bluuebunny/crossref_metadata_2025_split huggingface dataset:
Premorbid musical experience influences socio‐emotional functioning in behavioural variant frontotemporal dementia
Authors: Hooft Jochum J. , Benhamou Elia , Herreros Claudia Albero , Jiang Jessica , Levett Benjamin , Core Lucy , Requena‐Komuro Mai‐Carmen , Hardy Chris JD , Tijms Betty M. , Pijnenburg Yolande A.L. , Warren Jason D 
Published: December 2023

AbstractBackgroundWhile it is well established that musical expertise can shape brain structure and function, the potential of premorbid musical training to modify the clinical expression of neurodegenerative brain pathologies has been largely unexplored. In healthy subjects, long‐term musical exposure is associated with both enhanced emotion recognition and increased connectivity and functional integration in the salience network, a core target of the pathological process in behavioural variant frontotemporal dementia (bvFTD). Premorbid musical experience might therefore potentially affect socio‐emotional expression of bvFTD.MethodsIn 14 patients with bvFTD, premorbid musical experience (training and/or performing on an instrument), current musical listening habits and general socio‐emotional behaviours were scored using a bespoke semi‐quantitative musical survey and standardised functional scales administered to their primary caregivers. Patients were assessed on tests of pitch perception and melody recognition, referenced to a matched healthy cohort. Socio‐emotional behaviours were assessed using the Cambridge Behavioural Inventory (Revised) (CBI‐R), the Modified Interpersonal Reactivity Index (MIRI), and the Revised Self‐Monitoring Scale (RSMS). Higher CBI‐R scores reflect more behavioural impairments and higher MIRI and RSMS reflect better socio‐emotional functioning. Associations of musical scores with socio‐emotional functioning were assessed using a linear regression model adjusted for age, sex, educational attainment and overall cognitive severity.ResultsThe bvFTD patients were matched to a healthy cohort on age, sex, education, peripheral hearing, musical experience, and music listening behaviour, but had worse performance on the pitch perception and melody recognition tests (Table 1). Greater premorbid musical experience (but not current listening habits or musical skill) was associated with significantly lower CBI‐R (β±SE = ‐16.5 ± 6.5; p = .03) and higher MIRI perspective‐taking scores (β±SE = 2.7 ± 1.1; p = .04) (Results are plotted with Pearson correlations in Figure 1).ConclusionsMusical experience in earlier life may ameliorate socio‐emotional functioning in bvFTD. Future work in larger cohorts is required to substantiate the robustness of this association, establish its mechanism and evaluate its clinical potential.
The PPA Platform: A unique knowledge translation tool on PPA
Authors: Laforce Robert , Lafleur Philippe , Bédard Andréane , Drouin Marie‐Jeanne , Cyr Nancy , Parent Nancy , Sablonnière Justine De La , Poulin Elizabeth , Carrier‐Auclair Julie , Tastevin Maud , Lavoie Monica 
Published: December 2023

AbstractBackgroundVery limited web‐based information is available for patients and families affected by Primary Progressive Aphasia (PPA). When accessible, it is often incomplete or worded in complex terminology. One of the objectives of the Research Chair on PPA – Fondation de la famille Lemaire (app‐ffl.ulaval.ca) is to educate the general population and healthcare professionals on PPA to promote earlier diagnosis and better care. We present the development of the PPA Platform, an innovative knowledge transfer tool.MethodWe carried out a focus group with patients and their relatives to understand their needs. We developed templates for ‘Patients/Relatives’ and ‘Health Professionals’ and adapted content and terminology for both sections. Content was then validated with experts in the field (neurologists, SLP). Videos were selected to illustrate the symptoms (eg, naming, repetition, etc.) and we included testimonials to further capture caregivers’ experience (eg, first symptoms, challenges, etc.). The French version of the platform was launched in 2020 and the English one in 2022.ResultSince its inauguration, the PPA Platform has been consulted by more than 27 000 individuals in over 85 countries. Moreover, its content has been presented to approximately 500 healthcare professionals over training sessions either in person or by videoconference. Content is regularly updated and translation in other languages (Mandarin, Hindi, Spanish, Arabic and German) is ongoing.ConclusionThe PPA Platform is an outstanding knowledge translation tool for patients, families and healthcare professionals. In a short amount of time, it positioned itself worldwide as a key reference on PPA.
Metformin and dietary restriction pathway are associated with neuroprotection in Alzheimer’s disease context. A key role for glial autophagy
Authors: Saravia Flavia Eugenia , Pomilio Carlos Javier , Gregosa Amal , Pérez Nicolás Gabriel González , Beauquis Juan 
Published: December 2023

AbstractBackgroundThe global rise of type 2 diabetes and obesity prevalence has elicited a great interest in understanding how changes in metabolic function lead to premature brain aging. The inflammation and insulin resistance interplay represent a potential target to prevent neurodegeneration.MethodWe evaluated the effect of the antidiabetic drug metformin‐considered a dietary restriction (DR) mimetic‐ on patients enrolled in ADNI, an observational and longitudinal study including patients from all around the world. We employed data from patients diagnosed with mild cognitive impairment (MCI) due to AD and we performed a principal component analysis focusing on biomarkers associated to AD measured in cerebrospinal fluid.We analyzed memory performance and hippocampal alterations in a model of AD, the PDAPP‐J20 transgenic mouse (Tg) and evaluated the effects of a periodic DR protocol (3 cycles of 40% DR for 5 days and ad libitum diet for 9 days).ResultMCI metformin‐treated patients were characterized as subjects with a better CSF biomarkers profile than the mean population of MCI patients (p<0.05). Control subjects and T2D patients were paired by age, gender, ApoE allele and education, defining three groups: MCI, MCI+T2D and MCI+T2D+metformin. We evaluated the effect of T2D and metformin treatment employing the PACC score and composites defined from standardized ADNI variables to evaluate the memory/learning function. We found that MCI+T2D patients have a worse cognitive performance than MCI patients (p<0.01), but this effect was absent in MCI+T2D+metformin patients. These cognitive variations were associated with changes in cortical thickness and hippocampal volume (p<0.001). Our study shows a beneficial effect of metformin treatment on cognitive performance, CSF biomarkers profile and neuroanatomical measures in MCI due to AD patients.We observed cognitive impairment, low adult neurogenesis and progressive Aβ deposition in the hippocampus of Tg mice. Periodic DR was associated to cognitive improvement, increased hippocampal neurogenesis, and reduced hippocampal amyloid load; we found that autophagy is modulated in Tg mice with a high proportion of LC3/Aβ colocalizing in astrocytes, probably contributing to the reduction in amyloid plaques associated to DR.ConclusionOur data suggest that metformin and DR may be potential interventions to promote healthy aging and prevent dementia.
The aftermath of boxing: Longitudinal changes of cerebral retention patterns of 18F‐florzolotau (18F‐APN‐1607) in the former professional boxers
Authors: Takahata Keisuke , Kubota Manabu , Tagai Kenji , Endo Hironobu , Miyata Mari , Saito Fumie , Tatebe Harutsugu , Matsuoka Kiwamu , Kurose Shin , Ichihashi Masanori , Kataoka Yuko , Hirata Kosei , Matsumoto Hideki , Seki Chie , Kokubo Naomi , Shinotoh Hitoshi , Oya Masaki , Sano Yasunori , Yamamoto Yasuharu , Kawamura Kazunori , Zhang Ming‐Rong , Tabuchi Hajime , Sahara Naruhiko , Tokuda Takahiko , Mimura Masaru , Higuchi Makoto 
Published: December 2023

AbstractBackgroundChronic traumatic encephalopathy (CTE), formerly known as “boxer’s encephalopathy” is a neurodegenerative disease associated with mild‐repetitive TBI. CTE is characterized by the deposition of hyperphosphorylated tau as neurofibrillary tangles around small blood vessels of the cortex, typically at the sulcal depths. Although tau PET studies on American football players reported findings consistent with neuropathological changes identified by postmortem brains, there are no reports of tau PET studies in boxers, and longitudinal changes of tau depositions following boxing remains unknown. The present study was aimed to characterize cerebral retention patterns of 18F‐florzolotau (18F‐APN‐1607) in the former professional boxers.MethodTwenty‐nine former boxers (43.4 ± 10.3 years) and 27 age‐matched healthy control (HC) subjects underwent PET scans with 18F‐florzolotau and 11C‐PiB. Eleven former boxers underwent a second tau PET scan (average interval: 874days). Standard uptake value ratio (SUVR) with the optimized reference tissue was calculated. Regions of interest were defined on brain regions of the gray matter (GM), white matter (WM) and the gray‐white matter boundary (GWB). Association of regional SUVR values with neurocognitive symptoms and various indexes related boxing was investigated.ResultOne boxer was [11C]PiB positive. Former boxers showed higher 18F‐florzolotau retentions than HC subjects in the bilateral frontal GM, right parietal GM, bilateral frontal WM, right parietal WM (P < 0.001). There was a significant correlation between SUVR values in the whole GM and the total number of bouts (p = 0.07,r = 0.40). Subtyping using z‐score heatmap with predetermined criteria revealed heterogeneity in 18F‐florzolotau retention patterns in boxers. Of the 29 boxers, (1) 10 showed increased retention of 18F‐florzolotau in GM (GM dominant), (2) 4 showed increased accumulation mainly in WM (WM dominant), (3) 5 showed increased accumulation in GWB (GWB dominant), and (4) 10 showed no significant increased accumulation in the brain (No tau). These types vary in longitudinal changes of 18F‐florzolotau retention patterns, as well as in clinical features.ConclusionThe present study not only supports pathological heterogeneity of late‐sequalae of professional boxing, but also suggests utility of 18F‐florzolotau PET in detection of late‐life neurodegenerative diseases following mild‐repetitive TBI.
Familiar olfactory stimulation related to self‐awareness in Alzheimer’s disease
Authors: Arbeláez María Alejandra Castro 
Published: December 2023

AbstractBackgroundAlzheimer disease is extended everyday, Latinamerica is not an exception. Patients with AD have a decline about remembering events of general knowlage and past events about their life. Therefore episodic and semantic autobiographical memory is affected in patients with AD. This study shows how is that memory in Dominican Republic and Colombian Population. Also aim to see the difference after an olfactory stimulation with chocolate.MethodFifty people with mild and moderate A.D participated. The Control group, had an olfactory stimulation without familiar smell (placebo) and the experimental group, had an olfactory stimulation with familiar smell (chocolate). Before intervention post olfactory stimulation, of self‐consciousness, was made. After intervention an evaluation of autobiographical episodic memory and self‐consciousness was made. During intervention placebo stimulation with control group and an olfactory familiar stimulation with experimental group was incorporated. Afterwards, an evaluation of episodic autobiographical memory was conducted.ResultPreliminary results shows that patients with AD improves their episodic autobiographical memory.ConclusionThis findings shows a big impact for research because it will be a no farmacological trial that will help the patients with AD. Therefore it will be goood to their families, because it diminished the emotional impact of AD. Finally, will impacts the literature because is the first study in Caribbean region, a area in wich the research is not frequen because of the resources.
Analysis of persistence rate of cognitive enhancers in Alzheimer’s disease using the common data model
Authors: Jang Jae Won 
Published: December 2023

AbstractBackgroundAchEIs are used by first‐diagnosed Alzheimer’s dementia patients. The effect of drug has been proven in safety and efficacy but it is known that the drug cannot be taken continuously due to side effects of about 10% in existing studies. However, studies report higher drug discontinuation rates. Cognitive function improvers or ‘nootropics’ such as choline alfocerate are used together with AchEI. Therefore, purpose of this study was to analyze the usage patterns of cognitive enhancers in Alzheimer’s patients and to confirm retention rate using a common data model.MethodFrom 2010 to 2019, using the data of Alzheimer’s patients registered in the common data model server of Kangwon National University Hospital, we will investigate the prescription rate of cognitive function improving drugs (choline alfocerate) and drug analysis patterns such as ChEI and combination therapy. The analysis is conducted using the FeederNet‐based ATLAS WEB tool, and additional analysis is compared with the results obtained through the DBMS approach using SQL.ResultAs a result of the analysis of treatment trends and persistence for 10 years, among 2,658 newly diagnosed patients with Alzheimer’s disease, donepezil was prescribed the most with 1,518 patients (57.11%), choline alfocerate with 654 patients (24.6%), and memantine with 214 patients. (8.05%), rivastigmine in 74 (2.78%), and galantamine in 147 (5.53%) each. During observation, trend of increasing prescriptions was Donepezil (31.5% in 2010 to 68.7% in 2019), Nootropics (24.6% in 2010 to 34.2% in 2019), Memantine (3.7% in 2010 to 7.9% in 2019), and Rivastigmine(0.53% in 2010 to 3.32% in 2019), while galantamine decreased (12.2% in 2010 to 0.3% in 2019). Persistence was approximately 50% for donepezil and memantine and approximately 40% for rivastigmine, galantamine and choline alfocerate over 12 monthsConclusionComparing treatment trends of cognitive function improvers, donepezil, memantine, ribistigmine, and choline alfocerate showed a tendency to increase, whereas galantamine showed a tendency to decrease. Also, donepezil and memantine were associated with longer persistence than rivastigmine and galantamine and choline alfocerate. In particular, in case of Nootropics, a high rate of initial prescription is given to patients with dementia, but rate of continuous prescription is not high.
Xenon gas (Xe) treatment to restore microglial functions in Alzheimer’s disease (AD)
Authors: Brandao Wesley N , Yin Zhuoran , Kleemann Kilian , Zhang Xiaoming , Rosenzweig Neta , Jain Nimansha , Jones Mathew Blurton , Holtzman David M. , Ilin Ilya , Weiner Howard L , Butovsky Oleg 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) is the most prevalent neurodegenerative disorder. Emerging evidence shows that homeostatic dysregulation of the brain immune system orchestrated by microglia plays a significant role in the onset and progression of the disease. Our aim is to develop a therapy based on Xenon inhalation that addresses 1) penetration through the blood‐brain barrier, 2) microglial modulation, and 3) neuroprotection.MethodThrough a special chamber that can control the supply of Xenon gas in a closed‐circuit system, we evaluated the Xenon effect in microglia biology in models of acute and chronic neurodegeneration and humanized AD mice.ResultWe found that Xenon‐treatment can directly modulate the microglia phenotype, by increasing their phagocytic response and decreasing their proinflammatory signature. Weekly‐based Xenon inhalation decreased Ab‐plaque load and tauopathy and maintained microglial phenotype in an intermediated state associated with IFNg signaling and lipid biosynthesis signatures. Moreover, Xenon treatment also affects the peripheral immune response with a decrease in B cell and an increase in the tolerogenic signature in myeloid cells, which was validated by scRNAseq and FACS analysis. Importantly, Xenon treatment, directly modulated IPS‐derived microglia (iMGL) in vitro by suppressing their inflammatory signature and inducing lipid biosynthesis. Finally, treatment of humanized 5xFAD mice transplanted with iMGLs reduced Ab plaque load.ConclusionXenon treatment modulates microglia and peripheral immune cells phenotype towards a reparative phenotype. This modulation is accompanied by reduction in Ab pathology in both mouse and humanized AD models, showing that Xenon inhalation can be used as a possible treatment for AD.
Alzheimer’s disease genetic risk score and neuroimaging biomarkers in the FINGER multidomain lifestyle randomized controlled trial
Authors: Hossain Gazi Saadmaan , Dalmasso Maria Carolina , Ramirez Alfredo , Hiltunen Mikko , Kemppainen Nina , Lehtisalo Jenni , Ngandu Tiia , Rinne Juha O. , Soininen Hilkka , Stephen Ruth , Kivipelto Miia , Solomon Alina 
Published: December 2023

AbstractBackgroundA comprehensive genetic risk score (GRS) for Alzheimer’s disease (AD‐GRS) was recently developed based on 83 genome‐wide significant variants (Bellenguez et al. Nat Genet. 2022), excluding APOE. This study investigated AD‐GRS and APOE4 in relation to neuroimaging biomarkers in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER).MethodFINGER included at‐risk individuals without dementia from the general population, aged 60‐77 years. Participants were randomized to either 2‐year multidomain lifestyle‐based intervention or regular health advice. At baseline, 132 participants underwent MRI scans, of which 48 also underwent PET scans (PiB/FDG). Two years later, 112 and 39 repeated their scans, respectively. MRI measures included hippocampus, total gray matter and white matter lesion volumes, and cortical thickness. Composite indices were calculated for PiB and FDG uptake values. We report preliminary results from linear regressions (standardized β‐coefficients, p‐values).ResultAt baseline, higher AD‐GRS tended to relate to lower hippocampus volume (β = ‐0.15, p = 0.07) and FDG‐PET index (β = ‐0.23, p = 0.08); this remained after APOE adjustment. APOE4 was associated with lower hippocampus volume (β = ‐0.27, p = 0.001) and higher PiB‐PET index (β = 0.48, p = 0.001). Overall, AD‐GRS was not related to the 2‐year change in neuroimaging measures, while APOE4 was related to decreasing hippocampus (β = ‐0.27, p = 0.01) and total gray matter (β = ‐0.25, p = 0.01) volumes, and cortical thickness (β = ‐0.28, p = 0.003). There were no significant interactions of AD‐GRS or APOE4 with randomization group in relation to neuroimaging changes. However, in analyses stratified by AD‐GRS (below vs above median), there was less PIB index increase in intervention vs control in the higher AD‐GRS group (β = ‐0.60, p = 0.03); no intervention control‐difference was found in the lower AD‐GRS group (β = 0.04, p = 0.86). In analyses stratified by APOE4, PIB index tended to increase less in intervention vs control in non‐carriers (β = ‐0.38, p = 0.078), with no intervention‐control difference in carriers (β = 0.05, p = 0.89).ConclusionUnlike APOE4, AD‐GRS was not related to 2‐year change in AD‐related neuroimaging measures. AD‐GRS and APOE4 may also have very different impact on potential intervention effects on amyloid, i.e. less accumulation in the higher‐risk group (AD‐GRS) vs lower‐risk group (APOE). However, these exploratory findings need to be verified in larger studies.
Single cell profiling of Microglia from PLCG2 and ABI3 Missense Variant Carriers in Alzheimer’s disease
Authors: Bergman Jeremiah , Is Ozkan , Wang Xue , Cherukuri Yesesri , Duvuuri Venkata N.S. , Quicksall Zachary , Atik Merve , Tutor‐New Frederick Q , Sotelo Katie , Nguyen Thuy , Dickson Dennis W. , Allen Mariet , Ertekin‐Taner Nilufer 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) is a complex, multicellular disease with immunological and genetic components. Previous studies demonstrated associations between AD and the missense variants ABI3‐rs616338‐T and PLCG2‐rs72824905‐G. The perturbed expression of these genes has been demonstrated to disrupt microglial function. To date, the transcriptomic profiles of variant carriers in the context of microglial subtype and state have not been explored in human brain. This represents a knowledge gap in our understanding of AD risk and resilience. We have developed and optimized a single nucleus RNAseq (snRNAseq) approach to study the impact of ABI3 and PLCG2 variants on microglial enriched nuclei from frozen human brain.MethodDOCK8 was identified as a nuclear microglial marker based on previous brain snRNAseq data. DOCK8 based microglial enrichment using fluorescent activated nuclei sorting (FANS) was validated using RT‐qPCR and snRNAseq in human cerebellum and temporal cortex (TCX), respectively. We are applying this enrichment and snRNAseq approach to TCX tissue from a cohort of 30 donors harboring ABI3 or PLCG2 missense mutations, or neither. Standard snRNAseq alignment and quality control pipelines will be applied, and nuclei annotated based on putative microglial markers. Differential gene expression will be assessed using pseudo bulk and MAST approaches, for association with ABI3 and PLCG2 genotype, diagnosis groups, risk factors, and pathology scores.ResultDOCK8 has several commercially available antibodies, making it an ideal microglia‐selection marker. Using RT‐qPCR in microglia enriched nuclei, we demonstrated an enrichment of microglia marker genes and depletion of other brain cell type markers. This is further supported by snRNA‐seq data from DOCK8‐sorted TCX tissue that yielded a 5x increase in microglia proportion (56% vs. 11% in unselected nuclei), enabling analyses of microglia sub‐populations. Leveraging this approach, we will investigate affected genes and pathways and uncover the resilience and risk mechanisms within microglia sub‐populations in ABI3 and PLCG2 variant‐carriers.ConclusionOur study presents a novel method for enriching microglial nuclei from frozen human brains and enables transcriptomic profiling of microglial subpopulations in ABI3 and PLCG2 missense variant‐carriers. We expect these insights will reveal novel genes and pathways that may play a key role in microglial function in AD.