bluuebunny/crossref_metadata_2025_split huggingface dataset:
Not all lipoprotein plays a crucial role in Alzheimer’s disease
Authors: An Dinghao , Xu Yun 
Published: January 2025

AbstractBackgroundHyperlipoprotein cholesterolemia increases the risk of Alzheimer’s disease(AD). LDL is mainly responsible for the risk. However, lipoprotein have different densities, different particle sizes, and different compositions. We wanted to know how lipoprotein increases the risk of AD and whether it is related to its particle size and different compositions.MethodThe GWAS summary data of the lipoprotein panel comes from Borges CM in 2020, data of AD is from Benjamin Woolf in 2022. We investigated the causal relationship between different‐density lipoprotein particles, their compositions, and AD by performing bidirectional Mendelian Randomization analysis. The study is divided into four parts. First, we performed correlation analyses of particle sizes of different‐density lipoprotein. Second, we performed correlation analyses of the concentration of particles of different particle sizes in different‐density lipoprotein. Third, we performed correlation analyses of the content of specific compositions in different‐density lipoprotein with different particle sizes, respectively. Fourth, we performed correlation analyses of specific compositions and specific ratios of different particle sizes in different‐density lipoprotein, respectively.ResultIn the panel, we found that some factors could increase the risk of developing AD, which included Phospholipids in IDL(p = 0.008) Free cholesterol in LDL(p<0.001) Total lipids in LDL (p = 0.001) Cholesterol in small LDL(p = 0.001) Phospholipids in large LDL(p = 0.001) Free cholesterol in medium LDL(p<0.001) Cholesterol in medium VLDL(p = 0.003) Cholesteryl esters in medium VLDL(p = 0.003) Free cholesterol in medium VLDL(p = 0.012) Cholesterol to total lipids ratio in large HDL (p = 0.033) Phospholipids to total lipids ratio in medium LDL(p<0.001) Free cholesterol to total lipids ratio in small HDL(p = 0.009) Cholesteryl esters to total lipids ratio in small VLDL(p = 0.004) Free cholesterol to total lipids ratio in small VLDL(p<0.001) Cholesterol to total lipids ratio in very large VLDL(p = 0.013) Cholesteryl esters to total lipids ratio in very large VLDL(p = 0.010). On the contrary, Phospholipids in medium HDL(p = 0.035) could decrease the risk of AD. However, we did not find other factors that affect the risk of AD.ConclusionWe first found a genetic association between AD and different parts of lipoprotein, specifically about particle size and lipoprotein compositions. Therefore, not all lipoprotein can affect the risk of AD. The continuous advancement of electrophoresis technology allows for the stratification of different particle sizes of lipoprotein and compositions.
Potential causal association between mucosal proctocolitis and Alzheimer’s disease: A Mendelian Randomization Study
Authors: An Dinghao , Xu Yun 
Published: January 2025

AbstractBackgroundThe gut microbiota plays a certain role in Alzheimer’s disease, and various types of enteritis can also cause disturbances in the gut microbiota. Recently, researchers have substantially highlighted the effect of some enteritis on Alzheimer’s disease incidence and development. In this study, we elucidated the correlation between mucosal proctocolitis and Alzheimer’s disease and possible mechanism.MethodThe association between mucosal proctocolitis and the risk of Alzheimer’s disease was evaluated by using two‐sample Mendelian randomization(MR), Five methods were used to perform MR analysis: the inverse variance‐weighted, weighted median, MR‐Egger, Simple mode, and Weighted mode methods. Furthermore, Heterogeneity test, MR‐Egger intercept test, MR Pleiotropy Residual Sum and Outlier test, and leave‐one‐out analysis were performed to analyze sensitivity. MR‐PRESSO and MR‐RAPS were performed to further evaluate the robustness.ResultAfter implementing multiple test corrections, we observed that genetic susceptibility to mucosal proctocolitis was associated with an increased risk of Alzheimer’s disease. However, a causal relationship between mucosal proctocolitis and markers of Alzheimer’s disease was not observed. We also found mucosal proctocolitis can also affect a certain microbial community that can cause a high risk of developing Alzheimer’s disease. Sensitivity analysis confirmed the robustness of the results.ConclusionWe confirmed the causal relationship between mucosal proctocolitis and Alzheimer’s disease, thereby providing a novel viewpoint on the prevention and treatment of Alzheimer’s disease. However, we did not observe any AD‐related gut microbiota may play a mediating role. Our findings suggest the integration of intestinal system protection and maintenance of intestinal probiotics health into routine clinical care to enhance the effectiveness of Alzheimer’s disease treatment.
Robustness and generalizability of a speech‐based digital biomarker derived from recordings of the Clinical Dementia Rating (CDR) interview
Authors: Spilka Michael J , Xu Mengdan , Toth Balazs , Hashemifar Somaye , Amora Rainier , Robin Jessica , Teng Edmond , Monteiro Cecilia , Simpson William 
Published: January 2025

AbstractBackgroundProgressive language changes are established clinical characteristics of Alzheimer’s disease (AD). Advances in Natural Language Processing (NLP) enable more objective, nuanced measurement of language, facilitating the development and validation of speech biomarkers for tracking longitudinal decline in language function. We examined the robustness and generalizability of our previously published speech biomarker score (Robin et al., 2023) in an independent clinical trial dataset.MethodWe analyzed CDR interview recordings at screening, baseline, week 25, and week 49 from 81 English‐speaking mild‐to‐moderate AD patients enrolled in the placebo arm of the Lauriet Phase 2 trial of semorinemab (NCT03828747). We extracted acoustic and linguistic features from the “recent experience” section of the interview, and computed our previously published biomarker score by combining 9 features (6 linguistic, 3 acoustic), derived from recordings from the development dataset (a subset of patients with prodromal‐to‐mild AD from the Tauriel Phase 2 study [NCT03289143]). We then compared the longitudinal trajectory, correlations with clinical endpoints and test‐retest reliability (by computing the difference between screening and baseline recordings) between the development dataset and Lauriet.ResultComparison of baseline speech biomarker scores confirmed that the AD population in Lauriet had more severe language dysfunction than the development dataset. The biomarker showed a significant effect of change over time (β = 0.26, p = 0.0003), in line with the development dataset (β = 0.29, p<0.0001). Test‐retest reliability was also comparable (Lauriet ICC = 0.616, p<0.0001; development ICC = 0.50, p<0.0001). Baseline correlations with clinical endpoints were broadly similar (Lauriet vs. development dataset: ADAS‐Cog11 r = 0.22 vs. r = 0.21, CDR‐SB r = 0.24 vs. r = 0.37, ADCS‐ADL r = ‐0.28 vs. r = ‐0.29), while change score correlations showed greater variation (Lauriet vs. development dataset: ADAS‐Cog11 r = 0.37 v. r = 0.17, CDR‐SB r = 0.31 vs. r = 0.45, ADCS‐ADL r = ‐0.35 vs. r = ‐0.22). While the magnitude of individual correlation values differed between datasets, all baseline and change score correlations maintained their direction of association and achieved statistical significance (p’s<0.05).ConclusionWe replicated prior speech biomarker findings in an independent, more severe AD population, suggesting that the speech characteristics within this score are robust and aligned with clinical progression across disease stages. Additional validation work is ongoing, including the development of comparative biomarkers leveraging the combined dataset.
Salience Network Segregation Mediates the Effect of Tau Pathology on Mild Behavioral Impairment
Authors: Iordan Alexandru D , Ploutz‐Snyder Robert , Ghosh Bidisha , Rahman‐Filipiak Annalise , Koeppe Robert A. , Peltier Scott J , Giordani Bruno , Albin Roger L. , Hampstead Benjamin M. 
Published: January 2025

AbstractBackgroundThe recently developed construct of mild behavioral impairment (MBI) provides a diagnostic framework for early signs of behavioral dysfunction that may appear even before other symptoms of cognitive decline and dementia in older adults. However, the links between MBI, brain function, and Alzheimer’s disease (AD) biomarkers are unclear.MethodUsing data from 128 participants with diagnosis of amnestic mild cognitive impairment or mild dementia of the Alzheimer’s type, we test a novel model assessing direct relationships between AD biomarker status (amyloid and tau PET) and MBI symptoms, as well as mediated effects through the functional segregation of the salience, default‐mode, and frontoparietal control networks from the other high‐level, association networks.ResultWe identified a mediated effect of tau positivity on MBI through functional segregation of the salience network from the other association networks. Specifically, individuals who were positive for both amyloid and tau showed lower overall segregation of the salience network compared to those who were AD biomarker negative (β = ‐0.25, p = 0.007). Lower overall segregation of the salience network was associated with more severe MBI symptoms (β = ‐0.441, p = 0.013). There were no direct effects of AD biomarkers status on MBI.ConclusionOur findings suggest that the effect of tau pathology on MBI may operate through the modulation of salience network functional integrity. This mediated relationship was unique for the salience network since including the default‐mode and frontoparietal control networks in our models did not change the tau‐specific findings. To the best of our knowledge, this is the first study to integrate MBI with AD PET biomarkers and network‐level brain functionality within a unified framework.
Analysis of the types of social activity participation of older adults living in the community and the health level and quality of life by types: Applying Latent Class Analysis
Authors: Kim sang Geun , Jeong Yunyeong , Hwang chae Yeon , Park Kang‐Hyun 
Published: January 2025

AbstractBackgroundParticipation in various social activities of elderly has a significant impact on overall health and quality of life, including physical and metal health. Therefore, in this study, we aim to analyze the types of social activity participation among community‐dwelling elderly and examine differences in characteristics, health status, and quality of life according to these types of participation of social activities. Thus, we purpose to utilize the findings of this study as a foundation basis for research aimed at promoting services and intervention related to social activities of elderly in community.MethodThis study utilized the 9th wave (2022) panel data from the Korean Longitudinal Study of Elderly Employment(KLoSA). Latent class analysis was utilized to explore types of social activities. To assess the goodness of fit of the latent model, χ² (Chi‐square) test, Akaike Information Criteria (AIC), Bayesian Information Criteria (BIC), Sample‐Size Adjusted Bayesian Information Criteria (SABIC) indices, and Lo‐Mendell‐Rubin adjusted Likelihood Ratio Test (LMR‐LRT) were employed. One‐way ANOVA was conducted to examine characteristics across different types.ResultThe study included a total of 6,057 elderly individuals aged 60 and above residing in the local community for analysis. The results demonstrate four distinct types of social activity participation among the elderly. These four groups were named based on the types of social activities they engaged in: “Religious and Social Activity Centered,” “Social and Leisure Activity Centered,” “Social Activity Centered,” and “Inactive.” The analysis of characteristics across these types showed statistically significant differences in demographic factors such as age, marital status, and religion. In terms of health‐related aspects, subjective health and overall quality of life indices exhibited statistically significant differences among the types.ConclusionSocial activities among the elderly were analyzed into four distinct types based on the activities they engaged in. The participation of elderly individuals in various social activities is considered a crucial indicator for improving health and quality of life. It is hoped that this study will serve as a foundational basis for developing services and intervention programs for elderly individuals in the community, aimed at facilitating their participation in diverse social activities.
Development and Validation of the Dementia‐Perceived Abuse and Neglect Questionnaire (D‐PANQ) among Family Caregivers of People Living with Dementia
Authors: Peter Seelia , Devi Elsa Sanatombi , Prabhu Mukhyaprana , Bhandary Rajeshkrishna , Chakrabarthy Jyothi , V Binil 
Published: January 2025

AbstractBackgroundAbuse of older adults is a sociopolitical issue that is often hidden. People living with dementia are more vulnerable to abuse due to their cognitive and physical impairments. Caring for a person with dementia is quite challenging. The caregivers abuse the older adults they take care of due to the increasing caregiving demands, caregiver burden, stress, depression, or anxiety. The caregivers often know what the potentially abusive behaviors are and what not to do, but at times they tend to behave in an abusive way. Some of the situations that happen in a day that are abusive are not perceived as such by them due to the normalization of what they have been doing for years. A vignette‐based tool helps to collect data regarding sensitive issues like abuse. The objective of this study was (1) to analyze the psychometric properties of the Dementia‐Perceived Abuse and Neglect Questionnaire (D‐PANQ) among family caregivers of people living with dementia regarding abuse using a newly developed vignette‐based tool. (2) to assess the perception of family caregivers of people living with dementia regarding abuse.MethodThis cross sectional study will be completed among 300 caregivers of people living with dementia. The study is ongoing, with data collected from 190 caregivers. The tool is a 22‐item, 4‐point scale with a maximum score of 66. The higher scores show a high perception of abuse, and the low scores show a low perception of abuse.ResultThe interim analysis among 190 caregivers shows that the perception of abuse is high. The mean DPANQ score was 42.86, with a standard deviation of 16.01. The reliability of the tool was established by Cronbach’s alpha. It was found to be 0.82. Further analysis of the questionnaire’s feasibility, reliability, internal consistency, content validity, and construct validity (factor analysis and convergent validity) will be done once the study is completed.ConclusionThe initial analysis shows that the tool is valid, reliable, and feasible to assess the perception of family caregivers of people living with dementia regarding abuse, and this would be the first tool to assess the perception of dementia carers towards abuse and neglect.
Communication Training For Medical Professionals: Proof Of Concept
Authors: Brown Nancy L 
Published: January 2025

AbstractBackgroundDespite the prevalence of patients living with dementia, physicians and medical students, in particular, have received little or no dementia‐specific training to help them communicate effectively with this population. Connecting and communicating with persons living through cognitive change requires specific skills: developing empathy and identifying coping mechanisms, symbols, and the stages of resolutions for those living with cognitive decline. These skills were taught in the beta test, Validation for Physicians and Medical Provider training, based upon the evidence‐based Validation method by Naomi Feil.MethodThe pilot program included physicians and other healthcare professionals. In this single‐group design, pre‐ and post‐surveys consisted of a knowledge scale and SRDB (self‐efficacy) ranked on a Likert scale of 1 to 5 and analyzed using SPSS. Post‐training individual interviews concluded the beta‐testing. Thirty professionals enrolled in the training; eight participants completed every aspect of the beta‐testing.ResultDespite the small sample size, the validated measurements used showed trends approaching significance in knowledge and self‐efficacy. Participants highly valued the training’s content and pedagogy.ConclusionTechnical problems were the main reason for attrition. Overall, the Validation method was found useful in practice and improved confidence, knowledge, and communication behaviors. Improvements are needed in the choices for validated measures and the online platform. “Validation has made me a better doctor. It has changed my perspective on aging” (participant).
Site‐specific hyperphosphorylation of tau and C‐terminal alteration of PP2A catalytic subunit in tau pathogenesis seeded by proteopathic tau
Authors: Liu Fei , Gu Jianlan , Zhou Yan , Hu Wen , Wu Ruozhen , Tung Yunn Chyn , Gong Cheng‐Xin , Iqbal Khalid 
Published: January 2025

AbstractBackgroundRegional distribution of neurofibrillary tangles consisting of hyperphosphorylated tau correlates strongly with the progression of Alzheimer’s disease (AD). Misfolded proteopathic tau templates the conversion of naive tau into a pathological state in a prion‐like fashion, which underlies the spreading of tau pathology in the brain. Whether hyperphosphorylation triggers tau aggregation or hyperphosphorylation occurs after aggregation is under much debate.MethodIn the present study, by using oligomeric tau derived from AD brain (AD O‐tau) as proteopathic tau seeds, we determined the role and molecular mechanism of site‐specific hyperphosphorylation in seeded‐tau aggregation in cultured cells and in vivo in mice.ResultWe found that seeded‐tau aggregation in cultured cells and in vivo was accompanied by site‐specific hyperphosphorylation of tau and by reduction in the level of PP2A catalytic subunit (PP2Ac) determined by a body of antibodies targeting its C‐terminus, but not its middle region. PP2Ac immunoreactivity with the C‐terminal antibodies was reversely correlated with the hyperphosphorylation of tau in cultured cells and in AD brain. Site‐specific hyperphosphorylation of tau and reduction of PP2Ac immunoreactivity were co‐existed in RIPA‐insoluble fraction and associated with seeded tau aggregation. Blocking the site‐specific hyperphosphorylation by mutating Ser/Thr to Ala suppressed the seeded‐tau aggregation and the decline of PP2Ac immunoreactivity. Knockdown and overexpression of PP2Ac enhanced and suppressed seeded‐tau aggregation in cultured cells and tau pathology in vivo, respectively.ConclusionThese findings strongly suggest that site‐specific hyperphosphorylation of tau is essential for seeded‐tau aggregation. Site‐specific hyperphosphorylation of tau, tau aggregation, and C‐terminal alteration of PP2Ac work synergistically to produce tau pathology. Interrupting this vicious cycle may enable inhibition of the propagation of tau pathology and the progression of AD and related tauopathies.
Examining the impact of hormone therapy and Alzheimer’s disease risk factors on depressive symptoms in the Harvard Aging Brain Study
Authors: Garcia Kelly A. Lopez , Klinger Hannah M , Properzi Michael J , Gatchel Jennifer R. , Marshall Gad A , Donovan Nancy J , Shirzadi Zahra , Schultz Aaron P , Chhatwal Jasmeer P. , Sperling Reisa A , Coughlan Gillian T , Buckley Rachel F 
Published: January 2025

AbstractBackgroundHormone therapy (HT) is often used to manage symptoms related to menopause, but its longer‐term effects on depressive symptoms in older women remains unclear. Previous literature reports inconclusive results on whether HT use is protective against or associated with increased depressive symptoms over time in older women. The objective of this study was to examine the associations of self‐reported HT use with baseline and longitudinal later life depressive symptoms. We also investigated whether Alzheimer’s disease (AD) risk factors such as APOEe4 status, white matter hyperintensities (WMH), and Aβ status moderated the association between HT use and depressive symptoms.MethodWe identified 593 participants from the Harvard Aging Brain Study and ancillary studies (58% Female, Agemean(SD) = 72(8) years) with longitudinal data for the 30‐item Geriatric Depression Scale (GDS) and baseline self‐reported HT use for women. A subset of 355 participants had baseline Aβ status available and 266 participants had baseline WMH MRI data available. Linear regressions and linear mixed‐effects models examined the associations between baseline HT use and baseline and longitudinal GDS, using HT users as our reference group. We also tested the interaction of baseline HT use with 1. APOEe4 status, 2. Log transformed baseline WMH normalized to intracranial volume, and 3. Baseline Aβ status on longitudinal GDS. All models adjusted for age, education, and ethnicity.Result42% of women reported past or current HT use. HT use was not associated with GDS at baseline. HT users reported significantly greater depressive symptoms over time relative to men (β = 0.11, p = 0.035) and exhibited a sub‐threshold trend of higher depressive symptoms relative to non‐users (β = 0.10, p = 0.069). APOEe4, WMH, and Aβ status did not modify the effect of HT status on longitudinal GDS.ConclusionWhile our study revealed that HT users exhibit increased depressive symptoms over time relative to men, further research is needed to confirm this trend relative to non‐users and to better understand how AD risk factors moderate this relationship. Our findings are limited by lack of information on HT use, such as type, dose, and duration, which should be considered to provide insight into the complexities of women’s brain health in aging populations.