bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of Interpretable Speech Biomarkers for Monitoring Alzheimer’s Disease and Mild Cognitive Impairment Progression
Authors: Favaro Anna , Dehak Najim , Thebaud Thomas , Oh Esther S , Moro‐Velazquez Laureano 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) is a progressive neurodegenerative disease. Like for other dementias, biomarkers may help characterize distinct aspects of the underlying pathology, predict decline, and monitor disease progression. We extracted a composite array of 24 speech‐based biomarkers using machine learning and signal processing techniques. We then determined which of the given biomarkers was predictive of MCI and AD progression from baseline by conducting a correlation analysis.MethodSpoken responses to a Cookie Theft Picture description task were recorded from 2 subjects with AD, 4 subjects with Mild Cognitive Impairment (MCI) due to AD (biomarker confirmed AD), and 4 subjects with MCI. We automatically extracted acoustic, linguistic, and cognitive biomarkers using speech recognition, acoustic, and language modeling techniques. We later computed Kendall’s tau‐b (τb
) correlation between the biomarker values and Montreal Cognitive Assessment (MoCA) scores. Recordings and MoCA scores were collected at baseline, at 6 months after baseline, and at 12 months for a subgroup of the subjects. To perform the correlation analysis, we used scipy.stats.kendalltau library in Python.ResultWith respect to the acoustic biomarkers, a strong negative correlation (τb= ‐0.50) was observed between the MoCA scores and features such as pause time, pause percentage, and pause speech ratio, while a moderate positive correlation (τb= 0.2) was found for rhythm standard deviation. With respect to the linguistic biomarkers a strong positive correlation(τb= 0.50) for the features of corrected type‐token ratio, average sentence length in words, and noun count was reported, while a moderate positive correlation (τb= 0.27) was found for the features of word type count, word token count, and moving average type‐token ratio. The other acoustic, linguistic, and cognitive biomarkers showed a very weak (τb= 0.00 ‐ 0.10) or weak correlation (τb= 0.10 ‐ 0.20).ConclusionAltogether, these results suggest that speech‐based interpretable biomarkers may help clinicians to diagnose AD at earlier stages and monitor disease progression. Our preliminary data suggest that AD patients encounter more problems delivering longer and linguistically elaborated narratives as the disease progresses.
Association of platelet aggregation to amyloid and tau PET in the Framingham Heart Study
Authors: Cejudo Jaime Ramos , Scott Matthew R , Beiser Alexa S. , Tanner Jeremy A. , Ghosh Saptaparni , Johnson Keith A. , Salinas Joel , Osorio Ricardo S , Wisniewski Thomas , Berger Jeffrey S , Johnson Andrew D , Seshadri Sudha 
Published: December 2023

AbstractBackgroundPlatelets are key mediators of inflammation and vascular dysfunction. Prior work highlighted a role of platelet function in Ab and tau dynamics, and dementia risk. We hypothesized that platelet aggregation may associate with amyloid and tau brain levels in middled age people at risk of cardiovascular disease.MethodWe examined cross sectional associations of platelet aggregation with brain amyloid and tau PET levels (11C‐labeled Pittsburgh Compound‐B (PiB) and tau (18F‐Flortaucipir (FTP)) in middle aged cognitively normal participants at the Framingham Heart Study (FHS) Gen3 Cohort. Platelet aggregation was measured by light transmission aggregometry. The response to 0.98uM ADP stimulation was primarily evaluated followed by additional agonists and stimulation doses for sensitivity analysis. The associations were explored in multivariate regression models adjusted for age, age squared, sex, the time from blood to PET examination, and PET camera used.ResultThe final study sample included 356 participants (median [Q1,Q3] age, 55 [49, 61]; 51% women) of which 82 (23%) were on preventive platelet modifying treatments (PPT) (Table 1). We found significant interaction between PPT and platelet aggregation in their association with amyloid and tau PET levels, motivating a stratified analysis by the use or not of PPT. The platelet aggregation response was not associated with PiB or FTP retention in non‐PPT users (n = 274) (Table 2). In PPT users, the platelet aggregation response was positively associated with amyloid levels in the precuneus (β±SE: 0.36±0.14, P<0.05), and tau levels in the rhinal (β±SE: 0.49±0.15, P<0.01) and temporal regions (β±SE: 0.39±0.17, P<0.05).ConclusionOur results indicate that platelet aggregation is not associated with amyloid and tau PET levels in the general population. In people who are on PPT for primary prevention of CVD, platelet aggregation associates with amyloid and tau PET in Alzheimer’s disease (AD) relevant brain regions. This result reinforces the need for further examining the mediator role of platelet aggregation in the association of cardiovascular risk and AD.
Adiposity and Insulin Resistance Moderate Brain Electrophysiology and Affect Regulation in Young Adults
Authors: Larsen Brittany A , Klinedinst Brandon S , Wolf Tovah , McLimans Kelsey E , Pollpeter Amy , Li Tianqi , Wang Qian , Barnett Neil , Fili Mohammad , Moody Shannin , Parvin Mohammadiarvejeh , Willette Sara A , Willette Auriel A 
Published: December 2023

AbstractBackgroundObesity and insulin resistance (IR) may negatively influence affect regulation in young adulthood. The paucity of studies that have investigated such associations have predominantly used functional magnetic resonance imaging. However, electroencephalography (EEG) can evaluate neural signatures in real‐time that may be complementary. Thus, this study investigated how adiposity and IR moderated brain activity and underlying affect regulation using EEG.MethodReal‐time EEG was recorded in 28 lean and obese young adults with and without IR (18‐39 years, 46.4% female). Two event‐related potential (ERP) components of affect regulation, early posterior negativity (EPN) and late positive potential (LPP), were quantified from EEG data. Participants completed the Interactional Picture Affective System task to measure affect regulation, from which mean valence ratings and stimulus‐to‐response‐onset reaction times were calculated. ERP components and affect regulation parameters were then contrasted in three conditions, as follows: 1) Negative – Neutral; 2) Positive – Neutral; and 3) Negative – Positive. Height, weight, body fat percentage (%BF), and serum proteomics were collected. Fasting glucose and insulin readings were obtained to quantify Homeostatic Model Assessment for Insulin Resistance (HOMA‐IR). Hierarchical moderated regression analysis was utilized to test the interrelationships between adiposity, IR, neural activity, and affect regulation.ResultAcross all contrasted conditions, HOMA‐IR and %BF were found to moderate the relationships between frontal and parietal LPP amplitudes during the late latency window and affect regulation. Specifically, higher late frontal LPP amplitudes were associated with less negative and more positive valence ratings to unpleasant and pleasant stimuli, respectively, among participants with low, but not high, IR and %BF levels. In the Negative – Neutral and Negative – Positive conditions, lower late parietal LPP amplitudes were also associated with less negative overall valence ratings in response to unpleasant stimuli, but only in lean, insulin sensitive participants. These results overall suggest that modulation of negative and positive affectivity only occurs in lean young adults without IR.ConclusionYoung adults with greater adiposity and IR showed worse affect regulation than those without obesity and IR. Furthermore, AD‐associated characteristics may start early in life, and EEG signatures may be a useful neuroimaging approach for tracking such events.
Correlational analysis of plasma metabolome and brain imaging in a humanized APOE mouse model
Authors: Bhattrai Avnish , McLean John W. , Simmons Hannah , Raikes Adam C. , Wiegand Jean‐Paul L. , Kaddurah‐Daouk Rima F. , Brinton Roberta Diaz 
Published: December 2023

AbstractBackgroundApolipoprotein E (APOE) ε4 is the strongest genetic risk factor for the development of late‐onset Alzheimer’s disease (LOAD). Additionally, females have a 2x greater risk of developing LOAD than males. LOAD patients show brain glucose hypometabolism and severe reduction in hippocampal volume. Hippocampal atrophy has also been linked with plasma ceramide and phosphotidylcholine (PC) levels in these patients. This study explores the effects of sex and genotype on the plasma metabolome and potential correlations to brain imaging metrics in an aged humanized APOE (hAPOE) mouse model.MethodPlasma samples from 23–25‐month‐old hAPOE mice (37M/32F) expressing ε3/3, ε3/4 or ε4/4 genotypes were analyzed via mass spectrometry using the Biocrates MxP® Quant 500 platform. In a subset of these animals (24M/20F), in‐vivo FDG‐PET and high‐resolution ex‐vivo MRI were obtained. Cerebral FDG‐PET standardized uptake values were normalized to cerebellum (SUVr). Cerebral SUVr and regional volumes were correlated with detected metabolites and metabolic indicators using Pearson correlations. Two‐way ANOVAs were used to identify sex and genotype effects with post‐hoc t‐tests to determine statistical significance.ResulthAPOE ε3/3 mice had significantly greater cholesteryl ester (54%; p < 0.026) and lysophosphotidylcholine (lysoPC; 27%; p < 0.031) levels compared to ε4/4 mice. Females had lower levels of PCs (93%; p < 0.007), lysoPCs (82%; p < 0.018), triglycerides (62%; p < 0.045), and 1‐Met‐His (p = 5.84E‐25) than males. Significant positive correlations were observed between cerebral SUVr and PCs (45%; p < 0.049) as well as lysoPCs (82%; p <0.017). Total brain volume was negatively correlated with plasma 3‐Met‐His:creatinine ratio, indicative of muscle protein degradation (r = ‐0.44; p = 0.003) and positively correlated with (LysoPC+ arachidonic acid): PC ratio, indicative of phospholipase A2 activity (r = 0.42; p = 0.004). Right hippocampal volume percentage was significantly positively correlated with PCs (64%; p < 0.045) and 1‐Met‐His (p = 0.00067).ConclusionAt a comparable human age of ∼ 70 years, within the humanized APOE mouse, sex was the major contributing factor to metabolic differences in peripheral blood plasma. Levels of peripheral metabolites correlated with brain volumetrics and glucose metabolism, highlighting potential therapeutic targets for interventions designed to preserve neuronal health in AD.
Urban but not rural patterns of ambient air pollution exposure is associated with an accelerated rate of late life memory decline in the Wisconsin Longitudinal Study
Authors: Williams Victoria J. , Sicinski Kamil , Herd Pamela , Asthana Sanjay 
Published: December 2023

AbstractBackgroundExposure to ambient air pollution is an emerging risk factor for dementia, yet air pollution levels are found to vary by neighborhood affluence and across rural/urban settings. In this study, we leverage data from the Wisconsin Longitudinal Study (WLS) to evaluate the effects of ambient air pollution exposure on the rate of memory decline in late life, while accounting for both local (neighborhood) and regional (urbanization) residency characteristics.MethodAnnualized rate of change for both immediate and delayed recall trials of a 10‐item word list were calculated between 2010‐1 (baseline) and 2021‐2 (follow‐up) data collection waves. Yearly averages of geocoded regional air pollution data were obtained for 5 pollutants at baseline: particulate matter > 2.5um (PM2.5), ozone (O3), sulfur dioxide (SO2), nitrogen dioxide (NO2), and carbon monoxide (CO). Principal component analysis was performed to reduce multicollinearity among the 5 pollutants in subsequent analyses. Annualized rate of change in memory measures were regressed on resultant pollutant factor scores, additionally controlling for baseline age, adolescent IQ, education, health conditions (heart disease, stroke, hypertension, diabetes), neighborhood‐level deprivation, ApolipoproteinE‐4 (ApoE‐4) status, and sex.Result3,601 WLS participants were included in analyses, with a mean age of 70.4±3.4 years at baseline and 80.1±3.4 years at follow‐up. PCA yielded a 2‐factor solution classifying air pollutants into distinct urban (PM2.5, NO2, and CO2) versus rural (SO2 and O3) composites. Linear regression analysis revealed that greater annualized decline in delayed recall was predicted by higher exposure to urban air pollutants (but not rural), adolescent IQ, older age at baseline, and a history of heart disease. Air pollution exposure did not predict annualized change in immediate recall.ConclusionUsing longitudinal data from the WLS cohort, we find that higher levels of urban ambient air pollutant exposure predicted a more precipitous decline in delayed memory across late life. This finding remained significant after controlling for relevant confounders including neighborhood disadvantage, adolescent IQ, and ApoE‐4 status. Although the effect size of pollution exposure on the rate of memory decline was small, it remains a modifiable risk factor and stands to inform public policies to optimize late life cognition.
Building a normative sample for smartphone‐based measures of cognition and motor functioning: Study design and initial feasibility findings
Authors: Dhanam Sreya , Staffaroni Adam M. , Taylor Jack C , Sanderson‐Cimino Mark E. , Wise Amy B. , Clark Annie L , Heuer Hilary W. , Kwang Winnie , Kramer Joel H. , Boeve Brad F. , Rosen Howard J. , Weiner Michael S. W. , Nosheny Rachel L , Boxer Adam L. 
Published: December 2023

AbstractBackgroundSmartphone‐based cognitive and motor tests enable frequent remote assessments in observational research studies and clinical trials, limiting travel burden and increasing access to research for underrepresented groups. One such smartphone tool is the ALLFTD Mobile App, which was designed to capture the clinical features of neurodegenerative diseases via a battery of cognitive, speech, and motor tasks. In this study, we focus on recruiting a demographically diverse normative sample. We have partnered with the UCSF Brain Health Registry (BHR) to recruit 1,000 cognitively healthy participants across the lifespan. Here we describe the study design and initial feasibility results.MethodsWe designed an automated workflow in which participants never interact with the study team except for troubleshooting. BHR participants without reported cognitive impairment were contacted by email to participate in this study (n = 668). Interested participants downloaded the app onto their smartphone and completed in‐app electronic consent. They were asked to complete three ∼30‐minute sessions of cognitive, motor and speech measures over two weeks. Adherence was determined by evaluating the completion rate of app tasks. In a subset who completed a user experience questionnaire (n = 116), responses were quantified using descriptive statistics.ResultsThe current enrollment rate is 23.20% (155/668) of contacted participants. Average age is 62 (SD = 8.2, range = 25‐84). Average adherence is 76%. Participants reported a range of perceived task difficulty: 38% indicated tasks were “very easy” or “somewhat easy”, 26% indicated they were “neutral,” 36% found the tasks “somewhat difficult,” and none reported them to be “very difficult.” The time commitment was reported to be acceptable by 97% of participants, and 20% were willing to complete additional tasks. Over half (59%) of participants indicated that they preferred using a smartphone to complete cognitive assessments over traditional pen‐and‐paper measures.ConclusionsOur preliminary results demonstrate the feasibility and acceptability of recruiting participants, including older adults, through a registry and conducting remote smartphone testing via a fully automated workflow that is highly scalable. Future analysis will study the effects of demographic factors on feasibility and investigate the reliability and validity of the app measures in this sample.
Multimorbidity and competing risks for incident dementia and dementia‐free death in an ADRC cohort
Authors: Choate Radmila , Kucharska‐Newton Anna M. , Jicha Gregory A , Abner Erin L 
Published: December 2023

AbstractBackgroundOlder adults are often affected by more than one coexisting chronic disease, a condition referred to as multimorbidity. Multimorbidity associates with poor physical and mental health outcomes, cognitive decline, and higher mortality. This study aims to assess the association between the number of self‐reported chronic conditions (CC) and risks for dementia and dementia‐free death in a cohort of older adults.MethodWe examined data from the University of Kentucky Alzheimer’s Disease Research Center cohort, a convenience sample of community‐based older adults followed longitudinally until death. Adults ≥50 years with normal cognition at baseline and data available on 11 measured CC and mental and physical components of SF‐36 (health‐related quality of life measure) were included in this study. The cohort was stratified at baseline based on self‐reported CC into 3 groups: 0, 1, and ≥2. A competing risk analysis using Fine‐Gray subdistribution hazard models was performed to estimate associations between the number of comorbidities and incident dementia or dementia‐free death.ResultAmong 772 adults (mean age 73.1±6.7 years, 66.6% female, 89.0% white), a majority (64.4%) reported ≥2 of the measured 11 CC at baseline; 22.8% had one, and 12.8% had none (Figure 1). These groups did not significantly differ in main demographic characteristics (Table 1). Individuals with multimorbidity had lower physical component scores of SF‐36 indicating worse self‐perceived physical health than other groups. Almost half (45.9%) of the overall cohort reported a history of smoking, which was most common in the ≥2 CC group. Unadjusted and adjusted Fine‐Gray models did not show an association between the number of CC at baseline and incident dementia, accounting for competing risk of death during mean 6.8±3.9 annual follow‐up visits. There was a significant association between the number of CC at baseline and dementia‐free death, accounting for competing event dementia, in unadjusted analyses; this association did not remain significant in the adjusted analyses(Table 2).ConclusionMultimorbidity is prevalent in this cohort of older adults. When accounting for competing risks of death, the number of CC was not associated with incident dementia. Further studies are needed to examine associations with mild cognitive impairment and cognitive decline.
Dementia vs Alzheimer’s Disease – Perceptions from Latine individuals and its implications for health communications
Authors: Pinzon Maria C Mora , Benito Melanie Nicole , Kurasz Andrea , Li Zhanhai , Carlsson Cynthia M 
Published: December 2023

AbstractBackgroundHealth communication best practices include the development, testing and refinement of messages as a way to increase the reach of information and to promote engagement of target audiences. In the field of Alzheimer’s Disease (AD) and Related dementias there are multiple terminologies and misunderstanding that we need to account for at the time of developing new messages. The present study seeks to describe how Latine individuals interpret different terms.MethodThis is a mixed‐methods concurrent study, in which qualitative data was collected from structured interviews with Latine adults .A card‐sorting technique was used to explore perceptions about ADRD. Quantitative data was also collected by a mail‐in survey in English and Spanish that was distributed in metropolitan areas of WI with high proportion of Latine individuals during fall 2021. We used inductive content analysis to analyze the data qualitatively. Descriptive analytics are provided, and Chi‐square test was used to assess statistical significance for categorical variables. All p‐values were considered significant if <0.05. All analyses were done by Statistical Analysis System (SAS) version 9.4, NC, Cary.ResultQualitative data from 23 interviews (ages 50 – 87 years old, 65% Women) showed that Latine individuals perceived that cognitive conditions are a spectrum of different conditions where “memory problems” are the initial stage, which then progresses to dementia, and then develops into AD. Even among those with family members diagnosed with AD, there was a perception that AD was a different condition from dementia. The mail‐in survey was completed by 117 individuals (79% female, 47% Hispanic, Median age 56) provided similar information: 44% of respondents considered AD a mental illness, 60% considered that dementia was different from AD, and 45% considered that AD is more severe than dementia. Table 1 shows survey responses and how responses varied by gender, ethnicity, and age group. Table 2 shows some quotes that elaborate how individuals explained their perceptions.ConclusionLatine individuals perceived dementia and AD as separate entities, which indicates that healthcare providers and public health agencies need to adjust their communication strategies to promote conversations about ADRD risks and prevention.
The effects of ApoE e4 genotype on plasma p‐tau181 concentrations on clinically diagnosed Alzheimer’s disease (AD) compared to controls
Authors: Hsiung Ging‐Yuek Robin , Kumar Pankaj , Mousavi Ali , Encarnacion Mary , Frykman Hans 
Published: December 2023

AbstractBackgroundThe association between ApoE e4, a powerful genetic risk factor for AD, and beta‐amyloid (Aβ) pathology has been reported, but the evidence for the correlation with tau pathology is not as clear. The current study examined the relationship between ApoE e4 allele and plasma concentrations of p‐tau181 in patients with clinically diagnosed AD compared with an age‐matched controls with normal cognitive function.MethodWe examined 302 EDTA plasma samples of patients assessed at the UBC Hospital Clinic for Alzheimer’s disease. The cohort was clinically characterized as controls (n = 59) if no significant cognitive impairment was found, and AD (n = 243) if they fulfilled the NIA‐AA criteria (McKhann 2011). The plasma ptau‐181 levels were measured using an ADx‐developed p‐tau181‐specific Simoa assay. ApoE genotyping was performed on extracted DNA from blood samples. We examined the association of presence of ApoE e4 allele and plasma p‐tau181 concentrations using two‐by‐two ANOVA using SPSS 29.ResultThe plasma concentrations of p‐tau181 in AD who are ApoE e4 carriers (75.4 pg/ml) were slightly higher than but not significantly different from in AD non‐ ApoE4 carriers (70.1 pg/ml) (p = 0.64). The plasma levels of ptau‐181 in control cases with and without the ApoE allele were 24.8 and 24 pg/ml respectively (p = 1.000). There was no statistical significant interaction between the effects of AD and ApoE e4 carrier status on plasma p‐tau181 (F (1, 298) = 0.21, p = 0.65, ηp2 = 0.001).ConclusionWhile the plasma p‐tau181 concentrations were significantly higher in AD groups compared to controls (p<0.001) it was no significant effect of ApoE e4 genotype on the levels of plasma p‐tau181 in the control or AD groups (p = 0.94, p = 0.21). This suggests that the ApoE e4 carrier status does not affect plasma p‐tau181 concentrations significantly, independent of the AD clinical status.