bluuebunny/crossref_metadata_2025_split huggingface dataset:
TaPiscine: An effort‐based decision‐making task for apathy assessment in people with neurocognitive disorders
Authors: Zeghari Radia , Lockwood Patricia L , L'Yvonnet Thibaud , Jo Cutler , Robert Philippe , Manera Valeria 
Published: December 2021

AbstractBackgroundApathy is a common neuropsychiatric symptom in Neurocognitive Disorders (NCD). It is characterized by a significant reduction of goal‐directed behaviors in the domains of cognition, behavior, emotions, and social interactions. Goal‐directed behaviors can be investigated using effort‐based decision paradigms, allowing computational models to quantify sensitivity to effort and reward (and their combination) in a systematic way [1]. Our study used an effort‐based decision paradigm to investigate apathetic symptoms in a clinical context with older people with NCD and subjective cognitive decline (SCD).MethodWe recruited 33 participants with mild NCD or SCD from the Memory Center in Nice (24 females, mean age= 74 years, mean MMSE score = 27.1). We assessed self‐reported apathy using the Apathy Motivation Index (AMI) and the Dimensional Apathy Scale (DAS). We also assessed self‐reported fatigue (Multidimensional Fatigue Inventory, MFI), anhedonia (Snaith‐Hamilton Pleasure Scale, SHAPS), and depression (Geriatric Depression Scale, GDS). The effort‐based decision task consisted of choosing to perform an action (taping as quickly as possible on a tactile tablet to fill a virtual pool corresponding to 25%, 50%, 75% and 100% of the maximum individual effort) to obtain a specific reward (3, 6 or 9 credits to discover pictures), or to rest to ensure 1 credit. For each subject, we extracted a parameter (K) representing the degree to which a reward is devalued by effort.ResultsWe divided participants into two groups with high and low AMI scores using a mean split. Results suggested that the K‐parameter was almost significantly lower in subjects with higher apathy (U=86, p=0,072). Further and more detailed analyses will be performed once reached a sample size of 50 subjects (end of June 2021).ConclusionsEffort‐based decision tasks may be employed also in people with NCD, and may help to differentiate patients with low and high apathy. The study is ongoing, and a bigger sample will allow to better characterize these results. Reference: [1] Lockwood, P., Hamonet, M., Zhang, S. et al. Prosocial apathy for helping others when effort is required. Nat Hum Behav. 1, 0131 (2017). https://doi.org/10.1038/s41562‐017‐0131
Metabolomic signatures of dual decline in memory and gait: An aging phenotype of high risk of dementia
Authors: Tian Qu , Shardell Michelle D. , Tanaka Toshiko , Kuo Pei‐Lun , Resnick Susan M. , Ferrucci Luigi 
Published: December 2021

AbstractBackgroundOur recent meta‐analysis of 6 geographically and culturally diverse aging studies has shown that older adults with dual gait and memory decline had a synergistically greater hazard of dementia than those with memory decline or gait decline only. Mechanisms underlying this increased risk are unknown. We hypothesize that those with dual decline have specific pathophysiological pathways to dementia.MethodIn the Baltimore Longitudinal Study of Aging, we compared rates of change in 455 plasma metabolites from 26 biochemical classes among dementia‐free participants aged 50 and older who experienced dual decline (n=114), gait decline only (n=167), memory decline only (n=168), and no decline (n=406) using linear mixed‐effects models. Longitudinal data on gait, memory, and Biocrates p500 metabolomics were collected simultaneously over an average of 6.6 years. Analyses were adjusted for batch, demographics, baseline memory and gait, education, and APOE e4 carrier status. We further performed enrichment analysis.ResultAfter covariate adjustment, rates of change in 18 metabolites significantly differed among four groups (q<0.05). Top 10 ranked metabolites were from classes nucleobases (hypoxanthine), lysophosphatidylcholines (LPC C18:0, C16:0, C17:0, C18:1, C18:2), and ceramides (d16:1/24:0, d18:2/24:0, d16:1/23:0, d18:1/24:0) (Figure 1). LPCs, ceramides, and amino acids were significantly enriched (p<0.05). Compared to no decline group, memory decline only group had greater changes in 21 metabolites enriched for PCs, LPCs, and amino acids. Gait decline only group had greater changes in 106 metabolites enriched for triglycerides, ceramides, and cholesteryl esters. Dual decline group had greater changes in 121 metabolites enriched for LPCs, amino acids, and triglycerides (p<0.05). After multiple comparisons adjustment, LPC C18:0 showed greater decrease in dual decline group, and PC C32:2 showed greater increase in gait decline only group (q<0.05).ConclusionMetabolite changes over time may underlie age‐related decline in memory, gait speed, or both, especially in LPCs, ceramides, and amino acids. Older adults experiencing dual decline have the most extensive alterations in metabolic profiling, especially in LPCs, triglycerides, and amino acids. Notably, these metabolites are main building blocks for cardiolipin, an essential lipid for regulation and assemblage of electron transport complexes and mitochondrial morpho‐functional architecture. Pathway analyses and further validation are warranted.
Amyloid status is associated with deficits in connected speech language
Authors: Van Hulle Carol A. , Jonaitis Erin M. , Betthauser Tobey J. , Kollmorgen Gwendlyn , Suridjan Ivonne , Andreasson Ulf , Carlsson Cynthia M. , Asthana Sanjay , Johnson Sterling C. , Zetterberg Henrik , Blennow Kaj , Mueller Kimberly D. 
Published: December 2021

AbstractBackgroundSubtle changes in connected speech language (CSL) comprising fluency disruptions and limited semantic content are present in preclinical stages of Alzheimer’s disease (AD) and dementia. Our prior research suggests that individuals identified by PET imaging as amyloid‐positive experience more rapid decline of semantic content than those without amyloid. Here we expand our analyses to additional CSL measures sensitive to nascent deficits in communication.MethodStudy participants were enrolled in Wisconsin Alzheimer’s Disease Research Center (n= 103) or the Wisconsin Registry for Alzheimer’s Prevention (n= 223), had available cerebrospinal fluid (CSF) measurements, and 1‐4 CSL samples. CSF biomarkers were measured using the exploratory Roche NeuroToolKit assays, a panel of automated robust prototype immunoassays (Roche Diagnostics International Ltd). Speech samples (N=740) were recorded while describing the “Cookie Theft” picture from the Boston Diagnostic Aphasia Examination. The majority of participants (65%) provided ≥ 2 language samples across biennial visits. Moving average types‐tokens ratio (MATTR), content information unit (CIU) density, CIUs per minute, words per minute, and filled pauses were extracted from speech samples. Linear mixed effects models were used to test moderation of age related changes CSL samples by amyloid status (Aβ42/Aβ40 ≥ .046), where age at study visit is the measure of time. ovariates gender, years of education, and number of CSL visits (i.e., practice effects) were included as fixed effects.ResultBaseline demographics and study variables stratified by amyloid status are shown in Table 1. CSF amyloid status did not moderate longitudinal changes in any of the CSL outcomes (Figure 1). After dropping these non‐significant interactions, amyloid‐positive individuals expressed fewer CIUs total and per minute and slightly more filled pauses (Table 2). We also found a significant decline with age in CSL outcomes MATTR, CIUs per minute, and words per minutes. The pattern of results was unchanged after excluding nineteen individuals with cognitive impairment from analyses.ConclusionWe found that amyloid burden associated with connected speech measures reflecting semantic content and word retrieval. CSL is a ‘digital biomarker’ that shows promise as a measure of language; future work will continue to explore longitudinal relationships between CSL and AD biomarkers.
Associations between gut microbiota composition and AD biomarkers
Authors: Verhaar Barbara J.H. , Hendriksen Heleen M.A. , Leeuw Francisca A. , Doorduijn Astrid S. , Leeuwenstijn Mardou , Teunissen Charlotte E. , Berckel Bart N.M. , Barkhof Frederik , Scheltens Philip , Kraaij Robert , Duijn Cornelia M. , Nieuwdorp Max , Muller Majon , Flier Wiesje M. 
Published: December 2021

AbstractBackgroundSeveral studies have reported alterations in gut microbiota composition of Alzheimer’s disease (AD) patients. However, the observed differences are not consistent across studies. We aimed to investigate associations between gut microbiota composition and clinical biomarkers of AD using machine learning models in patients with AD dementia, mild cognitive impairment (MCI) and controls.MethodWe included 169 patients from the NUDAD project, comprising 33 with AD dementia (66±8 years, 46%F, MMSE 21[19‐24]), 21 with MCI (64±8 years, 43%F, MMSE 27[25‐29]) and 115 controls (62±8 years, 44%F, MMSE 29[28‐30]). Fecal samples were collected and gut microbiome composition was determined using 16S rRNA sequencing. Clinical parameters of AD included clinical diagnosis, cerebral spinal fluid (CSF) amyloid and phosphorylated tau (pTau) status, positron emission tomography (PET) amyloid status, and MRI visual scores. Associations between gut microbiota composition and dichotomized clinical parameters of AD were assessed with separate machine learning classification models using XGBoost with nested cross‐validation. The model with the highest area under the curve (AUC) was selected for logistic regression, to assess associations between the 20 best predicting microbes (cumulative sum scaled counts) and the outcome measure from this machine learning model while adjusting for age, sex, and BMI.ResultThe machine learning prediction for amyloid status (CSF) from microbiota composition had the highest AUC. Top predicting microbes included several short chain fatty acid (SCFA)‐producing species. In the logistic regression models, these microbes were significantly associated with lower odds of amyloid positive status, and included Eubacterium ventriosum group spp. (OR 0.49 (0.30‐0.76) per SD increase in counts, p = 0.002), Marvinbryantia spp. (OR 0.55 (0.34‐0.85), p = 0.009), Coprococcus catus (OR 0.58 (0.36‐0.89), p = 0.017), Roseburia hominis (OR 0.59 (0.38‐0.90), p = 0.018), Odoribacter splanchnicus (OR 0.51 (0.30‐0.82), p = 0.008), Lachnospiraceae spp. (OR 0.58 (0.36‐0.89), p = 0.014), and Ruminococcaceae spp. (OR 0.44 (0.25‐0.71), p = 0.002).ConclusionGut microbiota composition had the strongest association with amyloid status among the clinical biomarkers examined. We extend on recent studies that observed associations between SCFA levels and AD biomarkers by showing that higher abundances of SCFA‐producing microbes were associated with lower odds of amyloid positive status.
Thinking outside of the box through adaptive reuse of closed malls for dementia programs and services: Community workshop outcomes
Authors: Roberts Emily 
Published: December 2021

AbstractBackgroundIt is estimated that 5.4 million Americans have some form of dementia and these numbers are expected to rise in the coming decades, leading to an unprecedented demand for memory care housing and services. In searching for innovative options to create more autonomy and better quality of life in dementia care settings, repurposing existing structures, in particular vacant urban malls, may be one option for the large sites needed for the European model of dementia villages. These settings may become sustainable Dementia Friendly City Centers (DFCC), because in the case of enclosed mall construction, the internal infrastructure is in place for lighting, HVAC, with varied spatial configuration of public spaces. This presentation describes the community engagement research being conducted by a research team at a Midwestern university, laying groundwork for the DFCC model for centralized dementia programs, services and attached housing. An online community workshop was held with 50 participants from multiple stakeholder groups including architect, urban planners, landscape architects, memory care administrators, medical doctors, family caregivers, university professors and students and public health employees. 5 breakout sessions were held after the initiative was introduced to the participants with topics covered which included the themes of community revitalization, building sustainability, urban regreening, onsite housing and medical care and innovation and culture change in dementia care This presentation provides the qualitative data collected through the recorded breakout sessions and the participants agreed that the DFCC model is one opportunity to make life better not only for those with needs associated with dementia now, but also for ourselves in the future. Others saw education of future stakeholders about the value of this model of care as critical in transforming current hurdles into future opportunities.
MoCA Test: Validation of a five‐minute telephone version
Authors: Nasreddine Ziad S 
Published: December 2021

AbstractImportanceThis study validates the use of a telephone version of the MoCA Test, which helps health professionals assess patients remotely.ObjectivesThis is a validation study for a 5 minute telephone version of the MoCA.Study designThe subjects’ performances were compared to results obtained from the full version of the MoCA test, at an average of 50.8 days, prior to having completed the 5 Min Telephone MoCA.Participants84 consecutive subjects were approached to participate in the study. Subjects had to be over 50, male or female, an education level of 6 years.SettingsSubjects were recruited in a memory clinic setting.Outcomes and MeasuresCorrect classification and correlation between the Telephone MoCA and full MoCA was evaluated, with area under the curve (AUC) analysis, and Pearson Coefficient respectively.Results81 subjects were recruited, and 3 subjects declined participation. The average age of the subjects was 69 (Range 47‐92) with a sex distribution of 42 females and 41 males. The average education level for the subjects was 12.6 years. The 5 Min Telephone MoCA results correlated well with the full version of the MoCA, with an area under the curve of 0.864 and a strong Pearson Coefficient of 0.74.Conclusion and RelevanceThe 5 Min Telephone MoCA is feasible, practical, and reliable, when compared to the full, in‐clinic, MoCA. Clinicians are already familiar with the use of the full MoCA Test, and this new 5 min telephone version, can help them reliably assess patients who cannot make to an in clinic evaluation.
Establishing a relationship between semantic clustering and language performance
Authors: Mae de la Cruz Raelynn , Jeffers Sharlene L , Miller Justin B ,   Cleveland Clinic Lou Ruvo Center for Brain Health
Published: December 2021

AbstractBackgroundSemantic clustering (SC) is an implicit learning strategy commonly utilized on verbal list‐learning tasks. While research has examined SC and executive functioning and memory, little has been done relating SC and language. In the present study, we calculated a SC score on a common list‐learning task and explored relationships with language performance. We predicted weaker SC in individuals with MCI compared cognitively normal individuals, which could potentially be used as an additional measure to help identify MCI and Alzheimer’s disease.MethodArchival test data from an outpatient neurology clinic were extracted (N=355), including the Hopkins Verbal Learning Test – Revised, Boston Naming Test, WAIS‐IV Similarities, D‐KEFS Verbal Fluency Letter Fluency (FAS) and Category Fluency (CF) tests, and Wide Range Achievement Test‐Reading (WRAT). Diagnostic subgroups of MCI and CN were created using actuarial diagnostic criteria. SC was calculated as the sum of novel consecutive recalls belonging to the same category, without repeats or semantically‐related intrusions. A chi‐square test was conducted to assess differences between demographic factors. ANCOVA was used to compare performance of SC and selected language measures between the MCI and CN groups using age and WRAT‐Reading as covariates; SC and language measure raw scores were treated as dependent variables and diagnostic grouping as the independent variable.ResultDifferences in age(X2
=36.39,p<0.01), education(X2
=21.44,p<0.05), and WRAT‐Reading SS(X2
=45.43,p<0.01) were found. ANOVA found significant differences between the groups’ SC scores, as well as performance on language measures (p<0.05). The CN group showed a trend of being stronger than the MCI group across all measures, including SC. Generally, language measures were significantly positively correlated with SC scores for both groups (p<0.05), including BNT and CF, and FAS for the CN group.ConclusionOverall, findings support our hypothesis that both SC and language scores vary as a function of clinical diagnosis with the CN group having stronger abilities than those with MCI. As such, SC scores derived from verbal learning tests may be able to contribute to knowledge of one’s language skills. Further research should aim to help establish this relationship. SC scores could assist in screening for MCI or cognitive deficiencies resulting from AD.
Phase 1b study of XPro1595 in Alzheimer's patients with biomarkers of inflammation
Authors: Barnum Christopher , Tesi Raymond , Malberg Jessica 
Published: December 2021

AbstractBackgroundXPro1595 is currently being tested in a proof of biology Phase 1b study in Alzheimer’s patients with biomarkers of inflammation.MethodInflammatory and neurodegeneration protein and imaging biomarkers were measured 3 months after weekly treatment with multiple doses of XPro1595.ResultXPro1595 dose‐dependently reduced All CSF inflammatory protein levels and neuroimaging inflammatory markers (free water white matter). Moreover, we observed a strong correlation between MRI inflammation (Free water white matter) and CSF inflammation was observed (R2 =0.761). In addition to the reduction in neuroinflammation, XPro1595 reduced biomarkers of neural injury and synaptic dysfunction as assessed by CSF protein and neuroimaging. Additional data on novel MRI metrics to assess neuroinflammation and white/gray matter quality will be presented.ConclusionXPro1595 achieved its primary goal of reduced markers of neuroinflammation, neural injury, synaptic dysfunction across multiple measures and assays. Data support advancement to Phase 2.
Cell‐type specific variations of within pathway interaction in AD using covariance regression
Authors: Lu Xiaoyu , Zhang Chi , Zhao Yi , Cao Sha 
Published: December 2021

AbstractBackgroundAlzheimer’s disease (AD) and related dementias are among the greatest public health challenges in the United States. A deeper understanding of the disease pathology on a molecular and cellular level is critical to devise treatments to slow down the disease progression and better understand the mechanisms behind AD. Recent advancement in single‐cell technology provides new avenues for molecular profiling of AD at the single‐cell resolution, which improves the omics studies by making greater precision and granularity possible.MethodWe here present a statistical framework for extracting the variability of gene‐gene interaction in a disease‐, sex‐ and cell type‐ specific manner, to identify AD‐associated markers and pathways and to articulate disease mechanisms on cellular and molecular levels. We applied our method to the Religious Orders Study and Memory and Aging Project (ROS/MAP) single nucleus dataset, with single cells of five cell types including astrocyte, microglial, neuron, oligodendrocyte, and oligodendrocyte progenitor cell (OPC).ResultExisting methods for AD gene and biomarker detection mainly focus on comparative and univariate analysis, with the lack of adequate statistical power in detecting abnormal gene‐gene interaction structure in the same pathway. Our covariance regression based analytical pipeline represents a statistically solid tool to investigate the abnormalities in genetic interaction on pathway‐level using single‐cell RNA sequencing data, and to make inference on key covariates. Importantly, such a pathway‐level analysis is robust to the severe drop out events in single cell RNA‐Seq data. Compared with enrichment‐based pathway analysis, our method has much higher statistical power in detecting significant differentially co‐expressed pathways in comparing AD vs healthy control cells in a sex and cell type specific manner.ConclusionMajority of the pathways tend to have lower co‐expression strength among its genes in AD cells than healthy cells for female subjects in astrocyte, neuron and microglial. While not much pathways are differentially co‐expressed in male AD vs healthy subjects, neuron and astrocyte are the two major cell types with the largest number of alternatively co‐expressed pathways in female subjects, with 3972 and 4218 pathways. These altered pathways belong to known pathway categories, such as synapse, neuronal development, lipid metabolism, calcium transport, etc.
Changes in alkaline phosphate and calcium levels during early mild cognitive impairment, indicating a role for bone in the progression of Alzheimer’s disease
Authors: Suryadevara Vidyani , Monte Willis S. 
Published: December 2021

AbstractBackgroundOver 50 million people worldwide have dementia, one of its most common form being Alzheimer’s disease. It’s one of the top ten leading causes of death attributing to the extraneuronal effects in the bone, skeletal muscle, liver, kidney, and heart. Falls and fractures are one of the predominant causes of mortality in AD patients, indicating the cross talk between the bone and brain during AD. Women with lower femoral BMD were two times more risk‐prone to develop AD than women with higher BMD and this was found to be independent of other risk factors of AD. In this study, we are investigating the changes in the bone markers during early stages of the AD.MethodThe Alzheimer’s Disease Neuroimaging Initiative(ADNI) is a multisite, longitudinal study of normal cognitive aging, early Mild cognitive impairment(EMCI), late MCI and AD individuals, wherein specific recruitment methods are used to recruit participants. We analyzed data from the ADNI‐1, ADNIGO and ADNI‐1 focusing on the relationships between the severity of dementia (mini‐mental state scores), the clinical musculoskeletal findings, and the laboratory data from these participants, which included fluid biomarkers. A total of 1765 patients were included, 57% male and 43% female.ResultWe observed in females that there was robust decrease in the alkaline phosphate levels in EMCI group compared to normal cognitive group, whereas a significant increase in alkaline phosphate levels between EMCI and AD groups. The higher alkaline phosphate levels at EMCI indicates the activity of bone cells and thus bone remodeling. In males, there was a significant reduction in the alkaline phosphate levels during EMCI when compared to cognitive normal groups; however, alkaline phosphate levels were significantly increased both in LMCI and AD groups when compared to EMCI group. Also, in males, there was significant decrease in the calcium levels from cognitive normal group to EMCI group, which was further significantly reduced in the AD groups. However, there was no change in calcium across the groups in the females.ConclusionDetecting changes in the bone biomarkers early on, will help in better management of AD, thereby improving the quality of life in these patients.