bluuebunny/crossref_metadata_2025_split huggingface dataset:
Feasibility of a health coaching intervention with mobile health technology in older adults with mild cognitive impairment or risk factors for dementia
Authors: Krivanek Taylor , McFeeley Brittany , Daffner Kirk R , Gale Seth A 
Published: December 2020

AbstractBackgroundThere is growing evidence that adherence to brain‐healthy behaviors can reduce the risk of dementia and rate of decline. Current standard of care, however, does not systematically promote or monitor adherence to brain health guidelines. We recently demonstrated that a health coaching intervention, which included weekly phone calls, facilitated greater adherence to lifestyle recommendations and improved quality of life. The current study is investigating the impact of supplementing health coaching with digital health technology, including a mobile platform and wearable fitness trackers.MethodIn an ongoing six‐month trial, we are measuring the effect of a clinic‐embedded, technology‐augmented health coaching program on adherence to brain health recommendations. Forty patients with mild cognitive impairment (MCI) or risk factors for dementia are being randomized to the Brain Health Champion (BHC) intervention or a counseling and education (CE) control. In BHC, participants work with a health coach to set personalized goals, reinforced by weekly video calls, mobile messaging, and in‐person visits every six weeks. In CE, usual clinical care is supplemented with educational materials mailed every six weeks. Using validated questionnaires, wearable fitness trackers, and photographed food logs, changes in physical activity, diet, and social/cognitive engagement are being determined.ResultOf the 12 participants enrolled to date, 83% have been adherent to use of mobile technology and fitness trackers. In BHC, 93% of weekly video calls have been completed, and coaches and participants have exchanged an average of 7 text messages per week. BHC participants have been more likely to continue wearing and monitoring their fitness trackers after the required assessment period (75% BHC vs. 40% CE). 66% of all participants report that they would like their doctors to have access to data from mobile health applications, and 56% report that they would like to incorporate mobile health into their regular medical care.ConclusionA health coaching intervention for MCI patients and at‐risk older adults using digital health technology is feasible and shows promise for use in wider health care settings. The intervention’s impact on the adoption of brain‐healthy behaviors is being measured and an interim report will be provided.
Regional cerebral perfusion alterations in subjective cognitive decline measured by arterial spin labeling MRI
Authors: Schwarz Claudia , Hetzer Stefan , Benson Gloria , Horn Nora , Wurdack Katharina , Wirth Miranka , Flöel Agnes 
Published: December 2020

AbstractBackgroundIndividuals with subjective cognitive decline (SCD) are at high risk of developing Alzheimer's disease (AD) (Jessen et al., 2014). Changes in cerebral perfusion, particularly cerebral blood flow (CBF), are a feature of AD and has also been shown in pre‐dementia stages (Binnewijzend et al., 2016). This study investigates regional CBF and its association with cognition in individuals with SCD and healthy older adults.MethodCognitive performance and cerebral perfusion were assessed in 81 individuals with SCD (age 68±5 years) and 46 healthy controls (age 71±6 years). Regional CBF (mL/100g/min) was assessed by arterial spin labeling MRI and quantified in AD‐vulnerable regions (Wirth et al., 2016). The preclinical Alzheimer’s cognitive composite (PACC5) and composite scores for selected cognitive domains were calculated. General linear models were conducted to assess group differences in regional CBF as well as associations between regional CBF and cognitive performance. Interaction effect of group and regional CBF on cognitive performance was determined using the same method. All analyses were adjusted for potential confounders (including sex, age, and body mass index).ResultParticipants with SCD showed decreased CBF in the hippocampus (p=.038) and the basal ganglia (p=.014) compared to healthy controls. Moreover, participants with SCD exhibited greater CBF in the inferior temporal gyrus than healthy controls (p=.006). Across all participants, CBF in the basal ganglia was positively associated with executive function (p=.016), memory (p=.018), and PACC5 (p=.001). Exploratory investigations within each group revealed these associations only in healthy controls (p=.032, .037, .004, respectively). However, no effect of group was found on the relationship between regional CBF and cognitive performance.ConclusionOur findings indicate that alterations of cerebral perfusion are already detectable in the stage of SCD, in particular in the hippocampus, basal ganglia, and inferior temporal gyrus. In addition, cognitive performance was positively associated with CBF in the basal ganglia across all subjects; however, this effect was mainly driven by the healthy controls. Thus, our findings may point towards early pathological changes affecting the association between regional CBF and cognition in SCD, which needs to be evaluated in further studies.
Endothelial progenitor cells are depleted in older adults with cognitive impairment and white matter volume loss
Authors: Marshall Anisa J. , Gaubert Aimee , Yew Belinda , Ho Jean K. , Jang Jung Yun , Blanken Anna E. , Dutt Shubir , Sible Isabel J. , Kapoor Arunima , Li Yanrong , McIntosh Elissa C. , Rodgers Kathleen E. , Nation Daniel A. 
Published: December 2020

AbstractBackgroundDepletion of endothelial progenitor cells (EPCs) has been linked to vascular disease and both mild cognitive impairment (MCI) and Alzheimer’s disease (AD) dementia. EPCs have been shown to support oligodendrocyte precursor cell proliferation in the oligovascular niche, suggesting a potential role in protecting white matter (WM) integrity. We studied the relationship between in vitro EPC proliferation and both WM volume and cognitive function.MethodSixty‐three community dwelling older adults (Mage = 70.94; SDage = 7.39), free of dementia or clinical stroke, underwent venipuncture, neuropsychological testing, and brain MRI. Blood leukocyte fractions were cultured over one week in colony forming unit (CFU)‐Hill media to produce EPCs. On the 5th day, colonies were counted. Cognitive function was measured by a comprehensive neuropsychological battery and the Clinical Dementia Rating (CDR) Scale. WM volumes were measured by Region‐of‐interest (ROI) analysis on T1‐MPRAGE scans using FreeSurfer 5.3. Univariate Analysis of Covariance (ANCOVA) compared CFU‐Hill counts and CDR scores, and multiple linear regression analyses determined the relationship between CFU‐Hill counts, neuropsychological tests and WM ROIs, after controlling for age, sex and education.ResultCFU‐Hill counts were depleted in participants with CDR = 0.5 [F(1, 51) = 5.84, p = 0.02]. Lower CFU‐Hill counts were associated with worse performances on tests of executive functioning [(1) Animals: F(4, 60) = 4.10, p = 0.005; ΔR2 = 0.16; β= 0.41; ΔF = 12.51, p = 0.001; (2) Fruits and Vegetables: F(4, 60) = 4.00, p = 0.006; β=0.36; ΔR2 = 0.12; ΔF = 7.54, p = 0.009; (3) Trails B: F(4, 44)=9.43; p <0.001; β= 0.24; ΔR2 = 0.057; ΔF = 4.69, p = 0.036]. Posterior corpus callosum volume positively predicted CFU‐Hill counts [F(5, 42)=2.62; p =0.038; β= 0.41; ΔR2 = 0.14; ΔF = 7.69, p = 0.008].ConclusionFindings suggest EPCs may be linked to impaired cognition and WM volume loss in older adults, potentially implicating EPCs in protecting against vascular‐related WM injury and resulting executive dysfunction. Further studies of EPCs, WM integrity, and executive dysfunction are warranted to evaluate a potential protective role for EPCs in cerebrovascular disease with implications for dementia risk assessment and prevention.
Behavioral RCT using internet‐based social interactions: Why some gain and some do not
Authors: Dodge Hiroko H , Hampstead Benjamin M , Potempa Kathleen , Struble Laura , Asgari Meysam , Silbert Lisa C , Croff Raina , Wild Katherine , Lahna David , Schwartz Daniel L , Kaye Jeffrey , McDonald Mattie , Lindsley Jacob , Team I‐CONECT 
Published: December 2020

AbstractBackgroundIncreasing social interaction could be a promising intervention for improving the cognitive well‐being of socially isolated older adults. However, we expect that the efficacy of a social intervention can differ across subjects due to personality traits, preference for specific activities, and different pathological stages, even within the same clinical diagnosis. For most behavioral intervention studies, the priority of randomized controlled trials is not necessarily to gain a statistically significant intervention effect, but to find which subjects benefit from the specific intervention. Factoring this potential heterogeneity into the efficacy analysis of randomized controlled trials (RCT) will be discussed.MethodsBuilding upon our previously completed NIH‐funded project (ClinicalTrials.gov #: NCT01571427), we developed a multi‐site RCT to examine whether conversation‐based cognitive stimulation has a positive effect on domain‐specific cognitive functions and higher‐order objectively measured IADL (Instrumental Activities of Daily Living). We target socially isolated older adults with either normal cognition or mild cognitive impairment (Internet‐Based Conversational Engagement Clinical Trial (I‐CONECT), ClinicalTrials.gov # NCT02871921). The experimental group engages in semi‐structured video‐chat conversation with trained conversational staff 4 times per week for 6 months (high dose) and twice per week for additional 6 months (maintenance dose). In addition to the main outcomes of neuropsychological test scores, we aim to determine factors which lead to heterogeneities in efficacy including: baseline brain atrophy and connectivity using MRI/fMRI, personality, Apoe genotype, mood and nature of social isolation (emotional vs. structural).ResultsWhile recruiting socially isolated subjects is challenging, as of January, 2020, our study has reached out 26,000 subjects, screened 195 subjects, and 131 subjects were ultimately randomized with 40% of those being eligible for MRI assessment. Baseline recruitment will continue until March of 2021. Carefully considered outcomes, covariates and mediating factors are being collected in this RCT. This presentation will examine some of the key heterogeneities observed in our ongoing baseline sample, and discuss potential implications these differences may have on our future efficacy analysis.ConclusionsOur project serves as a reference for developing individualized, targeted community intervention strategies with high adherence with maintainable life style modifications.
Factors affecting computerized cognitive training performance: The relations between age, education level, and repetitive use
Authors: Şahiner Melike , Cınar Nilgun , Şahiner Türker AH 
Published: December 2020

AbstractBackgroundData on CCT performances of the population over 40 is rather complicated. Rehabilitation focused approaches widely believe that repetitive use would improve the CCT performance in time. Yet as evaluation period decreases, the error margin increases, often leading to false positive or negative results. In this study, CCT performances were evaluated according to age, education level and number of repeated courses.MethodBEYNEX is a non‐commercial web‐application that allows users to do daily cognitive activities, including playing 3 different 5‐minute long computer games and answering questions on ADL. For this study, BEYNEX provided personal access to 100 individuals, who applied online to participate, yet didn’t have any cognition related diagnosis or treatment. The group completed the activities daily, and exercised with a 3‐minute physical exercise video. All exercises designed within the parameters used by clinicians and are completely unique. Patients’ total activity time, ADL and game performances were monitored only by clinicians under 9 different graphics (ADL, Memory, Visual Perception, Speed, Problem‐solving, Flexibility, Attention, Language Skills, Arithmetic). The acceptance criteria was based on completing at least 1 course (*completing 20 minutes of exercises for 33 times) within any period of time.Result100 individuals are between the age of 38‐89 and are educated between 5‐18 years. Each completed at least 1 to maximum of 90 courses in total (Fig.1,2). No significant correlation was found between the “number of courses” completed by the individual and 8 cognitive parameters BEYNEX measures. While “Memory, Speed, Flexibility, Attention, Visual Perception” parameters and “Age” showed significant negative correlations, there was no relation with “Problem Solving, Language, Arithmetic” and “Age” parameters. Only “Attention” level parameters shows positive correlation with the “Education Level” increases, (Fig 3).ConclusionWhen monitoring cognitive parameters with CCT, the most important performance indicator is the age of the patient. Exercises should be chosen according to age. The education level of the patient and the effect of exercising are often negligible. The results of this study are promising for diagnostic software. In near future, it may be possible to remotely diagnose with smart software systems which are not affected by repetitive use or education levels.
Lower average daily step count is associated with poorer executive function and rurality in a veteran cohort
Authors: Silbert Lisa C , Wall Rachel C , Beattie Zachary , Dodge Hiroko H , Mattek Nora , Riley Thomas , Kaye Jeffrey 
Published: December 2020

AbstractBackgroundAn active lifestyle is associated with better cognitive health in older individuals. This relationship is understudied in U.S. Veterans, a population at risk of cognitive impairment due to the high prevalence of associated risk factors and comorbidities. Passive monitoring of daily activities provides objective measures of activity that may serve as a sensitive index of day‐to‐day function and dementia risk.MethodParticipants (age > 57) were enrolled as part of Collaborative Aging Research using Technology (CART), a multi‐site study examining the feasibility of unobtrusive remote sensing and monitoring of physical, cognitive, and health‐related activities. The Veteran cohort consists of volunteers living in largely rural communities in the Pacific Northwest, self‐identified as being a Veteran, and included their cohabitant, if applicable. Daily step counts were acquired using a wrist‐worn device. Baseline one‐month averages were compared with rurality and cognitive function.Result114 nondemented participants residing in 67 homes underwent neuropsychological assessment and passive monitoring of daily activities (55% male, age 70.7, MOCA 23.4). 70% resided in a rural area (rural‐urban commuting area (RUCA) score > 4 ) and 29% had > three vascular risk factors. Participants with 14+ days of gait activity measured within a one‐month period near baseline cognitive assessments not using a walker in the home were included (n = 107). Average daily step count obtained over an average of 27.7 days was 3,065 (median 2,515) and was greater in large rural towns compared with small‐isolated rural (p = 0.07) or urban (p = 0.04) towns. After adjusting for potential confounders, lower average daily steps were associated with worse performance in executive function, a relationship observed in Veterans in large rural, but not urban or small rural towns.ConclusionIn a cohort comprised primarily of rural Veteran’s and their spouses, lower average number of steps per day is associated with poorer executive function and this relationship varied by rurality. Real‐world monitoring of daily activities may identify those at greatest risk of cognitive decline for interventional studies aimed at dementia prevention in older individuals, and is of particular relevance in rural settings, where access to specialty care is limited.
Differential alterations of spatial and nonspatial memory circuits within hippocampal CA1 in 3XTG‐AD mice
Authors: Tian Chengju , Reyes Isabel , Masurkar Arjun V. 
Published: December 2020

AbstractBackgroundArea CA1 of hippocampus is highly vulnerable to Alzheimer’s disease (AD), with denser pathology towards the subiculum versus the CA2 border. Spatial and non‐spatial memory processing in CA1 is also segregated along this transverse axis. Towards CA2, deep and superficial CA1 pyramidal neurons (PNs) uniquely process spatial information from medial entorhinal cortex (MEC) and CA3. Towards subiculum, deep and superficial CA1 PNs differentially integrate non‐spatial information from lateral entorhinal cortex (LEC) and CA3. It is unclear how AD affects these distinct processing architectures, and if it is reflective of the known gradient of AD pathology within CA1.MethodMEC or LEC of 3xTg‐AD (12‐24 month old) and age‐matched wild type (WT) mice were injected with an AAV expressing channelrhodopsin (ChrR2). Acute hippocampal slices were prepared two weeks later. Whole cell patch clamp recordings were performed on deep and superficial CA1 PNs, with MEC or LEC axons optogenetically activated by blue light and CA3 axons activated by extracellular stimulation in stratum radiatum. In separate mice, immunohistochemistry (IHC) was performed for AD pathology.ResultIHC confirmed increased AD pathology in 3xTg‐AD mice towards subiculum versus CA2. Near CA2, 3xTg‐AD mice (compared to WT) showed reduced MEC input responses in both deep (0.7mV vs. 1.8mV, n=7 each, p<0.05) and superficial PNs (0.8mV vs. 2.0mV, n=8 each, p<0.05). In contrast, CA3 input responses were unchanged in deep PNs but was surprisingly increased in superficial PNs (10.4mV vs. 6.6mV, n=8 each, p<0.05). Near subiculum, 3xTg‐AD mice (compared to WT) showed a reduction in LEC input response only in superficial PNs (0.9mV, n=8, vs. 1.7mV, n=7, p<0.05). Response to CA3 input was also selectively reduced in superficial PNs (3.0mV, n=8, vs. 8.2mV, n=7, p<0.01).ConclusionSpatial and non‐spatial memory circuits in CA1 are differentially affected in 3xTg‐AD mice, in a synapse‐ and cell type‐specific manner. Furthermore, they are not merely a direct reflection of AD pathology gradient in CA1, and may be also reflective of indirect or compensatory mechanisms related to the disease. These results also have implications on dysfunctional in vivo activity of CA1 PNs related to AD‐induced memory deficits.
PRADI cohort case‐control study on related factors of Alzheimer’s disease
Authors: Feliciano‐Astacio Briseida E. , Beecham Gary W , Silva Concepcion , Mena Pedro Ramon , Inciute Jovita D. , Tejada Sergio , Adams Larry D. , Rodriguez Vanessa C. , Celis Katrina , Prough Michael , Bussies Parker , Sierra‐Lopez Carolina B. , Contreras Maricarmen , Manrique Patricia , Feliciano Nereida I. , Chinea Angel , McCauley Jacob L , Acosta Heriberto , Vance Jeffery M. , Cuccaro Michael L. , Pericak‐Vance Margaret A. ,   PRADI: Puerto Rico Alzheimer’s disease and related Dementias Initiative
Published: December 2020

AbstractBackgroundAlzheimer’s disease (AD) has become a burden of social and economic importance, affecting millions of families and society at large. The Puerto Rico Alzheimer and Related Dementias Initiatives (PRADI) cohort was developed to investigate AD and genetics factors of AD in the Puerto Rican population. PRADI recruitment was a snowball sampling, with both island‐wide geographic distribution, as well as extensions to PR communities in the continental US. In this study we assessed the relationship between AD and cardiovascular risk factors of AD in the PR population.MethodWe assessed over 700 elderly PR individuals for dementia, as well as medical history. Affection status was assessed using standard AD clinical criteria (NINCDS‐ADRDA) or mild cognitive impairment. All medical history was obtained by a self‐report or informant report. Differences between affected and unaffected were initially tested using a chi‐square test (for sex, diabetes, hypercholesterolemia, heart disease, hypertension, and stroke) and a t‐test for the age of the exam. Follow‐up analyses on stroke were performed using logistic regression with age at exam and sex as covariates in the model.ResultThe analysis revealed no differences sex differences between AD and unaffected (p‐value > 0.05). Similarly, affected and unaffected showed similar levels of type 2 diabetes, hypercholesterolemia, heart disease, and hypertension (p‐value > 0.05). Affected individuals did however show an increase in stroke incidence (14.0% vs 5.2%; p‐value = 8.3e‐5). This difference persisted even when controlling for age of exam and sex. We did see a difference in age of exam between cases and controls, but this is likely due to ascertainment scheme.ConclusionThis analysis suggests that stroke may be a contributing factor to dementia in the PR population. However, given biases in the ascertainment scheme, additional assessments need to be performed. Additionally, work is ongoing to assess the role of ancestry and genetic factors in this association.
Analysis of individual families implicates noncoding DNA variation and multiple biological pathways in Alzheimer’s disease risk
Authors: Wijsman Ellen M. , Day Tyler R. , Thornton Timothy A. , Horimoto Andrea R. , Blue Elizabeth E. , Bis Josh C. , Sohi Harkirat K. , Nato Alejandro Q. , Nafikov Rafael A. , Navas Patrick , Saad Mohamad , Tsuang Debby W. , Barral Sandra , Vardarajan Badri N. , Beecham Gary W. , Martin Eden R. , van Duijn Cornelia M. , Pericak‐Vance Margaret A. , Mayeux Richard ,   Alzheimer’s Disease Sequencing Project
Published: December 2020

AbstractBackgroundLate‐onset Alzheimer’s disease (AD) is a complex disorder with multiple genetic risk factors. Linkage and association analysis have mapped dozens of loci in pooled analysis of many pedigrees or large numbers of unrelated cases and controls. Identification of the underlying DNA risk variants in the regions of interest (ROIs) has been complicated by both the genetic heterogeneity and the cost, until recently, of comprehensive DNA sequencing in ROIs. The known loci also leave much heritability unexplained.MethodWe used the families in the AD Sequencing Project (ADSP) discovery family sample to identify variants of interest from whole genome sequences (WGS), and through the variants, genes implicated in risk. We used SNP‐based multipoint linkage analysis to identify ROIs with rare VOIs, carrying out analysis without trimming pedigrees. We pursued all ROIs with family‐specific lodmax scores >1.9, reducing the variants of interest by several filters. We carried out pedigree‐based genotype imputation from the available WGS data, followed by family‐based association analysis, filtered for low population minor allele frequency. We prioritized genes with a low false‐discovery rate for association of single‐cell transcription in brain with AD disease state (PMID:31209304), and genes with high expression in bulk brain (PMID: 24309898).ResultWe obtained 46 distinct ROIs representing lodmax1.9‐3.5 per ROI in each of 26 of the 110 ADSP discovery families analyzed. 29 ROIs further investigated in 16 of the families yielded 59 prioritized genes, with 1‐11 genes/ROI. Only 4 out of 321 variants that passed all filters in these genes were in exons, with minimal overlap with genes identified in AD GWASs. Only one ROI occurred in two families, with evidence for a shared‐haplotype between these families, implicating FBXO2 and FBXO44. Both genes are implicated in ubiquitination, while FBXO2 interacts with BACE1. Multiple pathways, both known and new, are implicated, including the ubiquitin‐proteasome system, neural development and maintenance, and mitochondrial functions.ConclusionThis analysis underscores the evidence for extensive genetic heterogeneity and rare variants underlying AD risk, along with multiple potential mechanisms. The preponderance of prioritize non‐coding variants suggests alterations in gene regulation and/or expression as an aspect of AD genetic risk.