bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aerobic exercise effects on the peripheral plasma lipidome in mild cognitive impairment: The influence of prediabetes
Authors: Gross Thomas J. , Cheema Amrita K. , Espeland Mark A. , O'Bryant Sid , Cotman Carl W. , Baker Laura D. , Mapstone Mark 
Published: December 2020

AbstractBackgroundSubclinical glucose intolerance (pre‐Type 2 diabetes; pre‐T2D) likely influences cognitive decline in older adults. Disordered glucose metabolism may itself be a feature of early Alzheimer’s disease or mild cognitive impairment (MCI). While aerobic exercise may benefit episodic memory, the plasma lipidomic alterations associated with aerobic exercise in older, at‐risk or cognitively impaired adults remains unclear.MethodWe performed a retrospective analysis of 95 participants randomly assigned to Aerobic Exercise (n = 54) or Stretching (n = 41) arms in the Piedmont Aging, Cognition, and Exercise (PACE) studies. Analysis of blood lipids was conducted using the QTRAP® 5500 LC‐MS/MS (Sciex) targeted mass spectrometry platform. Co‐expressed lipid modules were identified and submitted to differential expression (DE) analysis.ResultsFactorial analysis of co‐expressed lipids revealed a pattern of complex expression heterogeneity. We found a significant metabolic status (pre‐T2D/ MCI/ comorbid) by treatment arm (Aerobic Exercise/ Stretching) by time point (pre/post intervention) interaction (p = 0.02). Specifically, we see a significant reduction of long chain/ very long chain triacylglycerides (TAGs) in the comorbid (pre‐T2D + MCI) group following aerobic exercise (p=0.03).ConclusionThese findings suggest a complex interrelationship between aerobic exercise and peripheral dyslipidemia associated with pre‐T2D in the context of MCI. Specifically, we see reductions in TAGs following exercise only when the two risk factors are comorbid, but not when they occur alone. These findings may be of value as biomarkers of exercise‐intervention response and suggest specific populations that may benefit from aerobic exercise. Future study of these interrelated risk factors modifying exercise benefit is warranted to understand which MCI patients will benefit from aerobic exercise.
Heart rate variability changes during task shifting testing in pre‐symptomatic Alzheimer’s disease
Authors: Arechavala Rebecca Johnson , Kloner Robert , Hung Shao‐Min , Harrington Michael G. , Arakaki Xianghong , Kleinman Michael T. 
Published: December 2020

AbstractBackgroundEarly detection of Alzheimer’s disease (AD) is vital to begin and monitor treatments. However, as AD pathology begins long before the onset of symptoms, early detection is difficult. Previous studies have suggested differences in the cardiac and autonomic nervous systems (ANS) in AD patients, providing a possible non‐invasive marker of disease onset. The goal of this study is to compare heart rate variability (HRV) measures, representative of cardiac and ANS function, at rest as well as during cognitive testing to assess the use of HRV as a possible marker of pre‐symptomatic AD.MethodAll participants are cognitively healthy (CH) separated into two subgroups based on ratios of amyloid/tau proteins in cerebrospinal fluid (CSF): normal (CH‐NAT, n=22) and pathological (CH‐PAT, n=36), which represents pre‐symptomatic AD. Heart rate variability (HRV) was assessed during 5‐minute intervals at rest and during Task Shifting testing. Participants were required to name the color or word of a colored word for each stimulus by pressing a button, with two sequential stimuli per trial. The trial could be switching (color‐word or word‐color) or repeat (color‐color or word‐word). ECG traces from subgroups of CH‐NATs (n=8) and CH‐PATs (n=13) were initially screened to remove ectopic beats, followed by identification of normal RR‐intervals (NN). HRV was analyzed as standard deviation of NN (SDNN), root mean squared of successive differences (RMSSD) in the time domain as well as high (HF) and low frequency (LF) in the frequency domain to assess changes to autonomic, and particularly parasympathetic, input to the heart.ResultComparing HRV changes assessed during rest and the task shifting testing in each individual, differences became apparent between CH‐NAT and CH‐PAT groups. In the CH‐NAT group, little to no change in SDNN and RMSSD occurred during cognitive testing from rest. The CH‐PAT group however showed a 20 percent drop in both SDNN and RMSSD during testing, indicating an imbalance of the ANS.ConclusionThis study provides a new approach and technique using HRV to non‐invasively differentiate between normal and pre‐symptomatic AD in cognitively healthy people.
Steroidal inhibitor of Na/K‐ATPase marinobufagenin in a mouse model of Alzheimer’s disease
Authors: Fedorova Olga V , Zahariadis Eleni , McDevitt Ross , Grigorova Yulia N , Wei Wen , Zernetkina Valentina I , Juhasz Ondrej , Zheng Lucy , Petrashevskaya Natalia , Camandola Simonetta , Mattson Mark P , Lakatta Edward G 
Published: December 2020

AbstractBackgroundCardiotonic steroids (CTS), Na/K‐ATPase (NKA) ligands, have potential neuroprotective effects. Despite the importance of the NKA and CTS in the brain physiology, their roles in Alzheimer’s disease (AD) pathology are not fully elucidated. Bufadienolide CTS, marinobufagenin (MBG), was lower in 15‐month old double‐mutant Alzheimer’s mice (APPswe/PS1dE9; AD) compared to age‐matched wild type (WT) controls. The present study examined whether the treatment with MBG affects behavioral and other parameters in the mouse AD model.MethodsFifteen‐month old male AD and WT mice were administered MBG (100 µg/day/kg body weight; AD‐MBG, n=8; WT‐MBG, n=4) or vehicle (control: AD‐C, n=8; WT‐C, n=4) using subcutaneous ALZET osmotic minipumps for 3‐month. Systolic blood pressure (SBP; by tail cuff plethysmography), open field test (OFT), home cage activity (HCA), plasma and brain cortex were collected in 18‐mo old mice. SBP was assessed because MBG may increase blood pressure. Statistical analysis: 2‐way ANOVA, t‐test; data presented as mean±SEM.ResultsSBP and heart rate did not differ between WT‐C and AD‐C. MBG administration did not affect SBP, and increase heart rate in WT‐MBG vs. WT‐C. Plasma MBG was lower in AD‐C vs. WT‐C and increased in both WT‐MBG and AD‐MBG (Table). No differences were found in HCA, and in OFT for total distance traveled, nor for time spent in the center between AD‐C and WT‐C, and between AD‐C and AD‐MBG. MBG caused a greater reduction in distance traveled in the center for WT mice than it did for AD mice (Table). AD‐C mice had 1.6‐fold higher expression of inflammatory marker interleukin‐6 (IL6) mRNA in cortex vs. WT‐C; MBG treatment reversed this expression in AD‐MBG (Table).ConclusionAD mice had lower endogenous plasma MBG and higher brain pro‐inflammatory mRNA marker IL6 vs. WT mice. Treatment with MBG significantly reduced levels of this inflammatory marker. WT mice exhibited more exploratory behavior than AD mice in the OFT; MBG decreased exploratory behavior. The additional behavioral tests may be needed to assess the MBG effects on different cognitive components. The association of the brain inflammatory response, cognitive functions and MBG will be further explored in this AD mouse model. Supported by the NIH/NIA Intramural Research Program.
Increased neuroanatomic risk for Alzheimer’s disease at preclinical stage: Exploring the interaction of fine particle exposure and psychosocial stress
Authors: Younan Diana , Wang Xinhui , Petkus Andrew J , Gruenewald Tara L , Casanova Ramon , Serre Marc , Vizuete William , Beavers Daniel P , Braskie Meredith N , He Ka , Woods Nancy , Garcia Lorena , Wallace Robert B , Resnick Susan M , Manson JoAnn E , Gatz Margaret , Chui Helena C , Espeland Mark A , Chen Jiu‐Chiuan 
Published: December 2020

AbstractBackgroundAmbient air pollution, especially fine particulate matter (aerodynamic diameter <2.5 μm; PM2.5), is a novel neurotoxin. Psychosocial stress has been linked to Alzheimer’s disease (AD) and other dementias (ADRD). We test the hypothesis that PM2.5 and psychosocial stress may interact to accelerate brain aging, by investigating their potential joint effects on neuroanatomic risk for AD.MethodCommunity‐dwelling older women (aged 71‐89) from the Women’s Health Initiative (WHI) Memory Study of MRI completed two structural brain MRI scans (MRI‐1: 2005‐6; MRI‐2: 2010‐11). To focus on the preclinical stage, we excluded women who developed MCI or dementia over follow‐up. The AD pattern similarity (AD‐PS) score, developed by supervised machine learning and validated with the AD Neuroimaging Initiative data, was used to determine the degree of high‐dimensional gray matter atrophy in brain areas vulnerable to AD. Residential three‐year average PM2.5 exposure preceding MRI‐1 were aggregated from daily estimates, based on nationwide spatiotemporal modeling. A structured questionnaire was administered to gather information on the frequency of stressful life events (SLEs) and self‐reported sleep duration. Sleep disturbance was measured using the WHI Insomnia Rating Scale, with higher numbers indicating greater insomnia. We examined whether the source (frequency of SLEs) or behavioral manifestation (sleep disturbance; sleep duration) of psychosocial stress modified the association between PM2.5 and AD‐PS scores (5‐year standardized difference) using generalized linear models.ResultAmong 542 women, PM2.5 (per 2.87 µg/m3 increase) was significantly associated with increased AD‐PS scores (β=0.020; p=0.028), adjusting for geographic region, age, socioeconomic status, lifestyle, clinical characteristics, hormone therapy use, and intracranial volume. This negative association with PM2.5, equivalent to a 7% increase in the relative risk for ADRD, was greater among women reporting high (β=0.041; p=0.004) vs. low (β=0.008; p=0.460) frequencies of SLEs (pinteraction=0.06) and among women reporting high (β=0.040; p=0.003) vs. low (β=0.005; p=0.702) sleep disturbance (pinteraction=0.04). There was no evidence of effect modification by sleep duration.ConclusionOur novel findings suggest psychosocial stress may increase susceptibility to PM2.5 neurotoxicity based on neuroanatomic AD risk at the preclinical stage. Psychosocial stress may lower the brain’s threshold to neurotoxicity, further accelerating the PM2.5‐induced neurodegeneration.
Do benefits of own education for cognition differ by parental education? Influence of intergenerational educational trajectories and cognitive performance in the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) cohort
Authors: Eng Chloe W. , Gilsanz Paola , Glymour M. Maria , Mayeda Elizabeth Rose , Mungas Dan M. , DeCarli Charles , Whitmer Rachel A. 
Published: December 2020

AbstractBackgroundLittle is known about the influence of parental education on late life cognition or whether parental education modifies the association between own education and cognitive outcomes. Parental education influences own educational access/attainment as well as early cognitive environments and resources (social, financial capital) known to affect health. We investigated whether benefits of own education differed by parental education using intergenerational education trajectories.MethodsThe Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) cohort is a diverse sample (approximately equal White, African‐American, Asian, and Latinx) of long‐term members of a managed care organization; cognitive domains of verbal episodic memory, semantic memory, and executive functioning were obtained using the Spanish and English Neuropsychological Assessment Scales (SENAS). Parental education (low defined as either parent with <9 years of schooling) and own education (low defined <college degree; includes some college) were reported by 1,633 participants. Intergenerational education was categorized as stable low (reference), low‐high, high‐low, and stable high. Cognitive domains were analyzed as a z‐score composite and as independent domains using linear mixed models adjusting for age, gender, race, and nativity; potential effect heterogeneity was evaluated as interactions between educational trajectories and (1) SENAS domains, (2) race/ethnicity, (3) gender.ResultsAll participants with high own education had higher average cognitive scores than those with low own education; those with low‐high trajectories had higher average cognitive scores (B̂=0.33; 95% CI: 0.23, 0.42) than those with stable high trajectories (B̂=0.19; 95% CI: 0.09, 0.29). Those with high‐low trajectories had lower average cognitive scores (B̂=‐0.16; 95% CI: ‐0.25, ‐0.07) than those with stable low trajectories. Effect sizes but not overall patterns differed by cognitive domain (p<.0001) and gender (p=0.0097); there was no evidence of effect heterogeneity by race (interaction P‐value=0.6691).ConclusionOwn education was associated with late‐life cognition across all levels of parental education. Effect estimates were largest for an upward trajectory of intergenerational education with similar patterns across cognitive domains. Education may open cognitively beneficial opportunities for individuals with low parental education indicating the importance of supporting college entry/completion, though this may reflect the selection process of individuals who complete college despite low parental education.
Prediction of antipsychotics use in patients with mild cognitive impairment and dementia
Authors: Söderlund Maria Elvira , Guajardo Maria Elena , Cavagna Marina , Labos Edith , Rodriguez Pablo Oscar , Schapira Marcelo , Seinhart Daniel Bernardo 
Published: December 2020

AbstractIntroductionAntipsychotic medications are widely prescribed to manage neuropsychiatric symptoms (NPS) of dementia. NPS produce a negative impact on the caregiver and represent a cause of institutionalization. The benefit of antipsychotics is controversial and should be the last treatment option.ObjectiveTo detect potential predictors of antipsychotic drug (risperidone, quetiapine, olanzapine, clozapine, haloperidol) use in patients with mild cognitive impairment and mild dementia.MethodsData was collected as part of the prospective study of home‐dwelling people with cognitive impairment and their caregivers. The associations between antipsychotic medication use and cognitive‐clinical measures were analyzed using a multivariate binomial generalized linear model.Results228 patients were evaluated at baseline. MCI and dementia were diagnosed in 125 and 30 subjects respectively. After a median (25th to 75th percentile range) of 4.5 (4.1‐4.9) years 21 patients died. Antipsychotics were prescribed in 46 cases (16 with dementia and 30 with MCI). In the multivariate model, baseline Boston naming test (OR: 0.93, 95% confidence interval: 0.89‐0.98, p=0.004) and instrumental activities of the daily living score (OR: 0.65, 95% confidence interval: 0.47‐0.90, p=0.009) were independently related to antipsychotic use (table).ConclusionWithin 4 years of follow‐up, thirty percent of the patients with cognitive impairment received antipsychotic drugs. Baseline instrumental activity of the daily living and Boston naming test were identified as independent predictors.
Diffusion MRI metrics of brain microstructure in Alzheimer’s disease: Boosting disease sensitivity with multi‐shell imaging and advanced pre‐processing
Authors: Thomopoulos Sophia I , Nir Talia M , Reina Julio E Villalon , Jahanshad Neda , Thompson Paul M 
Published: December 2020

AbstractBackgroundDiffusion MRI (dMRI) provides novel measures of white matter (WM) microstructure, offering biomarkers that provide insight into brain aging and Alzheimer’s disease. As advanced acquisitions are implemented (multi‐shell/multi‐band; MB), novel models are developed to more accurately represent tissue microstructure. In its third phase, the Alzheimer’s Disease Neuroimaging Initiative (ADNI‐3) updated their acquisition protocols to include MB dMRI. As acquisition protocols are being updated, it is important to understand which processing steps consistently improve dMRI model fit and derived measure sensitivity to biological effects. Here, we compared state‐of‐the‐art processing methods for ADNI‐3 MB scans to (1) establish an updated dMRI ADNI processing pipeline, and (2) fit more sophisticated tissue parameters sensitive to clinical measures of burden.MethodBaseline MB ADNI‐3 scans (N=137; Table 1) were downloaded and processed with both the dMRI pipeline we established during ADNI‐2 (Pipeline‐A) and the one we have updated during ADNI‐3 (Pipeline‐B; Fig. 1). We obtained scalar diffusion tensor imaging (DTI) maps from the down‐sampled preprocessed dMRI, and higher model metrics using all diffusion volumes using NODDI. Covarying for age, sex, age*sex, and modeling acquisition site as a random effect, we tested associations between regions of interest (ROI; Table 2) diffusion scalar measures and a set of standardized clinical measures (Fig. 2). We modeled effects of age in controls, covarying for sex, age*sex and modeling site as a random effect. All results were corrected for multiple comparisons (FDR). Within WM, voxel‐wise DTI model error (RMSE) was compared across pipelines with paired t‐tests in controls (Fig. 3).ResultFractional anisotropy measures were most affected by the different preprocessing methods, while diffusivity metrics were most strongly correlated with standard clinical measures of cognitive disease burden, such as CDR‐sob. Metrics from NODDI, such as ODI, behaved similarly to FA, showing greatest differences in effect sizes across pipelines.ConclusionWe are currently applying Pipeline‐B to all available ADNI‐3 dMRI scans, to make the data available to the imaging community. As new preprocessing and denoising tools are available and acquisition protocols become more complex, our analyses indicate that preprocessing steps can sensitize diffusion metrics to differences in clinical disease burden.
Distinct and common biomarkers and phenotypes in cerebral palsy and mild cognitive impairment: An exploratory study
Authors: Ng Ted Kheng Siang , Tagawa Alex , Larbi Anis , Kua Ee‐Heok , Mahendran Rathi , Carollo James , Heyn Patricia C 
Published: December 2020

AbstractBackgroundCerebral palsy (CP) patients have accelerated aging, impairments in various pathology and anthropometry, and may develop geriatric syndromes, particularly cognitive impairment. Mild cognitive impairment (MCI) is an intermediate stage between healthy aging and dementia. Owing to their intriguingly parallel yet “inverted” disease trajectories, CP and MCI might share both distinct and similar pathology and phenotypes. Thus, we aimed to examine this hypothesis by developing a unique collaboration between two laboratories specialized in these two populations.MethodThe CP study was conducted at a clinical motion analysis laboratory at Children’s Hospital Colorado, while the MCI participants were recruited for a randomized controlled trial in Singapore. A total of eight measures, including blood biomarkers, neurocognitive and anthropometric measures were compared. Multivariate linear regressions were performed to examine the similarities and differences in these measures between the two cohorts and the associations between biomarkers and neurocognitive/ anthropometric measures, in the total and sub‐samples.ResultCompared to MCI, brain‐derived neurotrophic factor (BDNF) levels and diastolic blood pressure were significantly lower in CP, upon controlling for covariates. In CP, BDNF was significantly correlated with hs‐CRP and BMI. Furthermore, the variance of diastolic blood pressure in CP could be explained largely by chronological age. The other six measures, including impaired neurocognitive functions, were similar between CP and MCI.ConclusionThese findings supported our hypothesis on both distinct and common pathology between CP and MCI, which could be partly attributed to either aging or pathophysiology. In CP, BDNF levels were lower than MCI, and it plays significant roles in inflammation and weight, whereas aging effect contributed mainly to the variability in diastolic blood pressure. Future studies using longitudinal follow‐up with larger sample sizes and examining accelerated biological aging is warranted.
Brain imaging data quality and denoising: Impact on the study of sex differences in Alzheimer’s disease
Authors: Caldwell Jessica ZK , Yang Zhengshi , Kaplan Nikki , Leavitt MacKenzie , Miller Justin , Mishra Virendra R , Shan Guogen , Cordes Dietmar 
Published: December 2020

AbstractBackgroundRecent research highlights sex effects in Alzheimer’s disease (AD). However, examining sex effects presents challenges, for example due to Magnetic Resonance Imaging (MRI) methodological differences and effects of sex on resting state functional MRI (rsfMRI) being small compared to effects of factors like age. Attention to data processing methodology may help to address this challenge. The present discussion will highlight the results of our recent examinations of the effect of sex on success of automated MRI volumetric analysis with clinically‐obtained MRI, and the role of rsfMRI data denoising on measuring sex effects in AD.MethodVolumetric quality was assessed in 438 patients seen in an outpatient neurology clinic specializing in diagnosis and treatment for neurodegenerative diseases (47.7% women), and rsfMRI in 168 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI: 49 Cognitively Normal (CN); 67 early Mild Cognitive Impairment (eMCI); 52 AD; 52% women). MRI data were processed using Freesurfer 6.0, with in‐house quality assessment. Resting state data were preprocessed with realignment, slice‐time correction, coregistration and normalization to standard MNI space, and then denoised using traditional nuisance regression methods with global signal, mean white matter and cerebrospinal fluid time series, and motion parameters; Compcor; and a novel in‐house developed, deep neural network approach.ResultIn‐house quality assessment resulted in discarding 43% of segmented images. Individuals whose images were discarded were significantly older than individuals with retained images, but sex did not impact retention. In contrast, using our novel rsfMRI denoising technique, CN women showed significantly lower degree centrality, global efficiency, local efficiency, and clustering coefficient, and significantly longer path length. Differences were less significant in MCI and not significant in AD. Traditional denoising approaches revealed weak differences or no differences by sex.ConclusionThese findings suggest that quality control approaches to clinical imaging processing may be important to the study of AD generally, but that data denoising techniques in rsfMRI may have impact specifically on the study of AD‐related sex differences.