bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expectation and perspectives of patients and physicians on new treatment for early Alzheimer Disease: Results of a physician survey and patient focus group interview
Authors: Bell Joanne , Kurzman H. Ricky , Borentain Stephane , Paulsen Russ , Holzapfel Andrew , Hampel Harald 
Published: January 2025

AbstractBackgroundWith the recent approval of disease modifying therapies (DMT) for early Alzheimer’s disease, there is a need for prescribing physicians to accurately communicate expectations of treatment effects to patients and their care partners. To better understand potential challenges and solutions to enhance this communication, physicians were surveyed, after which patients and care partners participated in focus groups.MethodStep one consisted of an online survey of 100 US‐based neurologists, geriatric medicine specialists and Alzheimer’s disease specialists to ascertain physician perspectives on meaningful benefits associated with anti‐amyloid monoclonal antibody treatment (DMT) over currently available symptomatic treatments. Informed by the physician survey findings, six focus groups collected qualitative narratives from patients and their care partner(s). The objectives were to explore patient and care partner treatment goals, their experience with symptomatic treatment and their expectations for new therapies.ResultsPhysicians reported that the main concerns for patients and their care partner are memory loss (84%) behavioral and mood changes (51%) and ability to complete daily activities (51%). Most physicians expected a DMT to be effective in slowing the disease progression, and 66% expected to see cumulative benefit over time with continued treatment. Physicians reported that being able to perform activities of daily living (84%), maintaining quality of life (79%) and remaining independent (77%) are the most meaningful treatment outcomes for patients. Physician expectations were largely similar between symptomatic treatment and DMT. During the focus groups, patients and care partners noted the impact on financial status, social interaction, and loss of independence to be the three major areas of concern associated with their diagnosis. Focus group participants noted that maintaining their current state longer is a meaningful treatment outcome and prioritized three domains: effective communication, thinking clearly and less fear while performing daily activities.ConclusionThis research suggests the need for a better physician/patients‐care partner communication on appropriate treatment expectations and for the development of tools to facilitate this communication. Findings from this research need to be confirmed by a large survey of a nationally representative sample of US patients.
Spatial and sex‐specific hippocampal proteomic analysis of an early Alzheimer’s disease mouse model using MALDI‐imaging
Authors: Contreras Ana , Jimenez‐Herrera Raquel , Djebari Souhail , Mulero‐Franco Jaime , Navarro‐López Juan D. , Jimenez‐Diaz Lydia 
Published: January 2025

AbstractBackgroundA key neuropathological feature in the early stages of Alzheimer's disease (AD) involves hippocampal dysfunction arising from the accumulation of amyloid‐β (Aβ). Previously, our laboratory identified a shift in the synaptic plasticity long term potentiation (LTP)/long term depression (LTD) induction threshold, leading to memory deficits in a non‐transgenic murine model of early AD generated by intracerebroventricular (icv.) injections Aβ1‐42 oligomers (oAβ1‐42), one of the most predominant pathogenetic factors in initial stages of the disease. However, the specific alterations in proteins within hippocampal subfields remain uninvestigated. Here, we hypothesized that there might be unique protein changes in the hippocampus induced by oAβ1‐42 and potentially influenced by sex‐dependent factors.MethodTo do so, we evaluated hippocampal‐dependent memory using a Barnes maze and the Object location memory test (OLM) in the non‐transgenic model of early AD. Both memory encoding and retrieval deficits were shown 1 hour post‐icv. injection, although no significant sex differences were found. Then, an innovative spatial proteomic study was performed to assess the hippocampal proteome using matrix‐assisted laser desorption/ionization (MALDI) imaging mass spectrometry that allows peptide detection with spatial resolution directly on tissue sections.ResultResults from sixteen brains from C57BL/6 adult male and female mice 1 hour post‐icv. injected with oAβ1‐42 or vehicle were analyzed. MALDI imaging was performed using a RapifleXTM MALDI TissuetyperTM TOF/TOF mass spectrometer followed by protein identification by traditional MS/MS directly on the tissue. To precisely delineate anatomical hippocampal region and subfields, a Nissl staining was performed at adjacent tissue sections. More than 600 peptides were detected, and several of them showed significant differences in expression levels due to treatment or sex. To further analyze the data, the protein‐protein interaction (PPI) between the identified changed proteins was analyzed using the STRING database.ConclusionThe specific hippocampal subfields changes in the proteome caused by early amyloidosis provide new insight in the pathogenesis of AD and valuable potential biomarkers for early diagnosis and potential therapies.Acknowledgements: Grants PID2020‐115823‐GB100/ MCIN/AEI/10.13039/501100011033 and SBPLY/21/180501/000150/ JCCM and “ERDF A way of making Europe” both to LJ‐D and JDN‐L. Margarita Salas Postdoctoral Research Fellow to AC funded by European Union NextGenerationEU/PRTR.
Implementation of Digital Cognitive Assessment for Early Detection of Cognitive Impairment: A Davos Alzheimer’s Collaborative Flagship Site
Authors: Kowa Hisatomo , Morimoto Kohei 
Published: January 2025

AbstractBackgroundIn Japan, the number of patients with dementia is increasing and there is a shortage of human resources who can conduct detailed psychological examinations, and the development and implementation of new tools is essential for improving dementia care. Japan is one of seven sites across the globe focusing on healthcare system preparedness as part of the Davos Alzheimer’s Collaborative Early Detection flagship program. As part of this program, Japan implemented new tools including a digital cognitive assessment (DCA) and blood‐based biomarker (BBM) to increase rates of early detection of cognitive impairment.MethodsPatients 60+ years old were given a Mini‐Mental State Examination (MMSE), a common pen‐and‐paper test of cognitive function, and based on the score, primary care providers recorded a pre‐referral diagnosis. Patients who scored abnormal or borderline on the MMSE were then referred to a specialist center and completed a full work‐up including a clinical and psychological examination, a DCA (Cogstate Cognigram), blood test for reversible causes, imaging (i.e., MRI, perfusion SPECT), and a BBM (C2N PrecivityAD). Based on the results from the full clinical work‐up, the specialist provided a post‐referral diagnosis.ResultsIn the early detection program, the MMSE detected 46 total patients with cognitive impairment (MMSE scores ≥10 and <28), with 33 (72%) cognitively abnormal and 13 (28%) borderline scores. The number and type of pre‐referral diagnostic assessment made based on the MMSE scores and from the post‐referral diagnosis following the full clinical work‐up are provided in Table 1. There was good agreement between the initial and final diagnosis, with 8 total changes in diagnosis. The most notable changes came in the Alzheimer Disease diagnosis category where there was a net increase in 4 diagnoses of AD (2 were reversed and 6 new diagnoses of AD were added).ConclusionComprehensive assessments, including implementing new tools like a DCA and BBM, along with traditional clinical examination are necessary to make an accurate diagnosis. Initial findings from the Japan flagship site contribute to the global learnings to help speed and scale future innovations and developments in order to reach the right patients at the right time.
Presymptomatic Detection and Monitoring of Alzheimer’s Disease Using a Multi‐Disease Diagnostic Platform Employing Autoantibodies as Blood‐based Biomarkers
Authors: DeMarshall Cassandra , Viviano Jeffrey , Sahin Mert , Nagele Robert ,   the Parkinson’s Study Group (PSG), and the Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Published: January 2025

AbstractBackgroundIt is well known that Alzheimer’s disease (AD)‐related pathological changes can begin up to a decade before patients experience telltale symptoms, yet presymptomatic detection remains an unmet goal. In the present study, we demonstrate the utility of a panel of autoantibodies capable of detecting AD‐related pathological processes at the earliest points along the AD continuum, including presymptomatic AD (up to 10 years before onset of symptoms) and prodromal AD (mild cognitive impairment, MCI).MethodUtilizing Duritect‐ADTM, a blood‐based test employing a customized panel of autoantibody biomarkers and Luminex xMAP® technology, sera from ADNI subjects with confirmed presymptomatic or prodromal AD (MCI) were screened to detect the presence of AD‐related pathology. Autoantibodies in this panel showing consistently increased titers in MCI and presymptomatic AD relative to controls were evaluated using Random Forest and Receiver Operating Characteristic curves for their ability to distinguish diseased subjects from age‐ and sex‐matched controls, as well as from individuals with other neurodegenerative and non‐neurodegenerative diseases.ResultHere, we present results from analytical validation of the Duritect‐ADTM Test. Previous published results showed that a panel composed of eight autoantibody biomarkers differentiated ADNI participants with confirmed prodromal AD from corresponding age‐ and sex‐matched controls with 96% accuracy, 92% specificity and 100% sensitivity. These same autoantibody biomarkers were also capable of identifying cognitively normal subjects who later converted to MCI or AD, years before the onset of symptoms.ConclusionResults demonstrate the utility of the Duritect‐ADTM blood‐based autoantibody test as an accurate, non‐invasive, and inexpensive diagnostic screener, not only for detection of early, AD‐related pathology associated with prodromal AD (MCI), but also at earlier presymptomatic disease stages, several years before the onset of clinical symptoms.
Effect of diagnostic and genetic status on the relationship between rs‐fMRI complexity and tau & amyloid PET in Alzheimer’s disease
Authors: Jann Kay , Cen Steven , Santos Mariella I , Wijesinghe Dilmini , Zhang Ru , Ringman John M , Wang Danny JJ 
Published: January 2025

AbstractBackgroundNon‐linear statistical analyses on resting‐state fMRI (rs‐fMRI) using complexity measures have demonstrated progressive decline in complexity from cognitively normal subjects (CN) to patients with Mild Cognitive Impairment (MCI) and patients with Alzheimer’s disease (AD). While complexity has been shown to be negatively associated with tau‐PET, the association with amyloid or effects of genetic characteristics (APOE4) remains unknown.MethodFrom the Alzheimer’s Disease Neuroimaging Initiative (ADNI3) we identified participants with tabulated SUVR values for amyloid and tau as well as one resting state fMRI scan for the same visit. The rs‐fMRI complexity was calculated as Multiscale Sample Entropy (MSE) (r=0.5, m=2, scale=6). SUVR values from precuneus, parahippocampal, inferior temporal and entorhinal regions were used in a multivariate generalized linear model to investigate the adjusted independent effects to corresponding rs‐fMRI complexity. Whether such effects were modified by either diagnosis (CN, MCI, AD) or APOE4 status (# alleles) were tested using the interaction terms in the multivariate model. Age and gender were controlled for all models.ResultThe final cohort consisted of 127 subjects (Table 1). We observed statistically significant negative associations between complexity and tau in parahippocampus, inferior temporal gyrus and precuneus (Table 2A). Diagnostic status does not modify these associations, however, APOE4 status showed a statistically significant interaction effect for tau and complexity in precuneus (Table 2C). For amyloid no associations nor interaction effects were found (Table 2B).ConclusionOur study confirmed previously reported statistically significant inverse relationship between rs‐fMRI complexity and tau‐PET, which is indicative of disfunction of neuronal signaling in the presence of tauopathy. While diagnostic classification showed no effects, the APOE4 genetic risk had a strong modifying effect leading to a stronger negative relationship between tau‐PET and fMRI‐complexity. The null‐finding for amyloid was expected, since, while the presence of amyloid increases risk for cognitive decline, it is the occurrence of tau that leads to cognitive decline and neurodegeneration. Overall, genetic risk potentially increases the prevalence of amyloid in this cohort and consequentially leads to a cumulative and more pronounced decrease in rs‐fMRI complexity in the presence of tau.
TTR cardiac amyloidosis, polyneuropathy, and dementia at old age – bystander, cause or “smoking gun” guilty by association
Authors: Petrea Rodica Elena , Turk Katherine W. , Knobel Mark D , Charidimou Andreas , Budson Andrew E. 
Published: January 2025

AbstractBackgroundMixed dementia type – Alzheimer’s Disease (AD), cerebral amyloid angiopathy (CAA), and vascular ‐ is vastly recognized as a cause of dementia in older adults. Whereas CAA, primarily leptomeningeal, is a frequent complication in hereditary transthyretin cardiac amyloidosis (TTRCA), it is unusually reported in association with wild‐type TTR, with or without polyneuropathy. The knowledge of mixed dementia and wild‐type TTR association is even scarcer.MethodsCase Report. 81‐year‐old, Right‐handed man, with a 5‐year history of diagnosed wild‐type TTRCA and polyneuropathy, treated with Tafamidis, vascular risk factors, and remote history of benign head injuries, was seen in our Memory Disorders Clinic for evaluation of moderate dementia. MOCA score was 7/30 on the day of evaluation.ResultsOur patient had 2 brain MRIs over 5‐year follow‐up. The first MRI was performed at initial memory complaints of mild cognitive impairment (MCI) concurrent with the diagnosis of cardiac amyloidosis and polyneuropathy. A second brain MRI was performed during prolonged transient neurological deficit ‐ aphasia with prominent word‐finding difficulties – accompanying delirium following septic knee arthritis surgery. The second MRI revealed foci of susceptibility weighted imaging (swi) artifact in line with superficial cerebral hemosiderosis in the left frontal lobe, and within the bilateral thalami, all new from the first MRI, which only revealed one focus of right periventricular white matter SWI microhemorrhage and moderate confluent white matter hyperintensities, more prominent in the left frontal and parietal lobes, progressed on the second MRI. The cognitive impairment (MCI to moderate dementia) and supporting MRI brain imaging evolved over 5 years and we indicate contributory components of probable CAA, vascular, and AD pathology.ConclusionsWe report a rare association between probable AD, CAA, and vascular dementia, in a patient diagnosed with wild‐type TTRCA and polyneuropathy. We aim to increase awareness of dementia following the cardiac onset of wild TTRCA, possibly similar to the hereditary TTRCA. We inquire about the fortuitous or causative association of mixed dementia type and wild TTRCA, with or without polyneuropathy. We propose to study the intricately mixed etiology of cognitive impairment and its relationship to AD in wild TTRCA through a national registry.
Longitudinal Change in Proper Names from Logical Memory Tasks are Sensitive to Plasma pTau217 Levels
Authors: Basche Kristin E , Langhough Rebecca E. , Jonaitis Erin M. , Du Lianlian , Bruno Davide , Wilson Rachael E , Hermann Bruce P , Johnson Sterling C. , Mueller Kimberly D 
Published: January 2025

AbstractBackgroundPrevious studies have found connections between recall of proper names (PN) and amyloid positivity in cognitively unimpaired (CU) adults at risk for Alzheimer’s Disease (AD; Mueller et al., 2020). Given the promising prospect of employing plasma‐based biomarkers to determine amyloid burden, we looked at associations between longitudinal change in PN and total score recall from Logical Memory (LM) story recall test and plasma pTau217.MethodParticipants from the Wisconsin Registry for Alzheimer’s Prevention (WRAP) study, who were CU at baseline LM visit; had item‐level, longitudinal LM and plasma pTau217 data from a recent blood draw (n=412; EDTA plasma samples analyzed using the ALZpath pTau217 Simoa assay on a Quanterix HD‐X). Linear‐mixed effects models were utilized to examine whether the last available plasma pTau217 measure moderated retrospective age (centered at mean=63) trajectories associated with LM Total Score and PN subscores; pTau217 interactions with quadratic age were removed if they were non‐significant. Models included a person‐level random intercept term, sex, practice effects, and WRAT‐III reading standard scores as covariates.ResultsSample characteristics overall and by last observed plasma pTau217 category (Ashton et al, 2023 pre‐print) are shown in Table 1. The sample was mostly female (n=278, 67.5%), and white (n=393, 95.4%), with an average age of 58 (sd=6.44) at baseline visit. The interaction term of pTau217 was significant for all of the models for linear age (Table 2, β ranging from ‐0.50 through ‐0.08, p<0.001); the interaction of pTau217 was also significant for quadratic age in the PN delayed subscore (β=‐0.00, p=0.010) and the LM delayed total score (β=‐0.01, p=0.031).ConclusionChange in LM total and PN subscores are sensitive to amyloid burden via plasma pTau217. Participants with high levels of pTau217 performed more poorly over time than those with intermediate or low levels (Figure 1). Despite being limited to only nine items on LM tasks, PN subscores continue to demonstrate their strength as a potential indicator of amyloid accumulation as measured by a quick and lower‐burden blood test.
Deep Learning based Automated Segmentation of Hippocampus and Hippocampal Subfields from Postmortem MRI
Authors: Nirmala Anoop Benet , Li Karl , Rashid Tanweer , Honnorat Nicolas , Wang Di , Li Jinqi , Fadaee Elyas , Charisis Sokratis , Walker Jamie M. , Richardson Timothy E. , Wolk David A , Fox Peter T , Bieniek Kevin F. , Seshadri Sudha , Wisse Laura E.M. , Habes Mohamad 
Published: January 2025

AbstractBackgroundThe hippocampus and its subfields in the human brain play a pivotal role in forming new memories and spatial navigation. The automated assessment of the hippocampus and its subfields are useful tools for the early diagnosis of Alzheimer's disease and other neurodegenerative diseases such as primary age‐related tauopathy, Lewy body dementia, limbic‐predominant age‐related TDP‐43 encephalopathy (LATE), and frontotemporal lobar Dementia. Postmortem brain magnetic resonance imaging plays a crucial role in neuroscience and clinical research, providing valuable insights into the structural and pathological features of the brain after death. Postmortem MRI can be used to validate findings from in vivo imaging studies, link these findings to histopathological data. Deep learning methods such as convolutional neural networks are widely used in image segmentation. However, deep learning methods have not previously been applied to segmenting the hippocampus and its subfields (Head, Body, Tail, and Dentate Gyrus) from postmortem MRI.MethodDouble U‐Net is a convolutional neural network architecture that combines two U‐Net architectures. The U‐Net architecture is widely used for semantic segmentation tasks, particularly in medical image analysis, where it has shown success in functions such as tumor segmentation. We have trained a double U‐Net model on 15 annotated postmortem MRI scans include scans from nine females and six males, with an average age of 78 and a standard deviation of 7, which have been collected at our university brain bank (Figure 1). Before feeding the data to the model, all the data were registered, intensity normalized, and cropped to a size of 64 x 96 x 48. The model is trained with a learning rate of 0.0001s and dice loss as the objective function.ResultThe model's performance is evaluated quantitatively (Table 1) and qualitatively (Figure 2). The qualitative analysis is performed with metrics such as Dice, Precision, and Recall. In whole hippocampus segmentation, the model achieved an overall Dice score of 93.01%, and for subfield segmentation, it reached a Dice score of 87.30%.ConclusionDeep learning‐based segmentation of the hippocampus and its subfields can be performed on postmortem brain images and may be helpful in diagnosing Alzheimer's and other neurodegenerative diseases.
Advocate the Voice of People with Dementia ‐ Design of Dementia Care Educational Package for the Practitioners with the 16 Principles of Proper Caring Attitude (DemenTitude®) in Hong Kong
Authors: Chui Kenny Chi Man 
Published: January 2025

AbstractListening to the voices of people with dementia and understanding their perception of the surrounding world is one of the keys to providing person‐centred care in daily practice. The care not only focuses on the specific knowledge and skills but also the proper caring attitude towards dementia. Stigma is still severe in Hong Kong, and the implementation of dementia‐inclusive language is not practical due to the lack of education in this aspect. An educational package with 16 principles of proper caring attitude was designed regarding the local context and cultural adaption. Qualitative research with in‐depth interviews and participatory observations was conducted in the community care and residential care homes of Hong Kong. Following the theoretical framework blending interpretivism and the sociocultural perspective on dementia in Hong Kong, the 16 principles of proper caring attitude, called DemenTitude®, were formulated from the findings. The aims are to reduce the stigma of dementia among the caring staff and to raise awareness of dementia‐inclusive language.The 16 principles were translated from Cantonese to English: (1) Unveiling limitless interpretations; (2) Listening more than criticise; (3) Memories fade, history endures; (4) Communication is all about interaction; (5) Trusting their feeling and perception; (6) The same stays the same; (7) Behavior speaks; (8) Beyond the matter‐of‐fact; (9) Process is the key for assessment; (10) Dignity through equality, treat as adults; (11) Meaningful engagements form life; (12) Mind your words; (13) The power of touch is better than words; (14) Person‐centred Care always as the root; (15) Quality and Quantity, both counts; (16) Care takes priority, “attitude” over “speed”. The evaluation of this educational training and care philosophy showed a significant improvement in the positive perception of dementia among the participants. Further development and promotion of “attitude” training should be needed.