognition impairment (CDR> = 0.5). Figure 3 shows the scatter plot of cPWV vs. MoCA. Overall, cPWV increased with lower MoCA. However, there was no significance (r = ‐0.5294, p = 0.0767) obtained between cPWV and MoCA given a small sample size and the presence of a suspicious data point indicated by a green circle in Figure 3. After excluding this potential outlier, a significant negative correlation between cPWV and MoCA was obtained (r = ‐0.8113, p = 0.0014).ConclusionThe pilot study demonstrates that increased cPWV is associated with cognitive impairment, suggesting cPWV measured using 2D OS PC‐MRI could be an imaging marker for cognitive impairment.
Association between different dementia diagnosis and kidney function decline: A Swedish registry study
Authors: Xu Hong , Garcia‐Ptacek Sara , Lindholm Bengt , Eriksdotter Maria , Carrero Juan Jesus 
Published: June 2023

AbstractBackgroundPopulation studies have shown that chronic kidney disease(CKD) and CKD progression are associated with dementia, particularly Alzheimer’s dementia(AD) and vascular dementia(VD). However, the impact of different brain pathogenesis on these associations is not known.MethodObservational study of patients with recently diagnosed dementia disorders from the Swedish Dementia Registry(SveDem) 2007‐2018 linked with complete information of kidney function tests [estimated glomerular filtration rate(eGFR)] over time from the Stockholm CREAtinine Measurements(SCREAM) registry. The study exposure were different dementia diagnosis [AD, VD, mixed dementia, dementia with Lewy Bodies(DLB) and Parkinson’s disease dementia(PDD), frontotemporal dementia(FTD), unspecified dementia(UNS) and other dementia types]. The study outcome was CKD progression, defined as the composite of a sustained eGFR decline of>30% from baseline, initiation of kidney replacement therapy or death attributed to kidney disease. We performed competing risk analyses where death from non‐renal causes was considered as competing events for CKD progression. Confounders included demographics, comorbidities, and baseline kidney function.ResultWe included 20,618 patients, of whom, 6,452(31%) had AD, 7,012(34%) had mixed dementia, 3,987(19%) had VD, 764(4%) had DLB or PDD, 312(2%) had FTD, and 2,091(10%) patients were diagnosed with unspecified or other dementia diagnoses. The mean age was 80 years (60%female). During median follow‐up time of 2.5 (IQR1.0‐4.5) years, 2,225(11%) events of CKD progression occurred, along with 8,684(42%) non‐renal deaths. After adjusting for confounders and accounting for competing risks, a higher risk of CKD progression compared to patients with AD was observed for patients with VD [sub‐HR, 95%CI 1.19;1.05‐1.34], mixed (1.13;1.02‐1.26), UNS or other dementia types (1.13;0.96‐1.32), while patients with DLB or PDD dementia had 46% lower risk of CKD progression (0.54;0.39‐0.76), and those with FTD showed no difference compared to AD (0.99;0.64‐1.51).ConclusionVD and mixed dementia (vs AD diagnosis) were associated with a higher risk of CKD progression, whereas DLB or PDD dementia were associated with lower risk of CKD progression. Since DLB and PDD dementia involve less and VD and mixed dementia more vascular pathology, this suggests that vascular mechanisms may play an important role in the brain‐kidney axis. Future studies are needed to explore this hypothesis.
Protocol for investigating brain health risk and protective factors in 18‐40 year olds: The PREVENT Next Generation study
Authors: Booi Laura , Farina Francesca R , Wells Katie , Dounavi Maria‐Eleni , Gregory Sarah , Jenkins Natalie D , Low Audrey , Mak Elijah , Newton Coco , Saunders Stina , Lawlor Brian , Ritchie Craig W. 
Published: June 2023

AbstractBackgroundEvidence suggests that the early detection and management of modifiable risk factors can reduce, or partially prevent, incidence of neurodegenerative diseases. While there is consensus that risk factors should be addressed as early as possible, research has largely focused on childhood or mid‐ and later‐life. As a result, there is a significant gap in our understanding of risk (and protective) factors in younger adulthood, as well as attitudes towards brain health in this group. The PREVENT Next Generation (PNG) study builds on the PREVENT Dementia project to investigate risk and protective factors in 18‐40 year olds.MethodThe first phase of the PNG study will establish a foundational understanding of knowledge and attitudes towards brain health and risk reduction among adults aged 18‐40 years. We will conduct focus groups with adults aged 18‐40 years with and without a family history of neurodegenerative disease (n = 10 per group). Participants will be recruited via links with volunteer and community centre enterprises in the UK. To ensure inclusion of equitable perspectives, we will emphasise recruitment of diverse populations, including racialized and neurodiverse communities, and those with lower socioeconomic status. Focus groups will be recorded and transcribed. Data will be analysed using thematic analyses.ResultThemes identified will be used to inform the next phase of the PNG study, which is to develop and distribute an online survey about brain health to an international sample of adults aged 18‐40 years.ConclusionSurvey findings will inform the development of a large cohort study aimed at identifying biological, psychological and lifestyle factors that influence brain health in adults up to mid‐life.
Interdisciplinary antipsychotic stewardship between operator and neurobehavioral consultant
Authors: Posar Steven Laurence , Reid Anita , Heiser Daniel , Kinzie Janean , Pinon Jose D 
Published: June 2023

AbstractBackgroundAntipsychotic utilization in skilled nursing facilities (SNFs) is a major focus of regulatory compliance and a key theme in resident care. At first, improvements via national rate lowering initiatives were effective, but as of late, reductions have slowed. Due to a slowing of industry‐wide advancements in the care of behavioral and psychological symptoms of dementia (BPSD), the Federally mandated patient centered care initiative has not widely incorporated “best practices” for BPSD care. This has opened an opportunity for innovations in clinical care of BPSD. In a shared initiative with this operator, we have implemented a joint program focused on rigorous clinical diagnosis and “best practices” in pharmacology support, specifically aimed at assessing and reducing antipsychotic use whenever appropriate.MethodsIn three targeted buildings, all patients identified as receiving antipsychotic medication were enrolled in a specific assessment and treatment protocol designed to mitigate antipsychotic use where possible. Diagnoses were reviewed by Clinical Psychology, Psychiatry, Consultative Gerontology (where indicated), and building Social Service. Additionally, behavioral documentation for each resident was reviewed, and a team approach to polypharmacy, all psychotropic medications, and antipsychotic reductions were implemented. Data was verified by facility pharmacy records, and reports detailing the proportion of residents taking antipsychotic medications were generated in January, March, and July of 2021.ResultsPrior to full implementation of the protocol (January 2021), antipsychotic rates were 32%, 14% and 18% in the three buildings. Immediately following initial review, rates were noted to be similar to baseline (Table 1). After implementation of clinical protocols, we found that the proportion of residents using antipsychotic medications declined to 9.6%, 4.2% and 6.3% respectively (Table 1, Figure 1). In addition, there were no noted harms, nor deteriorations related to the discontinuation of these medications.ConclusionImplementation of a shared cooperative clinical protocol between the SNF facility staff and clinical treatment team resulted in a reduction of antipsychotic use of more than 65% with no noted harms nor clinical decline.
DNA Methylation in Risk for Cognitive Impairment and Type 2 Diabetes in a Mexican American Cohort
Authors: Daniel Ann Abraham , Silzer Talisa , Hall Courtney , Sun Jie , Zhou Zhengyang , Phillips Nicole , Barber Robert 
Published: June 2023

AbstractBackgroundAlzheimer’s disease (AD) and type 2 diabetes (T2D) are among the leading causes of mortality among the growing aging Mexican American population (≥ 65 years old) in the US (Vega et al. 2017). In comparison to their non‐Hispanic white counterparts who most likely develop inflammation associated AD, aging Mexican Americans have an earlier onset of AD and metabolism related predisposition for AD (O'Bryant et al. 2010). Mild cognitive impairment (MCI) is a phenotype that often leads to AD and is also prevalent in this cohort (O'Bryant et al. 2013). The risks for AD, MCI and T2D are multifactorial, involving a form of epigenetic regulation called methylation where a methyl group is added to the cytosine base in DNA (Shao et al. 2017; Juvinao‐Quintero et al. 2019). We aim to elucidate an epigenetic association between cognitive impairment (identified here as AD and MCI), and T2D that is unique to the Mexican American population.MethodA total of 551 aging participants from the Texas Alzheimer’s Research and Care Consortium (TARCC) consisting of 252 non‐Hispanic white individuals and 299 Mexican Americans were selected, after quality control. First, participants were stratified into groups of individuals diagnosed with cognitive impairment (CI) alone and controls without CI within each ethnic group. Secondly, this cohort was stratified into individuals with T2D alone and controls without T2D. Thirdly, participants were stratified into those with both CI and T2D versus normal healthy controls. Lastly, any differential methylation associated with each ethnic group will be compared and contrasted. Peripheral blood drawn from participants was used to obtain individual methylation profiles using the Illumina Infinium MethylationEPIC chip array. Differential methylation was assessed using the Chip Analysis Methylation Pipeline (ChAMP), limma and cate packages in R. The Beta MIxture Quantile dilation (BMIQ) method was used for data normalization.ResultResults will be analyzed using gene set enrichment and pathway analysis tools.ConclusionIdentifying possible methylation sites associated with CI and T2D could contribute towards developing ethnicity‐specific biomarkers for Mexican Americans.