bluuebunny/crossref_metadata_2025_split huggingface dataset:
“Continu‐A‐Mente”: continuity of care between hospital and community for people living withdementia and their caregiver with Tailored Activity Program
Authors: Pozzi Christian , Staglianò Andrea , De Ponti Chiara , Ballabio Claudia , Bartoli Federica , Antolini Laura , Ferrara Maria Cristina , Morandi Alessandro , Cavalli Stefano , Gitlin Laura N. , Bellelli Giuseppe 
Published: January 2025

AbstractBackgroundNonpharmacological approaches have been identified as first line treatments for the behavioral and psychological symptoms (NPS) of persons living with dementia (PLWD).MethodsThis is a single‐arm study to evaluate the feasibility of the TAP approach to promote continuity of care between hospital (S. Gerardo hospital ‐ Italy) and community. Inclusion criteria were presence of NPS; autonomy in activities of daily living (Katz’s index ≥ 2); presence of caregiver. On recruitment, PLWD underwent a multidimensional assessment, Clinical Frailty Scale (CFS), Neuropsychiatric Inventory (NPI), Katz’s Index, Timed‐Up‐and‐Go‐test (TUG), number of drugs taken by the patient and caregiver’s sense of competence (SCQ questionnaire). After recruitment, the dyad PwD+caregiver received 8 TAP sessions performed by two occupational therapists, at hospital (two sessions) and at home (6 sessions). Follow‐up was set after 4 mouths. The attrition rate (% of dropouts) was the primary outcome.Results51 patients identified as potentially eligible, 21 declined to participate in the project. Currently, 30 dyads have been recruited, with 16 having completed the follow‐up. Overall, there were 6 (20%) dropouts. The mean patient’s age was 81 ±4.8 years. The median CFS patient’s score was 6 and half of patients were taking more than 7 medications per day. Wilcoxon signed‐rank test was conducted on the 16 dyads. From baseline to follow‐up (median, IQR 75%‐25%), there was a significant reduction in the NPI total score (NPI baseline = 17 (10.7‐33.2) NPI follow‐up 15.7 (8‐2 – 24.0), p = .002), caregiver distress (NPI caregiver distress baseline = 9.5 (6.0‐17.0); NPI caregiver distress follow‐up 6.5 (2.2‐11.5); p = .003) and TUG score (TUG baseline = 18.0 (13.0 – 35.5); TUG follow‐up 13.4 (10.5‐21.5); p = .007). Moreover, there was a significant decrease in the SCQ scale (SCQ baseline = 49.0 (44.0‐64.5) SCQ follow‐up 43.0 (36.5‐56.5); p = .001). No patient experiences hospital admissions at follow‐up while 3 patients had accessed emergency department.ConclusionsPreliminary data are very promising and in line with what was hypothesized in the clinical trial design phase. TAP may be a valuable aid in monitoring the BPSDs of PLWD and avoiding re‐hospitalizations.
Depression and cardiovascular symptoms in a diverse Frontotemporal Dementia cohort, enriched for Caribbean Hispanic patients
Authors: Martinez Anisley , Gu Tianjie , Illanes‐Manrique Maryenela Z. , Tejada Sergio J. , Mena Pedro R. , Acosta Heriberto , Camargo Christian , Sun Xiaoyan , Alfonso Michelle Marrero , Baumel Bernard , Cornejo‐Olivas Mario , Castro‐Suarez Sheila , Vance Jeffery M. , Cuccaro Michael L. , Pericak‐Vance Margaret A , Nuytemans Karen 
Published: January 2025

AbstractBackgroundMost biomedical data currently available for any disease is derived from studies in non‐Hispanic white (NHW) populations. Specifically, clinical information, genetics as well as biomarkers for frontotemporal dementia (FTD) have been studied predominantly in those NHW populations. For example, a role for depression and cardiovascular symptoms in increased risk for cognitive impairment has been reported; but little information is available on their risk effect in (diverse) FTD.MethodOur current cohort consists of 135 FTD patients (71% Hispanic, 21% NHW, 6.5% Black/African American), with continuing enrollment from University of Miami (FL), Caribbean Center for the Study of Memory and Cognition (PR) and Instituto Nacional de Ciencias Neurologicas (Peru). All patients were evaluated using NACC Uniform DataSet or equivalent in their preferred language; ∼53% of the cohort also completed the FTD module forms. We compared clinical presentation (age‐at‐onset, ratio behavioral to language variant) in NHW versus Hispanic patients. Additionally, we studied association of Clinical Dementia Rating (CDR) scores with cardiovascular symptoms and depression (Geriatric Depression Score or Cornell Score for Depression).ResultWe did not identify a significant difference in age‐at‐onset, global CDR or ratios of behavioral FTD (bvFTD) versus primary progressive aphasia (PPA) as first symptoms between the NHW and Hispanic patients. We observed association of depression with global CDR≥2, across all patients (p = 0.003) and in Hispanic or Black/African American patients specifically (both p∼0.04). This difference was not driven by bvFTD or PPA subtypes specifically. No significant association was observed for global CDR with diabetes, hypertension or hyperlipidemia in all, Hispanic or NHW patients.ConclusionBiomedical research of FTD in underrepresented population groups is necessary as data from research in NHW is not always generalizable across race/ethnicity. Our data suggests that the reported association of depression with higher CDR scores is valid in diverse FTD patient groups; whereas we see less evidence for cardiovascular symptoms being associated with risk for FTD. We are working to expand our efforts characterizing the full clinical and biological presentation of FTD in non‐NHW population groups. The biomedical characterization of FTD across race/ethnicity will help the understanding of disease mechanisms in all patients, ultimately preventing further health disparities.
Knowledge and barriers to implementing dementia risk reduction among older people and health professionals in community daycare centers
Authors: Aravena Jose M , Torres Waldo , Gallardo Javiera , Sobarzo Fernanda , Saavedra Gillian , Briceño Rocio , Miranda Camilo , Levy Becca R 
Published: January 2025

AbstractBackgroundAssessing knowledge of dementia prevention from both the individual (patients) and the structural level (health professionals) in the same settings is vital to implementing dementia risk reduction programs. However, most studies have only focused on one level. Thus, this was the aim of our study.MethodA qualitative study was conducted with two populations: patients aged 60 and older with no dementia and health professionals, attending and working at community daycare centers for older adults in Chile, respectively. People from 10 different daycare centers were invited to participate in two separate focus groups per center (patients: 5‐15 participants; health professionals: 3‐7 participants). Focus groups included the topics of cognitive changes of aging and dementia, dementia risk factors, and barriers to brain health. Thematic analysis following grounded theory and inductive analysis was performed to generate main themes.ResultIn 19 focus groups, 115 patients and 51 health professionals participated. In the main results, older adults frequently mentioned memory problems as a ‘normal part of aging’ and Alzheimer’s disease as ‘the severe stage of dementia.’ Health professionals recognize signs and symptoms of dementia. Both groups agreed that uncertainty about memory loss and Alzheimer’s disease can generate anxiety and isolation in older people. Patients showed more agreement on dementia risk factors than health professionals and were able to mention risk factors not mentioned by health professionals (e.g., TBI, air quality, neighborhood factors). Patients from high‐income municipalities were more prone to attribute Alzheimer’s disease to genetic factors than patients from other municipalities, but health professionals showed no differences. Interestingly, patients used popular figures in media with a diagnosis of dementia (e.g., Ronald Reagan) as examples of why ‘Alzheimer’s disease can’t be prevented.’ Structural barriers to brain health were similar between groups (negative experiences with healthcare and ageism). Patients referred to intergenerational contact and health professionals increasing awareness among patients' families as opportunities for brain health.ConclusionHealth professionals highlighted the need for updates and homogenization regarding dementia risk reduction. Patients’ knowledge may be influenced by social determinants and portraits of aging and brain health. Addressing structural factors could benefit dementia prevention in both groups.
Improper modification and cleavage leads to irregular aggregation of TDP‐43 in Neurons
Authors: Xavier Joyal , Singh Meenakshi , Tamhankar Sampada P , Amin Raj 
Published: January 2025

AbstractBackgroundTAR‐DNA‐binding protein 43 (TDP43), is a pathologic marker in neurodegenerative diseases including frontotemporal lobar degeneration and amyotrophic lateral sclerosis. The aggregation of TDP‐43, a crucial RNA‐binding protein, is a consequence of post‐translational modifications (PTMs) that disrupt its normal function. PTMs such as phosphorylation and ubiquitination contribute to the aberrant accumulation of TDP‐43 aggregates, leading to neurodegenerative disorders like amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). This pathological process disrupts RNA metabolism and cellular homeostasis. The current study focuses on better understanding the mechanisms associated with TDP‐43 PTMs and aggregation. Findings from these studies are essential for developing targeted therapeutic strategies to mitigate neurodegenerative diseases associated with TDP‐43 pathology.MethodOverexpressing TDP‐43 in Ht22 hippocampal cells was accomplished by Lentiviral technology. TDP‐43 GFP over‐expressing stable cell lines were exposed to either an acidic environment (pH 6) or a neutral environment (pH 7.4) or sodium arsenate. Mitochondria, nuclei, and cytosolic fractions were isolated, and proteins were resolved by Western analysis to measure levels of TDP43. Asparaginyl endopeptidase (AEP) inhibitor (Compound 11), was used to determine its effect on aggregation of TDP43. The Aggregation assay kit was used to measure the levels of TDP‐43 aggregation. Physiological assays were used to measure the consequence of TD43 aggregation in the mitochondria (Seahorse, mitochondrial respiration) and nuclei (transcriptome analysis).ResultWe have observed the localization of AEP in the mitochondria under normal physiological pH conditions as well as total and cleaved TDP43. However, under acidic conditions and following sodium arsenate exposure, we observed an increase in pTDP43 levels as well as full‐length TDP43 in the mitochondria and nucleus when compared to normal media. Alternatively, we observed a decrease in pTDP43 in the mitochondria and nucleus following compound 11 treatment in the acidic media or sodium arsenate.ConclusionWe observed an increase in pTDP43 in cells exposed to an acidic environment. We believe this leads to aggregation levels and helps explain the consequences of cleaved TDP43 on cellular energy regulation and cell viability. Consequently, compound 11 reduces the levels of TDP43 aggregation patterns in the mitochondria and nuclei.
Development of a multi‐faceted intervention for hearing/vision support for residents with dementia in long term care'
Authors: Leroi Iracema 
Published: January 2025

AbstractContextThe development of new effective and sustainable dementia care interventions requires active engagement of all service users in research studies. This ensures that interventions are tailored to meet individual needs and preferences. Here, we describe modelling and development of a multi‐faceted sensory health support intervention for residents with dementia in long‐term care, co‐designed with dementia care users and their supporters. There is a high rate of unrecognised hearing and vision loss in people with dementia, particularly in long term care (LTC) settings, which can hasten cognitive and functional decline, contribute to neuropsychiatric challenges, and increase the impact on health resource utilization.MethodsWe undertook a multistage process with key user stakeholders, interdisciplinary health experts, LTC professionals, and Patient and Public Involvement (PPI) representatives, following the UK’s Medical Research Council’s framework for the development of complex interventions.In the first stage, we crafted an outline of the intervention by extending a previously evaluated home‐based sensory support intervention and incorporating evidence from a systematic survey of hearing rehabilitation interventions. The ‘Sensory‐Cognitive Model of Place’ served as the theoretical framework.In the second stage, qualitative feedback from professional and PPI stakeholders, along with insights into existing care sensory health training approaches, were integrated to form a multi‐component sensory support intervention ready for field testing.The third stage involved pilot‐feasibility trialing in a single LTC facility, with subsequent design modifications based on feedback.The resulting Sensory Support Intervention for Residents with Dementia in Care (SSI‐RC) comprises four tiered components addressing (1) resident, (2) staff, (3) environmental, and (4) organizational levels. These include personalized sensory health status checks, staff awareness training, sensory environment audits, and organizational pathway assessments.ConclusionWith the guidance of service users, we successfully developed and field tested the SSI‐RC, highlighting its potential for implementation in a cluster‐randomized pilot trial in LTC facilities. The collaborative approach with dementia care users and supporters ensures the intervention’s relevance and effectiveness in enhancing sensory‐cognitive health for residents with dementia. The research contributes to the broader goal of tailoring dementia care interventions to individual needs and preferences.
Boost Your Brain Health: Methods and Baseline Characteristics for a Randomized, Controlled Trial of an Online Study to Reduce Dementia Risk Factors
Authors: Turo Patricia , Benjamin Cynthia , Brodaty Henry , Sudore Rebecca L , Chesney Margaret A , Chao Linda L , Barnes Deborah E 
Published: January 2025

AbstractBackgroundNearly 1 in 3 older adults are living with mild cognitive impairment (MCI) or subjective cognitive decline (SCD), which places them at increased risk of developing Alzheimer’s disease or related dementias (ADRD). Behavioral interventions can improve cognitive function and reduce dementia risk factors, but most are in‐person and time‐intensive. We are conducting a randomized, controlled trial to assess the impact of 12‐ and 24‐week online interventions on cognitive function and dementia risk.MethodStudy participants are English‐speaking adults aged 55 years or older living in the U.S. who self‐report MCI or SCD, have 2 or more modifiable ADRD risk factors, and have an electronic device with video camera to participate in online classes. Participants are randomized to Brain Health Academy (asynchronous expert videos, 30 hours over 12 weeks), Brain Health Together (synchronous group Brain Health Education and Moving Together classes + individual brain health coaching, 30 hours over 12 weeks), or Brain Health Together Plus (Brain Health Together plus an additional 12 weeks of group classes and individual brain health coaching, 45 hours over 24 weeks). We used descriptive statistics to summarize self‐reported demographics and motivators and barriers to participation.ResultOf 397 individuals who have completed screening, 40% were ineligible, 25% declined, and 35% enrolled and have been randomized to date. Enrolled participants have a mean (SD) age of 70 (8) years and 3 (1) modifiable risk factors; 75% are female, 24% are non‐White or Hispanic, and 23 states from across the US are represented. The greatest motivators to study participation are wanting to keep one’s brain as healthy as possible (89%) and being worried about changes to memory or thinking (81%). Time commitment was perceived as the greatest barrier (30%). Most participants indicated they were already making changes to improve brain health.ConclusionMany older adults with MCI/SCD and modifiable risk factors for ADRD are interested in participating in online brain health programs and are highly motivated to make lifestyle changes to keep their brains healthy. We anticipate that enrollment will be completed by May 2024.
Activation of the glutamate transport in astrocytes via GLT‐1 reshapes the glutamatergic brain network
Authors: Martins Gabriel Colissi , Limberger Christian , Peixoto Guilherme G. Schu , Aliaga Antonio , Aliaga Arturo Aliaga , Rosa‐Neto Pedro , Zimmer Eduardo R. 
Published: January 2025

AbstractBackgroundGlutamate is the main excitatory neurotransmitter in the brain, acting through ionotropic and metabotropic receptors, such as the neuronal metabotropic glutamate receptor 5 (mGluR5). The radiotracer [11C]ABP688 binds allosterically to the mGluR5, providing a valuable tool to understand glutamatergic function. We have previously shown that neuronal [11C]ABP688 binding is influenced by astrocyte activation. Specifically, the activation of glutamate transport in astrocytes via glutamate‐transporter‐1 (GLT‐1) results in an elevated [11C]ABP688 binding within the ventral anterior thalamus, but no changes in other regions. However, whether changes at the network level occur remains elusive. We evaluated Glutamatergic Brain Networks (GBNs) before and after activating astrocytes.MethodMicro‐PET acquisitions were performed in adult Sprague‐Dawley rats (n = 5) at baseline and after a pharmacological challenge to activate astrocytes. Before the scan, rats received either saline (vehicle) or ceftriaxone (CEF, 200mg/kg), an antibiotic that induces GLT‐1 activation. Then, [11C]ABP688 was administered i.v., followed by a 60‐minute dynamic scan. The nondisplaceable binding potential (BPND) was estimated using the simplified reference tissue model, with the cerebellum as a reference region. [11C]ABP688 BPND was extracted for 12 volumes of interest. GBNs based on [11C]ABP688 regional BPND were assembled with a multiple sampling scheme in MATLAB (p‐value < 0.05).ResultAstrocyte activation induced GBN hyperconnectivity after astrocyte activation, with the strength of association between the cerebral hemispheres, such as in the frontal and parietal cortices (Figure 1, A‐B). After GLT‐1 activation, the connections were diffused, including regions that were not part of the network at baseline, such as the cerebellum. Graph measures show a significant increase in global efficiency, average degree, density, and average clustering coefficient (Figure 1, C‐G). These measures indicate an increase in connections and network cohesiveness. The reduction in assortativity can be related to the new regions on the GBN after the challenge.ConclusionOur results show that GBNs assessed with [11C]ABP688 are sensitive to astrocyte activation. Alterations in glutamate levels, as observed in dysfunctions like glutamatergic excitotoxicity present in AD, could disrupt the cohesion of the glutamatergic network, leading to brain dysfunction.
Modifier Effects of APOE E2 and E4 Alleles on the age at onset of Alzheimer Disease in Puerto Rican G206A Mutation Carriers: A Family‐Based Study
Authors: Kannappan Balaji , Cheng Rong , Nguyen Tu , Jimenez‐Velazquez Ivonne Z. , Piriz Angel , Maldonado Aleyda , Vardarajan Badri N. , Reyes‐Dumeyer Dolly , Lantigua Rafael A. , Jin Zhezhen , Mayeux Richard , Lee Joseph H. 
Published: January 2025

AbstractBackgroundAPOE E4 (APOE4 henceforth) is recognized as a major genetic risk factor for late‐onset Alzheimer's disease (AD), with its impact varying across ethnic subgroups. We investigate the risk of APOE4 and the protective effect of APOE E2 (APOE2 henceforth) in individuals carrying the high‐risk G206A mutation in the PSEN1 gene (G206A henceforth), known to cause early‐onset AD. Despite the G206A mutation's strong association with AD, there is noticeable variability in age at onset among carriers. We aim to elucidate the modifying effects of APOE2 and APOE4 alleles on age at onset for AD among G206A carriers and non‐carriers, accounting for known confounders and their genetic background differences.MethodThis study examined the modifying effects of APOE2 and APOE4 on the risk of AD onset between non‐carriers and carriers of the G206A mutation using multivariable Cox proportional hazards models, examining 505 individuals from 87 Puerto Rican families. We further examined whether APOE2 or APOE4 behave differently in the 2 ethnic subgroups: the Hispanic Whites (H‐White) vs. Hispanic Non‐Whites (H‐Non‐Whites).ResultAs expected, the G206A consistently showed a significant increase in AD risk (HR=10.61, p=9.60E‐30). When APOE4 was examined together with the G206A, it weakly increased the risk (HR=1.72, p=1.81E‐3), while APOE2 showed a weak protective effect but was not significant (HR=0.83, p=0.53). We then examined the APOE effects in ethnic subgroups. Given the small sample size in the H‐Non‐Whites, we compared the mean age at AD onset rather than computing HR. For H‐Whites carrying both G206A‐APOE2, the average age at onset was 60.3 years. Among H‐Non‐Whites, there was only one G206A‐APOE2 carrier, and this person remained unaffected until 87.5 years. Although based on a single case, this significant delay in AD onset signals a potentially critical area for future research in understanding the mechanisms behind the APOE2 protective effect.ConclusionThe APOE2 allele shows protective effects on AD onset in G206A carriers, specifically in H‐Non‐Whites. A single case of late‐onset in a H‐Non‐White G206A‐APOE2 carrier highlights the need for in‐depth research into APOE2's role across ethnicities. G206A notably heightens the risk of early AD onset, with APOE4 contributing moderately.