bluuebunny/crossref_metadata_2025_split huggingface dataset:
Baseline differences of cognition and psychiatric symptoms according to plasma amyloid‐status in the SILCODE study
Authors: Shao Kai , Kuhn Elizabeth , Hu Xiaochen , Yu Xianfeng , Li Yuxia , Zhang Mingkai , Wei Min , Liu Lin , Yang Jie , Guo Tengfei , Jessen Frank , Wagner Michael , Han Ying 
Published: December 2023

AbstractBackgroundSubjective cognitive decline (SCD) is supposed to appear early in the course of Alzheimer’s Disease (AD). Although subtle cognitive deficits and psychiatric symptoms have been described in SCD, their association with amyloid pathology is still unclear.MethodWe collected SCD and normal controls (NC) from Sino Longitudinal Study on Cognitive Decline (SILCODE), a Chinese longitudinal observational study, which aims to develop risk prediction models of conversion to mild cognitive impairment in individuals with SCD. Subjects with memory complaints and concerns, recruited by public outreach or memory clinics, were considered as SCD. Subjects without concerns but with or without memory complaints were deemed NC. The assessment consisted of a neuropsychological test battery, an SCD‐interview, an SCD questionnaire (SCD Q9), an Ecog test and a determination of the Aβ 42/40 ratio in blood plasma. A z‐standardized composite score including the global cognition, memory, language, and executive function was created to describe the objective cognition in general. General linear model of baseline cognition and psychiatric symptoms according to group and amyloid status was performed.Result130 SCD (age 65.89 ± 5.37y, 60% Aβ+) and 92 NC (age 65.85 ± 5.17y, 66% Aβ+) were analyzed. No proportional differences of plasma Aβ+ were detected in the two groups. Aβ status makes little difference for cognition in NC, but is associated with cognition in SCD. There was a significant association of plasma Aβ with overall cognition (p = 0.01) and memory function (p = 0.03) only in SCD, after regression of age, sex, education and the interaction between plasma Aβ and the group. Both Aβ+ and Aβ‐ SCD showed a higher score of SCD Q9, Ecog, more SCD complain domains, more SCD plus features, more serious depression and anxiety symptoms compared to NC subjects.ConclusionPlasma Aβ pathology is more strongly associated with subtle cognitive deficits in SCD as compared to NC. This replicates results from other studies and suggests that, across different cultural and recruitment settings, current SCD criteria can capture stage 2 of Alzheimer’s Disease in amyloid‐positive individuals, when subtle cognitive impairments due to AD first become visible.
Cross‐omics integration analysis revels synaptic dysregulation across brain regions at later stages of Alzheimer disease
Authors: Eteleeb Abdallah M , Novotny Brenna C , Soriano‐Tarraga Carolina , Sohn Christopher , Dhungel Eliza , Brase Logan , Nallapu Aasritha , Buss Jared , Farias Fabiana H.G. , Bergmann Kristy , Norton Joanne , Gentsch Jen , Wang Fengxian , Davis Albert A , Morris John C , Karch Celeste M. , Perrin Richard J. , Benitez Bruno A. , Harari Oscar 
Published: December 2023

AbstractBackgroundThe clinical and molecular heterogeneity of Alzheimer disease (AD) is increasingly recognized as a major factor impacting diagnosis accuracy, the design of therapeutic interventions and clinical trials, and the development of effective treatments for AD. Recently, research efforts have leveraged molecular data to characterize AD patients into subgroups. However, the influence that such AD molecular profiles may have on cognitive decline trajectories remains poorly understood. Comprehensive studies that aggregate multiple modalities of omics have proven to be a powerful way to identify molecular profiles for human diseases including cancer. Here, we sought to determine whether cross‐omics integration can reveal molecular profiles of AD that have clinical and biological relevance.MethodWe leveraged machine learning approaches, digital deconvolution, and traditional statistical approaches to integrate and analyze multiple high‐throughput omics data from different cortical regions and cohorts, including the parietal cortex (N = 278) from the Knight Alzheimer Disease Research Center (Knight ADRC), the dorsolateral prefrontal cortex (N = 237) from the Religious Orders Study and Memory and Aging Project (ROSMAP) cohort, and the parahippocampal gyrus (BM36; N = 116) from The Mount Sinai Brain Bank (MSBB) study.ResultWe identified four distinct molecular profiles, one of which was associated with significantly worse Clinical Dementia Rating (CDR) at death, shorter survival after symptom onset, more severe neurodegeneration and astrogliosis, and unique metabolomic profiles. This profile, present in multiple cortical regions affected at distinct stages of AD progression, showed significant dysregulation of synaptic genes and pathways, indicating neuron/synapse losses and dysfunction at later stages of AD and associated with worse cognitive function. Among other molecules, we found that the expression of alpha‐synuclein (SNCA) and SNAP25 were downregulated in this profile. The synaptic dysregulation associated with this profile was further validated in a mouse model of pathological aSyn aggregation.ConclusionTogether, our results demonstrate that cross‐omics approaches can reveal multiple molecular pathways associated with AD progression, and reinforce that, in AD, prominent synaptic loss and dysfunction are closely associated with worse cognition. This may open the possibility for new biomarkers for the molecular staging of AD and cognition, as well as potential therapeutic targets to ameliorate cognitive decline and AD progression.
Preliminary validation of a dual‐task gait assessment in early Alzheimer’s Disease
Authors: Wolfer Arnaud M , Kurniawan Irma T , Lipsmeier Florian , Taylor Kirsten I , Perumal Thanneer M 
Published: December 2023

AbstractBackgroundEarly stages of Alzheimer’s disease (eAD) are marked by changes in gait characteristics that may be measured using simple smartphone‐based gait tasks. Here we present an assessment of cognitive‐motor‐interference where participants walk for 30 seconds with a smartphone placed in a running belt while counting backwards, called the 30‐Second Walk Test Dual Task (30sWTDT). We report the preliminary reliability and validation of the 30sWTDT in a cohort of healthy individuals (HC), individuals with subjective cognitive decline amyloid‐PET negative and positive (SCDn and SCDp, respectively) and eAD.Method123 participants (32 HC, 31 SCDn, 30 SCDp and 30 eAD) were recruited as a part of a Proof‐of‐Concept study of the Alzheimer’s Disease Digital Assessment Suite (AD‐DAS) (https://www.isrctn.com/ISRCTN17035495). Participants performed 9 sessions of 30sWTDT over 28 days on provisioned smartphones. Feasibility was evaluated as the proportion of completed 30sWTDT relative to the total number of expected sessions. Two gait characteristic metrics were estimated: variability in step frequency (VSF) and the 25th percentile in step power (25SP). Intraclass correlation coefficients (ICC) tested the metrics’ reliability. Convergent validity was established as partial correlation between VSF/25SP and adjusted mean duration in Timed 25 foot Walk Test (T25WT). Clinical validity was evaluated using a proportional odds logistic regression model to differentiate between groups.ResultAmong the 97.5% of participants who completed the study (i.e., n = 120), participants completed 88.9% of all assigned 30sWTDT tasks, with no group difference in adherence. VSF and 25SP metrics showed moderate (ICC = 0.74) and good (ICC = 0.79) reliability, respectively. Both metrics significantly distinguished between HC and all other study groups (odds ratio = [0.012,0.029]), and were associated with T25WT adjusted mean duration (adjusted r2 = [0.09,0.069]).ConclusionPreliminary findings demonstrate that a smartphone‐based 30sWTDT can be successfully self‐administered by cognitively healthy participants and individuals on the eAD continuum. Participants show high adherence in an ecologically valid environment. 30sWTDT differentiated HC from all other groups with subjective or objective cognitive problems, indicating a lack of specificity of gait characteristics to differentiate between increasing levels of cognitive impairment. These findings require replication in larger independent datasets.
Closing the sex/gender gap in dementia: homing in on the vasculature (animal models)
Authors: Carare Roxana O. O 
Published: December 2023

AbstractFemales are more at risk of Alzheimer’s disease compared to males. The deposition of amyloid‐beta in the extracellular spaces of the brain as plaques and as cerebral amyloid angiopathy is more frequent in females. It is only in the recent years that experimental work on mice has embraced resting hypotheses in both sexes. Results show that cerebral microbleeds, spatial working memory and fear conditioning are more frequent in old Tg‐SwDI females compared to males (Michael E. Maniskas et al). While the rodent vasculature does not develop arteriolosclerosis with ageing as human vasculature does, the administration of a high fat diet to adult wild‐type mice impaired the spatial memory in females only and experimental hypoperfusion reduced cerebral blood flow mostly in females (Abigail E Salinero). Failure of clearance of fluids and solutes such as Abeta from the brain along Intramural Periarterial Drainage Pathways (IPAD) is a key pathogenic factor in CAA. All future experimental studies should include both sexes when analysing the clearance and other mechanisms that underlie the pathogenesis of ADRD and CAA.
Spatial gradients of gene expression, amyloid PET and functional connectome for predicting regional rates of tau‐PET increase: towards tau‐PET outcome ROIs in clinical trials.
Authors: Luan Ying , Zheng Lukai , Rubinski Anna , Franzmeier Nicolai , Ewers Michael 
Published: December 2023

AbstractBackgroundIn clinical trials, an important question is which brain regions show high tau accumulation within 1‐2 years. Building upon our previous epicenter‐connectivity‐based distance model for predicting the progression of tau‐PET accumulation from initial seed regions of high tau (epicenters) to other regions (Franzmeier et al. Sci Adv. 2020), we incorporate here epicenter‐based distance within spatial gradients of gene expression and amyloid‐PET to enhance the predictive power.MethodWe included 351 participants encompassing Ab(+) non‐demented subjects (controls & MCI), characterized by cross‐sectional 11‐F florbetaben amyloid‐PET and longitudinal 11‐F flortaucipir tau‐PET (longitudinal, n = 172, mean/range = 1,7 yrs (0.7 – 5.2 yrs)) from ADNI. For transcriptomic gene expression maps obtained from the Allen Human Brain Atlas, we computed for each of the 18,686 genes maps spatial correlations with the average tau‐PET map in a randomly selected training sample (n = 106), and retained the top 5% of positively/inversely tau‐correlating gene maps. For each imaging modality, spatial gradients were subsequently computed across amyloid‐PET scans in the training sample, the subset of gene expression maps, and functional connectivity (FC) matrices from Human Connectome project. In the test sample (n = 245), tau‐PET epicenters at baseline (Franzmeier et al. Sci Adv 2020) were projected onto the gradient maps and epicenter‐based gradient distance was computed. In step‐wise spatial regression analyses, we tested which gradient distances predicted the spatial patterns of cross‐sectional and longitudinal tau‐PET accumulation, accounting for spatial autocorrelations.ResultFor cross‐sectional tau‐PET (Fig. 1A), a total of 54.6% (p < 0.0001) of the spatial tau pattern could be explained, where an amyloid‐PET gradients and a FC gradient (spanning the transmodal axis from primary sensory to DMN regions) showed the strongest effects (Fig. 2, upper row & Fig. 3A). For longitudinal tau‐PET (Fig. 1B), a total of 47.8% (p < 0.0001) of tau increases could be explained, where gene‐expression gradients showed the strongest effects (Fig. 2 lower row & Fig. 3B).ConclusionEpicenter‐based gradient distances of connectivity and molecular brain properties show additive, high predictive accuracy for predicting regions of high future tau‐accumulation, providing an attractive approach to define tau‐PET outcome ROIs in clinical trials.
Alzheimer’s disease clinical management is determined by presence and severity of apathy
Authors: Oliveros‐Cid Antonio , Martinez Esther Sierrra , Moreno Lisbed Rondon , Oliveros‐Juste Antonio , Lopez Maria Angeles Cid , Hojas Sarai Garcia , Lorente Victoria Celorrio , Luque Laura Cano , Catalan Claudia Ovejas , Carrasco Ana Chacon 
Published: December 2023

AbstractBackgroundApathy and agitation influence daily life and care in dementia. We believe it may also influence the diagnosis, especially in early stages. We intend to examine apathy among the symptoms and the relationship with the referral schedule and early diagnosis.MethodOutpatients referred for possible cognitive impairment included in a database of “apathy and cognitive impairment”. Clinical history, complete neuropsychological battery, MRI, MRI, laboratory, and treatment. In addition, some patients also undergo EEG, CSF and/or amyloid PET scans. Neuropsychological battery with special attention to the assessment of apathy and behavioral symptoms. Additionally, semi‐structured rating of the severity of apathy when patients were referred for the first time.Result64 finally diagnosed as Alzheimer’s disease (CDR 0.5 to 2). Group differences according to the frequency and severity of apathy. Those who showed apathy or depression (Independently) as a predominant symptom when referred were more often treated with psychopharmacological therapy by Primary Physician or referred to Psychiatry, where AD was generally less considered. The level of apathy showed negative correlations with MMSE, for the same group (CDR) of patients. Significantly higher levels of apathy higher levels of apathy associated with intake of antidepressants and cognitive enhancers.ConclusionWe observed different patterns of apathy in outpatients with MCI and patients with dementia; significant negative effect on early neurological assessment of those patients, and therefore deleterious effect on their opportunities for a correct approach in the early stages of the disease.
Prospective cohort of elderly patients after hospitalization due to COVID‐19: preliminary results
Authors: da Cunha Cintra Fabiana Carla Matos , Cintra Marco Túlio , de Barros Simão Gabriel Rabelo , de Souza Campos Brenda Flaviano , Rodrigues Fabricio Groppo , Almeida Daniella Cristina Brites , de Moraes Edgar Nunes , de Faria Fortini Iza , de Mattos Viana Bernardo , Bicalho Maria Aparecida Camargo ,   Aging and neurodegenerative diseases
Published: December 2023

AbstractBackgroundPost Covid‐19 syndrome can cause cognitive impairment and may be associated with a higher risk of developing dementia in older people.MethodThis is a cohort study that is evaluating over 12 months the functional status and cognition of elderly people after hospital discharge. One group is composed of elderly people admitted to the hospital for Covid‐19 and the other group is composed of elderly people hospitalized for other clinical reasons. The groups are evaluated with The Mattis (DRS), AD8, ADCS‐ADL, PCL‐C, GDS‐15, FIM, COPM, CFS, FSS, mMRC and SARC‐calf. We will describe the preliminary results of the first 31 patients included in the COVID‐19 group on functional status, cognition, mood and quality of life.ResultThirty‐one patients with COVID‐19 were evaluated three months after hospital discharge. One was excluded due to previous mental disorder and another due to a request to be excluded from the study. We found a mean age of 69.55 ± 7.72 years, schooling 7.14 ± 4.48 years, 51.7% female, Charlson Comorbidity Index 2.21 ± 1.84, 48.3% with smoking history and 62.9% had incomplete vaccine protection for COVID‐19. Considering cognition, 13.9% of the sample had no impairment, 55.1% had mild cognitive impairment (MCI) (17.2% amnestic MCI and 37.9% non‐amnesic MCI) and 31% had dementia. 24.1% declared their health status and quality of life as fair or poor. Mean CFS was 4.45 ± 1.18, GDS‐15 4.28 ± 3.38, FSS 30.76 ± 19.24, PCL‐c 29.34 ± 10.41, SARC‐calf 4.03 ± 4.61. All had mMRC dyspnea classified between 1 and 4.ConclusionThere was a high prevalence of mild cognitive impairment and dementia among patients after three months of discharge, with a predominance of mild frailty due to CFS and the presence of fatigue. It is noteworthy that a quarter of the sample reported low quality of life.
Applying Implementation Frameworks to Health IT Development in Dementia Care: Lessons from the CareHeroes Project
Authors: Ruggiano Nicole , Brown Ellen L , Clarke Peter J , Roberts Lisa , Framil C Victoria , Chevez Hamilton , Hurley Shannon , Kopcsik Chrystine , Allala Sai Chaithra , Hristidis Vagelis , Agronin Marc , Geldmacher David S. 
Published: December 2023

AbstractBackgroundCaregiving and clinical care for people living with dementia (PLWD) is complex and complicated by communication challenges among caregivers and providers (Gaugler et al., 2022; Ruggiano et al. 2012; 2019). These challenges can constrain decision making about treatment options (Hinton et al., 2007; Miller et al., 2016; Wolff et al., 2020) and may contribute to negative mental health outcomes often reported by family caregivers (Gaugler et al., 2022), which disproportionately impact vulnerable caregivers (e.g., underserved racial/ethnic groups, rural caregivers (Abner et al., 2016; Fabius et al., 2020)). Health information technology (HIT) has been identified as a potential solution to communication challenges in dementia care (Ruggiano et al., 2019; Vedel et al., 2013). However, few studies have reported how to effectively integrate new HIT into practice to support provider‐caregiver communication. In this study, a four‐stage implementation science framework (Meyers et al., 2012) was used to integrate a newly developed web‐based application (app) technology, called CareHeroes (Brown et al., 2016), into clinical practice at two memory clinics to promote caregiver‐physician communication. CareHeroes is multi‐functional and allows secure sharing of patient‐related clinical information between caregivers and providers. It also provides education and support, including an educational chatbot that provides tailored, expert feedback to caregiver questions.MethodEarly stages of implementation involved interviews with caregivers and focus groups with clinic providers to develop a clinical workflow integration plan for the new app. Then, the research team collected user data collected through the app during implementation as well as caregiver psychosocial outcome data (e.g., depression, burden) at baseline and 3‐month follow‐up to evaluate implementation.ResultThirty‐six caregivers and eight clinic providers provided qualitative data that informed the clinical workflow integration plan. The same providers and 21 additional caregivers enrolled in the CareHeroes implementation demonstration study. While user data demonstrated that it was feasible for caregivers to share clinical information and engage in self‐support using CareHeroes, expected outcomes were confounded by complications during the COVID‐19 pandemic.ConclusionThrough using the implementation framework, several lessons were learned regarding potential success and challenges in integrating new HIT into clinical care to support dementia care and caregiving.
Discrepancies Between Informant vs. Patient Ratings of Functional Abilities: Association with Objective Cognitive Performance in Mild Cognitive Impairment and mild dementia
Authors: De Wit Liselotte 
Published: December 2023

AbstractBackgroundSelf‐ and informant‐ratings of functional abilities are used to diagnose mild cognitive impairment (MCI) versus dementia and are a common outcome measure in clinical trials. These ratings are assumed to be accurate, yet they are subject to biases. Biases in patient ratings of daily function have been found in individuals with dementia who are older and more depressed (Martyr et al., 2012, 2019, 2022). Biases in informant ratings have been found in caregivers with higher distress and burden (Mangone et al., 1993; Martyr et al., 2014, 2022) and higher education (Hackett et al., 2020). The current study examined discrepancies in informants’ ratings of daily functioning in individuals with MCI/mild dementia.MethodParticipants were 118 patients clinically diagnosed with MCI or mild dementia and their care partners/informants who were referred to the Emory Cognitive Empowerment Program. Table 1 shows details regarding all measured constructs and variables. The discrepancy between informant rating of daily function and patients’ cognition (i.e., informant daily function rating and patient cognition discrepancy) and the informant‐ and patient discrepancy in ratings of daily function (i.e., informant/patient daily function rating discrepancy) served as dependent variables. Two forward linear regression models were run.ResultTable 2 shows demographic information. For the informant daily function rating and patient cognition discrepancy, informants with higher perceived stress reported worse patient functioning. For the informant/patient daily function discrepancy score, worse ratings of daily function by the informant than the patient were found for informants with higher caregiver burden, worse communicative effectiveness, and patients with higher self‐efficacy.ConclusionThis study highlights the potential for biases in patient and informant ratings of functional abilities in MCI/mild dementia. The risk for underreporting functional abilities in informants with higher burden and stress levels and lower communicative effectiveness aligns with previous research indicating that ratings can be biased by individual factors. Worse ratings by informants than patients for patients with higher self‐efficacy may also be due to individual factors in patients such as presence of anosognosia. These findings have implications for the use of perceived functional ratings for diagnostic purposes and as outcome measures in clinical trials.