bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating cortical brain volumes three years after ischemic stroke
Authors: Khlif Mohamed Salah , Werden Emilio , Bird Laura J. , Brodtmann Amy 
Published: December 2020

AbstractBackgroundCortical atrophy is associated with cognitive decline and dementia, but few studies have examined cerebral atrophy after ischemic stroke. In this exploratory study, we examined changes in cortical volumes over 3 years in ischemic stroke patients and healthy age‐ and sex‐matched controls.MethodParticipants with first‐ever stroke were sampled from the Cognition And Neocortical Volume After Stroke (CANVAS) study. Cortical volumes were grouped contralesionally and ipsilesionally depending on the stroke side. To avoid any effects from lesions on cortical parcellations, ipsilesional volumes from patients with cortical lesions were excluded. There were 105 and 84 contralesional volumes at the 3‐month and 3‐year post‐stroke timepoints. Ipsilesionally, there were 86 volumes at 3‐months and 68 volumes at 3‐years. Volumes from 40 and 38 controls at same timepoints were used for comparison. Longitudinal cortical volumes were estimated using the ‘Desikan‐Killiany' parcellation atlas in FreeSurfer (version 6.0). A linear mixed‐effect model with random intercept and slope was used to compare volumes between groups and timepoints. Volumes were corrected for age, sex, years‐of‐education, total intra‐cranial volume, and a composite cerebrovascular risk factor coded from the sum of known risk factors: obesity (body mass index ≥30kg/m2), hypertension, cholesterol, smoking (≥1 cigarette/day), and alcohol intake (≥14 units/week). A sum ≥2 was coded as a high risk.ResultContralesional volumes: Compared to control, the inferior‐temporal gyrus volume in stroke was significantly lower at both timepoints. Volumes of precentral and rostral‐middle‐frontal gyri were significantly lower at 3 years. Atrophy rates were significantly faster for the entorhinal cortex, paracentral lobule, and frontal pole (see Table 1). Ipsilesional volumes: Several stroke volumes (caudal‐anterior‐cingulate, caudal‐middle‐frontal, inferior‐temporal, and rostral‐middle‐frontal) were significantly lower at both timepoints. Precentral gyrus volume was only significantly lower at 3 years. Atrophy rates were significantly faster for pars‐opercularis, the entorhinal, isthmus‐cingulate, and rostral‐anterior‐cingulate cortices and for postcentral, precentral, and superior‐frontal gyri (see Table 2).ConclusionMore ipsilesional cortices atrophied at a faster rate within the first 3 years after stroke compared to healthy controls than did contralesional cortices. In particular, volumes of lesion‐free bilateral inferior‐temporal gyrus were greatly reduced in stroke patients and may represent a risk factor for post‐stroke cognitive impairment.
Physical activity and domain‐specific cognitive function: The Shanghai Aging Study
Authors: Wu Wanqing , Ding Ding , Zhao Qianhua , Xiao Zhenxu , Liang Xiaoniu , Luo Jianfeng , Hong Zhen 
Published: December 2020

AbstractBackgroundTo examine the association of physical activity (PA) and domain‐specific cognitive function among older adults.MethodThis cross‐sectional study analyzed the baseline data of the Shanghai Aging Study, which included 3,507 community‐dwellings aged >=50 years and with >= 6 years of education. The characteristics of the participants were collected via an interviewer‐administered questionnaire. Participants were asked about the average time of doing PAs during the past 12 months. A metabolic equivalent value (MET) was assigned for each type of activity based on the compendium of PAs. We categorized PA into low level (<10.5 METs/week) and medium‐to‐high level (≥10.5 METs/week), based on the tertile of the METs distribution. Each participant was administered a battery of neuropsychological tests including Mini‐Mental State Examination (MMSE); Conflicting Instructions Task(CIT); Stick Test (ST); Modified Common Objects Sorting Test; Auditory Verbal Learning Test (AVLT); and Trail‐making Tests A and B. Impairment in specific neuropsychological test was defined as having test score > 1 SD worse than the mean value in corresponding age‐specific groups. We used multivariate linear regression models to assess the relation between METs (as a continuous variable) and scores of each neuropsychological test. Multivariate logistic regression models were also applied to examine the association between PA levels (as a categorical variable) and domain‐specific cognitive impairment, adjusting for age, sex, years of education, smoking, drinking, hypertension, diabetes, body mass index, and APOE ε4.ResultParticipants with PA ≥10.5 METs/week were significantly younger, more likely to be male, had a lower prevalence of hypertension and diabetes, had a better performance in all the neuropsychological tests. After adjusting for confounders, higher levels of PA was associated with a better performance in MMSE (β=0.09, p=0.020; OR=0.58, 95% CI 0.37‐0.91), conflicting correct tapping in CIT (β=0.06, p=0.056; OR=0.55, 95% CI 0.40‐0.76), recognition in AVLT (β=0.10, p=0.047; OR=0.76, 95% CI 0.60‐0.97), and imitating in ST (β=0.03, p=0.005; OR=0.69, 95% CI 0.48‐0.98) (Table 2, Figure 1).ConclusionMedium‐to‐high level of PA was associated with a better performance in global cognition, executive function, visuospatial skill, and memory among older adults. Further prospective studies are required to validate our findings and explore their clinical implications.
Cognitive function, mental decline, and rural‐living effects on brain structure in an elderly Indian population
Authors: Keller Brenton James , Jovicich Jorge , Lee Jinkook , Toga Arthur W. ,   LASI‐DAD
Published: December 2020

AbstractBackgroundAge‐related cognitive decline is widely documented, but with substantial individual differences that are not yet understood (Vaque‐Alcazar et al., 2017). Using the recently collected neuroimaging data from the Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI‐DAD), we investigate the associations between cognitive function (global cognition score), mental decline (JORM IQCODE), and rural‐living on brain structure.MethodsA total of 103 subjects (female = 46, age = 68 ± 6 years) were studied from three clinical 3T MRI centers using the ADNI 3 MRI protocol (NIMHANS, Bangalore, N = 52, NM Medical, Mumbai, N = 23, and Institute of Kolkata N = 28). Brain morphometry data was studied with Freesurfer using volumetric ROI‐analysis and vertex‐based cluster‐corrected structural analysis. A global cognition score was derived by aggregating all cognitive tests administered, which included a set of common neuropsychological test battery from the Harmonized Cognitive Assessment Project protocol (HCAP) (Weir et al., 2016), as well as additional tests suitable for illiterate and innumerate population in India (Lee et al., 2019).ResultsROI‐based morphometry analyses identified the hippocampus (subiculum and CA4, 3‐5%) and pars orbitalis (4‐6%) volume as having a positive correlation with global cognition score. Left hemisphere rostal middle frontal gyrus and right hemisphere postcentral gyrus area were also found to be positively associated with global cognition scores. In comparison, healthy status according to JORM IQCODE was positively correlated with right hemisphere rostral middle frontal gyrus thickness. Other significant clusters, including bilateral superior frontal gyrus and superior temporal gyrus thickness were found to be positively associated with JORM IQCODE healthy scores, while also showing colocalized area reductions in those with healthy JORM IQCODE scores. Similar to JORM IQCODE, rural‐living was also found to increase thickness in bilateral superior frontal gyrus.ConclusionsThrough the use of an intensive structural MRI protocol and neuropsychological test battery, we examined factors influencing brain morphometry. Of note, this study is the first to examine the effects of general cognition, respondent‐based memory assessment, and rural‐living on brain structure in an elderly Indian population.
Cross‐sectional and longitudinal analysis of the association between hemogloblin concentrations and depression in older adults: The International Mobility in Aging Study
Authors: Ahmed Tamer , Vasiliadis Helen‐Maria 
Published: December 2020

AbstractBackgroundAnemia is a common hematological condition in older adults, with estimated prevalence increasing with age after the fifth decade of life. 1 We examined the cross‐sectional and longitudinal relationships between hemoglobin concentrations and depression in older adults and whether these relationships were modified by sex, social context, or cognitive function.MethodA total of 1608 community‐dwelling older adults from the International Mobility in Aging Study (IMIAS) aged 65 to 74 years were recruited in Natal (Brazil), Manizales (Colombia), Kingston (Ontario, Canada), and Saint‐Hyacinthe (Quebec, Canada). The study outcome was depression, defined by a score of 16 or over in the Center for Epidemiologic Studies Depression Scale (CES‐D). Poisson regression models were used to estimate prevalence ratios (PR) of depression, while longitudinal associations over four years follow‐up were examined using generalized estimating equations. Hemoglobin concentrations were used either as a continuous measure or categorized according to the severity of anemia. Models reported were adjusted for research sites, alcohol drinking status, body mass index, chronic conditions, activities of daily life disabilities, cognitive function, and polypharmacy.ResultIn multivariate cross‐sectional and longitudinal analyses, for every 1g/dL increase in hemoglobin concentrations there was a significant reduction in the prevalence (PR=0.90, 95% confidence interval (CI): 0.83 ‐ 0.97) and incidence (Odds Ratio (OR)=0.85, 95% CI: 0.77‐0.92) of depression. Moderate anemia was also a strong predictor of depression (OR=8.24, 95% CI: 1.45 ‐ 47.02). None of the multiplicative interactions by sex, research sites, or cognitive function were statistically significant.ConclusionIn international samples of older adults, hemoglobin concentrations, as well as the severity of anemia, were independent risk factors for depression. References: 1‐ Guralnik JM, Eisenstaedt RS, Ferrucci L, Klein HG, Woodman RC. Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia. Blood. 2004;104(8):2263‐2268.
A story of innovation: Building a national surveillance system for dementia in Canada
Authors: Toews Jennette , Pelletier Catherine , Shaver Larry C 
Published: December 2020

AbstractBackgroundAccurately capturing cases of dementia at the population‐level is complex, given the nature of the condition. Over the past decade, Canada has focused on this challenge, evolving and improving dementia surveillance in collaboration with multiple stakeholders.MethodOriginally based on self‐reported data, dementia data in Canada were limited to the prevalence of the condition and were significantly underestimating its burden. Canada sought to develop an innovative and systematic approach to enhance dementia surveillance by, initially, undertaking the National Population Health Study of Neurological Conditions and, then, exploring the feasibility of using linked health administrative data. The Canadian Chronic Disease Surveillance System (CCDSS), a network of provincial/territorial surveillance systems supported by the Public Health Agency of Canada, since became the core platform to support national reporting on dementia.ResultA validated case definition, incorporating data from hospitalizations, physician claims and drug prescriptions, was developed and applied to the CCDSS linked databases. As a result, since 2016, national and provincial/territorial estimates of dementia incidence, prevalence, and mortality over time (dating back to 2002) are released annually. With the recent adoption of Canada’s National Dementia Strategy in 2019, other innovative methods are being explored to enhance surveillance, including: analysing the trajectory of the condition, with the development of comorbidities and impacts on health outcomes; creating new data linkages to enrich the sociodemographic information on individuals living with dementia; assessing the feasibility to monitor early onset dementia.ConclusionUtilizing the unique capacity of the CCDSS, a new national surveillance system for dementia in Canada has been implemented. The evolution and innovation of dementia surveillance over the course of the past decade can provide valuable lessons for the surveillance of dementia and other complex conditions in other countries.
Neuronal trafficking dynamics and regulators
Authors: Feole Monica , Devoto Victorio Martin Pozo , Carna Maria , Stokin Gorazd Bernard 
Published: December 2020

AbstractBackgroundNeurons are highly polarized cells continuously relying on intracellular transport, through which they communicate with the external world. Among the somatodendritic and axonal compartments many proteins with different functions are sorted to reach long distances. The relevance of neuronal transport in ensuring cell development and homeostasis maintenance raises a big interest on this topic. Moreover, several neurodegenerative diseases, such as Alzheimer’s or Amyotrophic Lateral Sclerosis, exhibit significant axonal pathology, where transport impairment seems to have a crucial influence. However, the role of this process in neurodegeneration, remains poorly understood. In this study we aim to characterize neuronal transport dynamics of specific proteins, and the molecular machinery regulating this process. Furthermore, we aim to explore transport from the pathological point of view, evaluating the effect that mutant proteins (e.g. TDP43‐related) may have on it.MethodHuman Neural Stem Cells derived neurons were differentiated for 30 DIV. Plasmids encoding for different GFP‐coupled proteins were designed to express those who are involved in main neuronal functions (e.g. synaptic activity) and transfected in neurons. Time‐lapse movies of cargoes were acquired to detect changes in movement. Data analysis was performed using object segmentation and tracking algorithms. Raw data were processed to describe the main motion parameters: average velocity, directionality, track length, and others. Post‐imaging Immunocytochemistry was performed to assess cargoes localization and discriminate between axonal and dendritic transport.ResultAmyloid Precursor Protein (APP) cargoes with higher velocity in anterograde direction were observed compared with the retrograde one; meanwhile for Synaptophysin, a major population of stationary particles was found. Moreover, sorted data for axonal and dendritic transport description shown faster APP particles in axonal anterograde movement. Relying on the movement dynamics description, we decided to screen for protein‐protein interactions, using GFP‐trap and CoIP approaches followed by Mass Spectrometry analysis, which can shed light on possible partners involved in the transport regulation.ConclusionOur work describes an in vitro model for neuronal transport study and highlights the different behavior of proteins with various physiological functions. A complete view will elucidate details about transport regulation and will open a way to understand its role in neuropathological processes.
Circadian rhythm disturbance in agitation of Alzheimer's disease
Authors: Rosenberg Paul B. , Wu Mark N. , Spira Adam P. , Wanigatunga Sarah K. , Zipunnikov Vadim , Outen John D. 
Published: December 2020

AbstractBackgroundAgitation in Alzheimer’s disease (AD) is a major cause of distress and burden for AD caregivers and may be driven by disrupted circadian rhythms (often termed “sundowning”) and sleep. In healthy individuals, the circadian clock that generates these rhythms controls patterns in mood, wakefulness, and alertness. We examined the association of activity and sleep with agitation in AD in an observational study using wrist actigraphy, home sleep testing, and measurement of core body temperature.MethodWe studied 13 participants with AD+agitation (AgitAD+) and 7 with AD but without agitation (AgitAD‐) who completed wrist actigraphy for one week (to quantify rest/activity rhythms and sleep); consumed an ingestible, disposable temperature sensor for 1‐2 days (to quantify core body temperature, a marker of the endogenous circadian rhythm); and completed a single night of home sleep testing (HST) using NoxT3. Agitation was measured with the Neuropsychiatric Inventory‐Clinician Version (NPI‐C).Result20 participants have completed to date (7 controls/13 agitated, mean age of 68 years, 60% female, 10% African American). There were no statistically significant differences observed in actigraphy‐derived sleep parameters between agitated and non‐agitated participants (2‐group t‐test; see Table 1). However, significant differences between the groups have been observed in the rest/activity rhythms: compared to participants without agitation (AgitAD‐), AgitAD+ participants had lower amplitude in the morning and greater amplitude in the afternoon and evening (Figure 1). We also have performed function‐on‐scalar regression (FOSR) (Goldsmith et al., 2015, Biometrics 71:344‐353) using subject‐specific activity profiles as outcomes and age and Agitation/Controls status as scalar predictors. Figure 2 shows functional effects of age on Rest/Activity Rhythm (left panel) and the functional effect of Agitation status (right panel), the red background shows the pointwise statistically significant (p<0.05) times of the day. Adjusted for age, Agitation was associated with a lower amplitude in the morning period and a trend towards larger amplitude in the afternoon and evening period (not statistically significant).ConclusionThe collection of multimodal noninvasive data on sleep, activity, and core body temperature is feasible in agitated AD outpatients. We will present HST and core body temperature data at AAIC. Funding: R01AG054771.
Diastolic dysfunction and cognitive impairment
Authors: Parker Alicia S. , Himali Jayandra J , Beiser Alexa S. , Short Meghan I. , Kautz Tiffany , Vasan Ramachandran S. , Seshadri Sudha ,   Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, UT Health San Antonio
Published: December 2020

AbstractBackgroundThe relationship between diastolic dysfunction and cognition is undefined. Diastolic dysfunction is common, disproportionately affects females, and is increasing in the community. While earlier studies suggested that management of diastolic dysfunction did not improve cardiovascular mortality, there is increasing evidence that diastolic dysfunction affects patient outcomes. Our clinical observation is that patients with diastolic dysfunction tend to have increased white matter hyperintensities on imaging. If diastolic dysfunction is found to be associated with cognitive impairment, that would suggest diastolic dysfunction is a novel modifiable risk factor for the development of dementia.MethodEchocardiographic, MRI and neuropsychological data collected by the Framingham Heart Study, Offspring Cohort, at Exam 8 was reviewed. Diastolic measures were related to MRI measures of total cranial brain volume, hippocampal volume and white matter hyperintensities, and to neuropsychological evaluations.ResultData from 1438 participants (Figure 1) showed that increasing E/E’ ratio, indicating increasing diastolic dysfunction, was associated with increased executive function impairment in the Similarities (β±SE:‐0.29±0.09,p<0.002) and FAS Phonemic Fluency (‐1.27±0.33,p<0.001) tasks. Participants with moderate to severe diastolic dysfunction performed more poorly on Logical Memories (‐0.70±0.34,p<0.036) and FAS Phonemic Fluency (‐2.75±1.11,p<0.014), and trended towards increased impairment on Similarities (‐0.59±0.30,p<0.052) (Table 1). Data from 1217 participants (Figure 2) showed that those with mild diastolic dysfunction trended towards increased white matter hyperintensities (0.11±0.07, p<0.105); participants with moderate‐to‐severe diastolic dysfunction had increased white matter hyperintensities (0.30±0.09,p<0.001) (Table 2). Data from 1415 participants showed that increasing E/E’ ratio was associated with increased incident mild cognitive impairment (HR 1.29 [95%CI: 1.01, 1.66], p<0.043; Table 3).ConclusionDiastolic dysfunction was associated increased incident mild cognitive impairment. Increased diastolic dysfunction was associated with impaired executive function and verbal memory on neuropsychological testing, along with increased cerebral small vessel disease as demonstrated by white matter hyperintensities on MR imaging. As cerebral small vessel disease clinically presents with executive function impairment, these results align well. An amnestic impairment was also seen, such as can occur in Alzheimer’s disease. This study suggests that diastolic dysfunction is a novel modifiable risk factor for the development of dementia. Further research examining management of diastolic dysfunction on cognitive outcomes would be of benefit.
Scientific appraisal of the health app review tool: A validation and usability testing protocol
Authors: Faieta Julie , Erickson Kirk I , Digiovine Carmen , Best Krista 
Published: December 2020

AbstractBackgroundThere is a critical need to develop and evaluate effective tools to support the quality of life for those with Alzheimer’s disease (AD). Apps focused on health and function have great potential to fulfill this need through education, health and behavior tracking, and interactive capabilities. However, current app evaluation tools lack specificity to the AD and caregiver population and fail to assess factors specific to the unique needs of AD. The Health App Review Tool (HART) was designed to characterize the features of apps and then match these features to the needs and abilities of those affected by AD. The purpose of this study is to evaluate the reliability and validity of the HART and to refine the structure and content of the HART according to findings.MethodThis study will be carried out across Quebec, Columbus, and Pittsburg. A sample of ≥300 health care professionals working with the AD population will be recruited to complete the HART at two time points based on one of four apps and case studies. Inter and intra‐rater reliability will be assessed according to app/case study allocation and between time points. Confirmatory factor analysis and Rasch analysis of time 1 scores will be used to assess psychometric soundness. A sample of ≥12 researchers and clinicians will participate in focus groups according to the think‐aloud qualitative approach to systematically assess each item in the HART. Feedback from both psychometric and qualitative assessments will be used to refine the HART.ResultWe anticipate that the current version of the HART will be have redundant items as indicated by residual correlation and that the current factor loading will indicate the need for item relocation. In addition, we anticipate qualitative feedback will indicate that branching structure and more limited item list would be preferable.ConclusionInitial investigations into the HART indicate promise as a clinically valuable instrument, however, additional development of the HART content and structure are needed prior to its widespread use. The HART is anticipated to impact the uptake and use of health and function supporting apps within the AD and caregiver population.