bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regional differences in baseline demographic and clinical characteristics from the evoke and evoke+ trials of semaglutide for early Alzheimer’s disease
Authors: van der Flier Wiesje M. , Scheltens Philip , Feldman Howard H. , Hansson Oskar , Sano Mary , Bardtrum Lars , Johannsen Peter , Jeppesen Rose , Hansen Charlotte T. , Leon Teresa , Cummings Jeffrey L. 
Published: January 2025

AbstractBackgroundDifferences in patient characteristics across geographical regions may result in heterogeneity in clinical trial populations. evoke (NCT04777396) and evoke+ (NCT04777409) are two phase 3, multinational, randomised trials investigating semaglutide versus placebo in individuals with mild cognitive impairment or mild dementia due to Alzheimer’s disease (AD) (early AD). We present baseline characteristics across the geographical regions in evoke/evoke+.MethodBaseline data were pooled into five regions (Asia, Europe, Latin America [LATAM], North America and Rest of World [RoW]). Demographic and clinical characteristics were calculated for individual trials (evoke; evoke+), along with pooled data (evoke/evoke+ combined) for each region. Inclusion criteria were the same for both trials; except that evoke+ allowed the inclusion of participants with significant small vessel pathology (>1 lacunar infarct and/or >2 age‐related white matter changes [white matter >20 mm]).ResultOf the 3,806 individuals with early AD enrolled, there were 1,986, 707, 602, 303 and 208 in Europe, North America, Asia, LATAM and RoW, respectively. Screening failure rates were 54.6‐67.8% across regions and highest in North America. Mean age was 71.7‐73.3 years, and 46.3‐59.1% of participants were female (Table 1). Cognitive scores were similar across regions: mean (standard deviation) Mini‐Mental State Examination score was 23.6 (3.3) to 24.6 (2.9) and Clinical Dementia Rating‐Sum of Boxes score was 3.5 (1.6) to 4.2 (1.8) (Table 2). In evoke+, small vessel pathology was lowest in Europe (2.3%) and highest in Asia (3.8%). Apolipoprotein E4 carrier status was lowest in the LATAM region (51.4%) and highest in the RoW (70.5%), and the proportion of individuals with type 2 diabetes ranged from 11.3‐21.1%. Overall, 51.9‐64.3% of individuals received AD medication, with the highest and lowest use in Asia and North America, respectively.Conclusionevoke and evoke+ successfully recruited individuals with early AD from all over the world, ensuring that semaglutide will potentially benefit individuals of various races and ethnicities. Despite this diversity, cognitive scores were largely similar across all geographical regions. Understanding this baseline data will allow for generalisation of the evoke/evoke+ results to worldwide populations with early AD.
Improving the preanalytical stability of Alzheimer’s disease plasma biomarkers: the impact of blood collection tubes supplemented with protease inhibitors
Authors: Chen Yijun , Zeng Xuemei , Lee Jihui , Sehrawat Anuradha , Lafferty Tara K , Boslett James J , Klunk William E , Pascoal Tharick A. , Villemagne Victor L , Cohen Ann D , Lopez Oscar L. , Yates Nathan , Karikari Thomas K 
Published: January 2025

AbstractBackgroundThe detection and monitoring of Alzheimer's disease (AD) biomarkers in plasma are crucial for early diagnosis and prognosis. However, the stability of plasma AD biomarkers can be compromised by the degradation caused by endogenous proteases present in blood. The efficacy of protease inhibitors in mitigating this degradation is yet to be established. This study evaluated the stability of five plasma AD biomarkers (GFAP, NFL, Aβ1‐40, Aβ1‐42, and pTau181) in plasma over time under room temperature (RT) conditions. Samples were collected concurrently into either standard K2EDTA or BD‐P100 tubes, with the latter being coated with protease inhibitors. Our objective was to assess the effectiveness of protease inhibitors in preserving the stability of plasma AD biomarkers in plasma.MethodWe evaluated two experimental approaches. In Approach 1, whole blood samples (n=16) from the same draw were collected into K2EDTA and BD‐P100 tubes and stored at RT for 0h and 24h. In Approach 2, plasma samples (n=19) were isolated from whole blood collected into BD‐P100 and K2EDTA tubes and immediately stored at RT for 0h, and 24h. The levels of plasma AD biomarkers were measured using immunoprecipitation with mass spectrometry (IP‐MS) and Single Molecule Array (SIMOA). The IP‐MS assay replicated a protocol (Nakamura et al., 2018) for Aβ1‐40 and Aβ1‐42 measurement.ResultThe IP‐MS assay indicated that the use of BD‐P100 tubes significantly reduced Aβ peptide degradation compared with the K2EDTA tube. In Approach 1, the IP‐MS Aβ signal decreased by 23‐34% for samples collected in K2EDTA tubes relative to 17‐18% for samples collected in BD‐P100 tubes. In Approach 2, the IP‐MS Aβ peptide signal decreased by 14‐16% for K2EDTA tubes, with a lower decrease of 3‐7% for BD‐P100 tubes. The SIMOA assays produced similar results for Aβ peptides. No significant variations were detected in time‐dependent pTau181, GFAP, and NFL levels for samples collected using both tubes.ConclusionThe study showed that tubes supplemented with protease inhibitors significantly improve the preanalytical stability of Aβ1‐40 and Aβ1‐42 in plasma. These results have important implications for preanalytical procedures that are needed to enable widespread access and utilization of plasma biomarkers in resource‐limited settings.
Superiority of p‐tau217 among plasma biomarkers in diagnostic accuracy in non‐demented persons from the Geneva Memory Center cohort
Authors: Mendes Augusto J. , Ribaldi Federica , Lathuiliere Aurelien , Ashton Nicholas J. , Janelidze Shorena , Zetterberg Henrik , Scheffler Max , Assal Frederic , Garibotto Valentina , Blennow Kaj , Hansson Oskar , Frisoni Giovanni B. 
Published: January 2025

AbstractBackgroundThe identification of Alzheimer's disease (AD) pathology at an early stage utilizing plasma biomarkers has attracted significant interest due to its potential for improving global screening programs. Different forms of p‐tau measured in plasma, mainly p‐tau217, have demonstrated similar diagnostic accuracy when compared to traditional biomarkers. Moreover, plasma biomarkers associated with neuroinflammation and neurodegeneration, namely GFAP and NfL, respectively, have been found to be elevated in patients with amyloidosis and tau accumulation, even though these conditions are not exclusive to AD.MethodOur goal was to see if there were any differences in plasma biomarkers between amyloid (A+) and tau (T+) positive groups based on PET scans and compare their diagnostic accuracy in a Geneva Memory Center non‐demented group. Plasma, amyloid‐PET, and tau‐PET were assessed in a total of 100 subjects (CU = 33; MCI = 67). Plasma biomarkers included were p‐tau217, p‐tau231, p‐tau181, GFAP, and NfL. The differences in each plasma biomarker among A+/T+ groups were tested using Kruskal‐Wallis tests. Additionally, we calculated the receiver operating characteristic (ROC) and underlying area under the curve (AUC) in A+ and T+.ResultAll plasma biomarkers revealed significant differences between A‐/T‐ and A+/T+ (p < 0.05), where p‐tau217 showed a higher effect size (δ = 0.98) in comparison with other biomarkers (δrange = 0.31 ‐ 0.67). Moreover, p‐tau217 was the only biomarker displaying significant differences between A‐/T‐ and A+/T‐ (p < 0.001; δ = 0.89). Lastly, p‐tau217 showed a higher AUC for detecting amyloid and tau (AUCaverage = 0.96) than other p‐tau forms (AUCaverage = 0.77) and GFAP/NfL (AUCaverage = 0.69).ConclusionPlasma p‐tau217 revealed superior performance in AD pathology detection when compared to other p‐tau forms and plasma biomarkers of neuroinflammation/neurodegeneration. Our results suggest the potential of p‐tau217 to identify AD pathology in a non‐demented population.
Correlation Between Cognitive Impairment in Early‐Stage Amyloid‐Positive Alzheimer's Disease and CA1 Hippocampal Subfield Volume Loss Using 7T MRI
Authors: Adeyemi Oluwatobi F , Mougin Olivier , Penny Gowland , Bowtell Richard , Mukaetova‐Ladinska Elizabeta , Hosseini Akram A. , Shah Jagrit 
Published: January 2025

AbstractBackgroundEarly diagnosis is crucial in Alzheimer's disease (AD) for optimal treatment outcomes. Neuropsychometric assessments, particularly using the Uniform Data Set Neuropsychological Battery (UDSNB3.0) [1], provide insights into cognitive domains in early stages of Alzheimer’s disease before significant hippocampal atrophy occurs. This study leverages 7T MRI, which offers superior spatial resolution, to investigate these correlates.MethodForty‐seven participants were recruited (24 AD patients and 23 matched healthy controls [HC]; age range: 40 ‐ 76 years). Participants selected for the study met the ATN criteria [2] for symptomatic Alzheimer's disease with CSF‐Amyloid positivity. Participants with significant hippocampal atrophy (i.e. MTA score of >2 on clinical MRI at 1.5/3T [3] were excluded. Imaging was carried out on a Philips Achieva 7T scanner equipped with a Nova Medical single‐channel transmit and 32‐channel receive (1Tx32Rx) head coil. The acquired images included PSIR sequences (TE/TR=3.1/6.9ms; FA=60°) with isotropic 0.55 mm resolution, as well as T2‐weighted FSE sequences (TE/TR=119/5900ms; FA=90°) with a resolution of 0.38x0.39x1.50 mm³.ResultThe reduction in the volume of CA1 hippocampal subfield in patients with AD significantly correlated with multiple cognitive domains, highlighting its central role in various aspects of cognitive function (see Table 1 and Figure 2). The change in volume was not significant for the whole brain showing that the hippocampus was changing particularly and not simply as part of general brain atrophy.A significant linear correlation was evident between the volume of CA1 and the total MoCA score (R2 = 0.47; p=0.02), indicating a particularly strong correlation with the memory category with p<0.05. There were also significant correlations between CA1 and specific cognitive subdomains including executive function, attention, language, Orientation, Craft Story Immediate, Number Span Backward.ConclusionThe observed result, indicating a robust correlation between the CA1 hippocampal subfield volume and various cognitive measures, in the early stages of Alzheimer's disease, provides valuable insights into the intricate relationship between neuroanatomy and cognitive function.
Neurobiological and clinical characteristics of amnestic patients with Lewy body pathology
Authors: Silva‐Rodríguez Jesús , Moscoso Alexis , Labrador‐Espinosa Miguel , Sanchez‐Juan Pascual , Schöll Michael , Grothe Michel J. 
Published: January 2025

AbstractBackgroundWhile Lewy body (LB) pathology typically associates with a distinct clinical profile compared to Alzheimer’s disease (AD), early memory deficits are not uncommon and can confound clinical diagnosis of amnestic patients. Moreover, approximately 30‐60% of AD patients have concomitant LB pathology, which has been reported to affect the clinical phenotype and result in a more aggressive disease course. Recently developed α‐synuclein seed amplification assays (αSyn‐SAAs) have demonstrated high diagnostic accuracy for LB diseases, but the role of these novel biomarkers in the context of amnestic presentations typical for AD remains to be investigated in more detail.MethodWe studied 872 patients from the ADNI cohort with a baseline diagnosis of aMCI (N=661) or AD dementia (N=211), who had CSF and FDG‐PET data available. CSF samples were analyzed for peptide levels of Aβ1‐42 and p‐tau181, and αSyn positivity was evaluated using a novel αSyn‐SAA. Based on positive/negative results on the different biomarkers, subjects were grouped into “AD‐/LB‐” (A‐T‐αSyn‐, N=106), “AD+/LB‐” (A+T+αSyn‐, N=336), “AD+/LB+” (A+T+αSyn+, N=158) and “AD‐/LB+” ((A‐|T‐)αSyn+, N=68). We analyzed group differences in demographics, APOE4 positivity, neurodegeneration patterns (FDG‐PET), as well as baseline and longitudinal scores of global cognition (MMSE) and domain‐specific function (ADNI_MEM, ADNI_EXEC).ResultAt baseline, AD+/LB+ showed worse global cognition (MMSE: d=‐0.27, p=0.004) and memory performance than AD+/LB‐ (ADNI_MEM: d=‐0.26, p<0.006). AD‐/LB+ were less globally impaired (p<0.001) and characterized by a markedly more dysexecutive profile (d(MEM‐EXEC): p<0.002). AD+/LB+ progressed faster on all cognitive scores, but they did not develop a differential cognitive profile compared to AD+/LB‐ (Figure 1). APOE4 positivity was similar between AD+/LB+ and AD+/LB‐ (72% vs. 75%, p=0.28) but lower in AD‐/LB+ (28%, p<0.001). In FDG‐PET, AD+/LB+ was characterized by a temporo‐parietal hypometabolism pattern similar to that of AD+/LB‐ but with higher effect sizes (Fig‐2). By contrast, AD‐/LB+ showed a strikingly different posterior‐occipital pattern of hypometabolism.ConclusionLB co‐pathology in AD was associated with more severe neurodegeneration and faster cognitive decline, but an amnestic AD‐typical phenotype. By contrast, patients with relatively pure LB pathology were characterized by a more dysexecutive cognitive profile and a distinct hypometabolism pattern typically suggestive of LB disease.
The State of the Art in mobile Augmentative and Alternative Communication Devised for People with Dementia: Evaluation of Features and Functions
Authors: Muñoz Mariateresa (Teri) H , Okine Joana , Brown Ellen L , Ruggiano Nicole 
Published: January 2025

AbstractPatients with dementia (PWD) often face challenges with daily activities due to communication challenges, which may lead to negative outcomes for those with dementia and their family caregivers alike. Augmentative and alternative communication (AAC) devices have demonstrated to be feasible in supporting communication among PWD (May et al., 2019) through text, graphics, and/or sound. Traditional AAC devices have been non‐electronic memory and communication aids (May et al., 2019). However, in recent years many primary caregivers of PWD are seeking out mobile applications to address this challenge using their smartphone or tablet. However, mobile applications addressing communication skills specifically for dementia care are scarce despite their potential to improve quality of life (Ambegaonkare et al., 2021; Brown et al., 2023). To better understand the current landscape of AAC mobile applications, this systematic review identified and evaluated the features and design of commercially‐available mobile applications. A total of 27 AAC apps were identified through searches on the Apple IOS store and Google Play, after excluding duplicates and apps that targeted primarily children. Four research team members were involved in cataloging features and evaluating the apps using a modified version of the Mobile App Rating Scale (Stoyanov et al., 2015). The price of apps varied, though many listed as being free or low‐cost often required higher‐priced subscriptions or licensing fees. All apps were compatible for English speakers, though several were available in multiple languages. It was found that the apps varied in their potential for engagement, functionality, aesthetics, and information. It was also found that many apps are limited in their potential to support caregiving activities (e.g., mealtime, dressing) for those with communication barriers related to cognitive impairment. Apps that are limited in their ability to customize the interface to the user’s preferences for daily care may impede person‐centered care practices for PWD. Implications for practice, policy, and research are discussed.
Do glial‐reactivity and cerebral blood flow modulate cerebral glucose metabolism in Alzheimer’s disease?
Authors: Nowell Joseph , Femminella Grazia Daniela , Ritchie Craig , Holmes Clive , Walker Zuzana , Ridha Basil H , Lawrence Robert M , McFarlane Brady , Archer Hilary , Coulthard Elizabeth , Underwood Benjamin R , Koranteng Paul , Karim Salman , Prasanna Aparna , Junaid Kehinde , McGuinness Bernadette , Nilforooshan Ramin , Thacker Simon , Russell Gregor , Malik Naghma , Mate Vandana , Knight Lucy , Kshemendran Sajeev , Holscher Christian , Harrison John E , Hinz Rainer , Tadros George , Passmore Anthony Peter , Ballard Clive G , Edison Paul 
Published: January 2025

AbstractBackgroundAlzheimer’s disease is a devastating neurodegenerative disorder with a complex pathogenesis. One main pathological feature utilised in diagnosis is neurodegeneration or neuronal injury, which is reflected in reductions in cerebral glucose metabolism measured by [18F]Fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET). Here we evaluated the involvement of glial reactivity measured with magnetic resonance spectroscopy (MRS) and cerebral blood flow measured with arterial spin labelling (ASL) on [18F]FDG PET as a measure of cerebral glucose metabolism.Method123 people living with early Alzheimer’s disease who completed baseline evaluations on the evaluating liraglutide in Alzheimer’s disease trial were enrolled. Participants completed [18F]FDG PET scans with arterial input, T1 weighted MRI, single‐voxel 1HMRS, and pulsed ASL scans at Imperial College London Clinical Imaging Facility. The Totally Automatic Robust Quantitation in NMR (TARQUIN) package was used to process MRS scans and identify the concentration of myo‐inositol within the posterior cingulate cortex (PCC), a marker of glial activation. Oxford‐ASL was utilised to process ASL and quantify cerebral blood flow in the PCC. Finally, spectral analysis was performed on the [18F]FDG PET scans to assess the cerebral metabolic rate of glucose in the PCC.ResultPearson’s correlations were performed between the cerebral metabolic rate of glucose, cerebral blood flow and glial activity measured by the level of myo‐inositol in the PCC. Increased cerebral glucose metabolism was correlated with higher myo‐inositol in this sample of Alzheimer’s disease participants. In contrast, cerebral blood flow was not associated with cerebral glucose metabolism.ConclusionHere we demonstrate that increased glial reactivity contributes to [18F]FDG PET signal in the early stages of Alzheimer’s disease. In response to early neuronal injury, astrocytes and microglia may become activated and enhance regional rates of glucose consumption. Hence, the contribution from these cells in addition to neurons should be considered in interpreting [18F]FDG PET as a measure of cerebral glucose metabolism. Interestingly, cerebral blood flow did not influence glucose metabolism. Microglia and astrocyte reactivity may contribute to an increase the cerebral glucose metabolism while neuronal loss and synaptic function may contribute to lower glucose metabolism measured by [18F]FDG in the early stages of Alzheimer's disease.
A Clinical Decision‐Making Tool to Identify Red Flags for Remote Cognitive Assessment: An Expert Consensus Study from the Canadian Consortium on Neurodegeneration in Aging
Authors: Friedman Nathan , Itzhak Inbal , Desmarais Philippe , Fisk John D , Lee Linda , Henri‐Bhargava Alexandre , Pettersen Jacqueline , McLaughlin Paula M , Ismail Zahinoor , Khanassov Vladimir , Freedman Morris , Chertkow Howard , Camicioli Richard , O'Connell Megan E , Geddes Maiya R. 
Published: January 2025

AbstractBackgroundRemote diagnostic assessment of cognitively impaired individuals offers numerous potential benefits including increased access to care. However, remote cognitive and behavioral assessment also has limitations, and may not be appropriate for certain patients. Currently, evidence‐based guidance on virtual assessment readiness is lacking. Our goal was to develop a clinical decision‐making tool that outlines an approach to determining a patient’s suitability for undergoing remote cognitive and behavioral diagnostic assessment by identifying ‘red flags’ for remote assessment. To address this goal, a multidisciplinary workgroup was convened under the auspices of the Canadian Consortium on Neurodegeneration in Aging (CCNA). This workgroup was composed of experts in remote assessment and included behavioral neurologists, neuropsychiatrists, neuropsychologists, social workers, geriatricians, persons with lived experience and family medicine specialists.MethodsThe Delphi process is an iterative, systematic, group consensus method, used here to determine the features of the patient, caregiver, clinician and context/situation, or ‘red flags’, indicating that a remote cognitive diagnostic assessment should be avoided. The process consisted of anonymized data collection in three rounds among the multidisciplinary expert workgroup, culminating in two rounds of iterative scoring of potential red flags based on three quality indicators that assessed a potential red flag’s effectiveness, reproducibility, and efficiency. Red flags that received an overall mean score above the pre‐determined consensus threshold on the final round were included in the final clinical decision‐making tool.ResultIn the first round, 11 respondents, with an average of 12.4 years of clinical experience, generated 67 unique potential red flags. In the second and third rounds, 8 and 9 respondents, respectively, scored the flags on the three quality indicators. Applying consensus criteria yielded 14 red flags that achieved consensus.ConclusionTo enhance the translation and implementation of these findings, we developed a clinical decision‐making tool and infographic describing the final set of red flags in collaboration with the CCNA knowledge translation team. This infographic is designed to help clinicians determine a patient’s readiness to undergo remote cognitive assessment. This study directly impacts the clinical care of cognitively impaired individuals by providing clinical decision‐making guidance on a patient’s suitability for remote neurobehavioral assessment.
A Review of Dementia Patients in a Local Neuro‐cognitive Clinic
Authors: LAI King Son 
Published: January 2025

AbstractBackgroundIt is more ideal to manage dementia patients in memory clinics but not all of them are referred to such clinics. Also, the characteristics of these patients are less studied and local published data is limited. In 2004, the Neuro‐cognitive Clinic of Alice Ho Miu Ling Nethersole Hospital was established. Situated inside the Geriatric Day Hospital, this clinic receives full support from other allied health departments (e.g. physiotherapy and occupational therapy departments). It serves patients living in the district presenting with neuro‐cognitive problems, who are attended by geriatric specialists or higher trainees in geriatric medicine under specialists’ supervision.Objective and MethodIt is a retrospective study to analyse the characteristics of patients attending this clinic in the past 10 years and their changes in function over time. The demographic data, medical comorbidities, mobility status, functional level, neuro‐cognitive and neuro‐psychiatric functions of the patients at our clinic were reviewed and the changes over three years were analysed.ResultsAmong the 320 patients of age 65 or above, over 60% were female. More than 90% of them presented with memory deficit as the chief complaint. Alzheimer’s disease (AD) was the commonest dementia subtype, representing nearly half of all the cases, and was followed by mixed dementia and vascular dementia. The mean MMSE score at initial presentation was 16.4. Hypertension, hyperlipidaemia, diabetes mellitus and history of cerebrovascular diseases (stroke) were common medical comorbidities. Nearly all patients had an initial radiological neuroimaging for evaluation, mostly computed tomography scan of the brain. While findings of small vessel disease, lacunar infarcts and periventricular ischaemia largely predominated in vascular dementia patients (83.0%), such findings were also found substantially in AD patients (50.3%) in contrast to cerebral atrophy (18.3%) and normal (25.5%). More than half of all patients were prescribed with anti‐dementia drugs. AD patients taken anti‐ dementia drugs showed a slower decline of MMSE score at three years than those without anti‐dementia drugs.ConclusionThis study provided some important data on the characteristics of dementia patients in a local neuro‐cognitive clinic in various aspects, and many of them were comparable with other published international studies.