bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical efficacy of Brain and Body Rehab Training (BBRT) multi‐dimensional cognitive intervention digital therapeutic in patients with mild cognitive impairment: a three‐arm, randomized controlled trial
Authors: Li Yatian , Wu Jingnan , Wang Ziming , Xia Huanhuan 
Published: December 2023

AbstractBackgroundDespite lacking effective pharmacological therapeutic to delay the progression of mild cognitive impairment (MCI) to dementia, accumulative evidence showed that multi‐domain intervention including cognitive training, exercise, diet, etc., is an effective approach. With miscellaneous audio and visual stimuli, emerging digital therapeutic can be incorporated into the multi‐domain intervention and enhance the effect of cognitive interventions. This study adopted the Brain and Body Rehab Training (BBRT) multi‐dimensional cognitive intervention system to develop the BBRT‐online digital therapeutic (BBRT‐online, Figure 1) and will verify the efficacy of both BBRT and BBRT‐online on older patients with MCI.MethodThis study is a 2‐year, three‐arm, randomized controlled trial, intended to recruit 438 patients with MCI aged 50‐75, with 6 years of education or more, and no neurological disorders or other serious systemic diseases. The participants will be randomly assigned into the BBRT‐online intervention group (n = 200), BBRT intervention group (n = 38), or control group (n = 200). The control group will receive regular health education as the other two groups. Five BBRT‐online training units a day, 15 minutes at least, will execute remotely in the BBRT‐online group. Participants in the BBRT group will attend face‐to‐face BBRT cognitive training twice a week, 1 hour for each at least. Both intervention groups will receive intervention for 12 months and be followed up until the 24th month to assess the persistence of efficacy (Figure 2).ResultPrimary outcome of this study will be the ACE‐III total score. Secondary outcomes will include 1) neuropsychological scale scores including the MOCA‐B scale, NPI scale, AVLT scale, STT scale, BNT test, and SCS intelligent voice‐based cognitive assessment. 2) Biomarker outcomes: Aβ42, T‐tau, and P‐tau. 3) Neuroimaging outcomes. All participants will meet the research nurse at baseline, and at 6, 12, 18, and 24 months for outcome measurements. This study has been registered in the China Clinical Trials Registry (ChiCTR2200065212).ConclusionBBRT and BBRT‐online have been widely commercialized. This study will systematically evaluate the clinical effectiveness of both BBRT and BBRT‐online for Chinese MCI patients and provide insights into non‐pharmacological intervention mechanisms for improving cognitive function.
Transcranial Magnetic Stimulation based Network Integrity Assessment in Alzheimer’s disease
Authors: Ozdemir Recep , Fried Peter J. , Buss Stephanie S. , Budson Andrew E , Press Daniel Z. , Pascual‐Leone Alvaro , Shafi Mouhsin 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) has a relatively well‐characterized pathology of amyloid‐β and tau accumulation. Yet, disease progression from preclinical to clinical stage remains largely unpredictable at the individual level. Growing evidence shows disrupted synaptic signaling in functionally connected brain networks early in the preclinical stage, and suggests impaired network integrity, assessed with functional connectivity measures, as potential markers for disease symptomatology in AD.MethodHere propose a novel TMS‐induced causal connectivity measure reflecting integrity of multi‐synaptic signaling within the stimulated brain networks. In a preliminary sample of 9 cognitively normal older adults (Healthy Controls: HCs) and 11 patients with amnestic mild cognitive impairment or mild dementia (early AD), we applied 150 single pulses of TMS to inferior parietal lobule (IPL), a distinct brain region within the default mode network (DMN) showing decreased metabolism in early AD and recorded TMS evoked neural responses with simultaneous electroencephalography (TMS‐EEG). We also characterized spontaneous brain activity with resting‐state EEG (rsEEG) measurements. We performed source space spectral power analyses and seed‐based power envelope correlations (PEC) to estimate cortical distribution of relative alpha power and spontaneous IPL connectivity as rsEEG measurements. Network integrity was defined as the ratio of significantly activated vertices to the total number of vertices within the DMN following TMS of IPL.ResultAlthough relative alpha power (8‐12 Hz) was slightly lower and seed based connectivity was slightly higher within the IPL node in AD participants, no network specific differences was observed across the cortex for both rsEEG measures. On the other hand, DMN integrity was substantially lower in AD participants with an average ratio of 0.53 (0.79 in HC) indicating that almost half of the vertices within the DMN were not activated by TMS.ConclusionOverall, these preliminary analyses suggest that perturbation‐based (TMS‐EEG) measures may reveal neurophysiological signatures of brain network dysfunction that are not observable in spontaneous brain oscillations, and thus may characterize defining features of network failure in preclinical and mild AD.
Battery for the Assessment of Cognitive Reserve (BARC): development and clinical validation for the Portuguese population
Authors: Nogueira Joana , Gerardo Bianca , Santana Isabel , Simões Mário Rodrigues , Freitas Sandra 
Published: December 2023

AbstractBackgroundThe Cognitive Reserve (CR) is widely accepted as the active ability to cope with brain damage. The lack of a quantitative method for the assessment of CR including all the proxies commonly used for this purpose, highlight the need for a development of an assessment battery. The present study aims to present the final scores of the Battery for the Assessment of Cognitive Reserve (BARC).MethodThe BARC includes: (i) the Questionnaire of Literacy (QL), (ii) the Questionnaire for the Assessment of Cognitive Demand Level of Professional Activities (QANECAP), (iii) the Cognitive Reserve Questionnaire (CRQ), (iv) the Irregular Word Reading Test (TeLPI), and (v) the Wechsler Adult Intelligence Scale ‐ Vocabulary test(WAIS‐III). This new approach combined new questionnaires specifically developed by our team with other tests already validated for the Portuguese population, which also targeted the CR proxies. The BARC was administrated to 260 elderly participants (healthy controls: 200; dementia spectrum: 60). We also applied to respective available close informants.ResultThe last preliminary psychometric results of the new questionnaires evidenced the reliable and valid use in the Portuguese population. The validation of the QL and QANECAP allow the pursuit of analysis to establish the final score of the BARC, considering the individual weighting of each test/questionnaire.ConclusionWe developed a new battery to assess quantitatively the CR, which combined the several CR proxies in one single score. The BARC can be used in both clinical and research contexts.
Present and past hypertension in ADNI3 individuals with sub‐threshold total Hachinski ischemic score reflect greater hyperintensity burden irrespective of cognitive status
Authors: Pedersen Taylor J , Flores Jaqueline A , Sudhakar Tejaswi D , Anderson Cole E , Peskind Elaine R , Li Ge , Iliff Jeffrey J , Rane Swati ,   Alzheimer’s Disease Neuroimaging Initiative
Published: December 2023

AbstractBackgroundThe Hachinski ischemic score (HIS) scale is used to exclude as much as possible, individuals with dominant cerebrovascular pathology from those with dominant AD pathology. White matter hyperintensities (WMH) are the gold‐standard for evaluating cerebrovascular pathology and linked to worsening cognitive impairment. HIS ≤ 4 are used to minimize non‐AD pathology in ADNI participants. Here we sought to understand whether HIS scores for hypertension (HMHYPERT) in ADNI3 were associated with greater WMH burden (and hence cerebrovascular pathology) even within individuals with HIS ≤ 4.MethodWe compared HMHYPERT scores between individuals with normal cognition (CN) and with mild cognitive impairment (MCI), and participants and correlated with percent WMH burden. A total of 263 subjects screened for ADNI3 (92 MCI [38 F], age = 73 ± 6; 146 CN [94 F], age = 74 ± 7) who had HIS scores and FLAIR MRI acquisitions within a year of each other. 25 All AD participants were excluded. WMH burden was calculated by segmenting them using the Lesion Segmentation Toolbox and normalizing their volume by total intracranial volume. We used the HMHYPERT as a vascular risk factor, excluding those with any focal neurological symptoms. For analysis, we dichotomized participants into those with HMHYPERT = 0 and HMHYPERT>0. To examine whether a non‐zero HMHYPERT score corresponds to greater WMH burden, we examined the prevalence of WMH in between these 2 groups and within the MCI and CN groups.ResultAlthough not significant, HMHYPERT scores were higher in MCI. (Fig. 1A, MCI = 0.48±0.50, CN = 0.39±0.49). We found a greater proportion of MCI subjects had HMHYPERT>0 than CN subjects (Fig. 1B, HMHYPERT = 0: CN = 61.0% and MCI = 52.2%; HMHYPERT > 0: CN = 40.0% and MCI = 48.1%). WMH burden was greater in MCI (0.33±0.53) than CN (0.20±0.32) (Fig. 2A). MCI participants with HMHYPERT>0 had the highest WMH burden followed by MCI participants with HMHYPERT = 0, CN with HMHYPERT >0, and CN with HMHYPERT = 0 had the lowest WMH burden. (Fig. 2B).ConclusionCerebrovascular pathology increases significantly with diagnosis, but its severity increases further with findings of hypertension even when total HIS ≤ 4.
NIA’s qualitative message testing: optimizing how to communicate Alzheimer’s and related dementia research with the public
Authors: Thomas Christopher G 
Published: December 2023

AbstractBackgroundCommunicating the latest advances in Alzheimer’s disease and related dementias (AD/ADRD) research to the public is part of the NIH National Institute on Aging’s mission and strategic directions plan. To further this goal, the NIA Office of Communications and Public Liaison obtained insights from focus groups and in‐depth interviews (IDIs) to optimize language used in public outreach efforts.MethodNIA contracted the public opinion company Edge Research to conduct a qualitative study. NIA messages about AD/ADRD research were tested in five focus groups and six IDIs. Of the focus groups, three were with at‐risk Individuals (people with family history) and two were with caregivers for someone with Alzheimer’s or a related dementia. The six IDIs were with individuals who were experiencing symptoms of dementia or who had been diagnosed by their doctor with early signs of Alzheimer’s or a related dementia. The messages tested relayed information about AD/ADRD research basics, progress, future direction, and clinical trial participation.ResultThe results suggested that current NIA messaging communicates many key ideas and information as intended and that government sources of information about dementia generally are trusted. Nevertheless, even among those who are symptomatic, have a family history, or who spend their days as a caregiver, knowledge about AD/ADRD is imperfect and sometimes vague. Additionally, respondents could not recall information about the latest in dementia research; and they were hesitant to participate in clinical trials in part because of a misconception that all trials involve a medication.ConclusionThe results reinforced the need for ongoing efforts to communicate about AD/ADRD research to the public. NIA is incorporating feedback and recommendations in current and future materials.
Evaluation of functionality after three years of subjective cognitive complaint in the elderly
Authors: Marques Fernanda Mariotti , Gonçalves Eduardo C Q , Kahtalian Lais Lundstedt , Neubern Patricia Cardoso Buchain , Ribeiz Salma Rose Imanari , Filho Geraldo Busatto 
Published: December 2023

AbstractBackgroundSubjective cognitive decline (SCD) is defined as the self‐reported experience of cognitive decline in subjects with normal performance on neuropsychological tests, and expectedly with preserved functionality. This condition is associated with a higher risk for developing objective cognitive decline and dementia. The objective of this study is to carry out a descriptive analysis of the B‐ADL scale in elders 24 to 48 months after SCD identification.MethodForty‐three participants aged 60 years and over without clinically relevant depressive symptoms (CESD<16) and without cognitive impairment (MMSE≥14) were randomly selected from a group of users of basic health units in the city of São Paulo. The Clinical Memory Inventory and a questionnaire about perceived memory problems (i.e.: “have you had memory problems lately?”) were applied and 24 to 48 months later an informant answered the Bayer Activities of Daily Living Scale (B‐ADL).ResultThe mean age of the total sample was 70.7 years. There were 22 women, 45.5% of whom had SCD, and 21 men, 23.8% of whom had SCD. The group with SCD had a mean age of 70.1 years, while in the group without SCD the mean age was 71 years. The group without SCD had a mean B‐ADL score of 1.26 and the group with SCD had 1.32 . Eighteen subjects (41.9%) did not score in B‐ADL. Out of these, 12 (66,6%) were elderly without SCD while 6 (33,3%) had SCD.ConclusionAfter three years of identification, the SCD group showed no functional impairment. Other studies with larger samples may help elucidate the relationship between subjective cognitive decline and functionality.
Identification of Alzheimer’s disease in Veteran patients using clinical notes from electronic health records
Authors: Miller Donald R , Aguilar Byron J. , Li Xuyang , Shishova Ekaterina , Jasuja Guneet , Berlowitz Dan , Morin Peter J , O'Connor Maureen K. , Nguyen Andrew H. , Christiansen Cindy , Zhang Haixin , Monfared Amir Abbas Tahami , Zhang Quanwu , Xia Weiming 
Published: December 2023

AbstractBackgroundThere are challenges in studying and monitoring Alzheimer’s disease (AD) in large patient populations. Clinicians often have insufficient availability of resources to make the diagnosis (e.g. brain scanning, referral to specialists) and clinical inertia may be tied to the perception that there are no clinical benefits in making the differential diagnosis of this stigmatized disease. Consequently, diagnosis codes specifically for AD are underutilized and prevalence is generally underestimated. Our goal was to improve identification of probable AD in a large patient population with the development and application of a refined search algorithm of computerized clinical notes contained in electronic health records.MethodOur methods were developed using records for all Veteran patients in the national Department of Veterans Affairs Healthcare System (VA) in fiscal years 2010‐2019. Starting with initial searches for “Alzheimer” and related terms in all clinical notes, the algorithm was optimized through an iterative process. Multiple references to “Alz” in notes were evaluated separately and chunks were excluded when the term referred to family history, care facilities, or negative statements, or when it was part of text in assessment instruments or medication indications. The final algorithm was validated through manual reviews of over 2,400 randomly selected patient charts (predictive value positive = 86.3%; kappa = 0.76 among 2‐4 reviewers).ResultWhen the algorithm was applied to records for the nearly 5 million VA patients over 50 years of age in fiscal year (FY) 2019, we identified 141,816 with probable AD, nearly five times the count based on ICD‐10 codes (30,090). Prevalence, standardized to the 2010 census for age and sex, was 2.70%, with higher prevalence in women (3.26%) than in men (2.06%). Median age of probable AD patients was 75 years.ConclusionAs disease modifying treatments for AD enter the market, there will be more focus on proper diagnosis of AD, particularly early in the disease process, emphasizing the importance of better identification of the disease in patient populations. This method, based on searches of clinical notes, appears to be promising to identify patients with probable AD and study its progression in large patient populations.
Ambient RNA from CSF to capture brain cell‐type signatures in AD and other neurodegenerative diseases
Authors: Kaczaral Jacqueline , Buss Jared , Eteleeb Abdallah , Novotny Brenna C , D'Oliveira Albanus Ricardo , Brase Logan , Benitez Bruno A. , Karch Celeste M. , Piccio Laura , Ter‐Ovanesyan Dima , Harari Oscar 
Published: December 2023

AbstractBackgroundWe leveraged digital deconvolution methods to determine cellular changes from brain transcriptomics of Alzheimer’s Disease(AD), and identified a change in cellular proportion between neuropathology, and severity of the disease as determined by Clinical Dementia Rating[5]. We expanded these approaches to Cerebral Spinal Fluid(CSF), to evaluate cellular changes associated with disease progresses.MethodWe used RNAseq data from published sources to test and refine a gene panel to deconvolve ambient RNA from CSF. Candidate marker genes were selected via literature search and verified using the brainseq [1] along with the human brain single‐cell gene expression [2]. We optimized gene panels using the leave‐one‐out cross‐validation method to predict proportions of neurons, astrocytes, microglia, oligodendrocytes, macrophages and endothelial cells, using bulk and ambient RNA sequenced in single‐cell transcriptomics.ResultWe leveraged our deconvolution to ascertain whether ambient RNA captured in single‐cell gene expression from the CSF captures the cellular population structure of the brain. Preliminary results show that cellular signatures for non‐immune cells are present in CSF in AD (Gate et al. (n = 9, Control = 3, MCI = 3, AD = 3)[3] and Multiple Sclerosis(MS)(Ramesh et al. (n = 15, Control = 3, MS = 12)[4]), and the proportions of those non‐immune cells change depending on the disease state. In MS, there is an increase in the proportion of Astrocytes (p = 3.4×10e‐2) in MS samples. Similar results were found for Neurons (p = 4.4×10e‐2) and Oligodendrocyte Precursor Cells (OPC) (p = 8.2×10e‐3). In AD, we identified significant differences between AD, MCI and controls (p = 0.01) in OPC.ConclusionThese results show that ambient RNA in the CSF can capture subtle differences in cellular population structure in AD and MS. These analyses were done on a small sample size, but show the potential to analyze larger cohorts and cell‐type specific transcriptional states. We also plan to expand the process to other neurologic diseases.References:[1] Zhang et al. 2015[2] Brase et al. “A landscape of the genetic and cellular heterogeneity in Alzheimer disease” In press[3] Gate et al. “Clonally expanded CD8 T cells patrol the cerebrospinal fluid in Alzheimer’s disease” 2020[4] Ramesh et al. “A pathogenic and clonally expanded B cell transcriptome in active multiple sclerosis” 2020[5] Li et al. 2018
Validation of the effect of soundscape on the well‐being and behaviour of people with dementia: a randomized clinical trial
Authors: Talebzadeh Arezoo , Iaboni Andrea , Botteldooren Dick , Devos Paul , Vriendt Patricia De , de Velde Dominique Van 
Published: December 2023

AbstractBackgroundUsing the Soundscape approach to design an environment that improves people’s quality of life is crucial. This approach is more challenging for people with dementia. This project uses a personalized algorithm to play sounds at prescheduled moments throughout the night in patients’ rooms in a research hospital specializing in dementia care to evaluate the reduction in resistance to care and agitation.MethodA single‐blind repeated measure randomized clinical trial is designed to estimate the overall or average effects of the customized soundscape on people with dementia. Twenty‐six participants were randomized into two groups of AcustiCare (n = 13) and Treatment as usual (n = 13) for six weeks for each study group.ResultThe primary outcomes of this study were the NPI‐total score and the PAS‐resisting care subscale. In a linear mixed effects model, there were improvements in the NPI‐total scores over time in both groups (‐5.9 +/‐1.3; ρ<0.001). With the PAS‐resisting care subscale, a significant group x time difference, with a greater reduction in PAS‐resisting care score in the AcustiCare group (‐0.81 +/‐ 0.4; ρ = 0.042).ConclusionPeople with dementia can benefit from augmented sonic environments since auditory stimulation can reduce agitation and anxiety and provide safety and familiarity. The outcome of a small sample size showed improvement in resistance to care and reduction in agitation; These results can also be used to calculate effect size and determine the sample size for a future RCT.
Designing Intersectoral Environments to Address Isolation/Loneliness as a Risk Factor for Dementia: A Mixed Methods Health Promotion Program
Authors: Valente Thomas W. , Yang Seiyan , Francioni Arnaud , Walsh Chesley , Belchior Patricia , Bourdais Marie Christine Le , Park Melissa 
Published: December 2023

AbstractBackgroundIntersectoral partnerships are critical for effective and sustainable health promotion programs. The aim of our Public Health Agency of Canada Dementia Community Investment project, What Connects Us∼Ce Qui Nous Lie (2020‐2023) was to collaboratively cultivate sociocultural environments worth living in using shared activities and events. In this paper, we present initial results on the effectiveness of using shared activities and events to link academic, arts/culture, mental health, and community‐based organizations and generate a sustainable web of resources for, while positively impacting on, the quality of life and connectivity as a protective factor for persons living with Alzheimer’s and related disorders (PLWA) and their carers.MethodWe used a mixed methods ethnographic approach to describe and measure the impact of shared activities and events on the intersectoral networks by fielding pre‐/post‐partner social network surveys distributed across four social sectors using standard intersectoral network metrics such as density, clustering, centralization, and average path length; as well as measures of centrality and bridging among partners. We measured the impact of this intervention se with pre‐/post‐activity participant surveys using the UCLA Loneliness scale and the CDC health quality of life instrument. All partners and participants answered demographic questions.ResultNetwork measures showed an increase from the initial number of organizations who submitted letters of support for the project (N = 16), as well as increases in network density at the intersectoral level. Patterns of centrality and bridging in the partner data are still emerging, with arts/cultural organizations being the most engaged in facilitating activities and events. For the participants in activities who completed surveys, emerging data demonstrate that those who participated in multiple activities had lower loneliness scores (N = 117 of the 370). Descriptions of context across the project support its upscaling, including the mechanisms that supported the continued growth in number, variety, and modifications of activities despite the impact of Covid‐19 on social distancing.ConclusionCommunity‐based efforts to create environments to reduce loneliness are possible but require effort to create sustainable intersectoral networks amidst structural and other leadership changes.