bluuebunny/crossref_metadata_2025_split huggingface dataset:
The virtual adaptation of Innovations in Dementia Empowerment and Action – IDEA
Authors: Hoy‐Ellis Charles Pitre , Fredriksen‐Goldsen Karen I , Jones Brittany R , Kim Hyun‐Jun , Teri Linda , La Fazia David M. , McKenzie Glenise , Petros Ryan , Institute The Goldsen 
Published: December 2023

AbstractBackgroundIn contrast to their counterparts in the general population, sexual and gender minority (SGM) older adults and their care partners, have distinct susceptibilities that complicate living with dementia, including significant disparities in comorbid chronic conditions, social isolation, and systemic marginalization, such as discrimination and limited access to health services and supports. We developed a culturally responsive, psychosocial behavioral intervention for SGM older adults living with dementia and their care partners, the first‐ever randomized controlled clinical trial (RCT), Innovations in Dementia Empowerment and Action (IDEA). Initially designed to be delivered (and initially delivered) in‐person and in‐home, challenges associated with COVID‐19 (e.g., quarantining, socially isolating) also provided a unique opportunity to adapt and recalibrate IDEA to be fully delivered via virtual technologies.MethodWe were guided by principles of accessibility, quality, ease of delivery, and sustainability to ensure rigor during the adaptation process. Implementation needs included identifying a HIPPA‐compliant online virtual platform that was easy to use; adapting elements and materials in the intervention manual as needed; providing training for intervention coaches in best practices for virtual delivery; and training participants in the use of virtual technologies.ResultPreliminary findings suggest intervention coaches and most participants deemed the adapted intervention and virtual delivery to be acceptable. of IDEA. Only two of 22 dyads expressed discomfort with the virtual delivery to the degree they chose not to participate. Regarding difficulty in delivering the intervention virtually, 87% of coaches indicated that it was not at all or only a little difficult;12% somewhat difficult; and only 1% difficult. Virtual delivery also allowed us to expand beyond our initial 3‐site catchment area to 28 states, which also greatly increased access for rural and isolated SGM.ConclusionDelivering the adapted IDEA intervention virtually provided preliminary, potentially beneficial evidence to advance dementia interventions to address the growing, diverse population of people living with dementia and their care partners. Further systematic research is required to fully evaluate the benefits and limitations of virtual dementia interventions, including whether specific subgroups are better served by differing delivery modalities.
Cognitive activity, cognitive function, and neurological blood biomarkers
Authors: Krueger Kristin R , Desai Pankaja , Beck Todd , Wilson Robert S. , Evans Denis A , Rajan Kumar B 
Published: December 2023

AbstractBackgroundMore frequent engagement in cognitive activity is associated with better cognitive function in older adults, but the mechanism of action is not fully understood. Debate remains whether increased cognitive activity provides a meaningful benefit for cognitive health or if decreased cognitive activity represents a prodrome of cognitive impairment. Neurological biomarkers provide a novel way to examine this relationship in the context of cognitive aging.MethodsWe examined the association of cognitive activity, cognitive function, and concentrations of three biomarkers in community‐dwelling participants of a longitudinal, population‐based study. Cognitive activity was measured at baseline by asking participants to rate the frequency of 7 activities: 1) Viewing television, 2) Listening to the radio, 3) Visiting a museum, 4) Playing games, such as cards, checkers, crosswords, or other puzzles or games, 5) Reading books, 6) Reading magazines, and 7) Reading newspapers. Cognitive function was measured with a battery of four tests (Mini‐Mental State Examination, Digit Symbol Test, and the immediate and delayed recall of the East Boston Test) averaged into a composite score. At baseline, we evaluated the concentration of total tau (tau), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP).ResultsThe study sample comprised 1,168 older participants, primarily non‐Hispanic Blacks (60%) and women (63%). At baseline, they were an average of 77 years old with 12.6 years of education. Mixed‐effects models showed that cognitive activity was associated with better cognitive functioning at baseline and over time. These relationships remained after each biomarker was added to the model. Over an average of 6.4 years of follow‐up, cognitive activity was associated with cognitive decline in the model with tau (estimate = 0.0123; p‐value = 0.03) and was mildly attenuated in the models with NfL, (estimate = 0.0110; p‐value = 0.06), and GFAP (estimate = 0.0111; p‐value = 0.06). Biomarkers did not modify the association between cognitive activity and cognitive function over time.ConclusionThe benefits of cognitive activity on cognition appear to be independent of biomarkers: tau, NfL, and GFAP. More frequent cognitive activity may benefit the cognitive health of older adults with a wide range of potential disease risk and presentations.
Dysregulation of Alzheimer’s disease‐related gene expression in brain tissue of patients with major depression
Authors: Aleksynas Robertas , Mota Bibiana Castagna , Callado Luis F , Sastre Magdalena 
Published: December 2023

AbstractBackgroundMajor depressive disorder (MDD) is linked with a 2‐fold higher risk of developing Alzheimer’s disease (AD), yet the mechanisms behind this association are unclear and are confounded by psychotropic drug use. We, therefore, aimed to investigate AD‐related transcriptional changes in post‐mortem MDD brains without symptoms of dementia and their matched controls, taking into consideration psychotropic medication‐use history.MethodNanoString Technologies nCounter® analysis using their Alzheimer’s Disease Panel (770 genes) was performed on mRNA extracts from post‐mortem prefrontal cortex tissue of suicide victims with ante‐mortem MDD diagnoses, including 6 drug‐free cases and 6 with a previous history of psychotropic medication use whose serological screening included antidepressants, antipsychotics, benzodiazepines. The results were compared with 12 age and sex matched non‐neurological controls. The data was analysed using nSolver advanced analysis software and built‐in statistical analyses.ResultWhen comparing total MDD cases vs. healthy controls, genes involved in lipid metabolism and myelination (e.g., CDK18, 1.9‐fold; ABCA2, 1.91) and cytokines (CSF1, 1.93; LIFR, 1.26) were found upregulated in MDD, whereas the most downregulated genes included neurotransmitter synthesis and storage (RAB3A, 0.79), neurotransmitter release (CAMK4, 0.741) and vesicle trafficking (NPTX2, 0.519). In a comparison of MDD drug‐free group vs. MDD with drug use group, patients with drug use displayed upregulations of genes related to lipid metabolism and myelination (NKX6‐2, 4.5) autophagy (ABCA2, 3.32) and cytokines (CSF1, 2.53; LIFR 1.34), whereas drug‐free patients showed higher expression of neurotransmitter release (GRIA3, 0.742), transcription‐splicing (DDX42, 0.807) and trophic factor (NTRK2, 0.732) genes. TSPO, a gene related to microglial activation, was the most significantly upregulated gene (3.23‐fold) in MDD patients taking psychotropic medications.ConclusionThe study provides evidence that alterations in pathways involving neuroinflammation, metabolism and neurotransmission in the brains of MDD patients might provide the link with AD and highlights the need to investigate the role of psychotropic medications in modulating AD‐related pathways.
Multi‐cohort cerebrospinal fluid proteomics identifies robust molecular signatures for asymptomatic and symptomatic Alzheimer’s disease
Authors: Ali Muhammad , Timsina Jigyasha , Wang Lihua , Do Anh , Western Daniel , Sung Yun Ju , Cruchaga Carlos 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD), the most common form of dementia, is characterized by the accumulation of Amyloid‐β (Aβ42) and hyperphosphorylated Tau 181 (p‐tau181) proteins in the brain. Changes in these proteins in AD brains and cerebrospinal fluid (CSF) are detected years before AD symptoms. Studying AD proteome in CSF can reflect its diverse underlying pathophysiology and pave the way for reliable diagnostic and therapeutic advancements.MethodWe present one of the largest CSF AD proteomic profiles (7,029 protein analytes) in CSF of 3,065 individuals in three stages. Discovery was performed in 836 samples from the Knight ADRC and 618 samples from the FACE cohorts using the ATN framework (AT‐ = 680 and AT+ = 490). The identified proteins were tested in 832 individuals (AT‐ = 235 and AT+ = 358) from the ADNI and Barcelona‐1 cohorts. The proteins that passed multiple Bonferroni corrections on the meta‐analysis were utilized for AD prediction models and pathway enrichment analysis to gain mechanistic insights into AD pathophysiology.ResultIn discovery, we identified 3,565 proteins to be significantly (FDR < 0.05) altered. Of these, 2,543 passed FDR in replication with a consistent direction. In the meta‐analysis, we identified 2,233 proteins to be significantly (P‐Bonferroni < 0.05) altered in the AD CSF proteome. Some of the highly significant proteins included YWHAG (P‐Bonf < 4.5×10−219), SMOC1 (P‐Bonf < 5.8×10−208), NRGN (P‐Bonf < 3.2×10−119), and NEFL (P‐Bonf < 1.8×10−37). By using lasso, we identified a set of 39 proteins with high predictive power (Discovery AUC = 1.0; Replication AUC = 0.99) representing a robust and precise AD diagnostic biomarker. Enrichment analysis highlighted several neurological disorders (e.g. AD, tauopathy, and synucleinopathy) and neuronal functions (neuron projection morphogenesis, synapse assembly and organization, and neuron differentiation) as significantly enriched in the altered AD CSF proteome.ConclusionOur findings show the promising potential of AD CSF proteomics as a reliable and robust AD prediction model. We identified proteins and biological pathways that are compromised in AD, thereby, increasing our understanding of AD biology. Our findings may accelerate the development of effective intervention therapies that target the earliest molecular triggers of AD.
App‐based augmented reality to assess cognitive impairment in early Alzheimer’s disease
Authors: Brem Anna‐Katharine , Muurling Marijn , de Boer Casper , Curcic Jelena , Atreya Alankar , Coello Neva , Conde Pauline , Fröhlich Holger , Grammatikopoulou Margarita , Hinds Chris , Lazarou Ioulietta , Lentzen Manuel , Harms Robbert , Bügler Maximilian , Narayan Vaibhav A , Kozak Rouba , Nikolopoulos Spiros , Vairavan Srinivasan , Visser Pieter Jelle , Wittenberg Gayle , Aarsland Dag ,   RADAR‐AD Consortium
Published: December 2023

AbstractBackgroundAugmented reality apps merge real world with virtual experiences and can be used to remotely assess complex instrumental activities of daily living (iADL) that are affected early in Alzheimer’s disease (AD). Our aim was to compare standard clinical measures with an augmented reality app to assess iADL that are related to memory and spatial navigation in early AD and its feasibility in the home‐setting.MethodWe administered an augmented reality app (Altoida Inc., Washington DC, USA) in an on‐going cross‐sectional study (RADAR‐AD: Remote Assessment of Disease and Relapse – Alzheimer’s Disease) in three groups: 1) amyloid negative healthy controls (HC, N = 49); and amyloid positive 2) preclinical AD (PreAD, N = 17); and 3) prodromal AD (ProAD, N = 29) (Table 1). Altoida’s research algorithm DNS‐MCI (Digital Neuro Signature) produces the outcome of a machine learning model trained to identify cognitively normal individuals from those with cognitive impairment). DNS‐MCI reflects performance in app‐based tasks assessing memory and visuo‐spatial function (placing and finding virtual objects, fire drill simulation) further including attention and motor performance (reaction time, finger tapping, navigational trajectory). At baseline, app‐based tasks were performed in the clinic together with a standard neuropsychological assessment and iADL questionnaires (Figure 1). Participants were furthermore given the option of using Altoida in the home environment.ResultThe DNS‐MCI score could significantly distinguish HC and PreAD participants from the ProAD group and was correlated with all neuropsychological tests and iADL questionnaires (Figures 1 and 2). Participants used the app on average 3‐4 times at home (Table 1). Baseline in‐clinic assessments were strongly correlated with at‐home assessments (r = 0.53, p<.001).ConclusionApp‐based augmented reality tasks are applicable in the home setting and successful in capturing cognitive impairment in early AD. Future research should focus on fine graining algorithms to also detect possible subtle impairment in preAD.
This work has received support from the EU/EFPIA Innovative Medicines Initiative Joint Undertaking (grant No 806999). www.imi.europa.eu. This communication reflects the views of the RADAR‐AD consortium and neither IMI nor the European Union and EFPIA are liable for any use that may be made of the information contained herein.
Pharmacological treatment and use of monoclonal antibodies in Alzheimer’s disease: Analysis on a medical management in Argentina
Authors: Guillen Jonathan Cubas , Rojas Galeno , Demey Ignacio , Sarasola Diego , del Hierro Xavier Merchan , Persi Gabriel Gustavo , Aldinio Victoria , de Silva Nahuel Pereira , Boccazzi Julian Fernandez , Seguí Josefina , Muniagurria Santiago , Gilbert Afra , Gatto Emilia 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) is the most common cause of cognitive impairment and dementia. The objective of this work is to describe the pharmacological management of AD and the opinion on future pharmacological therapies in Argentina.MethodA cross‐sectional, descriptive study was carried out. An opinion anonymous survey about pharmacological treatments was designed. The survey was distributed electronically by the Argentine Neurology Society (ANS) to physicians who assessment patients with cognitive disorders (CD). Answers of specialists in CD (SCD) and non‐specialists in CD (NSCD) about recommended treatments (RT), non‐recommended treatments (NRT) and off‐label therapies were analyzed. Physicians who would indicate or were hesitant to indicate anti‐monoclonal beta amyloid protein antibodies (MABs) therapy were considered as potential MABs prescribers. A descriptive statistical and frequency assessment were performed.Result155 physicians (10,3% of the total to whom the questionnaire was directed) were surveyed. A 19,35% indicated at least one NRT for dementia and 78,06% prescribed at least one off‐label therapy or a NRT for mild cognitive impairment (MCI). A 31% would indicate MABs. For the management of psychotic symptoms, the most selected drug was quetiapine (88.4%) and for apathy, escitalopram (32,3%). One hundred physicians (64,5% of the total) were considered potential MABs indicators. Nevertheless, 42% of them were unaware of the adverse effects of MABs. Also, 70% would request biomarkers for brain beta amyloid in the initial assessment. There were significant differences in the responses of the SCD and the NSCD regarding indicating MABs (52.17% vs. 23.08, p<0.05) and considering knowledge of its adverse effects (76.09% vs. 38.46%, p<0.05). There were no significant differences between SCD and NSCD in the prescription for RT, NRT, and off‐label therapies.ConclusionIn the real life, our study shows that two‐thirds of the respondents would be potential MABs prescribers. At the same time, we identified a high rate of NRTs and off‐label medications indications for patients with CD. These results highlight the need for continuous medical education, particularly in low‐income countries such as Argentina considering the cost of biomarkers and the new therapies like MABs for AD and its impact on public health policies.
Trends in the first‐time hospitalisation with dementia: national registry‐based study between 1999 and 2015 from the Czech Republic
Authors: Kučera Matěj 
Published: December 2023

AbstractBackgroundThe number of people living with dementia in Czechia reached 156 thousand in 2015 with dementia in the Czech Republic with the burden of 44.7 billion Czech koruna. According to estimates, prevalence of dementia is supposed to reach 250 thousand by year 2050, but little is known about current trends of dementia incidence. In our study we aimed to identify trends in age‐ and sex‐specific incidence of first‐time hospitalisation with dementia in the Czechia between years 1999 and 2015.MethodData from two national registers in the Czech Republic were used: National Register of Hospitalized Patients and Register of Deaths. Complementary data about population structure per age and calendar year from the Czech Statistical Office for recalculation of the total sample were used. Descriptive analysis was performed to obtain crude and age standardized incidence rates of first‐time hospitalization due to dementia diagnosis. Poisson regression was performed in order to adjust for the calendar year and overall changes in hospitalisation over the study period. In secondary analysis we followed with age stratified crude and sex adjusted models that have been used to estimate the hazard ratio whether a person would receive a hospital diagnosis of dementia per 1 calendar year increase.ResultThe sample consisted of 3 324 399 people (65‐99 years, 57% women). The total amount of first‐time hospitalisations with dementia 164 741. Since 1999 the annual number of new cases increased from 5 433 in 1999 to 14 125 in 2015. The total age‐standardised incidence trends increased statistically significantly over time from 41,80/10 000 in 1999 to 71,30/10 000 in 2015, with a trend of stabilisation in the last three years of the study period. Gender differences have been observed with women having higher incidence rates. Most prominent changes were observed in the oldest 90‐99 age strata.ConclusionOur results provide evidence that number of new patients diagnosed with dementia may be currently stabilising and this trend may continue in future.
bioactive sulfonyl hydrazones with indole scaffold, characterization, adme properties, molecular docking studies and investigation of inhibition on choline esterase enzymes for the diagnosis of Alzheimer’s disease
Authors: Angelova Violina T 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) is a progressive and neurodegenerative disease that is primarily seen in the elderly population and is clinically characterized by memory and cognitive impairment. This study aimed to find new ChE inhibitors.MethodThe structures of the synthesized compounds were characterized by 1H NMR, 13C NMR and HRMS. The effects of the synthesized hydrazones on acetylcholinesterase and butyrylcholinesterase enzymes were measured using the microplate assay described in the Ellman test, with modifications added by López (2002).ResultAccording to the results, all the synthesized compounds inhibited AChE and BChE enzymes. When the IC50 values were compared, the compounds with indole scaffold and donepezil fragment showed potent inhibitory activity on the AChE enzyme. In addition, the predictive properties of all compounds in terms of drug similarity were scanned using five Lipinski rules and ADME. Also, to evaluate the binding interactions between the hydrazone compounds and enzymes, molecular docking studies were performed and the compounds with the best inhibition effect were tested. Promisingly, the compound 3d showed good permeability in the PAMPA‐BBB model and high in vitro antioxidant activity.ConclusionBoth in vitro and in silico results showed that two compounds could act as promising inhibitors of AChE and the data provided the way to guide future studies.FundingThis research was funded by the Bulgarian National Science Fund (Grant KP‐06‐Н63/11 14.12.2022).
Cerebellum Hyperactivity and its cortical connectivity in Alzheimer’s Disease (AD) utilizing FDG PET and Resting State Functional Magnetic Resonance.
Authors: Karunanayaka Prasanna , Ahmed Biyar , Elyan Rommy , Kalra Deepak , Eslinger Paul , Yang Qing 
Published: December 2023

AbstractBackgroundThe role of the cerebellum in Alzheimer’s disease (AD) is not fully understood. There are a few studies that have demonstrated impaired cortical – cerebellar connectivity in AD. Additionally, transgenic mouse studies clearly show amyloid‐β (Aβ) deposition in the cerebellum affecting synaptic transmission and plasticity, sometimes before plaque formation. To characterize metabolic activity in the cerebellum, we analyzed 18F‐fluorodeoxyglucose (FDG) positron emission tomography (PET) and resting‐state functional MRI (rs‐fMRI) data in AD, mild‐cognitive impaired (MCI), and age‐matched cognitively normal (CN) subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Our focus was on the intrinsic functional connectivity of the cerebellum with three brain networks: the default mode network (DMN), dorsal attention network (DAN), and the primary olfactory cortex (POC) in the medial temporal lobe. We hypothesized that the resting state functional connectivity of cerebellar regions (that showed differential FDG metabolic activity) would exhibit impaired brain‐wide network connectivity.MethodA group of 272 ADNI subjects (CN = 80, MCI = 149, AD = 43) with FDG‐PET scans were analyzed in this study. All 272 subjects did not have consistent rs‐fMRI data therefore, we analyzed 160 subjects (CN = 80, MCI = 84, AD = 29) that had consistent rs‐fMRI data acquisition parameters. The PET preprocessing was performed in SPM12. Partial volume correction was performed using the Van‐Cittert deconvolution technique. The rs‐fMRI data was preprocessed in DPABI; PET and rs‐fMRI data were normalized to the Montreal Neurological Institute template. DMN and DAN masks were downloaded from neurovault.org. The Statistical analyses were performed in DPABI.ResultThe SPM group analysis of PET data identified crus II, right cerebellum 4,5 and vermis lobule 6 as hyperactive (increased glucose metabolism) in AD and MCI compared to CN (Figure 1). Subsequent analyses identified brain regions within the DMN, DAN, and POC that are correlated with hyperactive cerebellar regions. Similarity analyses detected impaired resting state functional connectivity of hyperactive cerebellar regions with the three brain networks (Figure 2).ConclusionThe hyper‐metabolism in the cerebellum may reflect disruption of local and brain‐wide network connectivity due to neurodegeneration. Observed hyper‐metabolism may be related to inhibitory dynamics of the cerebellum — providing a hypothetical mechanism to explain the susceptibility of brain networks in AD.