bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Assessment of Functional Competence in a Clinical Sample of Older Adults along the Alzheimer’s Continuum
Authors: Rahman Aneela , Pare Nadia , Schmitter‐Edgecombe Maureen , Cunningham Reanne , Behm Lillian , Patel Ved , Schmidt Erica , Warren David E , Rabin Laura 
Published: December 2022

AbstractBackgroundDifficulties in performing “Instrumental Activities of Daily Living” (IADL) such as managing finances and medications can lead to loss of independence among older adults. Performance‐based assessments allow for an objective and systematic quantification of IADLs utilizing real life paradigms. In an ongoing NIA‐funded study, we evaluated the association of a recently developed performance‐based assessment of functional ability (Night Out Task, NOT, Schmitter‐Edgecombe, 2021) with a performance‐based measure of financial capacity and an informant‐based measure of functional and decision‐making capacity in non‐demented older adults with varying degrees of cognitive impairment.MethodParticipants (n = 22; mean age = 76) were classified as healthy control (HC, n = 4), subjective cognitive decline (SCD, n = 9), or mild cognitive impairment (MCI, n = 9) based on clinical criteria. The NOT was used to evaluate the ability to efficiently and accurately plan, multitask and complete eight activities in preparation for a night out. The primary outcome variable for the NOT was completion time. Additionally, participants completed the Financial Capacity Instrument (FCI‐SF‐short form), which assesses financial knowledge and problem‐solving skills (Marson, 2015). Meanwhile, informants completed the Assessment of Functional Capacity Interview (AFCI; Pare et al., 2020) which captures decision making related to home safety, financial, medical, and social competence.ResultNOT scores were normally distributed, as assessed by Shapiro‐Wilk’s test (p > 0.05). We observed a statistical trend for group on NOT completion time such that greater clinical impairment was associated with greater completion time: MCI (M = 916.38s, SD = 218.54) > SCD (M = 741.83s, SD = 212) > HC (M = 728.05s, SD = 167.45). Similar trends were observed for other NOT variables. Correct sequencing and overall efficiency of NOT tasks were negatively correlated with AFCI Financial domain, r(21) = ‐0.606 and r(21) = ‐0.487, both P <0.05, respectively. Overall NOT task accuracy was negatively correlated with FCI‐SF Total Score, r(21) = ‐0.528, P <0.05.ConclusionThe NOT showed impressive associations with informant reports of functional and decision‐making capacity and objectively assessed financial capacity. The NOT can potentially distinguish among healthy controls and preclinical dementia groups, offering promise for early detection and characterization of cognitive changes.
Microtubule associated protein tau p.R406W patient carriers present with a nonconforming clinical phenotype
Authors: Gossye Helena , Van Mossevelde Sara , Sieben Anne , Bjerke Maria , de Craen Elisabeth Henndrickx Van , van der Zee Julie , De Deyn Peter Paul , De Bleecker Jan , Versijpt Jan , Van den Ende Jenneke , Deryck Olivier , Bourgeois Paul , Bier Jean‐Christophe , Goethals Maarten , Engelborghs Sebastiaan , Van Broeckhoven Christine 
Published: December 2022

AbstractBackground
MAPT p.R406W is an autosomal dominantly inherited missense mutation associated with FTLD with an amnestic, AD‐like phenotype. Our group first described a carrier pedigree (labeled ADG) in 2003, with 47 relatives.We aim to delineate phenotypic and genetic characteristics of MAPT p.R406W carriers through 19‐year follow‐up, and to provide first data on mutation frequency in FTD and AD.MethodWe extended the ADG pedigree, obtained data over 19 years on symptoms, biomarkers and neuropathology. Furthermore, we screened FTD (n=647) and AD (n=1100) patient cohorts for new carriers.ResultThe ADG family now counts 38 mutation carriers. 7 unrelated carriers were identified in AD and FTD cohorts. Inclusion of additional relatives procured 56 mutation carriers (39 affected).p.R406W mutation frequencies were 0.62% (FTD) and 0.27% (AD). All probands shared genetic kinship, suggesting a common ancestor.Average onset age and disease duration were 60.9 and 12.4 years (ranges 54‐69, 5‐25). Remarkably, two distinct phenotypes (clinical AD(n=10) or bvFTD(n=9)) emerged. bvFTD patients had significantly worse prognosis. Disinhibition/aggression were highly common (100% of bvFTD, 40% of AD patients). CSF amyloid‐β1‐42 was decreased in all 5 patients with CSF data, 2/5 with concomitant tau elevation. Neuropathology was FTLD‐tau, notably showing only 3R‐tau‐isoforms.ConclusionWe are first to report MAPT p.R406W mutation frequencies, unexpectedly high in FTD ànd AD. Contrary to previous reports, we observed a unique phenotypic shift in Belgian p.R406W carriers, with prominent behavioral symptoms, as well as memory decline. Surprisingly, CSF biomarkers showed decreased amyloid‐β1‐42, and neuropathology was FTLD‐tau with isolated 3R‐tau, highly unusual findings for this tauopathy.
Voxel‐wise Staging of Tau Pathology using [18F]RO‐948 PET in the Early AD Continuum
Authors: Shekari Mahnaz , Milà‐Alomà Marta , Falcon Carles , Niñerola‐Baizán Aida , Operto Grégory , Garcia Marina , Sánchez‐Benavides Gonzalo , Brugulat‐Serrat Anna , Tonietto Matteo , Borroni Edilio , Klein Gregory , Ashton Nicholas J. , Karikari Thomas K , Rodriguez Juan Lantero , Snellman Anniina , Ortiz‐Romero Paula , Vanmechelen Eugeen , Minguillón Carolina , Fauria Karine , Perissinotti Andrés , Molinuevo Jose Luis , Zetterberg Henrik , Blennow Kaj , Grau‐Rivera Oriol , Suárez‐Calvet Marc , Gispert Juan Domingo 
Published: December 2022

AbstractBackgroundTau positron emission tomography (PET) is a useful biomarker for detecting tau aggregation, one of the hallmark pathological findings in Alzheimer's disease (AD). The goal of this study is to characterize and stage the pattern of spreading of tau pathology across the brain in the early AD continuum.MethodForty‐seven cognitively unimpaired individuals from ALFA+ cohort had [18F]RO‐948 and [18F]flutemetamol PET, T1‐weighted magnetic resonance imaging(MRI), two cognitive assessments, cerebrospinal fluid(CSF), and blood biomarkers. Standardized uptake value ratio(SUVr) maps of [18F]RO‐948 PET images in MNI space created using inferior cerebellum as reference region. Participants were categorized according to the A/T system using pre‐established thresholds for CSF amyloid(A) and tau(T) positivity(Table1). A voxel‐wise hierarchical staging model was constructed based on data from the control group(A‐T‐). Voxel positivity was defined as SUVr higher than mean plus two standard deviations of control group(Figure1). Then, each voxel was assigned to one of 3 stages based on the frequency of its abnormality across the control group, dividing the voxel frequency histogram into 3 equally‐distributed groups. A given stage was assigned to each scan if, at least, 50% of the voxels on the stage mask were positive, hierarchically. That is, to determine stage 2, stage 1 needs to be positive as well. Otherwise, the scan is labeled as non‐stageable. Staging model performance was evaluated by recording the number of non‐stageable scans as well as by performing non‐parametric correlations between tau stages and CSF, blood biomarkers, cortical thickness, Centiloid(CL) as well as changes in cognition composites. Post‐hoc between‐stage comparisons were performed using the Kruskal‐Wallis test followed by a Bonferroni correction.ResultsAll scans were stageable. Twenty‐three scans were assigned to stage 0, 11 to stage 1, and 3 to stage 2(Figure2). Significant correlations between tau stages and CSF, blood biomarkers, Centiloid, cortical thickness as well as memory and attention changes were observed(Table2). Between‐group comparisons of tau stages vs biomarkers and changes in memory and attention were statistically significant(Figure3).ConclusionOur results suggest that the proposed voxel‐wise staging model is sensitive to capturing the spread of early tau pathology and useful for studying early AD pathophysiological mechanisms.
Evaluating Template Generation Methods for Spatially Normalizing Down Syndrome Brain Magnetic Resonance Images
Authors: Luo Weiquan , Minhas Davneet S , Tudorascu Dana L , Cohen Ann D , Ances Beau M , Zaman Shahid , Christian Bradley T , Klunk William E , Handen Benjamin L , Laymon Charles M 
Published: December 2022

AbstractBackgroundMagnetic resonance (MR) image registration and segmentation algorithms commonly used in studies of neurodegeneration have a higher failure rate for Down syndrome (DS) populations due to anatomical and morphological differences. For example, the Desikan‐Killiany atlas used by FreeSurfer was defined using MR images from cognitively normal adults and patients with Alzheimer’s disease (AD). The aim of this work was to evaluate three template generation methods (or group‐wise image registration) for spatially matching DS MR images and generating a DS cohort‐specific template.Method138 scans of DS subjects from the NiAD consortium were employed. The three template generation methods evaluated were DARTEL, SHOOT, and SyGN. DARTEL and SHOOT are implemented in the SPM12 (v7771) software package and operate on tissue segmentation maps. SyGN is implemented in ANTs software and operates on MR images. The data processing pipeline is presented in Figure 1. Scan‐specific grey matter (GM) and white matter (WM) tissue probability maps were generated using SPM12’s Unified Segmentation method for DARTEL and SHOOT, and MR images were skull‐stripped for SyGN. To evaluate spatial matching, all MR images were warped to each template space using method‐specific deformation fields and an average MR image was generated specific to each template method. Structural similarity index measure (SSIM) and Normalized Mutual Information (NMI) metrics were calculated on a scan specific basis relative to the average MR image for each template method. Lower SSIM and NMI measures effectively reflect greater spatial variability across DS scans and therefore worse spatial matching performance.ResultThe DARTEL and SHOOT tissue map (GM and WM) templates and SyGN MR template are presented in Figure 2. Average MRs for each template method are presented in Figure 3. Consistent relationships were observed between the 3 template generation methods for the mean (SHOOT > SyGN > DARTEL) and standard deviation (SyGN < DARTEL < SHOOT) of SSIM and NMI (Figures 4 and 5, Table 1).ConclusionWith relatively high means and the lowest standard deviation, SyGN produced robust spatial matching across all scans. Future Down syndrome MRI and PET image processing will make use of the SyGN template.
Relationship between MTA visual scale scores and hippocampal volume measured by a medicaldevice in patients from a multicentric memory clinic population
Authors: dos Santos Clarisse Longo , Cavedo Enrica , Gordon Elizabeth , Samper‐Gonzales Jorge , Schwarz Adam J. ,   MEMENTO study group
Published: December 2022

AbstractBackgroundThe medial temporal lobe (MTL), including the hippocampus, undergoes atrophy in patients with Alzheimer's disease (AD). Visual rating of medial temporal lobe atrophy (MTA) is often performed in the assessment of patients with cognitive impairment. Calculation of hippocampal volumes (HV) can also be achieved by multiple automated and semi‐automated methods using T1‐weighted MR images. The current study investigated the relationship between HV and z‐scores calculated by an automated method, included in the QyScore® medical device, and visual MTA rating scores using Scheltens’ scale in a multicentric memory clinic population at baseline.Method1959 participants from the MEMENTO cohort (Age 71.02 +/‐ 8.61, 1218 Female, MMSE 27.95 +/‐ 1.91) had 3DT1 MRI scans analyzed with QyScore®, an FDA‐approved and CE‐marked image analysis software. HV are reported in mL, corrected for % Intra Cranial Volume (ICV), and in z‐scores calculated relative to a cognitively normal population. 814 had amyloid status from CSF or PET, of which 216 were Amyloid+. Correlation between MTA scores and quantitative HV measurements was ascertained by Spearman’s rank correlation.ResultThere was a significant negative correlation between MTA scores and HV in %ICV (Left ‐0.62, p<0.001; Right ‐0.59, p<0.001) and z‐scores (Left ‐0.47, p<0.001; Right ‐0.43 p<0.001) for the total sample, as well as in Amyloid+ individuals HV in %ICV (Left ‐0.63 p<0.001, Right ‐0.58 p<0.001) and z‐scores (Left ‐0.50 p<0.001, Right ‐0.47 p<0.001). The correlation was also strong when separated by clinical diagnosis: patients with Subjective Cognitive Complaint (SCC, N= 306, AGE: 69.82 +/‐ 8.03, 196 female, MMSE: 28.86 +/‐ 1.17) and MCI (N = 1646, Age: 71.23 +/‐ 8.71, 1018 Female, MMSE: 27.79 +/‐ 1.95) presented MTA scores correlated both with HV in %ICV (Right= ‐0.47 p<0.001, Left= ‐0.50 p<0.001 for SCC; Right= ‐0.60 p<0.001, Left= ‐0.63 p<0.001 for MCI) and z‐scores (Right= ‐0.26 p<0.001, Left= ‐0.33 p<0.001 for SCC; Right= 0.44 p<0.001, Left= ‐0.49 p<0.001 for MCI).ConclusionThe automated quantification of ICV‐corrected HV and z‐scores were well‐correlated to MTA scores. QyScore® z‐scores may improve specificity in patients with cognitive impairment, by providing automated quantification of hippocampal atrophy directly compared with healthy ageing
Longitudinal CSF biomarker trajectories from middle age to late adulthood
Authors: Pettigrew Corinne , Soldan Anja , Wang Jiangxia , Wang Mei‐Cheng , Greenberg Barry , Albert Marilyn S. , Moghekar Abhay 
Published: December 2022

AbstractBackgroundCurrent cerebrospinal fluid (CSF) biomarker data of preclinical AD are based largely on cross‐sectional studies across the disease spectrum and short‐term longitudinal studies, with most studies conducted among older adults. However, neuropathological studies indicate that AD pathology is present in midlife. To better understand within‐person biomarker trajectories, we examined longitudinal changes in CSF biomarkers, potential modifiers (e.g., demographics, APOE4 genotype), and changes with respect to MCI symptom onset among participants who were primarily middle‐aged and cognitively normal at baseline, and have on average 10.7y of follow‐up (max 23y).MethodCSF was collected from 278 BIOCARD Study participants (M baseline age = 57.5y; Table 1); 94 (33.8%) have since progressed to MCI or dementia. These analyses focused on z‐transformed values of AB42/AB40, p‐tau181, and t‐tau, measured using the Fujirebio Lumipulse G1200 assays.ResultIn longitudinal mixed‐effects models, there were accelerated (quadratic) increases in p‐tau181 and t‐tau over time, and a trend for accelerated (quadratic) decreases in AB42/AB40 (p=0.09). APOE4 carriers had lower levels of AB42/AB40 at baseline and greater rates of change in all biomarkers (Table 2; Figure 1). Older participants had more abnormal baseline biomarker levels and greater rates of change in AB42/AB40 and t‐tau. Biomarker levels and trajectories were unrelated to sex and years of education. In a separate set of models, low baseline AB42/AB40 was associated with increases in p‐tau181 and t‐tau over time, whereas baseline t‐tau and p‐tau181 were not associated with change in AB42/AB40. Finally, compared to those who remained normal, those who progressed to MCI/dementia had more abnormal AB42/AB40, p‐tau181, and t‐tau at baseline, and greater rates of change in t‐tau and p‐tau prior to MCI clinical symptom onset.ConclusionThese results indicate that, in preclinical AD, lower levels of amyloid are associated with increases in p‐tau181 and t‐tau, while accelerations in p‐tau181 and t‐tau are more closely linked to MCI symptom onset. They also suggest earlier and greater rates of pathology accumulation among APOE4 carriers, but that sex and education‐related differences in AD dementia risk are not due to differences in AD biomarker accumulation early in the disease course.
Monitoring abnormal nocturnal behaviour in the homes of patients living with dementia ¶
Authors: Soreq Eyal , Kolanko Magdalena A , Monica Ciro della , Ravindran Kiran K.G. , Revell Victoria Louise , de Villèle Paul , Barnaghi Payam , Dijk Derk‐Jan , Sharp David J ,   CRT group
Published: December 2022

AbstractBackgroundPeople living with dementia (PLWD) often exhibit marked sleep disturbances. These cause substantial care challenges and may be causally related to dementia progression. Collecting ecologically valid data on sleep disturbance in naturalistic settings has been difficult. As a result, sleep assessments in PLWD are generally limited to short studies in sleep laboratories or data collection from wearables, where compliance is problematic. Here, we demonstrate how passive internet of things (IoT) sensors can be used to monitor the effects of dementia on nocturnal behaviour and physiology.MethodUsing the Withings under‐mattress pressure sensor, we validated bed occupancy and physiological measures in 35 older adults tested both at home and in the laboratory. We then examined data collected between 2019 and 2021 from the general population (N=13,663) and from a cohort of PLWD taking part in the UK DRI study of home monitoring for PLWD (N=46). More than 4 million unique bed mat observations were analysed.ResultArise time across all subjects was negatively correlated with time to bed (Fig.1a, r(13,617)=‐0.5, p<.0001). Bed occupancy increased with age, but PLWD spent more time in bed than age‐matched controls (Fig.1b) and had more nocturnal awakenings (Fig.1c). Explainable gradient boosting machine learning was successfully used to classify data from individual nights (PLWD vs. general population). PLWD probability was related to specific changes, such as increased awakenings, high or low time spent in bed, high heart rate and low breathing rate (Fig.2). We also explored variations in night‐time behaviour and physiology over time for individual PLWD (Fig.3a). High within‐subject variability was present, which related to disease progression, intercurrent illness and changes in medication. Data from each night was transformed into a risk score for each metric (Fig.3b) and a compound risk score. These quantify the risk of abnormal night‐time behaviour and physiology produced by dementia (Fig.3c) and reflect clinically relevant changes in PLWD.ConclusionTaken together our work demonstrates how digital biomarkers collected passively using under mattress technology can be used to automatically monitor the nocturnal effects of dementia across large populations. The approach is also potentially applicable for preclinical screening and the evaluation of treatments effects.
Brain TSPO expression is associated with plasma pTau181 & pTau231 across the AD spectrum
Authors: Rahmouni Nesrine , Therriault Joseph , Tissot Cécile , Lussier Firoza Z , Stevenson Jenna , Stevenson Alyssa , Servaes Stijn , Ashton Nicholas J. , Kvartsberg Hlin , Arias Jaime Fernandez , Wang Yi‐Ting , Kang Min Su , Gauthier Serge , Pascoal Tharick A , Zetterberg Henrik , Blennow Kaj , Benedet Andréa Lessa , Rosa‐Neto Pedro 
Published: December 2022

AbstractBackgroundMicroglial activation is an important component of the immune response in the brain of AD patients and has been shown to follow a similar propagation pattern to tau tangle accumulation. However, it is unclear to what extent cerebral microglial activation is associated with biofluid concentrations of phosphorylated tau (pTau). The objective was to investigate whether concentrations of pTau181 and pTau231 are correlated with microglial activation indexed by [11C]PBR28 PET across the AD spectrum.MethodThe present study was conducted in a population of 130 individuals from the Translational Biomarkers of Aging and Dementia (TRIAD) cohort: 20 young cognitively unimpaired, 65 cognitively unimpaired elderlies, 31 with mild cognitive impairment and 14 with AD dementia. Participants were evaluated with blood biomarkers and [11C]PBR28 PET. Plasma pTau181 and pTau231 concentrations were quantified using a Simoa assay. Microglial activation was assessed via [11C]PBR28 PET, standardized uptake value ratios (SUVRs) were calculated between 0 and 90 minutes post‐injection, using cerebellum grey matter as the reference region. Voxel‐based regression models evaluated the relationship between plasma pTau181 and pTau231 with neuroinflammation as assessed by PET, correcting for age and sex.ResultIn the present study, positive correlations were found between concentrations of both pTau181 and pTau231 and neuroinflammation indexed by PET‐imaging. Voxel‐level analyses indicated that these associations prenominated in regions of the default mode network including the precuneus, posterior cingulate cortex and medial prefrontal cortex. These regional associations survived corrections for multiple comparisons.ConclusionPeripheral phosphorylated tau is associated with neuroinflammation in brain regions associated with AD. Our findings highlight the importance of neuroinflammation in the pathogenesis of AD.
Consensus automatic speech recognition (CASR) in the California Cognitive Assessment Battery (CCAB)
Authors: Woods David L. , Hall Kathleen , Williams Garrett , Baldo Juliana , Johnson David K , Chok Jas M. , Sucich Gabriel , Pebler Peter , Blank Michael , Geraci Kristi , Herron Tim 
Published: December 2022

AbstractBackgroundRecent reports have investigated the use of automatic speech recognition (ASR) to analyze and score verbal responses in cognitive tests. ASR scoring is objective, permits the efficient computerized administration of verbal tests, and generates timestamps that enable the detailed temporal analysis of responses. However, ASR transcription accuracy varies by engine, task, and participant, and ASR can incorrectly score responses from participants with atypical speech patterns. Here we describe the speech‐transcription pipeline of the California Cognitive Assessment Battery (CCAB), which incorporates consensus ASR (CASR) to produce more accurate transcripts than possible with any single ASR engine. We also developed a Transcript Review Tool (TRT) which facilitates the manual correction of mis‐transcribed words in problem subjects.MethodFigure 1 shows the CCAB speech transcription pipeline. Realtime ASR transcriptions are obtained along with the transcriptions of the digital recordings of responses using six cloud‐based ASR engines (e.g., Google, etc.). Individual transcripts are then combined to produce a “consensus” transcript, and a transcription confidence measure based primarily on the agreement between ASR engines (Figure 2). If needed, “consensus” transcripts can be manually corrected using the Transcript Review Tool which enables the review of all words or just those words below a predefined CASR confidence threshold (Figure 3).ResultASR transcriptions were obtained from 442 healthy adults (mean age = 65.1 ±14.4) who each underwent three days of cognitive testing that included 25 verbal tests. In all, approximately 276 hours of speech were transcribed. Preliminary analyses show that CASR transcription accuracy surpassed 99% for tests with limited response sets (e.g., digit span, verbal list learning, face‐name binding, etc.) and exceeded 95% for discursive speech tests (e.g., picture description and logical memory).ConclusionCASR transcription is more accurate than that of any single ASR engine. When combined with the TRT, “consensus” ASR can produce error‐free, timestamped transcripts that enable the detailed analysis of verbal responses from older individuals at risk of cognitive decline.