bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome‐wide association study of brain MRI and other phenotypes in the Tohoku Medical Megabank Organization
Authors: Taira Makiko , Saykin Andrew J. , Fuse Nobuo 
Published: December 2023

AbstractBackgroundThe Tohoku Medical Megabank Organization (ToMMo) is a large cohort study and biobank established in 2013 in the Miyagi Prefecture of Northern Japan following the Great East Japan Earthquake and Tsunami. ToMMo enrolled 150K individuals in a planned longitudinal study aiming to reveal numerous and diverse biological, psychological, and lifestyle characteristics associated with important diseases, and it collects and analyzes a rich set of biological data, including genomics, from participants to support innovative research on these diseases. Importantly, aging and Alzheimer’s disease are key areas of our research agenda, but little is known about common genetic variants that affect quantitative traits related to AD in Japanese people. MRI brain scans and cognitive screening on 12,164 cohort participants were collected at baseline (the TMM Brain‐MRI Study) since 2014 to 2019.MethodThe TMM Brain‐MRI study acquired multiple MRI sequences, including T1‐weighted imaging (T1WI). The ADNI Phantom was used, and each scan’s quality was checked. Following pre‐processing steps, Freesurfer (v7.2.0) was used with the Destrieux or Desikan‐Killiany atlas to parcellate multiple anatomical brain regions and derive cortical thickness data. We conducted a Genome‐Wide Association Study (GWAS) on all Brain‐MRI Study participants who were also genetically profiled with a Japanese‐oriented microarray (Japonica‐Array® v1, v2 and NEO) and WGS.ResultAlong with the other data types, the genotyping data for the TMM Brain‐MRI study participants represented etiological characteristics. The attached Figure shows the age distribution by decile for 7,630 male and female participants who were profiled with the Japonica‐Array® v2. The usable archived volumetric T1WI data demonstrated inverse correlations between brain volume and age, as well as very good agreement with correlations observed in previous clinical studies. We identified nominally genome‐wide significant loci (P < 5×10−8) associated with imaging phenotypes in this sample consisted of Japanese adults as the discovery stage of the study.ConclusionThe ToMMo MRI and genetic data provide insights into the genetic architecture of the brain that are relevant to understanding brain aging and AD. Our results require some replication stages and meta‐analyses using samples of Japanese individuals in other studies.
Investigating the relationship between sleep disturbances and white matter hyperintensities in healthy older adults, MCI, and AD
Authors: Kamal Farooq , Dadar Mahsa 
Published: December 2023

AbstractBackgroundRecent studies have shown sleep disturbances occur in people with Alzheimer’s disease (AD), with sleep being impacted before the onset of clinical symptoms. White matter hyperintensities (WMHs) are cerebrovascular disease‐related pathological changes that develop with increased age and are also associated with AD. While studies have shown that sleep disturbance can have profound negative effects on brain vasculature, its impact on WMH remains relatively unexplored. Our objective was to examine the relationship between sleep disturbances and WMHs in older adults. This study examined sleep disturbance and regional WMH differences between normal controls (NCs), people with mild cognitive impairment (MCI), and Alzheimer’s disease (AD).MethodWe included participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). History of insomnia was extracted from the ADNI database along with the Neuropsychiatric Inventory Sleep (NPI sleep) Questionnaire used to assess sleep disturbance. Participants were included if they had at least two WMH measurements and completed the NPI. A total of 1782 participants with 8771 follow‐ups met the inclusion criteria. Linear mixed‐effects models examined group differences in sleep disturbance and insomnia and the association between WMH burden and sleep in NC, MCI, and AD.ResultPeople with more sleep disturbance were found to have a greater WMH burden across all regions except temporal (p < .05). People with AD and MCI had more sleep disturbance than NC across all regions (p < .0001). Additionally, people with insomnia were found to have greater WMH burden across all regions (p < .001).ConclusionThese results suggest WMH burden and sleep disturbance increases from aging to AD. These findings indicate that people with MCI and AD with worse sleep have a higher WMH burden. In older adults, insomnia and sleep disturbances are strongly associated with increased WMH accumulation over time.
Deep Learning Derived Visceral Abdominal Fat Predicts Brain Atrophy at Midlife in 10,001 Individuals
Authors: Raji Cyrus A. , Meysami Somayeh , Hashemi Sam , Garg Saurabh , Akbari Nasrin , Gouda Ahmed , Chodakiewitz Yosef Gavriel , London Sean , Nguyen Thanh Duc , Merrill David A. , Attariwala Raj 
Published: December 2023

AbstractBackgroundVisceral abdominal fat can predict health outcomes with increasing interest in applications on brain health.MethodA total of 10,001 healthy participants from four sites were scanned on 1.5T MR machines with a short whole‐body MR imaging protocol. Core whole body sequences included coronal T1, STIR from vertex to feet, whole‐body axial DWI from vertex to proximal‐thighs and axial T2 TSE without fat suppression from skull base to pelvis. Brain sequences were T1 MPRAGE and 2D FLAIR. Deep learning with FastSurfer trained on 134 participants aged 27‐66 and segmented 96 brain regions. A separate deep learning model was trained to segment abdominal visceral fat from the whole‐body coronal T1. Partial correlation analysis of visceral abdominal fat volume and brain volumes were evaluated, controlling for age, sex, and total intracranial volume. Benjamini‐Hochberg False Discovery Rate of 5% controlled for multiple comparisons. Logistic regression models determined risk of brain total gray and white matter atrophy based upon the highest quartile of visceral fat and lowest quartile of these brain volumes.ResultThis cohort had an average age of 52.97 ± 13.04 years with a range of 11‐97 years with 52.8% men and 47.2% women. Mean visceral abdominal fat was 3417.81 ± 514.88 ml for overweight persons (BMI ³ 25) and 5355.24 ± 505.04 for obese persons (BMI ³ 30). Even accounting for co‐variates and multiple comparisons, deep learning segmented visceral abdominal fat predicted atrophy in multiple brain regions including: total gray matter volume (Partial R = ‐.09, p = 1.17e‐19), total white matter volume (Partial R = ‐.09, p = 2.25e‐21), hippocampus (Partial R = ‐.02, p = .005), frontal cortex (Partial R = ‐.09, p = 1.79e‐19), temporal lobes (Partial R = ‐.12, p = 2.6e‐30), parietal lobes (Partial R = ‐.04, p = .0004), occipital lobe (Partial R = ‐.03, p = .002), orbital frontal cortex (Partial R = ‐.09, p = 3.76e‐21). Visceral fat predicted increased risk for lower total gray matter (age 20‐39: OR = 5.9; age 40‐59, OR = 5.4; 60‐80, OR = 5.1) and white matter atrophy: (age 20‐39: OR = 3.78; age 40‐59, OR = 4.4; 60‐80, OR = 5.1).ConclusionDeep learning determined increased visceral abdominal fat volume predicts brain volume loss and may represent a novel modifiable factor in determining brain health.
Handwriting characteristics analysis for Alzheimer’s Disease and Mild Cognitive Impairments Assessment
Authors: Thebaud Thomas , Chen Casey , Moro‐Velazquez Laureano , Dehak Najim , Oh Esther S 
Published: December 2023

AbstractBackgroundMotor changes are early signs of neurodegenerative diseases such as Alzheimer’s disease (AD), but they are often difficult to detect, especially in the early stages. In the past, the examination of handwriting has been used to investigate motoric changes in different neurodegenerative diseases. In this study, we explore a wide array of explainable characteristics of the handwriting of patients obtained with signal processing, and study their potential for assessment of Mild Cognitive Impairment (MCI) and AD.MethodWe collected the written tasks from 37 participants, 7 with AD, 17 with MCI, and 13 for the control group (CTL) on a digital tablet. We analyzed 14 different tasks, including holding the pen over a point, copying images, free writing/drawing, and memory copying. We extracted multiple movement characteristics, including the length of each stroke, the ratio of the time the pen spent on‐air vs in‐tablet and the standard deviation of the distance between consecutive points. The drawings of each subject were manually supervised, then processed to extract multiple characteristics, and compared to identify the ones providing the most significant differences between the three studied groups using Welch’s t‐test, with false discovery rate (FDR) correction.ResultPreliminary results showed that the ratio between the time with the pen in contact with the tablet and without (on‐air vs in‐tablet) for writing tasks, significantly differentiate between AD and CTL patients (p‐value<0.01), as well as the position standard deviation when asked to maintain the pen at a fixed position (p‐value<0.05).The comparison between MCI and CTL populations also showed that the length of the strokes for drawings and copying tasks can deliver clues to distinguish both groups (p‐value<0.05).ConclusionAutomated analysis of a large variety of handwriting segments employing machine learning techniques can provide an assessment of patients with AD and MCI that may be useful in their early diagnosis and assessment of progression.
Workplace accommodations for individuals with dementia: experiences from three countries
Authors: Bak Katherine , Kokorelias Kristina Marie , Nygard Louise , Issakainen Mervi , Mäki‐Petäjä‐Leinonon Anna , Nedlund Ann‐Charlotte , Ryd Charlotta , Astell Arlene J. 
Published: December 2023

AbstractBackgroundIndividuals who develop Young Onset Dementia (YOD) or Mild Cognitive Impairment (MCI) when they are working, experience difficulties completing work tasks. Most legislative guidelines for workplace accommodations, are geared toward physical and mental health problems, and are not easily transferable to individuals with cognitive impairments. This study aimed to explore workplace accommodations for individuals living with YOD to maintain meaningful work.MethodSemi‐structured interviews about their experiences at work were conducted with 28 individuals in Canada, Finland, and Sweden.ResultThematic analysis uncovered an overarching theme of ‘workplace context’ plus cross‐cutting themes of ‘adapted accommodations’, ‘preparing for the future’, and ‘perceptions of support’. Factors relating to job role, organization, workplace culture, and workplace relationships influenced whether support was received.ConclusionPeople who develop MCI or dementia whilst working require accommodations and support from their employers to maintain meaningful work and prepare for an uncertain future. Currently there is a lack of specific resources and policies on supporting individuals with YOD in the workplace, with individuals frequently making their own adaptations.
Experiences of Discrimination and Interest in Alzheimer’s Disease Predictive Testing in the Health and Retirement Study
Authors: Hill‐Jarrett Tanisha G , Choi Minhyuk , Buto Peter , Sims Kendra D , Miramontes Silvia , Thomas Marilyn D , Yang Yulin , Kim Min Hee , Glymour M. Maria 
Published: December 2023

AbstractBackgroundRapid developments in Alzheimer’s disease (AD) biomarker research suggest predictive testing may soon become a feasible option available to the public. Future reduction of racial and ethnic disparities in AD requires understanding of potential differences in drivers of interest in AD diagnostic testing. Experiences of discrimination may influence attitude toward AD testing, particularly among racially and ethnically minoritized populations. This study examines whether everyday or lifetime discrimination shapes interest in AD predictive testing.MethodData were collected from 1,472 participants in the 2010 and 2012 waves of the Health and Retirement Study who answered a module on interest in receiving a free test that could tell whether they would develop AD in the future, along with measures of Everyday Discrimination and Lifetime Discrimination. Logistic models were controlled for deciles of propensity scores (estimated using demographic and socioeconomic variables) and odds ratios were re‐expressed as risk differences (RD). The RD is the difference in the probability a person expressed interest in receiving a future AD predictive test based on past experiences of discrimination.ResultThe mean age of the sample was 67 (SD = 10.2), 65.9% were white, and 80% endorsed interest in AD predictive testing. Most (64.1%) participants indicated experiencing everyday discrimination in at least one domain, and 34.8% experienced major lifetime discrimination in at least one domain. Those interested in predictive testing were younger (66 vs 70 years) and more likely to be Black (20% vs 15%) or Latinx (14% vs 8%) than participants uninterested in testing. The probability of wanting an AD test was not associated with discrimination experiences for Black (RD everyday discrimination = 0.104, p = 0.285; RD lifetime discrimination = ‐0.038; p = 0.626) or Latinx (RD everyday discrimination = ‐0.003, p = 0.974; RD lifetime discrimination = ‐0.053; p = 0.692) participants.ConclusionDespite historical and contemporary experiences of discrimination, Black and Latinx individuals express interest in AD testing. This finding implicates structural and systemic barriers, such as systemic racism and institutional gaps in access to clinical research, as likely explanations for underrepresentation of racially and ethnically minoritized persons in research on AD testing.
Neurodegenerative biomarkers of A‐T+ compared to A+T+ and A‐T‐ older adults
Authors: Jung Joon Hyung , Yi Dahyun , Byun Min Soo , Kong Nayeong , Chang Yoon Young , Keum Musung , Jung Gijung , Ahn Hyejin , Lee Jun‐Young , Lee Yun‐Sang , Kim Yu Kyeong , Kang Kyoung Mi , Sohn Chul‐Ho , Lee Dong Young 
Published: December 2023

AbstractBackgroundPrimary age‐related tauopathy (PART) is a neuropathological entity with neurofibrillary tangles in the absence of beta‐amyloid plaques in the brain. Recent advances in neuroimaging made it possible to identify amyloid PET‐negative (A‐) tau PET‐positive (T+) condition as a possible candidate for PART in living human brains. We tried to investigate neurodegenerative biomarkers of A‐T+ older adults compared to those of A+T+ and A‐T‐ [corresponding to Alzheimer’s disease (AD) and no AD pathology, respectively] individuals.MethodA total of 156 older participants (64 cognitively normal, 43 mild cognitive impairment (MCI), and 49 dementia), were recruited from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE). All participants underwent comprehensive clinical evaluation and multimodal brain imaging including amyloid and tau PET, and MRI. Global PiB retention measured by 11C‐PiB‐PET and tau deposition in the regions corresponding to Braak stages measured by 18F‐AV‐1451 PET were used in this study. A+ was defined as global mean Aβ deposition standardized uptake value ratio (SUVR) > 1.4 and T+ was defined as tau burden corresponding to Braak stages I/II, III/IV, or V/VI. Hippocampal volume, AD‐signature cortical thickness (AD‐CT), AD‐signature cerebral glucose metabolism (AD‐CM) and white matter hyperintensity (WMH) volume were also measured as neurodegenerative biomarkers. Multiple linear regression analysis controlling for age, gender, and APOE ε4 positivity was used to investigate the group differences of neurodegenerative biomarkers.ResultOf the 156 participants, 31 were defined as A‐T‐, 53 as A+T‐, and 72 as A+T+. A‐T+ group had higher levels of hippocampal volume (B = 683.448, p<0.001), AD‐CT (B = 0.267, p<0.001) and AD‐CM (B = 0.174, p<0.001), but not WMH volume (B = ‐1.188, p = 0.651), compared to A+T+ group. When compared to A‐T‐ group, A‐T+ group did not show significant difference in any of the neurodegenerative biomarkers.ConclusionOur findings suggest that, in regard of neurodegeneration, older adults with A‐T+ condition, close to pathological PART, are less severe than those with A+T+, while they appear similar to those with A‐T‐.
MicroRNA cargo in neuron‐derived small extracellular vesicles as a novel peripheral biomarker of brain insulin resistance and related cognitive impairment in patients with type 2 diabetes
Authors: Cleary Jacob Alexander , Kumar Ashish , Su Yixin , Howard Marjorie , Hayden Kathleen M. , Ding Jingzhong , Espeland Mark A. , Deep Gagan 
Published: December 2023

AbstractBackgroundBrain insulin resistance (bIR) is a critical risk factor for Alzheimer’s disease (AD); however, its relationship with peripheral insulin resistance remains unknown without blood‐based biomarkers to assess bIR. Here, we isolated highly pure neuron‐derived small extracellular vesicles (NDE) from plasma and characterized them with a panel of miRNAs related to bIR and cognitive impairment.MethodPlasma samples were obtained from the Look AHEAD‐MIND study with 28 cognitively normal subjects (18 female and 10 male) and 28 subjects with probable dementia (11 female and 17 male). This study was designed to investigate the effect of sustained weight‐loss interventions on cognitive trajectories in overweight/obese type 2 diabetics (T2D). NDE were enriched from plasma sequentially using L1CAM and synaptophysin surface markers by immunoprecipitation. The expression of specific miRNAs related to bIR (miR16‐5p, miR98‐5p, miR138‐5p, miR139‐5p, miR185‐5p, and miR342‐3p) and cognitive impairment (let7a‐5p, miR9‐5p, miR15b‐5p, miR29a‐5p, miR106‐5p, miR107, miR125b‐5p, and miR210‐3p) were analyzed by RT‐qPCR and correlated with corresponding clinical measures (MMSE score, Aβ1‐40, and Aβ1‐42 expression).ResultThe expression of miR106‐5p, miR125b‐5p, and miR‐210‐3p, exhibited significant upregulation in NDE from probable dementia cases (p = 0.0128; p = 0.0011; p = 0.0030, respectively), interestingly, only males exhibited these results. Similarly, miR185‐5p, and miR342‐3p, associated with bIR, exhibited significant upregulation in NDE exclusively from male probable dementia cases (p<0.0001; p<0.0001, respectively). Furthermore, while miR‐16‐5p upregulation was exclusive to male probable dementia cases (p = 0.0070), miR‐138‐5p was the only investigated miRNA that exhibited downregulation and was unique to female probable dementia cases (p = 0.0063). Aβ40 expression positively correlated with miR‐185‐5p, miR‐125b‐5p, miR‐342‐3p, and miR‐210‐3p (p = 0.0331; p = 0.0188; p = 0.0001; p = 0.0052; respectively) and Aβ42 positively correlated with miR‐125b‐5p, miR‐342‐3p, and miR‐210‐3p (p = 0.0058; p = 0.0027; p = 0.0089; respectively). MMSE score was negatively correlated with miR‐185‐5p, miR‐342‐3p, and miR‐210‐3p (p<0.0001; p<0.0001; p = 0.0089; respectively). However, miR‐106b‐5p and miR‐125b‐5p were negatively correlated with MMSE score only in males (p = 0.0337; p = 0.0140; respectively). Conversely, only one miRNA, miR‐138‐5p, positively correlated with MMSE score and was exclusive to females (p = 0.0164).ConclusionThis is the first study demonstrating the sex‐specific expression of AD‐ and bIR‐associated miRNAs in NDE, supporting the link between glucose metabolism dysregulation and the risk for dementia.
An innovative model using Promotores or Community Health Workers for home based dementia care
Authors: Patel Neela K. , Parker Cynthia De La Garza‐ , Davila Angelica , Garza Noe , Goss Monica , Satizabal Claudia L. , de Erausquin Gabriel A. , Maestre Gladys E. , Seshadri Sudha 
Published: December 2023

AbstractBackgroundHealth disparities and issues with trust building and relationship building are prominent in Hispanic and underserved populations in south Texas. Community health workers can play a bridging role with underserved communities and may be essential in improving the quality and value of health care. The Texas Health and Human Services Commission certifies the training Community Health Workers under the label of “promotores”.MethodCommunity health workers were integrated into the primary health care team to serve as a bridge between patient/caregiver dyads and the health care team.ResultCommunity health workers (CHWs) connected patients to social determinants of health resources such as transportation, food pantries and/or social benefits, Medicaid services, and home care provider services. Caregiver education and resources for respite care, caregiver support in person and virtually. Additionally, CHW’s provided education on dementia care resources, caregiver support, recruiting and engaging Hispanic underserve participants in research. Our team was able to increase home visits by 229% to homebound patients throughout several underserved zip codes in Bexar County. This is a success as our team was able to increase health care access to persons with dementia that are homebound that may have not been seen by a healthcare provider until they required emergency care. In fact, we saw roughly 11% decrease of inpatient admissions between 2021 and 2022.ConclusionTrust and familiarity allows the promotores to easily communicate interventions with cultural sensitivity and experiential knowledge of community values, leading to foster rapport with patients and families. The rapport and trust developed with the patients also helped to engage, and recruit Hispanic and underserved participants for research in dementia.