bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cognitive impairment prevention and healthy aging. A multidisciplinary team work
Authors: García‐Lluch Gemma , García Hernán Ramos , Pardo Juan , Gil‐Peinado María , Garcia Cristina Garcia , Climent Marta Sala , de Coca Teresa López , Sánchez‐Roy Rafael , Baquero Miguel , Sendra‐Lillo José , Royo Lucrecia Moreno 
Published: December 2023

AbstractBackgroundCognitive impairment (CI) is often diagnosed at moderate stages, with an estimated time for diagnosis of two years. However, the early diagnosis of CI allows the control of modifiable risk factors to prevent the development of dementia at later ages. In addition, the community pharmacy is a close, accessible, and trustworthy health establishment where the pharmacist often participates in disease prevention, becoming a suitable healthcare center for facilitating the detection of cases of CIMethodA cross‐sectional observational study was designed using a structured personal interview. Participants were aged 50 or older with subjective memory complaints. Pharmacies in the province of Valencia (Spain) were invited to participate voluntarily by the organization entities. Before the start‐up of the service, the participating pharmacists received specific training. In the personal interview with the patient, after signing the corresponding informed consent, three validated questionnaires were conducted to assess their cognitive status: Memory Impairment Screening (MIS), Semantic Verbal Fluency (FVS), and Pfeiffer’s Short Portable Mental State Questionnaire (SPMSQ). Whenever possible, a fourth questionnaire was carried out: Brief Informant Test (Brief TIN). Data collection was carried out through a computer platform. This project was approved by the Ethics Committee of the University CEU‐Cardenal Herrera (registration number CEEI21/198).ResultBetween February 2021 and July 2023, 44 pharmacies participated, and 534 patients were screened. Of them, 194 (36%) had at least one positive test result, therefore having possible CI. After their corresponding referral to the doctor, 52 (29%) patients were referred to the hospital neurology department, of which 42 (81%) had been diagnosed with cognitive decline. Finally, the average time from the first evaluation by a pharmacist to a diagnosis by the specialist was six months.ConclusionPreliminary results of the screening for cognitive impairment show that the community pharmacy is a critical point in the approach to early detection of dementia and that collaboration and coordination between different levels of care is enhanced through such programs.
Inflammatory and synaptic PET imaging in behavioural variant frontotemporal dementia caused by a repeat expansion in C9orf72 (C9orf72‐FTD)
Authors: Clarke Mica TM , Consortium MINDMAPS , Cash David M , Rohrer Jonathan D. 
Published: December 2023

AbstractBackgroundPathophysiological mechanisms associated with neurodegeneration include chronic neuroinflammation and synaptic dysfunction/loss. Radiotracer [11C]PBR28 is a marker of inflammation which binds to a translocator protein expressed by activated microglia. [11C]UCB‐J is a marker of synaptic density which binds to synaptic vesicle protein 2A. We evaluated both tracers as biomarkers of C9orf72‐FTD.MethodThree individuals with C9orf72‐FTD (mean age 62.7 years) underwent two PET scans between 3 and 13 months apart using [11C]PBR28 and [11C]UCB‐J. Dynamic PET data were acquired for 90 minutes following injection of each tracer. Arterial plasma input functions were generated from arterial blood samples. Participants also had volumetric MRI scans for each PET scan. Age‐matched controls from different cohorts underwent the same procedures (n = 5 for [11C]PBR28; n = 17 for [11C]UCB‐J).Regions of interest (ROIs) were defined on co‐registered T1‐weighted MR images using the CIC anatomical atlas. [11C]PBR28 BPND values were generated using a simplified reference tissue model with a cerebellar reference region. [11C]UCB‐J DVR‐1 values were generated using regional VT normalised to the VT in the centrum semiovale. ROI volumes were expressed as a percentage of total intracranial volume. W‐scores computed from each control cohort, using age and gender as covariates, illustrated the magnitude of differences between cases and controls. W‐scores >1.65 were considered abnormal for [11C]PBR28 and ←1.65 for [11C]UCB‐J and MRI.Result[11C]PBR28 w‐scores indicated significant neuroinflammation in FTD but varied between cases. Differences in BPND were greater than in volume in frontal/temporal/cingulate cortices in the individual with the longest disease duration (DD) (16‐17 years). Inversely, in the individual with the shortest DD (1‐2 years), there were greater differences in volume than BPND in most ROIs.[11C]UCB‐J w‐scores indicated significant synaptic dysfunction/loss and were lower than w‐scores of volume in all cortical ROIs. In the individual with the longest DD, differences in [11C]PBR28 were greater than in [11C]UCB‐J in most ROIs. An inverse pattern again observed in the individual with the shortest DD suggests synaptic dysfunction/loss may precede significant neuroinflammation.ConclusionInflammatory and synaptic PET may provide more sensitive biomarkers of C9orf72‐FTD than MRI. Variability in PET signal within this genotype may be explained by DD.
Designing new musical technologies for wellbeing – exploring the needs and preferences of those living with dementia
Authors: Christensen Justin , MacRitchie Jennifer , Neokleous Michael , Jackson Katherine , Timmers Renee , De Witte Luc 
Published: December 2023

AbstractBackgroundMusic has been found to provide numerous health and wellbeing benefits for people living with dementia. It is also quite open in terms of the forms of engagement it affords, offering numerous different ways to listen, play and create. Although technology has the potential to reduce barriers that people with dementia face when attempting to engage with music, little has been designed with them in mind. This study seeks to understand: i) the needs, rewards, and barriers that people with dementia and their carers face when engaging with music in their daily lives, and ii) how any specifically designed future musical interfaces will look and react.MethodA survey using a mixture of qualitative and quantitative questions was distributed online to people living with mild cognitive impairment or dementia and to those that provide care for them. Questions asked about motivations and contexts for engagement, barriers and enabling factors, the comparative importance of various musical activities, and the technologies people living with dementia currently use and why.ResultThe main tools for listening include smartphone apps, radio, virtual assistants, and YouTube. Most participants listen to music on multiple devices, with its ease of use, accessibility, and convenience for their current listening environment frequently influencing their choice. They also presented a wide range of motivations for engaging with music, but a majority of participants agreed that “feeling like myself” is their most important motivator. Most participants thought it was very important for devices to offer choice. It should also have a simple way for them to turn it off or switch to a safe song if they hear a distressing song or it experiences signal loss.ConclusionThe findings highlight that people living with dementia have diverse individual motivations for music, and they want it to perform different functions at different times (e.g. sometimes aiding in their relaxation and sometimes connecting them with others). The findings point to fruitful future directions for technology development: i) ready‐to‐use tools that can adapt to changing interests, and ii) tools that make it easy to access choice and variety while safeguarding against distress from unwanted or unexpected events.
CSF tau markers are associated with fine memory discrimination in older adults with amnestic MCI in the EXERT trial
Authors: Fenton Laura E. , Aslanyan Vahan , Jacobs Diane M. , Salmon David P. , Brewer James B. , Rissman Robert A , Feldman Howard H. , Shadyab Aladdin H. , LaCroix Andrea Z. , Baker Laura D , Pa Judy 
Published: December 2023

AbstractBackgroundCognitive assessments sensitive to the integrity of the medial temporal lobe, an area vulnerable to early tau deposition, may serve as a low‐cost, effective marker of underlying tau burden in older adults at risk of Alzheimer’s dementia. The current post hoc analyses from the EXERT study examined the relationship between CSF phosphorylated tau181 (p‐tau181), total tau (t‐tau), hippocampal volume, and cognitive performance on three distinct memory assessments in older adults with amnestic mild cognitive impairment (aMCI).MethodThe study used baseline data from 41 older adults with aMCI in the EXERT trial who consented to lumbar puncture and had CSF data available (mean age = 74.10±11.98 years, mean education = 16.24±2.39 years, 61% female). P‐tau181 and t‐tau levels were quantified using Lumipulse from CSF samples. Structural brain images were processed using NeuroQuant. Hippocampal volume measures were averaged across hemispheres and adjusted for intracranial volume. Memory measures included the computerized Cogstate Behavioral Pattern Separation of Objects task (BPSO; fine memory discrimination), the Auditory Verbal Learning Test (AVLT; long delay free recall), and the Logical Memory test (delayed recall). Linear regression models were adjusted for age, sex, and education.ResultLower CSF p‐tau181 was significantly associated with better fine memory discrimination (β = ‐0.11, SE = 0.03, p<0.01). Lower CSF t‐tau was significantly associated with better fine memory discrimination (β = ‐0.09, SE = 0.03, p = 0.01). Larger hippocampal volume was significantly associated with better fine memory discrimination (β = 0.08, SE = 0.02, p<0.01), better AVLT delayed recall (β = 1.69, SE = 0.32, p<0.01), and better Logical Memory delayed recall (β = 1.69, SE = 0.40, p<0.01). Neither p‐tau181 or t‐tau were significantly associated with AVLT delayed recall or Logical Memory delayed recall.ConclusionFine memory discrimination measured via the computerized BPSO test was associated with CSF p‐tau181, CSF t‐tau, and hippocampal volume, while more traditional verbal memory tests of list learning and story recall were associated only with hippocampal volume. The BPSO test may be a sensitive indicator of early pathology in individuals with aMCI with underlying tau burden. EXERT was supported by the Alzheimer’s Disease Cooperative Study (ADCS) and funded by the National Institutes of Health Grant U19 AG010483.
Using multimodal, low‐cost data to efficiently identify clinical subgroups and classify Alzheimer’s diagnosis
Authors: Ren Yueqi , Shahbaba Babak , Stark Craig E.L. 
Published: December 2023

AbstractBackgroundWith increasingly greater prevalence of Alzheimer’s disease (AD) worldwide, cost‐ and time‐efficient methods for identifying at‐risk individuals are needed. Survey, simple neuropsychological, and demographic information are low‐cost, but their lower levels of sensitivity or specificity when considered individually are problematic. However, past work has demonstrated the usefulness of statistical machine learning tools for predicting clinical diagnosis using multimodal data. To better understand and quantify Alzheimer’s risk and progression at follow‐up using lower‐cost data, we apply statistical and machine learning tools to screen, cluster, and classify individuals from the National Alzheimer’s Coordinating Center (NACC) dataset.MethodPreviously, we developed hierarchical classification strategies to use lower‐cost data for 3‐class prediction (unimpaired, AD‐MCI, and AD‐dementia). Building upon this idea, here we leverage a Gaussian mixture model to infer subgroup identities of subjects and use subgroup identity to further aid classification. Individuals belonging to homogeneous subgroups consisting primarily of a single diagnosis are more likely to also be given that diagnosis. This approach enables confidence in screening given a threshold for identifying the primary diagnosis within each cluster. Additional classification is performed on subjects that belong to heterogeneous subgroups. The NACC database is funded by NIA/NIH Grant U24 AG072122. NACC data are contributed by the NIA‐funded ADRCs.ResultThe proposed method unmasks the clinical subgroup trends within the sample and allows for detailed longitudinal risk tracking. We identified five subgroups within the sample, representing five clinical clusters. These subgroups include predominantly unimpaired individuals, mixtures of unimpaired and MCI, MCI and AD‐dementia, and individuals predominantly with AD‐dementia. A large proportion of individuals can be confidently screened based upon subgroup identity. Using only baseline visit information, predictions of clinical diagnosis post‐clustering is highly reflective of conversion to a worse diagnosis within 18 months. Changes in the conversion rate to a more severe diagnosis are dependent on the cluster identity.ConclusionUsing cost‐ and time‐efficient data enables more effective screening and tracking of disease progression. The proposed approach of clustering, screening, and prediction yields a measure of confidence in predictions of clinical diagnosis and allows for greater understanding of clinical profiles and progression.
T1 MRI reveals differential hippocampal atrophy in Lewy Body Disorders with and without Alzheimer’s copathology
Authors: Cohen Jesse S , Phillips Jeffrey S , Das Sandhitsu R. , Rhodes Emma , Cousins Katheryn A Q , Yushkevich Paul A. , Wolk David A. , Weintraub Daniel , Irwin David J. , McMillan Corey T 
Published: December 2023

AbstractBackgroundLewy body disorders (LBD) include Parkinson disease (PD), Parkinson disease dementia (PDD), and dementia with Lewy bodies (DLB). LBD are the second leading cause of neurodegenerative dementia after Alzheimer’s disease (AD). An estimated 50% of LBD patients have coexisting AD pathology (LBD+AD), which correlates with shorter time to dementia and death. Autopsy evidence suggests that verbal memory impairment correlates with the severity of hippocampal tau pathology in LBD. However, it is unknown whether greater hippocampal tau burden in LBD+AD causes neurodegeneration detectable by in vivo structural MRI, and whether hippocampal atrophy explains verbal memory impairment.MethodUsing a case‐control design, we studied 87 patients with clinical diagnoses of LBD (PD, n = 52; PDD, n = 12; DLB, n = 23) with available T1 MRI and AD biomarkers or, and cognitively‐normal controls (n = 131). AD copathology was defined hierarchically by: a) AD “intermediate” or “high” by ABC neuropathologic criteria; 2) positive amyloid PET; and 3) CSF total tau:β‐amyloid1‐42 ratio > 0.3 (autopsy‐validated cutpoint). The Automated Segmentation of Hippocampal Subfields (ASHS) pipeline was applied to subjects’ T1 MRIs. Hippocampal volume (HV) was compared between controls, LBD‐AD, and LBD+AD, and correlated with verbal memory scores. Linear regression was used to test the association of AD copathology (independent variable) and HV (dependent variable), covarying for age, sex, education, and clinical diagnosis.ResultStatistically significant differences (ANOVA p = 0.002) in bilateral HV (expressed as percentage of intracranial volume) were seen between groups (mean 0.456for controls, 0.444±0.045 for LBD‐AD, and 0.416±0.063 for LBD+AD). Tukey’s test showed significant differences between LBD+AD vs controls (p = 0.001) and LBD+AD vs. LBD‐AD (p = 0.047). Linear regression showed statistically significant association of LBD+AD with bilateral HV (p = 0.034). Among all LBD patients, hippocampal volume positively correlated with verbal memory (immediate recall: r2 = 0.24, p = 0.033, delayed recall: r2 = 0.22, p = 0.042, recognition discrimination r2 = 0.58, p<0.001).ConclusionIn patients with LBD, AD copathology is associated with increased hippocampal atrophy as measured by in vivo T1 MRI, which correlates with greater verbal memory deficits. This work supports the that AD copathology impairs cognition in LBD via hippocampal neurodegeneration.
Core outcome set for economic evaluation of dementia interventions: A consensus exercise with health economists who incorporate economic evaluations into dementia trial
Authors: Nguyen Kim Huong , Comans Tracy , Trepel Dominic , Saha Sanjib 
Published: December 2023

AbstractBackgroundHealthcare decision‐makers worldwide are increasingly seeking to optimise allocation of resources to dementia and the incorporation of economic evaluations into randomised control trials provide definitive information for such decisions. Economic evaluations are rapidly increasing in number in dementia and standardisation of methods ensure comparability of economic evidence.MethodCore outcomes sets (COS) aim to provide international recommendations on outcome measurement in trials and currently there exists no COS for economic evaluations of dementia interventions. Our systematic searches identified over 100 economic evaluations of dementia interventions, and critical appraisal demonstrates opportunities for greater standardisation of applied economic methods. This study aims to agree standardised methods for economic measures of a) health outcomes and b) resource use that should be measured and reported in future trial‐based economic evaluation in dementia.ResultThe COS for the economic evaluation of dementia interventions will be developed from two main steps:First, a systematic review (currently being finalised) extracts information on how costs and benefits are estimated, analysed and reported. All studies published before December 2022, and confirmed as trial‐based economic evaluation, are included. Included studies all contain economic measures and we will report participant characteristics (type of dementia, severity), study design and evaluation types, type of interventions, mode of data collection and instrument(s) used to derive the health outcomes and resource uses.Second, which speaks specifically to action research at AAIC 2023, we will conduct a Delphi consensus focus groups with economists who have collaborated with dementia‐trial teams. Data extracted during the systematic review will be presented to provide a basis for the consensus recommendations on measures commonly required for economic evaluation in dementia. In the case where consensus was not reached, we may conduct additional consensus exercises. We will also consider country contexts (high versus low‐middle income, or country‐level financing and reimbursement mechanisms) in finalising recommended COS of health and resource use measures.ConclusionFindings from COS for economic evaluations of dementia intervention will be published in a dementia‐focused journal and more broadly communicated to a broad range of stakeholders.
Ante‐mortem magnetic resonance imaging grey‐white matter contrast regional signatures of Alzheimer’s disease neuropathology
Authors: Almeida Francisco , Coelho Ana , Quintas‐Neves Miguel , Teylan Merilee A. , Mock Charles , Kukull Walter A. , Crary John F. , Oliveira Tiago Gil 
Published: December 2023

AbstractBackgroundGrey matter (GM), white matter (WM) contrast (GWC) in T1‐weighted MRI has been shown to decrease with age in healthy populations and cognitive impairment in clinical Alzheimer’s Disease (AD). However, the neuropathological determinants of this signal remain unknown. Here, we aimed to study whether GWC is associated with AD neuropathology and longitudinal hippocampal atrophy.Methods157 patients with neuropathological, clinical data and ante‐mortem MRI were selected from the National Alzheimer’s Coordinating Center database. Cortical volume and GWC (WM/GM intensity) in T1/MRI were obtained with Freesurfer 6.0. Hippocampal volume was divided into anterior, intermediate and posterior regions using a lab‐based algorithm. Correlational analysis was conducted for GWC with age, and GWC residuals after linear regression with age for volume, BRAAK stage (neurofibrillary tangles), CERAD score (neuritic plaque density) and Cognitive Dementia Rating Sum‐of‐Boxes (CDR‐SB). APOE genotypes were compared using one‐way‐ANOVA.ResultsGWC was negatively correlated with age in widespread brain areas (p < 0.05, FDR), but only the entorhinal cortex showed a positive correlation between volume and GWC. There were no significant correlations between GWC and BRAAK stage, CERAD score, CDR‐SB or differences according to APOE genotype. Entorhinal GWC correlated positively only with the posterior hippocampal volume in BRAAK III‐IV.ConclusionGWC is highly modulated by age, but not by classical AD neuropathology, APOE genotype or dementia severity in this cohort. Entorhinal GWC correlates with entorhinal and posterior hippocampal volume, suggesting it might reflect an early pathophysiological process distinct from classical AD neuropathology.
Association between brain [18F]FDG‐PET signal and genetic cell markers in the brain tissue
Authors: Machado Luiza Santos , Ant Marco , Bastiani De , da Rocha Andreia Silva , Bellaver Bruna , Soares Carolina , Povala Guilherme , Rahmouni Nesrine , de Souza Débora Guerini , Pascoal Tharick A. , Souza Diogo O. , Rosa‐Neto Pedro , Benedet Andrea Lessa , Blennow Kaj , Zetterberg Henrik , Ashton Nicholas J. , Ferreira Pamela C.L. , Zimmer Eduardo R. 
Published: December 2023

AbstractBackgroundBrain glucose hypometabolism, indexed by [18F]FDG‐PET, is considered a biomarker of neurodegeneration in Alzheimer’s disease (AD). However, other brain cells, such as astrocytes and microglia, also consume considerable amounts of glucose and may contribute to the [18F]FDG‐PET signal in the brain. Thus, the cellular source of the [18F]FDG‐PET signal remains controversial. Here, we aimed to evaluate whether canonical markers of different brain cell types (neuron, oligodendrocyte, astrocyte, and microglia) associate with brain [18F]FDG‐PET signal in humans and a rat model of human amyloidosis.Method[18F]FDG‐PET images were acquired in ten‐month‐old APP/PS1 (TgF344‐AD, n = 8) and wild‐type (WT, n = 6) rats. Next, we evaluated the gene expression of NeuN, Olig2, GFAP, S100B, and IBA1 in the frontal and temporoparietal cortices and cerebellum. Association maps integrating mRNA with brain [18F]FDG‐PET signal were conducted at the voxel level using RMINC. [18F]FDG‐PET and brain tissue mRNA (GFAP, ACSA2, S100B, GLAST, IBA1, CSF1R, TREM2, Olig2, Cldn11, NeuN) of cognitively unimpaired patients were obtained from ADNI and Allen Brain Atlas database, respectively. In humans, mean regional [18F]FDG‐PET SUVr (reference region: pons) and mRNA expression were used to evaluate their association using a gaussian model. Differences were considered statistically significant at p<0.05 (t>2).ResultGFAP and S100B mRNA levels in the temporoparietal and frontal cortices positively correlated with brain [18F]FDG‐PET signal (local maxima, GFAPt(13) = 9.4, S100Bt(13) = 6.6; Fig1B‐C). No associations were found with TREM2, Olig2 and NeuN (t(13)<2; Fig1D‐F). We expanded our analysis by comparing gene astrocyte markers and astrocyte gene cell markers in humans. At the regional level, we found that FDG‐PET SUVr and astrocyte mRNA were positively associated: S100B (R‐squared = 0.34), GFAP (R‐squared = 0.33), GLAST (R‐squared = 0.31) and ACSA‐2 (R‐squared = 0.31; Fig1G).ConclusionOur findings suggest astrocyte mRNA markers are more closely associated with brain [18F]FDG‐PET signal than neuronal, oligodendrocyte, and microglial mRNA markers.