bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and application of empowerment assessment tools for caregivers: a scoping review
Authors: wu junhong 
Published: January 2025

AbstractBackgroundTo systematically analyze the current situation and application of caregiver empowerment assessment tools at home and abroad, to provide a reference for the future development of caregiver empowerment assessment tools and the assessment of caregiver empowerment level.MethodAccording to the research method of scope review, the relevant literature from the establishment of the database to October 2023 was searched, and the references of the included literature were traced, and the relevant literature of the caregiver empowerment assessment tool was comprehensively collected.ResultA total of 856 articles were retrieved. According to the inclusion and exclusion criteria, 14 articles were finally included. After data extraction, a total of 13 kinds of caregiver empowerment assessment tools were summarized, mainly from China and the United States. The application group was mainly the caregiver group with limited behavioral activities or cognitive impairment, and the overall reliability and validity level was good.ConclusionThere are many kinds of caregiver empowerment assessment tools at home and abroad. Different tools have their own scope of use. Nearly half of the tools have not been further applied, and the reliability and validity test indicators are different. Follow‐up researchers should pay attention to the full test of reliability and validity when developing the caregiver empowerment assessment tool, and evaluate it with recognized standards, focusing on the application and promotion of the tool.
Preclinical Dementia Risk Estimation: Attitudes and Views of Relatives of Dementia Patients – The PreTAD‐Study
Authors: Gerards Michelle , Baumeister Annika , Hübner Constanze , Ribaldi Federica , Cantero‐Fortiz Yahveth , Braun Julia , Boada Mercè , Frisoni Giovanni B. , Schmitz‐Luhn Björn , Schwegler Carolin , Woopen Christiane , Jessen Frank , Rostamzadeh Ayda 
Published: January 2025

AbstractBackgroundDue to further development of diagnostic methods of early‐stage diagnosis of Alzheimer’s disease (AD) and new disease‐modifying treatment options that require early diagnosis, a new focus on predictive and preventive medicine arises. With progress in AD dementia risk estimation, guidelines for counseling, considering individual aspects of those affected, are becoming more important. As part of the trinational project PreTAD (The Predictive Turn in Alzheimer’s Disease: Ethical, Clinical, Linguistic and Legal Aspects) anticipated effects of AD dementia risk estimation for first‐degree relatives of people with AD dementia are evaluated.MethodIn the PreTAD project, the topics risk understanding, and anticipated effects of risk estimation were surveyed. First‐degree relatives of people with AD dementia were confronted with one of the following hypothetical AD dementia risk scenarios: 1) higher risk due to abnormal biomarker results or 2) a lifetime risk comparable to the general population. First results of the main study with 50 participants in Germany are reported.ResultAlmost all participants would undergo AD dementia risk estimation if offered. The preferred method was blood sampling compared to other diagnostic methods. Anticipated effects of AD dementia risk estimation were disadvantages at work, on one’s financial situation and when taking out insurance policies. Fewer disadvantages were expected on relationships with close others. Participants confronted with a higher risk of developing AD dementia were more likely to feel diagnosed with a disease and were less likely to share test results with close others. Those confronted with a higher risk were more likely to be willing to change their lifestyle, and make changes in further life planning. Anticipated effects on mental health (e.g. depressed mood, increased anxiety) were higher when confronted with a higher risk of AD dementia.ConclusionFirst results show that dementia risk estimation is desired by first‐degree relatives of people with AD dementia and may have an effect on various elements of personal life, including lifestyle, further life planning and mental health. Findings of the PreTAD project will help to inform the process of counseling and clinical management within preclinical predictive AD diagnosis.
Prognostic value of neuroinflammation [11C]PK11195 PET on longitudinal cognitive decline and survival up to 15 years after PET in Alzheimer's disease
Authors: Rikken Roos M. , Yaqub Maqsood , Coomans Emma M. , van der Vlies Anne E. , Barkhof Frederik , Windhorst Albert D. , Pijnenburg Yolande A.L. , van der Flier Wiesje M. , Boellaard Ronald , Vijverberg Everard G.B. , van de Giessen Elsmarieke 
Published: January 2025

AbstractBackgroundNeuroinflammation plays a key role in Alzheimer’s disease (AD) pathophysiology. However, whether neuroinflammation has a prognostic effect on disease progression is largely unknown. Therefore, we aim to investigate the role of neuroinflammation as measured using PET on longitudinal cognition and survival.MethodWe included 29 amyloid‐positive participants (N=10 MCI, N=19 AD dementia) from a historical cohort who underwent dynamic [11C]PK11195 (TSPO) PET to quantify neuroinflammation (Table 1). [11C]PK11195 BPND was obtained using supervised cluster analysis and quantified in the parietal and temporal cortex. [11C]PK11195 BPND values were z‐scored to young healthy controls (N=12). Longitudinal MMSE covering a period up to 11 years was used to measure cognitive decline (median: 3.9, range: 0.3‐11.6 years). We used linear mixed models with random intercept and slope corrected for age, sex and education to investigate the effect of neuroinflammation on cognition. Survival data were available for all participants, up to 15.7 years after PET. To examine the influence of neuroinflammation on survival time, we used age, sex, and diagnosis adjusted cox proportional‐hazards models for both regions.ResultDemographic characteristics and mean [11C]PK11195 BPND can be found in table 1. Overall, the group showed a mean annualized decline of ‐1.86±1.42 points on MMSE and had a median survival time of 7.6 years (range: 0.4‐15.7) after PET. Temporal or parietal [11C]PK11195 BPND did not predict longitudinal MMSE (parietal: β=0.15, p=0.438; temporal: β=‐0.11, p=0.660) (Figure 1). Higher parietal [11C]PK11195 BPND was marginally associated with shorter survival (HR = ‐0.39, P=0.043) (Figure 2A). There was no significant difference in survival time with higher temporal [11C]PK11195 BPND (HR= ‐0.42, P=0.053) (Figure 2B).ConclusionIn this initial set of analyses covering up to 11 years of cognitive follow‐up and survival information of 15 years after PET, we found preliminary evidence of a shorter survival with increasing parietal neuroinflammation, but no associations between neuroinflammation PET and the rate of cognitive decline. Future research could explore the effect of neuroinflammation PET on more specific cognitive domains and biological measures such as cortical thickness.
Multi‐modal AI screening for MCI and Alzheimer's Disease: results from an Argentine Cohort
Authors: Belloli Laouen , Keller Greta , Carello Agostina , Gauder Lara , Juantorena Gustavo , Corvalan Nicolas , Allegri Ricardo , Crivelli Lucia , Slezak Diego Fernandez 
Published: January 2025

AbstractBackgroundEarly detection of Mild Cognitive Impairment (MCI) is crucial for effective prevention. Traditional methods like expert judgment, clinical evaluations, and manual linguistic analyses are now complemented by Artificial Intelligence (AI). AI offers new avenues for identifying linguistic, facial, and acoustic markers of MCI. The exploration of these markers for MCI research is just beginning, especially in regions like Argentina. The effectiveness of AI‐methodologies hinges on local data calibration and validation prior to deployment. This study focuses on designing AI‐based neuropsychological instruments to differentiate healthy individuals from MCI subjects, emphasizing local data calibration and validation.MethodWe recruited 42 participants (30/12 healthy/MCI according to Petersen's criteria, 2016) aged 60 to 89 (mean ± SD: 70.95 ± 6.8) in Fleni, Argentina. During the assessment, which included neuropsychological tests (UDS‐3), participants were video and audio recorded while performing a language task on a web platform. They were required to describe two target images ('Cookie Theft' and 'Firefighter‐Oasis.') and two tasks without any target image (description of their favorite sandwich and reading a story). Markers were extracted from 5 modalities: Speech (automated speech transcription), Acoustics (audio), Face mesh (video), Blend shapes (video) and Emotion recognition (video and audio).ResultUnimodal analysis was performed to study shared information between proposed AI‐markers and traditional neurocognitive tests. Speech markers were correlated with language and memory, and overall, we obtained a total of 204 significantly correlated AI‐markers to traditional tests of a total of 432 (47%). Univariate AUC for MCI diagnosis was measured for all markers obtaining an average above chance performance of (0.57 ± 0.062). Finally, a multivariate random forest classifier was used to extract the performance of the modalities altogether, an AUC of 0.91ConclusionThe results of this preliminary study show the validity of the AI algorithms applied to the local argentine population. Validation of algorithms using data in Spanish language and with Latin American population is a key element for de dissemination and the diversification of AI tools. The next step of this research is to include more patients with MCI to gain a comprehensive understanding of differential communicational patterns.
Deciphering the enigma of atypical forms of Alzheimer's disease by employing connectomics in the context of early and late‐phase Amyloid PET and [18F]FDG PET Imaging
Authors: Cirone Alessio , Kreshpa Wendy , Garbarino Sara , MASSA FEDERICO , Raffa Stefano , Sambuceti Gianmario , Piana Michele , Chincarini Andrea , Roccatagliata Luca , Uccelli Antonio , Morbelli Silvia , Pardini Matteo 
Published: January 2025

AbstractBackgroundAlzheimer's disease (AD) is the most common form of dementia, predominantly manifesting as amnestic impairment. However, atypical presentations such as logopenic variant of primary progressive aphasia (lvPPA), posterior cortical atrophy (PCA), corticobasal syndrome (CBS) and frontal AD pose diagnostic challenges. This study presents preliminary data from a retrospective analysis investigating brain functional differences between typical and atypical AD forms. Specifically, a structural connectome, a comprehensive map of anatomical white matter connections in the brain, was employed alongside late‐phase amyloid [18F]FBB PET, which resembles focal regional amyloid uptake. Additionally, the research aims to examine whether early‐phase amyloid [18F]FBB PET can serve as a surrogate for glucose metabolism throughout various brain regions, similar to [18F]FDG PET.MethodThirty patients have been recruited, including 13 with atypical AD (median age 70; median MMSE 21) and 17 with typical amnestic phenotype (median age 71; median MMSE 23). Neuropsychological tests, 3D isotropic T1 MRI, [18F]FDG PET, and [18F]FBB PET (consisting of 3 early frames and 1 late frame) were performed for each subject. Structural and functional images underwent spatial registration, segmentation, and intensity normalization, using a custom Python pipeline based on FreeSurfer and ANTs tools. Basic statistics were employed to establish functional patterns and assess their statistical significance. Structural connectomes derived from probabilistic tractography on DWI images of 30 healthy subjects were employed.ResultResults revealed a significant preservation of the hippocampus in atypical AD phenotypes (p<0.05). The connectome analysis demonstrated variations in interconnections among late‐phase amyloid PET uptake regions, distinguishing between atypical and typical AD forms. Additionally, there is support for the hypothesis that early‐phase amyloid PET serves as a reliable marker for synaptic dysfunction.ConclusionIn conclusion, these preliminary findings suggest that structural connectomes in PET imaging can unveil unique neurodegenerative pathways in atypical AD patients. Moreover, the study supports the notion that early amyloid PET phases can provide insights into neurodegeneration among patients with atypical AD, akin to [18F]FDG PET.
Genetic Spectrum Features and Diagnostic Performance of Four Plasma Biomarkers in 245 Patients with Frontotemporal Dementia
Authors: Shen Lu , Xu Tianyan , Zhou Yafang , Zhang Cong , Tang Beisha , Jiao Bin , Weng Ling 
Published: January 2025

AbstractBackgroundFrontotemporal dementia (FTD) exhibits clinical phenotypic and genetic heterogeneity. However, reports on the clinical phenotypic characteristics and the frequency of genetic mutations in large‐sample Chinese populations with FTD are lacking. Furthermore, the FTD diagnostic performance of plasma neurodegenerative biomarkers remains unclear.MethodThis study included 245 clinically diagnosed FTD patients for an analysis of clinical characteristics. All FTD patients and 1,000 gender‐ and age‐matched healthy controls underwent targeted gene sequencing or whole‐genome sequencing. Additionally, plasma samples were analyzed for GFAP, α‐Syn, NfL, and P‐tau181 levels.ResultIt was found that 44.5% (109/245) of patients were diagnosed with bvFTD, 21.2% (52/245) with SD, 15.5% (38/245) with PNFA (20/245), 10.6% (26/245) FTD‐PD, and 8.2% with FTD‐ALS. After gene sequencing, 53 pathogenic or likely pathogenic (P/LP) variants in FTD‐related genes were identified in a total of 19.2% of the patients (47/245). The most common mutation was MAPT (4.9%, 12/245), followed by C9orf72 (3.3%, 8/245), CHCHD10 (2.4%, 6/245), and GRN (1.6%, 4/245) mutations. Other rare variants together were found in the other eleven genes. Elevated levels of GFAP, α‐Syn, NfL, and P‐tau181 were significantly observed in FTD patients compared to controls (P < 0.05), and among them, a combination of GFAP, α‐syn, and Nfl demonstrated high diagnostic value for varied FTD subtypes, with AUCs of 0.83‐0.93. We further confirmed that the gene variants could not have an impact on plasma biomarkers level.ConclusionThis research enhances comprehension regarding the genetic and phenotypic spectrum of FTD within the Chinese population, and underscores the diagnostic utility of biomarkers such as GFAP, α‐Syn, and NfL in identifying FTD.
APOE genotype, cognition and dementia: mediation of ε2 and ε4 effects by structural brain imaging markers in a population‐based study
Authors: Claus Jacqueline Josephine , Rosbergen Mathijs T. , Vernooij Meike W. , Wolters Frank J. , Ikram Arfan 
Published: January 2025

AbstractBackgroundInsight into APOE‐mediated pathways is important to unravel pathophysiology and identify therapeutic targets against late‐life cognitive decline and dementia. However, ante‐mortem studies on the mediated effect of APOE on cognition and dementia through different disease markers on structural brain imaging remain scarce, in particular for APOE‐ε2.MethodWe included all dementia‐free participants from the population‐based Rotterdam Study, who routinely underwent cognitive assessment and brain MRI between 2005‐2009, and were followed‐up for incident dementia until 1‐1‐2020. We standardized hippocampal volume (HV) and volume of white matter hyperintensities (WMH), and performed causal mediation analyses to quantify the mediation effects (i.e., natural direct effect, natural indirect effect and percentage mediated) of APOE ε4 and ε2 carriership on cognition operationalized as g‐factor and incident dementia, with ε3/ε3‐carriers as a reference group. We adjusted all models for potential mediator‐outcome confounders (i.e., demographics, education, cardiovascular factors) and for intracranial volume.ResultAmong 5,510 participants (mean age: 65.0[±10.9] years, 55.0% women), 3,244 were ε3/ε3‐homozygotes, 709 ε2‐carriers, and 1,557 ε4‐carriers. During a median 11 years follow‐up, 349 participants developed dementia, of whom 148/1,557 ε4‐carriers (9.5%), 172/3,244 ε3/ε3‐carriers (5.3%) and 29/709 ε2‐carriers (4.1%). APOE‐genotype was not significantly associated with hippocampal volume (Figure 1), whereas those carrying APOE ε2 or ε4 tended to have a slightly higher volume of white matter hyperintensities (Figure 2). In total, 4% of the effect of ε4, and 7% of the ε2‐effect on cognition were mediated by HV. The percentage of the effect on cognition mediated through WMH was 18% for ε4 and 0% for ε2. For incident dementia, there was little to no evidence of mediation by either HV (ε4: 3%; ε3: 0%) or WMH (ε4: 1%; ε3: 0%), which was consistent in sensitivity analyses stratified by duration of follow‐up and by age (≥75 years).ConclusionIn this population‐based cohort study, we found that one fifth of the effect of APOE‐ε4 on cognition was mediated by WMH, compared to only 4% by lower HV. For dementia, however, we found no significant mediation effects of both HV and MWH, suggesting the involvement of alternative pathways through which APOE exerts its effect on dementia.
Mapping local and distal effects of different neuropathologies on amygdala volume
Authors: Annettesdotter Amanda , Selezneva Katja , Denning Amanda E , Wuestefeld Anika , Ravikumar Sadhana , Ittyerah Ranjit , Levorse Lisa M , Bedard Madigan , Chung Eunice , Robinson John L. , Schuck Theresa , Lee Eddie B , Lim Sydney A , Trotman Winifred , Bahena Alejandra , Irwin David J , Jimenez Maria del Mar Arroyo , Vela Alicia , Buendia Esther , Martin Maria Mercedes Iniguez de Onzono , Rabal Maria del Pilar Marcos , Munoz Monica , Spotorno Nicola , Hansson Oskar , Insausti Ricardo , Yushkevich Paul A. , Wisse Laura E.M. 
Published: January 2025

AbstractBackgroundThe amygdala is a hotspot for neuropathologies; however, it is unclear 1) which neuropathologies lead to amygdala neurodegeneration, 2) what specific amygdala subnuclei are affected, and 3) if the neuropathologies related to amygdala volume are local (inside the amygdala), or distal (in other regions). We investigate the relationships between different neuropathologies (tau, amyloid‐β [Aβ], α‐synuclein [α‐syn], and transactive response DNA‐binding protein 43 [TDP‐43]) and amygdala volumes.MethodWe analyzed postmortem data from 73 individuals with and without neurodegenerative diseases (age: 77±11 [45–101] years; 26 [36%] females; 51 [70%] cognitively impaired). Volumes of the whole amygdala and three amygdala subregions (lateral, B/Ab [basal/accessory basal], Co/Me/Ce [cortical/medial/central] nuclei: for n=24 individuals) were manually segmented on 0.2x0.2x0.2 mm3 postmortem magnetic resonance images (Figure 1). We used semiquantitative scores (0–3) of Aβ, tau, α‐syn, and TDP‐43 in the amygdala, the dentate gyrus (DG), the Cornu Ammonis 1 and subiculum (CA1/SUB), the entorhinal cortex (ERC), and averaged between the medial temporal lobe (MTL) regions (excluding the amygdala). Partial Spearman correlations were performed to investigate the relationships between neuropathologies and amygdala volumes, adjusting for age, sex, and other pathologies.ResultsHigher ratings of amygdala TDP‐43, MTL TDP‐43, and MTL tau were associated with smaller whole amygdala volume (Figure 2A–B, Figure 3A). However, MTL TDP‐43 was no longer significant when adjusting for amygdala TDP‐43 (Figure 3B). As MTL tau was associated with amygdala volume, we looked into which MTL subregions could be responsible for this association. Here, tau in DG, CA1/SUB, and ERC were all negatively associated with whole amygdala volume (Figure 2B). For exploratory subregional analyses, amygdala α‐syn was initially associated with B/Ab volume (Figure 2C, Figure 3C), but this correlation did not survive FDR‐correction.ConclusionsThese preliminary results indicate that TDP‐43 has a local effect on whole amygdala volume, whereas tau seems to affect amygdala volume distantly through other MTL regions, with the largest effect seen in DG tau, followed by CA1/SUB and ERC. Subregional analyses will be updated once a larger sample is available, as well as further analyses on non‐MTL regions.
Mechanistic Insights of Gamma Sensory Stimulation: CSF Proteomic Analyses Reveal Changes in Myelin and Synaptic Proteins
Authors: Shpokayte Monika , Pandey Kiran , Singer Annabelle C , Doung Duc , Lah James J. , Levey Allan I. , Seyfried Nicholas T , Malchano Zach , Kern Ralph , Hajos Mihaly 
Published: January 2025

AbstractBackgroundPreclinical investigations in Alzheimer’s disease (AD) have highlighted the efficacy of gamma sensory stimulation in mitigating AD‐related pathologies. Cognito Therapeutics, Inc. (Cambridge, MA) has designed the Sensory Stimulation System for safe at‐home usage, to induce EEG‐confirmed gamma oscillations as a potential treatment for AD. In the present study, unbiased proteomic analysis of patient derived CSF samples was conducted to characterize the underlying mechanism of action and assess treatment effects of gamma sensory stimulation in AD.MethodThe FLICKER study (NCT03543878) recruited ten participants with MCI due to AD from the Emory Goizueta Alzheimer's Disease Research Center. The trial employed a delayed‐start study design with 4‐ or 8‐week daily gamma sensory stimulation. Cerebrospinal fluid (CSF) was collected at baseline, 4‐ and 8‐weeks and the proteome was analyzed (Emtherapro, Atlanta, GA) using tandem‐mass tag spectrometry. The CSF proteome of participants was mapped to previously established brain‐derived co‐expression modules (Johnson et al. 2022) of AD. Concordant and Discordant proteins were analyzed using Emtherpro’s internal AD proteome database.ResultA total of 2,785 CSF proteins were detected across all CSF samples. Differential expression analysis of proteins from baseline (N=5) vs. (N=5, 8 weeks) revealed 110 proteins that met the significance threshold. 60 proteins upregulated and 50 proteins downregulated as result of treatment. Treatment significantly impacted CSF proteins associated with AD‐related brain modules, including synapses, myelination, post‐synaptic density, and neurotransmitter regulation. Two key myelin‐related proteins that showed significant treatment time‐dependent changes over 8‐weeks of treatment were PLP1, a major structural component of myelin, and EV12A, a cell surface receptor primarily found on myelinating oligodendrocytes and precursor cells. Changes are also seen in cell surface receptors and molecules such as TENM3, EPHA7, and DSCAM which are involved in neuronal network failure, neurogenesis, and neuronal plasticity, respectively. Lastly, γSynuclein, a protein linked to neurofilament network integrity and memory dysfunction, exhibited significant decreases over 8 weeks.ConclusionThis study shows that sensory stimulation induces broad biomarker support, highlighting its impact on myelin changes, synaptic regulation, and network function. These findings contribute to our understanding of the underlying mechanisms of gamma sensory stimulation in the context of AD.