bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pilot trial of Dronabinol adjunctive treatment of agitation in Alzheimer’s disease (THC‐AD)
Authors: Rosenberg Paul B. , Outen John D. , Amjad Halima , Burhanullah Haroon , Vandrey Ryan , Nowrangi Milap A. , Schultz Meghan , Isesalaya Maria , Castaneda Ricardo , Agronin Marc , Walsh Patricia , Drury Mia , Ozonsi Rosain , Cohen Leah , Wilkins James M. , Harper David G. , Forester Brent P. 
Published: June 2023

AbstractBackgroundAgitation in Alzheimer’s Disease (Agit‐AD) is a common and troubling neuropsychiatric syndrome which adds significantly to disability and caregiver stress. Behavioral interventions lack consistent efficacy and there are no FDA‐approved medications. Neurobiological mechanisms that contribute to Agit‐AD include brain atrophy, degradation of neurotransmission, neuroinflammation, disrupted circadian rhythms, comorbidities and frailty. Agit‐AD is a major source of disease progression, patient disability, financial burden, and caregiver stress. Dronabinol is a synthetic cannabinoid (tetrahydrocannabinol, THC). Cannabinoids may improve Agit‐AD by providing protection against neuroinflammation and excitotoxicity, regulating neurotransmitters, improving comorbidities, stabilizing circadian rhythms, and increasing cerebral blood flow.MethodTHC‐AD is a three‐week placebo‐controlled, double‐blind, RCT of dronabinol (10 mg QD) in 80 patients with severe Agit‐AD. Twice daily administration maximizes daytime coverage for agitation and minimizes sundowning. Inclusionary criteria include a diagnosis of AD, severe agitation, and being 60‐95 years old, while exclusionary criteria include serious or unstable medical illness, seizure disorder, delirium, current use of lithium, and inability to swallow a pill. Primary outcomes include a change in the Pittsburgh Agitation Scale and NPI‐C Agitation/Aggression subscales.ResultWe have enrolled 58 out of targeted 80 participants (Table 1: mean age 77.8 years, 65.5% female, 87.9% Caucasian, mean education 13.8 years, 45.6% family history). On average, study participants are very cognitively impaired (Table 2: mean baseline MMSE of 8.1), very agitated (mean NPI‐C Agitation 14.6, mean NPI‐C Aggression 6.3) and in reasonable overall health (Figure 1: General Medical Health Rating, 12.1% “excellent,” 51.7% “good” and 34.5% "fair”). Recorded AEs have been tolerable (Figure 2). Due to the COVID‐19 pandemic, we expanded our inpatient trial to include outpatient enrollments and implemented hybrid visits with telemedicine to limit in‐person interactions. We also added a supplemental study to evaluate the effects of the pandemic on caregiver stress and burden. We are collaborating with additional clinical sites, increasing dementia bed capacity, and deploying recruitment strategies for outpatients, including referrals from providers and other research trials, social media ads, and virtual community outreach.ConclusionSafe and effective interventions for severe agitation are greatly needed. This pilot trial will help to examine the safety and efficacy of dronabinol for Agit‐AD.
Creutzfeldt‐Jakob Disease (CJD): Time from Symptom Onset Until Subnormal Magnetic Resonance Imaging (MRI) of brain
Authors: Shergelashvili Tea , Chabrashvili Tinatin 
Published: June 2023

AbstractBackgroundAbnormal MRI of brain is one out of three supportive diagnostic criteria for CJD along with abnormal EEG and positive 14‐3‐3 protein when there is rapidly progressive dementia (RPD), myoclonus, visual or cerebellar disturbance, pyramidal or extrapyramidal dysfunction, akinetic mutism. MRI can be normal in CJD even when the symptoms are advanced posing a diagnostic challenge. The goal of this study was to review cases of RPD suspected to be due to CJD and correlate with the diagnostic findings.MethodsCohort of patients with RPD and/or neuropsychiatric presentation suspicious for CJD over the 10 years at our institution was identified using EPIC Slicer Dicer tool to search electronic medical records. Clinical presentation and diagnostic markers including CSF (protein 14‐3‐3, RT‐QuIC, total‐tau), MRI and EEG findings were analyzed to determine the sensitivity of each at early disease state.ResultsTotal of 25 cases suspected of CJD were identified. 4 patients were confirmed to have probable CJD based on positive RT‐QuIC, protein 14‐3‐3 and elevated total‐tau. Initial suspicion for CJD was later not considered high enough to pursue CSF analysis in 4 patients. 1 patient didn’t have CSF study done due to technical error. 16 patients were tested negative for RT‐QuIC. Out of the 16 patients 4 had elevated protein 14‐3‐3, out of which 3 had elevated total‐tau. Out of 25 patients 24 had MRI, 1 couldn’t undergo MRI due to MRI incompatible cardiac pacemaker. Out of 24 patients 4 had findings suggestive of CJD on the initial MRI, 2 of them confirmed to have CJD based on CSF studies. 2 patients had normal initial MRI despite multiple symptoms of CJD. The first patient developed classic findings for CJD on repeat MRI 8 months from symptom onset and the 2nd had such MRI changes 4 months from symptom onset. These 2 patients had diagnosis confirmed by positive RT‐QuIC, 14‐3‐3 protein and elevated total‐tau.ConclusionWhile abnormal MRI findings support the diagnosis of probable CJD in the correct clinical setting, negative test results don’t exclude diagnosis of CJD. CSF markers and a repeated brain MRI are instrumental for correct CJD diagnosis.
Association between 10‐year cardiovascular mortality‐risk and neuroimaging biomarkers in the FINGER trial
Authors: Stephen Ruth , Hossain Gazi Saadmaan , Hall Anette , Barbera Mariagnese , Ngandu Tiia , Liu Yawu , Kemppainen Nina , Strandberg Timo , Antikainen Riitta , Lötjönen Jyrki , Rinne Juha O. , Tuomilehto Jaakko , Peltonen Markku , Vanninen Ritva , Soininen Hilkka , Kivipelto Miia , Solomon Alina 
Published: June 2023

AbstractBackgroundCardiovascular risk factors are associated with cognitive decline and dementia. Timely estimation and targeting of cardiovascular risk burden may contribute towards the prevention of cognitive decline. The cardiovascular risk scores of the European Society of Cardiology’s, SCORE (for adults up to 64 years) and SCORE‐OP (for older adults aged 65 years or more), are commonly used tool for estimation of 10‐year CVD mortality and may reflect the impact of cardiovascular risk burden on brain pathology if validated against neuroimaging biomarkers.MethodThis study investigated associations between (i) baseline SCORE/SCORE‐OP and baseline neuroimaging biomarkers (brain magnetic resonance imaging [MRI] and Pittsburgh Compound B‐positron emission tomography [PiB‐PET] measures) (ii) change in SCORE/SCORE‐OP and change in neuroimaging measures during the 2‐year Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER). FINGER targeted at‐risk older adults, aged 60‐77 years, from the general population. Participants were randomized to either multidomain intervention (diet, exercise, cognitive training, and vascular risk management) or control group (general health advice). Neuroimaging (MRI and PiB‐PET) data from baseline and 2‐year visits were used. A total of 112 participants had repeated brain MRI measures (hippocampus, total grey matter, and white matter lesion volumes, and Alzheimer’s disease signature cortical thickness). Repeated PiB‐PET scans were available for 39 participants.ResultPreliminary results suggest that at baseline higher SCORE/SCORE‐OP, indicating increased risk of CVD mortality was significantly associated with lower hippocampus volume (estimate = ‐0.010; p = 0.004), lower total grey matter volume (estimate = ‐0.016; p = 0.007), higher white matter lesion volume (estimate = 0.048; p = 0.015), and lower AD signature cortical thickness (‐0.004; p = 0.048) but not with PiB‐PET. No significant associations were found for change in neuroimaging measures and baseline SCORE/SCORE‐OP or change in SCORE/SCORE‐OP during the 2‐year follow‐up.ConclusionCardiovascular risk scores need to be validated against different brain pathology markers in diverse populations. This will enable more precise identification and estimation of dementia risk profiles, guiding at‐risk persons to precise intervention strategies, good for both, heart, and brain.
IPSC‐derived neurons with amyloid‐β treatment reflect features of Alzheimer’s disease patients
Authors: Shi Liu , Rowland Helen A , Ribe Elena Maria M , Koychev Ivan , Nevado‐Holgado Alejo J , Buckley Noel , Lovestone Simon ,   Deep and Frequent Phenotyping study
Published: June 2023

AbstractBackgroundThere is increasing evidence showing that induced pluripotent stem cells (iPSC)‐derived brain cells recapitulate disease‐relevant processes in patients with Alzheimer’s disease (AD). However, it remains unclear to what extent iPSC‐derived neurons treated with amyloid‐β (Aβ) reflect patient Aβ burden and other endophenotypes as determined by changes in protein expression.MethodTo investigate this, we firstly generated iPSC lines from 14 individuals with AD from the Deep and Frequent Phenotyping (DFP) pilot cohort. All of these individuals had undergone clinical measures (i.e. Mini Mental Score Examination) and neuropathological measures (i.e. Aβ, p‐tau and tau). We then differentiated these lines into cortical neurons and treated them with Aβ oligomers. We collected both cell media and cell lysates and measured over 5000 proteins in these samples using SOMAscan assay. In addition, proteins in the cerebrospinal fluid (CSF) and plasma of the same individuals were also measured using the same assay.ResultUsing Wilcox test, we identified 627 proteins that were differentially expressed in neuronal cultures under Aβ oligomers treatment after multiple correction. These proteins were significantly enriched in 14 pathways such as TGF‐β signaling pathway, Ras signaling pathway and MAPK signaling pathway etc. From protein co‐expression network analysis, we identified 12 modules (ranging from 45 to 2029 proteins) in neuronal cultures. Of them, eight were significantly associated with at least one endophenotype of the amyloid/Tau/Neurodegeneration/Cognition AT(N)C framework. We further checked the replication of these modules in human. We found that eight and nine modules were significantly preserved in CSF and plasma, respectively. Furthermore, some preserved modules were also significantly associated with some AD endophenotypes including Aβ.ConclusionThese results suggests that iPSC‐derived neurons with Aβ treatment reflect the patients’ endophenotypes, indicating that their use in capturing disease‐relevant processes in AD.
A national program to advance dementia research in Vietnam
Authors: Vu Huyen Thi Thanh , Pham Thang , Nguyen Thu Thi Hoai , Nguyen Anh Trung , Nguyen Huong , Nguyen Tuan Anh , Hinton Ladson 
Published: June 2023

AbstractBackgroundAs Vietnam and other low‐ and middle‐income countries (LMIC) experience a rapid increase in people living with Alzheimer’s disease and related dementias (ADRD), an acute need exists to strengthen research capacity to inform policy, improve care and supports, and develop of national dementia plans. We describe the development and early outcomes of an NIH/NIA‐funded national ADRD research capacity building program in Vietnam.MethodThe research capacity building program has three components: a mentored pilot grant program, research training and networking activities, and dissemination. The pilot grant program funds Vietnamese researchers for 1‐2 years to conduct research focused on ADRD research broadly defined. Each funded investigator is paired with an international expert who serves as a mentor. Grants are reviewed and scored using NIH criteria and priority is given to pilot grants with policy relevance and potential for future funding. Training and networking activities include workshops on ADRD research topics and regular meetings in conjunction with Vietnam’s annual national dementia conference. Dissemination is facilitated through targeted outreach and the creation of a national network of institutions.ResultOver the first three years (2019‐2022) of this five year program, we reviewed 46 applications and selected 17 for funding (4‐6 per year). Funded investigators were from diverse disciplines (e.g., geriatrics, neurology, neuropsychology, nursing, pharmacy, social work) and institutions across Vietnam with projects on a range of topics, including biomarkers, prevention, diagnosis, neuropsychological assessment, family caregiver support, dementia education, and clinical trials. An international pool of high‐income country (e.g., United States, Australia, United Kingdom) mentors has been engaged and mentors paired with each funded project. Research training has included 2 workshops at national conferences and 3 webinars that have features international speakers. A network of 11 leading academic and research institutions nationwide (i.e., Northern, Central, and Southern Vietnam) has been created to facilitate dissemination. The program has adapted to meet the challenges of the COVID‐19 pandemic. Additional process and outcome assessments of the program are planned.ConclusionThis research capacity building program is the first of its kind in Vietnam and may serve as a useful model for other LMIC.
An internet‐based support program for family caregivers of community‐dwelling people with dementia: A pre‐post pilot study
Authors: Park Myonghwa , Jung Jihye , Kim Jinju , Kim Jahyeon , Giap Thi‐Thanh‐Tinh , Dlamini Bonkhe Brian 
Published: June 2023

AbstractBackgroundCaregivers of people with dementia faces difficulties while constantly caring for their loved ones. Providing support programs should consider for promoting their experience of caregiving, quality of care, and will lead to delay institutionalization of dementia people. Implementing onsite support programs meets obstacles during the Covid‐19 pandemic, internet‐based interventions could be considered as a potential alternative.MethodsThis is a pre‐post pilot intervention study for primary family caregivers of community‐dwelling people with dementia. The 8‐week intervention program was delivered to the participants using ZOOM meetings software. This program consisted of 8 modules (one for each week): 1) reflecting on my caregiving journey, 2) understanding about dementia as a caregiver, 3) taking care of myself, 4) managing stress, 5) communicating with others, 6) learning how to take care of dementia people, 7) pleasant daily life, and 8) planning my caregiving journey. To assess the effects of the program, five caregiver’s outcomes were measured: Positive Aspects of Caregiving, (PAC), Caregiving Self‐Efficacy Scale (CgSES), Perceived Stress Scale (PSS), Health Risk Behaviors (HRB), and satisfaction.Results20 caregivers participated and 18 fully completed the pilot program. The participants have the mean age is 70.6, and 3.5 years playing the role of a family caregiver. The study findings found that the program significantly improved the PAC (P = .001), PSS (P = .027), and three sub‐domains of HRB: physical health (P < .000), mental health (P = .048), and leisure activities (P = .023). Whereas, though scores of the CgSES, and three remaining sub‐domains of HRB: care difficulty, building relationships, and getting help from others were better at the posttest compared with the pretest, these changes were not statistically significant. The participants scored 4.72 (maximum is 5) for their satisfaction with the program.ConclusionThis intervention program successfully improved quality of life and experience of the family caregivers related to their caregiving. Such online programs are a feasible solution in delivering supports to a huge subject anywhere while still mandated social distancing in this unpredictable Covid‐19 pandemic. Therefore, expanding this pilot should be considered.
The predictability and plausibility effects on N400 reflect the language deficit in patients with mild cognitive impairment
Authors: Chou Chia‐Ju , Liu Yi‐Chien , Lee Chia‐Ying 
Published: June 2023

AbstractBackgroundReliable markers of language decline in patients with amnesic mild cognitive impairment (aMCI) are critical for the early detection of Alzheimer’s disease. However, language impairments may be subtle and difficult to be detected from behavioral performance measures. N400 is an Event‐Related Potentials (ERP) component to index the semantic processing and has been used to reflect the deficit of language comprehension in aphasic patients (Chang et al., 2016). This study manipulated the predictability and plausibility of the Chinese classifier‐noun agreement to examine whether these two effects on N400 may serve as potential markers for the early detection of aMCI.MethodThis study recruited 16 MCI patients and 17 age‐matched healthy elders from the memory clinic of Cardinal Tian Hospital in Taiwan. All participants received [18F] florbetaben PET and a set of standardized cognitive tests, including Mini‐Mental State Examination (MMSE), verbal fluency, and Wechsler Memory Scale‐III (WMS‐III), for MCI diagnosis. The positivity rate of the aMCI group was 43.75%, and 31.25% for the healthy elder group. During the ERP recording, participants would read a series of classifier‐noun phrases, and each classifier was paired with a highly predictable, a low predictable, or an implausible noun.ResultWe performed the Linear mixed models to examine whether the predictability effect (high vs. low predictable nouns) and plausibility effect (high vs. implausible nouns) on N400 (300‐500ms) would be explained by the particpants’ cognitive performance. The data revealed that participants with higher scores of MMSE (b = ‐0.019, SE = 0.010, t = ‐1.969), verbal fluency (b = ‐0.023, SE = 0.008, t = ‐2.781), and WMS‐III (b = ‐0.002, SE = 0.001, t = ‐2.370) showed more pronounced predictability effects, which reflecting better semantic integration processing. Meanwhile, participants with poor memory engendered a reduced plausibility effect (b = ‐0.004, SE = 0.001, t = ‐3.972).ConclusionOur findings suggest that MCI patients would exhibit a deficit in semantic process. The predictability and plausibility effects on N400 may serve as ERPs markers to detect the language deficits in aMCI.
[18F]TRACK, a PET tracer for imaging of tropomyosin receptor kinases (Trk): Efficient radiosynthesis and preliminary evaluation in the TgF344‐AD rat model of Alzheimer’s disease
Authors: Kang Min Su , Thiel Alexander , Schirrmacher Ralf , Bernard‐Gauthier Vadim , Jaworski Carolin , Dorian Andreas , Hopewell Robert , Singleton Thomas A , Blinder Stephan , Soucy Jean‐Paul , Rosa‐Neto Pedro , Kostikov Alexey 
Published: June 2023

AbstractBackgroundA family of tropomyosin receptor kinases (TrkA/B/C) plays important roles in the regulation of neuronal differentiation, growth, and survival via their interactions with neurotrophins. A growing body of literature suggests the downregulation of Trk in many neurodegenerative conditions of the central nervous system (CNS), including Alzheimer’s disease (AD). We recently reported the development of [18F]TRACK, the PET tracers for in vivo imaging of TrkB and its first in‐human study. Here, we wish to report a fully automated GMP‐compliant radiosynthesis of [18F]TRACK at high radiochemical purity (RCP) and molar activity and its preliminary evaluation in wild‐type and a transgenic rat model of AD.MethodRadiosynthesis was performed using Scintomics GRP automated module via copper‐catalyzed 18F‐fluorination of the chiral boron pinacolate precursor. Brain imaging in wild‐type (n = 3) and TgF344‐AD rat models (n = 2) at 23 months was performed on microPET Concord R4 scanner.Result[18F]TRACK was synthesized with a 5.0±1.4% radiochemical yield not corrected for decay (activity range 95‐154 mCi) with >99% RCP and molar activities of 250 ± 75 GBq/µmol (n = 6). The synthesis was fully automated and all batches passed quality control procedures, including chemical purity, sterility and pyrogenicity. The tracer showed moderate brain uptake in wild‐type rats with the highest accumulation in the thalamus (SUVmax = 1.56 ± 0.28, 10 min post‐injection), consistent with the brain regional distribution in humans acquired in a parallel study. Preliminary data suggests lower tracer uptake in TgF344‐AD rat model of AD in thalamus, striatum and frontal cortex compared to wild‐type animals.ConclusionThis study demonstrated the feasibility of the GMP‐compliant production of [18F]TRACK in sufficient doses and molar activities for scanning multiple subjects per day or long range deliveries. Preliminary biodistribution studies showed moderate brain uptake of the tracer with preferential accumulation in the thalamus across species. These findings warrants further studies of Trk brain expression and its implication in neurodegenerative and psychiatric pathologies using [18F]TRACK.
Age‐related hearing loss and neural correlates of visual short‐term memory
Authors: Loughrey David Gerard , Reilly Richard 
Published: June 2023

AbstractBackgroundAge‐related hearing loss (ARHL) may be a potential modifiable risk factor for neurocognitive decline and dementia. Previous studies have reported HL is associated with decline in visual memory function. Evidence also suggests that following ARHL, there is neural reorganization in regions critical for memory. The aim of this pilot was to explore the association of ARHL with neural correlates of visual short‐term memory binding (VSTMB).MethodParticipants over the age of 65 were recruited and divided into three groups (controls (n = 14), mild HL (n = 21), and moderate or greater HL (n = 23)) based on results from a tablet‐based hearing measure. Volunteers completed the VSTMB task (shapes and binding conditions) while electroencephalography (EEG) data was synchronously recorded using a high‐density EEG array (128 scalp electrodes). Analysis was focused on comparing 5 different components (P1, N1, P2, P3, and late positive potential (LPP)) between both HL groups to controls for the memory encoding and testing phases on both shapes and binding conditions. Statistical analysis of source reconstructions (sLORETA) was also performed to explore neural regions underlying VSTMB.ResultThere was no difference between groups in behavioral performance on the VSTMB task. There were a limited number of differences in electrophysiological activity, primarily in P1, P2, P3 and LPP which increased from mild to moderate or greater HL. Analyses of source reconstructions suggested there were bilateral differences in frontal, central, parietal, temporal, and occipital neural regions between groups.ConclusionThere were no differences in behavioral outcomes in VSTMB with HL. There may be underlying differences in neural activity on this task with greater HL which is in accordance with prior research. Further investigation into differences in neural processes underlying episodic memory with HL would be informative, particularly to examine if such differences are associated with future memory function.