bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mild cognitive impairment and transitions in cognitive status in the Systolic Blood Pressure Intervention Trial (SPRINT)
Authors: Gaussoin Sarah A , Pajewski Nicholas M , Chelune Gordon , Cleveland Maryjo , Crowe Michael G , Launer Lenore J , Lerner Alan J , Martindale‐Adams Jennifer , Nichols Linda O , Ogrocki Paula K , Sachs Bonnie C , Sink Kaycee M , Supiano Mark A , Wadley Virginia G , Wilson Valerie M , Wright Clinton B , Williamson Jeff D , Reboussin David M , Rapp Stephen R 
Published: December 2021

AbstractBackgroundThe Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated a significant reduction in the occurrence of mild cognitive impairment (MCI) for adults with hypertension randomly assigned to intensive systolic blood pressure (SBP) lowering and a similar but non‐significant effect on incidence of dementia.. Given that individuals with MCI are at greater risk of progressing to dementia, an open question from the trial is the frequency of progression in cognitive status subsequent to an adjudication of MCI, and whether this associates with intensive SBP lowering.MethodRandomized trial of community‐dwelling adults (≥50 years) with hypertension. Participants were randomized to a SBP goal of <120 mm Hg (intensive treatment; n=4678) or <140 mm Hg (standard treatment; n=4683). Adjudication of MCI or dementia followed standardized procedures by a panel of expert clinicians. Multistate survival models were used to examine transitions in cognitive status between normal cognitive function, MCI, and dementia, accounting for the competing risk of death.ResultAmong 9361 randomized participants (mean age, 67.9 years; 3332 women [35.6%]), 91.5% completed at least 1 follow‐up cognitive assessment over a median follow‐up of 5.1 years. Based on multistate modeling, from a state of normal cognitive function, the risk of transitioning to dementia in the next 2 years was 1.1% [95% Confidence Interval (CI): 1.0% to 1.3%]), with 2.3% [95% CI: 2.1% to 2.5%] of participants dying over that same interval. Subsequent to an adjudication of MCI, the probability of progressing to dementia in the next 2 years increased to 6.4% [95% CI: 5.3% to 7.8%], with the risk of death increasing to 8.2% [95% CI: 6.9% to 9.7%]. We did not observe any significant associations between treatment groups and transition risk within the multistate model, though power for these analyses was likely limited given the focus on complex transitions between multiple outcomes.ConclusionAn adjudication of MCI in SPRINT was associated with an increased risk of progression to dementia and death in the following 2 years, highlighting the relevance of MCI as an outcome both within SPRINT and for future prevention trials of cognitive impairment.
How common is concurrent neurological and mood/anxiety disorder comorbidity over time? A population‐based cohort study in Ontario, Canada
Authors: Maclagan Laura C , Maxwell Colleen J , Harris Daniel A , Wang Xuesong , Guan Jun , Marrie Ruth Ann , Hogan David B , Austin Peter C , Vigod Simone N , Swartz Richard H. , Bronskill Susan E 
Published: December 2021

AbstractBackgroundNeurological disorders and mental health conditions, including mood/anxiety disorders, are a leading cause of disability and healthcare use. These disorders have shared risk factors and commonly co‐occur in older adults. Mood/anxiety disorders are often under‐diagnosed and under‐treated among those with neurological disorders, potentially leading to more rapid symptom progression, worse health outcomes and increased health care use. We estimated the relative and absolute rates of neurological and mood/anxiety disorder comorbidity among adults in Ontario, Canada.MethodWe identified adults aged 40‐85 years on April 1st, 2002 in Ontario, Canada using health administrative databases. These individuals were followed for up to 14 years until March 31st, 2016. We estimated the association between between having a prior neurological disorder (dementia, Parkinson’s disease (PD), and stroke) or mood/anxiety disorder and developing a different, incident neurological or mood/anxiety disorder using cause‐specific hazard models. Exposure to prior disorders was modeled as a time‐varying covariate and death was considered a competing risk. Individuals who were not at risk for the specific incident outcome disorder were excluded from that model.ResultAll prior disorders were associated with increased rates of dementia: PD (adjHR= 4.05, 95%CI, 3.99‐4.11), stroke (adjHR=2.49, 95%CI, 2.47‐2.52), and mood/anxiety disorder (adjHR=1.79, 95%CI, 1.78‐1.80). Increased rates of PD were associated with prior dementia (adjHR=2.23, 95%CI, 2.17‐2.30) and mood/anxiety disorder (adjHR=1.77, 95% CI 1.74‐1.81), but not stroke (adjHR=1.04, 95% CI, 0.99 to 1.10). Rates of stroke were highest in persons with prior dementia (adjHR=1.56, 95% CI, 1.53 to 1.58) and showed more modest associations with PD (adjHR=1.21, 95% CI, 1.16 to 1.25) and mood/anxiety disorder (adjHR=1.09, 95% CI, 1.08 to 1.11). The associations were generally strongest in the six months following the prior disorder diagnosis, lowest in the interim periods (>six months to 10 years) and elevated in the later periods (10+ years) following diagnosis.ConclusionWe observed associations between pairs of prior and incident neurological disorders and mood/anxiety disorder among middle‐ and older‐aged adults. Neurological and mental health comorbidity is common. This should be considered in clinical practice guidelines for these conditions and may necessitate care across multiple providers.
The COVID‐19 pandemic, a respiratory disease with a hidden time bomb in the brain: Impact on reserve and resilience
Authors: Amouyel Philippe , Dumont Magali , Dauchet Luc , Meirhaeghe Aline , Boulanger Eric , Hirsch Emmanuel 
Published: December 2021

AbstractBackgroundWe present an overview on the potential impact of COVID19 infection on cognitive reserve and resilience capacity. The presence of RNA virus in the brain and a pathognomonic symptom, the loss of smell and taste, suggest a long‐term brain impact that could directly affect cognitive reserve. A wide range of neurological manifestations associated with SARS‐CoV‐2 have been described and the list is still increasing, consistent with multiple pathogenic pathways as post‐infectious and immunity reactions. It includes stroke, brain haemorrhage or memory loss.MethodSuch events have already been observed in the course of other viral diseases. In addition, preventive actions to stop the exponential progression of the virus have been adopted by most of countries (masks, physical distancing, lockdowns or curfews), with a common impact: the reduction of our social and physical relationships. Thus, this dramatic stop of human interactions, known as the most effective brain stimulation, may also severely impair cognitive reserve and resilience. The global spread of the pandemic suggests that tens of thousands of individuals may have had cerebral symptoms. Hence, we must take actions to predict the consequences of COVID19 on cognitive reserve and brain resilience.ResultsAged and frail people are especially concerned: (1) due to their ages, they are at a very high risk of severe forms; (2) as the specific containment imposed to retirement home residents precluded any social relationships for long periods of time. This double punishment had tragic immediate and long‐term consequences on their cognitive reserve and survival. We now need to actively find ways to estimate and limit the brain health impact of the COVID19 pandemic by: (1) helping elderly to resist to social distancing by promoting public health tools as the COVID‐SCORE French experience; (2) setting long term international cohorts to follow‐up the largest numbers of COVID19 patients for their cognitive reserve evolution; (3) Improving cognitive reserve in COVID19 patients by launching prevention programs,ConclusionThe implementation of such an action plan will allow reducing the third possible consequence of the virus and the lockdown, i.e. a decrease of the cognitive reserve and resilience in older adults.
Greater psychological resilience during the COVID‐19 pandemic is associated with lower tau burden in cognitively unimpaired individuals
Authors: Vannini Patrizia , Gagliardi Geoffroy , Kuppe Madeline K , Dossett Michelle , Donovan Nancy , Gatchel Jennifer R , Quiroz Yakeel T. , Premnath Pranitha Y , Amariglio Rebecca E. , Sperling Reisa A. , Marshall Gad A 
Published: December 2021

AbstractBackgroundThe outbreak of the 2019 novel coronavirus SARS‐CoV‐2, causing the COVID‐19 pandemic, along with the global measures used to control the spread of the disease, have been particularly stressful for older individuals. Robust evidence suggests that stress‐related physiological processes may play a significant role in the onset of age‐related cognitive decline and dementia, such as Alzheimer’s disease (AD). For example, previous animal and human research have shown that stress exacerbates tau pathology and subsequent cognitive impairment. One important factor determining a person’s level of stress is psychological resilience, which refers to a person’s ability to return to equilibrium when difficulties occur. As such, resilience may buffer and protect individuals against the deleterious effects of stress. The objectives of this study were to examine the relationship between psychological resilience and tau burden in cognitively unimpaired individuals, and to evaluate whether amyloid (Aß) pathology modifies this relationship.MethodA total of 114 older adults (mean age=74.5;66 females (57.9%)) enrolled in the Harvard Aging Brain Study or the Instrumental Activities of Daily Living study completed an electronic survey online including measures of psychological resilience (Connor‐Davidson Resilience Scale‐10, where a higher score indicates greater resilience) during the COVID‐19 pandemic period (May 2020). We used previously collected (mean time from survey=1.75 year) PET imaging data to assess Aß and tau burden.ResultsOverall, participants demonstrated high levels of resilience (mean=29.5,range=9‐40). Multiple regression analyses (correcting for age, gender and time difference between survey and PET) demonstrated an interaction between resilience and amyloid on tau pathology (ß=‐0.01,p=0.015, Figure1). Specifically, in Aß+ individuals (SUVR>1.324), those with higher psychological resilience also had lower tau pathology. No relationship was seen in Aß‐ individuals.ConclusionOur findings suggest that greater resilience during the pandemic is associated with lower tau burden in individuals at higher risk of cognitive decline (i.e. preclinical AD). Future studies are needed to determine the impact of stress and psychological resilience on prospective pathological brain changes and subsequent cognitive decline. Furthermore, resilience may be an important target for interventions to support older adults navigating stressful situations and to lessen the influence of stressors on AD pathological processes.
Alzheimer’s disease risk prediction using automated machine learning
Authors: Gao Xiaoyi Raymond , Li Yi‐Ju , Martin Eden R. 
Published: December 2021

AbstractBackgroundAlzheimer’s disease (AD) is the most common late‐onset neurodegenerative disease. About 5.4 million Americans are living with AD. Unfortunately, there is no cure for AD at present, which makes early prediction crucial. Identifying individuals at increased risk of AD provides a better chance of benefiting from treatments. Risk prediction models are typically based on a limited number of predictors possibly with sub‐optimal performance. Here, we explore a state‐of‐the‐art automated machine learning (AutoML) framework for AD risk prediction, which can handle hundreds of predictors, including non‐traditional variables, with automatic feature engineering and model selection.MethodWe developed an AutoML model that aggregates polygenic risk scores (PRSs) and baseline individual characteristics (e.g., non‐genetic factors) for predicting AD. The PRSs were derived using summary statistics of the genome‐wide association studies from the Alzheimer Disease Genetics Consortium (ADGC) dataset (n = 19,918). The model was applied to 455,233 participants in UKBB without AD at baseline to predict development of AD at the final observation (n=1,452 developed AD). Our model was based on the H2O AutoML, an intelligent algorithm that can automatically select hyperparameters, tune ensembles of ML models, and carry out model assessment.ResultThe area under the receiver operating characteristic curve (AUC) for AD risk prediction was over 0.86. Polygenic risk scores ranked only second to age in feature importance. Furthermore, our AutoML model identified predictors that are not typically considered in traditional prediction models, such as an individual’s overall health rating and usual walking pace.ConclusionOur AutoML model improves the accuracy of AD risk prediction by efficiently exploring numerous predictors and ensemble models while greatly reducing manual coding hours. Furthermore, AutoML uncovered novel predictors for AD.
Cost‐effectiveness of non‐pharmacological interventions for patients with dementia: A systematic review and meta‐analysis
Authors: Huo Zhaohua , Chan Joyce YC , Lin Jiaer , Bat Baker Kwok Kwan , Chan Tak Kit , Tsoi Kelvin KF , Yip Benjamin HK 
Published: December 2021

AbstractBackgroundNon‐pharmacological interventions are widely used in the treatment of dementia, however, the cost‐effectiveness of them remains unclear. This study aimed to review and synthesize the economic evidence of non‐pharmacological interventions for patients with dementia (PwDs).MethodTrial‐based studies evaluating both the costs and effects of non‐pharmaceutical interventions for PwDs were searched from PubMed, Web of Science, EconLit, NHS EED and other five relevant databases. Study quality was assessed using the Cochrane Risk of Bias Tool and the Consensus on Health Economic Criteria list. Cost data were standardized in 2020 US dollars and analyzed from the healthcare perspective. Random‐effects models were used to synthesize the incremental cost and effects of different interventions, based on mean differences (MDs) or standardized mean differences (SMDs).ResultThirty‐one eligible studies were identified from 40,587 records. The follow‐up periods ranged from post‐discharge to three years. Care coordination and case management programs brought significant savings of $314 (95%CI: $47 to $582) per person in total healthcare cost, alongside more quality‐adjusted life years (QALYs) gained for PwDs (SMD: 0.197; 95%CI: 0.050 to 0.344). Cognitive‐oriented therapy improved patients’ cognitive functions (SMD: 0.105; 95%CI: 0.006 to 0.204), whereas psychological intervention and behavioral management improved the neuropsychiatric symptoms (SMD: 0.109; 95%CI: 0.033 to 0.185). However, they were accompanied with significant increases in total healthcare cost, $490 (95%CI: $70 to $910) and $338 (95%CI: $238 to $438), respectively. Psychological intervention and behavioral management also deteriorated patients' activity functions (SMD: ‐0.195; 95%CI: ‐0.360, ‐0.030).ConclusionCare coordination and case management for PwDs are most likely to be cost‐effective with lower healthcare cost and better QALYs gained. The acceptance of cognitive‐oriented therapy, psychological intervention and behavioral management depends on the society’s willingness to pay for the improvements in patients’ health. More economic evidence is required on other types of interventions, such as physical exercise, occupational therapy, and day care program.
Saliva biomarkers for Alzheimer’s disease risk in a rat model of low and high intrinsic exercise capacity
Authors: Almarghalani Daniyah , Hardy Ana Maria Gregio , Hasan Syed Abdul‐Moiz , Shah Zahoor A. , Koch Lauren Gerard 
Published: December 2021

AbstractBackgroundIdentifying a natural‐occurring animal model for Alzheimer's Disease (AD) and a non‐invasive early AD diagnostic are significant AD research challenges. Previously, we developed rat models by selectively breeding for low and high intrinsic exercise capacity. We found that compared to High Capacity Runners (HCR), Low Capacity Runners (LCR) have a reduced lifespan and greater risk for cardiovascular disease, diabetes, and obesity.1 LCR exhibit neurodegeneration, impaired memory, and decreased hippocampal neurogenesis. Saliva is a relatively new AD‐associated research area, and as a bioanalytic,2 is an important extension of protein changes in the autonomic nervous system and immune response. Our goal is to determine whether salivary biomarkers link with exercise capacity and brain health in LCR and HCR rats.MethodWe studied three‐generations of female rats (6 months: 9 LCR, 10 HCR), (20 months: 8 LCR, and 8 HCR), and (26 months: 7 LCR, 6 HCR). We assessed exercise capacity using a treadmill running test and cognitive function using a Y‐maze. Salivary gland weight and salivary flow rate (SFR) of a submandibular gland (SMG) were measured and compared. The acinar cells proliferation of SMG was assessed by IHC using PCNA. Biomarkers for p‐tau ser610 and amyloid‐beta were investigated in hippocampus tissue, saliva, and plasma using ELISA.ResultThe LCR and HCR groups were significantly different for maximal treadmill running distance and time spent in novel arm of the Y‐Maze. The SFR and acinar cell proliferation were higher in HCR. The size and mass of SMG were bigger in LCR rats. Levels of p‐tau in saliva and plasma were markedly greater in LCR than HCR, but no differences in the hippocampus. There was no difference between the two groups in the hippocampus or saliva regarding amyloid‐beta levels. However, it was significantly increased in plasma in the LCR group compared with the HCR group.ConclusionTaken together, the findings of this study provide experimental evidence that saliva biomarkers are significantly increased in the LCR group compared with the HCR group. This is the first study using novel and unexplored preclinical rat models that combines exercise capacity with AD risk by utilizing saliva biomarkers.
Cardiorespiratory fitness mitigates brain atrophy and cognitive decline in preclinical Alzheimer’s disease
Authors: Dougherty Ryan J , Jonaitis Erin M , Johnson Sterling C , Okonkwo Ozioma C , Cook Dane B 
Published: December 2021

AbstractBackgroundCardiorespiratory fitness (CRF) may be a mitigating factor for Alzheimer’s Disease (AD) progression. The purpose of this study was to examine the longitudinal associations of CRF with brain atrophy and cognitive function in a late‐middle‐aged cohort of adults at risk for AD.MethodOne hundred and ten adults (mean age = 64.2 ± 5.7 years, 65% female) from the Wisconsin Registry for Alzheimer’s Prevention (WRAP) completed a baseline graded treadmill exercise test, two brain MRI scans (over 4.67 ± 1.17 years) and neurocognitive assessments (2.18 ± .78 neurocognitive tests over 3.26 ± 1.02 years) as part of their WRAP study involvement. The oxygen uptake efficiency slope (OUES) was calculated for each participant and served as the CRF measure. Total gray matter and hippocampal volumes and the preclinical Alzheimer’s cognitive composite (PACC) score were the primary outcome measures. Linear mixed effects models examined the longitudinal associations adjusted for covariates. The CRF x age (i.e., time) interaction was centered and was the term of interest as it would indicate whether longitudinal decline in volumetrics or cognition differed as a function of CRF.ResultBaseline OUES values were 1.16 ± 0.28. Total gray matter and hippocampal volume declined at a rate of ‐0.73 ± 0.90% and ‐0.16 ± 1.30% per year, and cognitive trajectories decline ‐.047 points (standardized score) per year. The CRF × age interaction was significant for total gray matter volume (β=.26 SE .11; p=.020; Figure 1) and PACC score (β=.07 SE .03; p=.049; Figure 2), but not hippocampal volume (β=.002 SE .002; p=.347). These findings were most pronounced among APOE‐e4 carriers (p<.05).ConclusionCRF may be a modifiable physiological attribute to target during the preclinical stage of AD in effort to delay disease progression.
Association of retinal nerve fiber layer thickness with temporal lobe atrophy
Authors: Mathew Sunu , WuDunn Darrell , Mackay Devin , Vosmeier Aaron , Tallman Eileen F. , Garrett Makaylah N. , West John D. , Deardorff Rachael , Harris Alon , Farlow Martin R. , Brosch Jared R. , Gao Sujuan , Apostolova Liana G. , Saykin Andrew J. , Risacher Shannon L. 
Published: December 2021

AbstractBackgroundThe retinal nerve fiber layer (RNFL) is an extension of the brain that often reflects changes seen in the brain in neurodegenerative diseases. The purpose of this study was to examine the relationship of RNFL thickness measured using optical coherence tomography (OCT) with temporal lobe neurodegeneration in older adults along the Alzheimer’s disease (AD) continuum.MethodParticipants included 26 individuals with subjective cognitive decline (SCD), 21 mild cognitive impairment (MCI/{AD}) and 28 age‐matched cognitively normal (CN) from the Indiana Memory and Aging Study at the Indiana Alzheimer’s Disease Research Center. Participants were excluded from the study if they had significant eye disease determined to interfere with OCT and other ocular measures, non‐AD dementia, or exclusion for MRI. OCT scans were acquired from each eye to measure peripapillary RNFL among other metrics. Structural MRI scans were acquired and processed using Freesurfer version 6 to measure medial and lateral temporal lobe volumes. Finally, the association between the average RNFL thickness and bilateral mean hippocampus, amygdala, and lateral temporal lobe volumes was assessed using a partial Pearson correlation, covaried for age, sex, diagnosis, and total intracranial volume (ICV). A p‐value of p<0.05 was considered significant.ResultPeripapillary RNFL thickness was generally decreased in patients with AD compared to all other groups. In addition, average RNFL thickness across the retina was significantly correlated with brain atrophy, including bilateral mean hippocampal, amygdala, and lateral temporal lobe volumes.ConclusionRNFL thinning measured using OCT is associated with regional atrophy in medial and lateral lobes. Imaging of the eye may represent a useful biomarker to screen patients at risk for AD prior to more invasive and prolonged testing.