bluuebunny/crossref_metadata_2025_split huggingface dataset:
Caring of caregivers organically (COCO): Health education for Latinas caring for a family member with Alzheimer's disease or related dementia
Authors: Rocha Judith Susan 
Published: December 2020

AbstractBackgroundLatinos have a 1.5 times greater chance of having Alzheimer’s disease or related dementia (ADRD) as compared to their non‐Latino White counterparts. Higher prevalence is attributed to having longer life spans and more health‐related risk factors such as diabetes, high blood pressure and obesity. Those who assume caregiving for persons with ADRD are also affected. Affected by higher levels of caregiver burden and lower general health as compared to non‐Latino Alzheimer’s caregivers, Latinos are at larger disadvantage, considering the already existing health disparities in the community. Latino Alzheimer’s caregivers experience more bodily pain and somatic symptoms than non‐Hispanic White caregivers.MethodData were obtained from a mixed methods study that used focus groups of caregivers and other stakeholders to adapt a culturally responsive health education intervention. Participants (n = 20) for the adapted intervention pilot were randomized into the intervention or control group. The Promotoras de Salud peer educator model was used to carry out the intervention. Feasibility and acceptability were measured using qualitative data collected during a final focus group and a satisfaction questionnaire. Using T‐tests, pretest and post‐test data collected were analyzed to compare changes in health‐related self‐efficacy (measured on Chronic Disease Self‐Efficacy Scales), health behaviors (measured on Family Habits Scale), caregiver burden (measured on Zarit Burden Interview), and depressive symptoms (measured on CES‐D).ResultPhase I and II have rendered an 8‐week adapted intervention for Latinas that care for a family member/loved one with ADRD. Analysis of Phase III (pilot) of the study is currently underway.ConclusionThere are few established evidence‐based, culturally responsive interventions for Latino families. With the expected exponential growth of the Latino population and prevalence of ADRD, targeting health/healthcare disparities and supporting protective cultural factors is crucial for improving health and mental health outcomes of these caregivers. The pilot‐study will offer preliminary data to help determine if health education with the use of promotoras for Latina ADRD family caregivers is a viable, means of intervening with this highly vulnerable population.
Neurofilament light is a non‐specific marker of aging and white matter integrity
Authors: Meeker Karin L. , Gordon Brian A. , Sutphen Courtney L. , Schindler Suzanne E. , Morris John C. , Fagan Anne M. , Benzinger Tammie L.S. , Ances Beau M. 
Published: December 2020

AbstractBackgroundNeurofilament light chain (NfL) is considered a biomarker of neuronal injury and degeneration and is increasingly used to evaluate disease progression across multiple neurological conditions including Alzheimer Disease (AD). Despite growing attention as an injury marker, little is known about how NfL relates to brain structure and what other factors may influence this relationship. The objective of this study was to determine whether NfL level in the cerebrospinal fluid (CSF) is more strongly associated with total gray, white, and/or white matter hyperintensity (WMH) volume and assess how this association changes as a function of age and amyloid status.MethodCSF NfL was measured in 397 individuals who also underwent structural MRI and amyloid positron emission tomography (PET) using Pittsburgh Compound B (PiB). PiB positivity was defined as having a mean cortical standard uptake value ratio ≥1.42. Images underwent volumetric segmentation using FreeSurfer 5.3. Pearson’s r correlation analysis was used to determine the association between NfL and age. A multivariate regression model was used to determine whether NfL predicts total gray volume, white volume, and/or WMH volumes in PiB positive (PiB+) and negative (PiB‐) individuals. Correlation analyses also assessed the association between NfL and gray, white, and WMH volume. Additional regression models were used to determine region specific associations between NfL and white/gray matter volume. Age was accounted for in all models.ResultNfL was significantly correlated with age, r=0.63, p<0.001 (Figure 1). Accounting for age, NfL predicted total gray, white, and WMH volume, regardless of PiB status (ps<0.01; Figure 2 and 3). When including gray, white, and WMH volume in the same model, NfL was associated with total WMH volume (r= 0.43, p<0.001), but not gray or white matter volume (ps>0.05) across individuals.ConclusionCollectively, these results suggest that NfL is a non‐specific marker of aging and white‐matter integrity with limited sensitivity to amyloid status. Given the association with WMH volume across individuals, it is likely that NfL reflects other processes such as cerebrovascular disease.
Baseline correlations between [18F]GTP1 PET SUVR and MRI white matter hyperintensities in prodromal‐to‐mild Alzheimer's disease suggest independent contributions to cognitive impairment
Authors: Manser Paul T , Teng Edmond , Pickthorn Karen , Blendstrup Mira , Anegondi Neha , Krishnan Anithapriya , Song Zhuang , Carano Richard A.D. , Keeley Michael , Wildsmith Kristin R , Weimer Robby , Bohorquez Sandra Sanabria 
Published: December 2020

AbstractBackgroundWhite matter hyperintensities (WMH) on MRI are commonly seen in Alzheimer’s disease (AD) and thought to represent co‐morbid microvascular ischemic disease. However, the relationship between WMH and tau pathology in AD remains incompletely understood. We explored this question using screening/baseline data from a Phase 2 study of the anti‐tau antibody semorinemab (Tauriel; NCT03289143), which included both MRI and [18F]GTP1 tau PET imaging.MethodParticipants in the Tauriel study are aged 50‐80, meet criteria for AD dementia or mild cognitive impairment (MCI), have MMSE of 20‐30, global Clinical Dementia Rating (CDR) of 0.5 or 1, evidence of significant amyloid pathology, and significant episodic memory impairment (RBANS delayed memory index < 85), and undergo screening MRIs, with WMH quantified using the Fazekas scale. Analyses were performed on a subset of participants (n=381) who received baseline [18F]GTP1 tau PET scans. Relationships between WMH, [18F]GTP1 SUVR in an AD‐specific temporal lobe ROI, age, and cognitive scales were assessed graphically and quantified using Pearson correlations, Cohen’s D, t‐tests, and multiple linear regression.ResultTauriel participants had Fazekas scores of zero (n=161), one (n=208), or two (n=12). Per the Figure, participants with Fazekas scores > 0 tended to be older (Cohen’s D=0.69, p < 0.001) and have lower temporal [18F]GTP1 SUVR (Cohen’s D=0.35, p<0.001). The relationship between temporal [18F]GTP1 SUVR and baseline ADAS‐Cog13 (r=0.39, p<0.001) remained significant after adjusting for Fazekas score and age via multiple regression (p<0.001).ConclusionGiven the circumscribed range of disease severity seen in prodromal‐to‐mild AD participants at screening/baseline in the Tauriel study, the relationships between MRI WMH and [18F]GTP1 tau PET suggest that these pathologies have additive and independent contributions to cognition that may be age‐related. Clinical trials of anti‐tau therapeutics in similar patient populations may need to account for cerebrovascular co‐morbidities in patient selection and/or efficacy analyses.
Development of a functional 3D brain organoid with microvasculature and a blood‐brain barrier
Authors: Raval Urdhva , Zeng Emma , Pasinetti Giulio Maria Maria 
Published: December 2020

AbstractBackgroundBrain organoids are self‐assembled 3D cell aggregates developed from pluripotent stem cells with various cell types and extracellular structures that resemble the embryonic human brain. Induced pluripotent stem cells (iPSC) based organoids show great promise in disease modeling applications. Our previous work has validated the use of novel polyphenolic compounds to combat neurodegenerative diseases in animal and traditional cell culture models. The goal of the present study is to continue to explore the development of a functional brain organoid system with microvasculature and a blood‐brain barrier using iPSCs.MethodiPSCs were differentiated into neurons, astrocytes, pericytes, oligodendrocytes, brain microvascular endothelial cells, and other relevant cell types. The organoid was developed using previously published protocols. The blood‐brain barrier was constructed by co‐culturing the different cell types.ResultIn this ongoing study, we demonstrate the development of a more accurate and functional brain organoid system with microvasculature and a blood‐brain barrier using iPSCs.ConclusionOur organoid will serve as a model for neurodegenerative diseases, drug discovery and the screening of novel polyphenolic compounds from dietary flavanols which have been recently associated with reduced risk of developing Alzheimer’s Dementia.
Cardiovascular risk factors in adolescence and adulthood and late‐life cognition: Study of Healthy Aging in African Americans (STAR)
Authors: George Kristen M , Peterson Rachel , Gilsanz Paola , Barnes Lisa L , Glymour M Maria , Mayeda Elizabeth Rose , Mungas Dan M , DeCarli Charles , Whitmer Rachel A 
Published: December 2020

AbstractBackgroundMid‐life cardiovascular disease (CVD) risk factors are associated with late‐life cognition, but it is unknown whether CVD risk factors before mid‐life affect cognition. African Americans develop CVD risk factors at younger ages compared to other racial/ethnic groups. We examined the relationship between CVD during adolescence and adulthood (early through mid‐life) with late‐life cognition in the Study of Healthy Aging in African Americans (STAR).MethodSTAR evaluated cognitive aging in African Americans (N=676) and enrolled approximately equal proportions of participants ages 50‐64 and 65+. Participants were long‐term Kaiser Permanente Northern California members and completed Multiphasic Health Check‐ups (MHC) from 1964‐1985 at which body mass index (BMI), blood pressure, blood glucose, and serum total cholesterol were measured. At STAR baseline (2019), education, income, and cognition were assessed. Cognitive domains of verbal episodic memory, semantic memory, and executive function were measured using the Spanish and English Neuropsychological Assessment Scales (SENAS). Domain scores were z‐standardized and averaged to create a global z‐score. We used linear regression to analyze the association between adolescent and adulthood CVD risk factors with cognition, adjusted for age, gender, and education.ResultAt MHC, participants were adolescents (N=333; ages 14‐25) and adults (N=343; ages 26‐56). Mean age at cognitive assessments was 68 (SD=9) years. Being overweight/obese did not predict late‐life cognition regardless of age at MHC. Hypertension [pooled β=‐0.18 (‐0.33, ‐0.03)] and diabetes [pooled β=‐0.69 (‐1.15, ‐0.24)] were associated with worse cognition among both MHC age groups. Hypercholesteremia was associated with worse cognition in adults at MHC, but not adolescents [Adults β=‐0.22 (‐0.40, ‐0.05) vs. Adolescents β=0.02 (‐0.16, 0.21); interaction p=0.03]. Having 2+ cardiovascular risk factors predicted worse cognition for both MHC age groups [pooled β=‐0.24 (‐0.40, ‐0.08)]. Looking at cognitive domains separately, associations were consistent for executive function and verbal memory, but non‐significant for semantic memory.ConclusionHypertension, diabetes, or a combination of multiple cardiovascular risk factors at adolescence and adulthood were common and associated with worse late‐life cognition. Hypercholesteremia in adulthood, but not adolescence, was associated with worse cognition. Results suggest that cardiovascular risk as early as adolescence may influence late‐life brain health in African Americans.
A novel MRI contrast weighted ratio method for measuring myelin in older adults at risk for Alzheimer’s disease
Authors: Price Lauren Rose , Deardorff Rachael , Wu Yu‐Chien , West John D. , McDonald Brenna C. , Risacher Shannon L. , Saykin Andrew J. 
Published: December 2020

AbstractBackgroundMRI measures sensitive to myelin integrity such as the T1/T2 weighted ratio method (T1w/T2w; Glasser & Van Essen 2011) have been investigated as potential AD biomarkers. Many cohorts have transitioned to T1 and T2‐weighted Fluid Attenuated Inversion Recovery (FLAIR) acquisitions. Our goal was to validate the T1w/T2FLAIRw method in comparison to the T1w/T2w method in the same cohort.Method28 cognitively unimpaired (CU, cognitively normal and subjective cognitive decline) and 26 AD‐related cognitively impaired (CI, mild cognitive impairment and AD) individuals were analyzed to determine the correlative validity of association between T1w/T2FLAIRw and T1w/T2w methods. Image processing algorithms were designed in‐house for application to AD, building on previous methods and implemented in SPM12. White matter regions of interest (ROIs) from the Johns Hopkins ICBM‐DTI‐81 white‐matter labels atlas were masked excluding cerebrospinal fluid and white matter hyperintensities. Pearson correlation was used to test associations between the canonical method and our extension. Then, diagnostic group differences were assessed using regional independent sample T‐tests, with Bonferroni correction for independent components (8 independent factors identified by PCA of all white matter tracts).ResultMyelinated regions associated with cognitive decline, as well as all other atlas ROIs, demonstrated significant (p <.01) positive correlations between T1w/T2w and T1w/T2FLAIR values (r values between .590 and .915) with the exception of the fornix, which was significant at the .05 level in CU. Between‐group analyses using T1w/T2FLAIRw showed lower ratios (reflecting reduced myelin) in CI. Significant differences in group T1w/T2FLAIRw ratios were seen in the left hippocampal cingulum (left, p=.011; right, p=.024), uncinate fasciculus (left, p=.007; right, p=.015), and the right anterior limb of the internal capsule (p=.019) and superior fronto‐occipital fasciculus (p=.011). After Bonferroni correction only the left hippocampal cingulum, left uncinate fasciculus and right superior fronto‐occipital fasciculus approached significance (p = .088; .088; .056 respectively).ConclusionResults suggest T1w/T2FLAIRw is a valid alternative to T1w/T2w ratios. Between groups, T1w/T2FLAIRw pointed towards lower myelin in intersecting white matter tracts in cognitively impaired individuals. Although initial results appear promising with reasonably large effect sizes, a larger sample needs to be assessed to provide sufficient statistical power to effectively assess the proposed method.
Relationship between MRI and amyloid PET measures with cognition in the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study
Authors: George Kristen M. , Whitmer Rachel A , Glymour M Maria , Mayeda Elizabeth Rose , Mungas Dan M , Gilsanz Paola , DeCarli Charles 
Published: December 2020

AbstractBackgroundThe U.S. population is aging and becoming more diverse. The Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) Study enrolled 1,712 participants with the aim of evaluating how race/ethnicity and life‐course factors influence late‐life brain health. We examined the association between brain images and cognition in this cohort.MethodTo date, 164 participants have received MRI and PET imaging (25% Asian, 20% Black, 25% Latino, and 30% White). MRI analyses included regional gray matter, cerebrospinal fluid, and white matter hyperintensity (WMH) volumes. Amyloid PET used AV45 and standard SUVR analysis with cerebellar gray matter as the reference region. Participants underwent neuropsychologic testing and received diagnoses of cognitively normal or impaired (syndrome). Cognitive domains of verbal episodic memory, working memory, and executive function were measured using the Spanish and English Neuropsychological Assessment Scales (SENAS). Linear and logistic regressions were used to assess associations between imaging measures with cognition. Race/ethnicity interactions were tested (significant interaction p<0.10).ResultParticipants had a mean age of 75 (SD=6) years. Verbal memory was positively associated with hippocampal volume [β(95% CI):0.16(0.03, 0.28)] and negatively associated with amyloid burden [β:‐0.20(‐0.33, ‐0.06)]. Cerebral and parietal cortex volumes were associated with better working memory [cerebral β:0.21(0.07, 0.35); parietal β:0.15(0.03, 0.28)] and executive function [cerebral β:0.25(0.11, 0.38); parietal β:0.17(0.05, 0.30)]. Lateral and third ventricle volumes were negatively associated with working memory [lateral ventricle β:‐0.17(0.30, ‐0.04); third ventricle β:‐0.22(‐0.34, ‐0.10)] and executive function [lateral ventricle β:‐0.15(0.28, ‐0.02); third ventricle β:‐0.16(‐0.29, ‐0.04)]. Odds of syndrome were lower in those with greater cerebrum gray matter [OR:0.54(0.32, 0.90)], hippocampal [OR:0.27(0.14, 0.52)], and temporal cortex [OR:0.61(0.38, 0.98)] volumes. The positive associations of hippocampal (interaction p=0.08) and occipital cortex (p=0.02) volumes with verbal memory were significant for Asians and Latinos. Cerebrum gray matter (p=0.06) and parietal cortex (p=0.07) volumes were positively associated with working memory in Blacks. Occipital cortex volume (p=0.07) was positively associated with executive function in Asians. Racial/ethnic differences were seen in the relationship of WMH (p=0.07) and amyloid burden (p=0.04) with syndrome, but small numbers prevented race‐stratification.ConclusionRegional MRI and amyloid burden were associated with cognition and there were significant racial/ethnic differences.
Associations of orthostatic hypotension with dementia in older adults: A 12‐year follow‐up population‐based study
Authors: Xia Xin , Wang Rui , Vetrano Davide Liborio , Grande Giulia , Laukka Erika J , Fratiglioni Laura , Qiu Chengxuan 
Published: December 2020

AbstractBackgroundOrthostatic hypotension (OH) has been linked to dementia in older people in several longitudinal studies. We sought to examine the associations of OH with all‐cause dementia and subtypes of dementia, and further to explore the potential modifying effects of APOE ε4 allele and impaired walking speed on their associations.MethodThis population‐based cohort study included 2,525 dementia‐free participants who had their postural blood pressure measured at baseline (2001‐2004) and were regularly examined until 2013‐2016 in the Swedish National study on Aging and Care in Kungsholmen (SNAC‐K). OH was defined as systolic blood pressure decreases ≥20 mmHg or diastolic blood pressure decreases ≥10 mmHg when assuming the upright position. Dementia was diagnosed according to the DSM‐IV criteria. Alzheimer dementia and vascular dementia were diagnosed following the NINCDS‐ADRDA criteria and the NINDS‐AIREN criteria, respectively. Walking speed was measured through 2.4‐meter or 6‐meter walk test and impaired walking speed was defined as <0.8 m/s. Data were analyzed with Cox proportional‐hazards models after controlling for multiple potential confounders.ResultAt baseline, 613 (24.3%) participants were defined to have OH. During the 12‐year follow‐up periods, 370 people (14.7%) were diagnosed with dementia, including 198 with Alzheimer dementia and 67 with vascular dementia. OH was significantly associated with a multiple‐adjusted hazard ratio (HR) of 1.39 (95% CI: 1.10‐1.76) for all‐cause dementia, 1.58 (1.15‐2.16) for Alzheimer dementia, and 1.20 (0.70‐2.05) for vascular dementia. To further reduce the potential of reverse causality, we repeated the analysis after excluding dementia cases that were diagnosed within the first 3 years of the follow‐up periods, and the results suggested that OH was still significantly associated with all‐cause dementia (HR: 1.33, 95% CI: 1.01‐1.75) and Alzheimer dementia (HR: 1.63, 95% CI: 1.22‐2.19). There was no statistical interaction of OH with either APOE ε4 allele or impaired walking speed on the risk of dementia (p‐value for both interaction tests >0.10).ConclusionOH is associated with an elevated risk of dementia, especially Alzheimer dementia, among older adults. Neither APOE ε4 allele nor impaired walking speed could modify the association of OH to dementia.
Role of TREM2 deficiency in Alzheimer’s disease model mice expressing human APOE3 or APOE4
Authors: Fitz Nicholas F. , Nam Kyong Nyon , Letronne Florent , Wolfe Cody M. , Playso Brittany E. , Lefterov Iliya , Koldamova Radosveta 
Published: December 2020

AbstractBackgroundAlzheimer’s Disease (AD) is a multifactorial neurodegenerative disease influenced by aging, genetic, and environmental risk factors. Inheritance of APOEε4 and variants of Triggering Receptor Expressed on Myeloid cells 2 (TREM2) are two major genetic risk factors for AD, surprisingly little is known about the interplay between these two risks. TREM2 is a receptor of the innate immune system expressed on microglia, indicating a role in AD related neuroinflammation. Recent data showed APOE can bind to TREM2, in an isoform specific manner, thus raising the possibility of an APOE‐TREM2 interaction affecting TREM2 signaling and microglial function. We hypothesize that TREM2 deficiency will modulate the pathological phenotype and microglial transcriptome in AD model mice expressing human APOE3 and APOE4 in a disease progressions‐dependent manner.MethodIn this study, we crossed Trem2 expressing and Trem2ko
mice with APP/PSEN1dE9 mice expressing human APOE3 or APOE4 genes to investigate whether the loss of Trem2 impacts: amyloid pathology, glial response, and whole‐brain transcriptome. To determine the disease progression‐dependent impact of Trem2 deficiency we assessed the AD model mice at an early stage (3.5 mo) and more advanced stage (6.5 mo).ResultOur study provides evidence that Trem2 deletion worsened cognitive performance, diminished microglia barrier around amyloid plaques, but did not impact overall amyloid load in either APOE genotype at both age groups assessed. Using multi‐color time stamp in vivo plaque labeling for assessing growth kinetics of amyloid plaques, we determined that Trem2 deletion increased plaque diffusivity and growth of newly formed plaque in both APOE isoforms. To get further insight in the specific effects of Trem2 deficiency in relationship to APOE isoform, we performed RNA‐seq using whole brain tissue followed by comparison to known cell‐type specific genetic signatures including known disease associated microglial (DAM) genes. Transcriptionally, we identified: 1) a sub‐set of immune response genes including DAM and homeostatic microglial genes that are downregulated in all experimental groups and comprise the Trem2 signature, and 2) differentially expressed genes that are characteristic for each APOE genotype and age group.ConclusionThis study significantly increases our understanding of the interaction between APOE isoforms and TREM2 in association with AD pathology.