bluuebunny/crossref_metadata_2025_split huggingface dataset:
Old critically ill COVID‐19 survivors: Patient and in‐hospital factors associated with cognitive dysfunction
Authors: Martins Sónia , Ferreira Ana Rita , Fernandes Joana , Vieira Tatiana , Fontes Liliana , Coimbra Isabel , Paiva José Artur , Fernandes Lia 
Published: February 2022

AbstractBackgroundCognitive dysfunction (CD) commonly occurs in survivors of critical illness, namely in those with severe respiratory failure, invasive mechanical ventilation (IMV), deep sedation and delirium. Many critically ill patients with COVID‐19 are also expected to have an increased risk of CD, which may be exacerbated by specific conditions of hospitalization during COVID‐19 pandemic. This study aimed to estimate the frequency of post‐discharge CD in first wave COVID‐19 survivors and to identify baseline and in‐hospital associated factors.MethodsThis study is part of a multidisciplinary longitudinal project (MAPA‐Mental health in critically ill COVID‐19 patients), that is being conducted in Intensive Care Medicine Department of a Portuguese University Hospital. Patients >60 years, admitted due to COVID‐19‐associated Pneumonia, were included. Exclusion criteria were: Intensive Care Unit (ICU) length of stay (LoS)≤24h, terminal illness, major sensory loss or inability to communicate at the time of follow‐up. Participants were evaluated with Six‐item Cognitive Impairment Test (6CIT) by telephone. Baseline demographic, clinical and in‐hospital data were collected, including sedation, respiratory support, major complications and LoS. Patients with and without CD after‐discharge were compared.ResultsThirty‐two patients were included, with a median age of 72(IQR:64‐76) years, mostly were male (66%) and none had previous clinical registry of cognitive impairment or dementia. Nosocomial infection (75%) and difficult weaning from MV (63%) were the most frequent complications. Deep sedation was used in 81% of the patients (median=20 days; IQR:15‐42). About 81% needed IMV and 13% were supported with Extracorporeal Membrane Oxygenation (ECMO). Median ICU and hospital LoS were 29(IQR:144‐56) and 66(IQR:33‐102) days, respectively. Follow‐up assessment occurred 93.4 days (IQR:68‐120) after‐discharge. Based on 6CIT, 16% of survivors had CD. Comparing both groups, those with CD were older (73vs.64; p=0.020), had a higher duration of IMV (73vs.22; p=0.017) and mostly were supported with ECMO (75%vs.25%; p=0.008).ConclusionData suggest that CD is more frequent among older COVID‐19 survivors, and those who needed prolonged IMV and ECMO support. Despite full clarification of all mechanisms involved, these findings highlight the importance of a timely and organized post‐intensive care response composed by multidisciplinary teams to optimize assistance to survivors of critical illness.
APOE‐ε4 status moderates the relationship between body mass index and hippocampal structure in older African Americans
Authors: Fausto Bernadette A. , Osiecka Zuzanna , Gluck Mark A. 
Published: February 2022

AbstractBackgroundGrowing evidence suggests that traditional body mass index (BMI) cutoff values may overestimate adiposity and its health consequences in African Americans. Further, while obesity disproportionately affects African Americans, obesity is inconsistently associated with Alzheimer’s disease (AD) in older adulthood. Examining the influence of BMI and its interaction with the strongest genetic risk factor of AD, the APOE‐ε4 allele, on hippocampal‐dependent cognitive performance and medial temporal lobe (MTL) structure may provide insights into the complex relationship between obesity and AD in older African Americans.MethodAnalyses included 70 cognitively normal older African Americans (mean age=69.50 years, SD=7.18; mean education=14.12 years, SD
2; 38.60% APOE‐4 allele carriers) who completed cognitive testing, saliva sampling for APOE genotyping, and structural neuroimaging to extract MTL cortical region/hippocampal subfield volumes and surface areas. Cognitive tests included the following measures of generalization and episodic memory: Concurrent Discrimination and Transfer Task, Acquired Equivalence Task, and Rey Auditory Verbal Learning Test. ANCOVAs were used to compare BMI groups (normal: 18‐24.9 kg/m2; overweight: 25‐29.9 kg/m2; class 1 obesity: 30‐34.9 kg/m22) and to test for BMIxAPOE interactions on cognitive and neuroimaging outcomes, while controlling for age, sex, education, literacy, and depressive symptomology.ResultThere was a statistically significant difference between BMI groups on Concurrent Discrimination and Transfer Task performance, p=.01, partial η
2=.18. The normal and class 2 obesity group committed significantly greater errors than either the overweight or class 1 obesity group, ps < .05. Significant BMIxAPOE interactions were identified for the following hippocampal subfield volumes and surface areas: left DG/CA3 and left CA1, ps < .05. For APOE‐ε4 non‐carriers, the normal BMI group had significantly smaller left DG/CA3 and CA1 subfields than the other groups. Among APOE‐ε4 carriers, the class 2 obesity group had smaller left DG/CA3 and CA1 subfields than the other groups.ConclusionBeing overweight may confer cognitive protection in older African Americans. However, obesity appears to be selectively detrimental to hippocampal subfield structure among APOE‐ε4 carriers while normal BMI may be deleterious to hippocampal subfield structure among APOE‐ε4 non‐carriers.
Characterizing communication in dementia family caregiving: Identifying breakdown and repairs using the trouble source repair (TSR) framework via video observations
Authors: Coleman Carissa K , Williams Kristine N , Berkley Amy , Dunham Ashlyn , Savundranayagam Marie Y 
Published: February 2022

AbstractBackgroundFamilies who provide care at home for people living with dementia (PLWD) are an integral part of dementia care worldwide and improving in‐home care is crucial. Communication is fundamental for daily care and communication breakdown presents additional stress to the caregiver‐PLWD dyad. In order to identify effective strategies that will minimize communication breakdown, we adapted the Trouble Source Repair (TSR) framework, a linguistic tool, to create a second‐by‐second behavioral coding scheme for video observations. This pilot study used the adapted TSR coding scheme to reliability identify communication breakdown and repair.MethodThis pilot study analyzed videos from a randomized controlled trial of a family caregiver telehealth intervention (FamTechCare). The videos were created by caregivers in their home, providing observations of natural caregiver‐PLWD interactions across a variety of daily care activities. Operational definitions from the TSR were adapted to create a coding scheme (Table 1). Video data collection and analysis were completed using Noldus software. Two independent coders obtained reliability.ResultThe video sample includes 51 dyads with 201 videos averaging 5.8 minutes in length. Caregivers were primarily female (80%), mean age 65 years, and were mostly a spouse (69%) while the PLWDs were primarily male (55%) with moderate to severe dementia (64.7%). The mean interrater reliability was excellent; Kappa = .93. Preliminary descriptive results (n=106) indicate 53.7% of the dyad communication was interactive, 8% was communication breakdown, and the remainder was silence or talking to others. During a typical breakdown sequence, the caregiver’s communication creates the breakdown (Trouble Source, 67%), the PLWD indicates not understanding (Flag, 71%) and the caregiver initiates the Repair (72%). Breakdowns were successfully resolved 71% of the time. Types of trouble sources, flags, and repairs can be seen in Table 2.ConclusionThe results support the use of the adapted TSR framework to reliability identify communication breakdowns via video observation. Future analyses will identify the most effective strategies to prevent and repair communication breakdown as well identify how strategies varies by dementia stage, diagnosis, and dyad characteristics.
Improvement in distinct cognitive functions between tablet PC and workbook in the SUPERBRAIN study
Authors: Park Hee Kyung , Na Hae Ri , Jeong Jee Hyang , Moon So Young , Hong Chang Hyung , Park Yoo Kyoung 
Published: February 2022

AbstractBackgroundWe aimed to compare the effect in cognition according to the type of cognitive training in the SUPERBRAIN study, a 24‐week multi‐domain lifestyle intervention program to prevent dementia.MethodBoth cognitive training programs, targeting five or six cognitive domains, were conducted in a group session or individually at home. The primary outcome was the change in the total scale of index score of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) after 6 months of training. Analysis of covariance was used to compare the index score of the RBANS between the three groups.ResultThere were significant improvements in the total scale index score (adjusted mean of change of the score, standard error; 6.2, 1.3; controls, ‐1.3, 1.6; p <0.001), attention (2.0, 1.3; controls, ‐2.0, 1.7; p=0.020), and delayed memory (9.9, 1.3; controls, 4.9. 1.8; p=0.014) in the tablet PC group compared to control group. The degree of improvement in immediate memory (6.4, 1.5; p=0.029) was larger in tablet PC group compared to the workbook group (0.1, 2.1). Improvement in visuoconstruction (1.2, 2.5; controls, ‐9.4, 2.3; p=0.002) was shown in the workbook group compared to the control group.ConclusionThe degree of improvement in total scale index score of the RBANS, immediate and delayed memory, and attention was more pronounced in the tablet PC group compared to the control group or workbook group. The workbook group displayed a larger degree of improvement in visuoconstruction compared to the control group. These findings implicate that cognition can be improved through cognitive training programs in at‐risk population and cognitive training programs using tablet PC or workbook seem to show improvement in different cognitive functions.
Practising brain health through traditional teachings and arts: A project funded by the Centre for Aging and Brain Health Innovation
Authors: Legare Marlin 
Published: February 2022

AbstractBackgroundThe loss of Indigenous culture in Canada through colonial interventions such as Residential Schools and the 60’s Scoop have left Indigenous Peoples and communities with deep‐rooted trauma. This type of trauma, in addition to the social isolation of living in remote communities, places Indigenous populations at risk for developing dementia. There is a need to increase opportunities for aging Indigenous populations to engage in social interaction that is culturally‐relevant and based in Traditional ways and culture.MethodMorning Star Lodge, an Indigenous Health Research lab, has developed workshops for aging Indigenous adults who are at risk for developing dementia and their caregiver(s) to engage in traditional activities such as: games, arts and crafts, prayer (smudging). Research circles were conducted with Indigenous community members aging in place along with their caregiver(s) to discuss their perceived impacts on social functioning and cognitive health.ResultThe community members engaged in social interaction through Indigenous languages and story‐sharing. Traditional Knowledges and teachings were also weaved into the project design as many aging individuals expressed a feeling of isolation from cultural events and ceremonies due to immobility or lack of assistance with transportation, other needs, and the COVID‐19 pandemic. Through the data collected via an Indigenous, community‐led qualitative data analysis method the research team was able to identify central themes regarding practising Traditional arts and the cognitive health benefits that caregivers would like integrated in their communities.ConclusionFurther research is needed to evaluate the long‐term benefits of health outcomes for Indigenous Peoples living with dementia and the effects on caregiver stress. Indigenous caregivers have expressed a desire for Traditional arts and teachings in their communities to alleviate stressors caused by dementia.
Neuroanatomical signatures of genetic risk for Alzheimer's disease in healthy adults
Authors: Waters Sheena , Watson Cameron , Jacobs Benjamin M. , Foote Isabelle F. , Dey Sumit , Noyce Alastair J. , Marshall Charles R. 
Published: February 2022

AbstractBackgroundEarly detection of Alzheimer’s disease (AD) is critical for the development of interventions that delay or prevent neurodegeneration. Previous studies suggest that genetic liability to AD may be associated with structural brain changes that start 20‐30 years before symptoms manifest.MethodWe derived an optimised AD polygenic risk score (AD‐PRS) using imputed genotype data from 488,377 participants in UK Biobank. We examined the structural brain correlates of AD‐PRS in 27,496 healthy UK Biobank participants using voxel‐based morphometry (VBM) with multiple regression and additionally performed regression analyses using image‐derived phenotypes (IDPs) from T1‐weighted and diffusion‐weighted magnetic resonance images.ResultVBM revealed that high AD‐PRS was associated with reduced grey matter volume (GMV) in bilateral hippocampus and putamen (family wise error correction, p<0.05). IDP analysis further revealed GMV deficits in a bihemispheric limbic network incorporating hippocampus, parahippocampal gyrus, ventral striatum, orbitofrontal cortex, and thalamus, as well as reduced white matter integrity in the major white matter tracts of this network (fornix, cingulum hippocampus, and thalamic radiation).ConclusionGenetic liability to AD is associated with preclinical neurodegeneration in grey and white matter components of the limbic system. Integrity of this network could serve as a marker of preclinical AD and an outcome measure in prevention trials.
Multi‐center study of regulation of cerebral perfusion using spontaneous time‐series data shows impairment of CO2 vasoreactivity in MCI & AD patients
Authors: Marmarelis Vasilis , Billinger Sandra A. , Chui Helena C. , Joe Elizabeth B. , Shin Dae , Cardim Danilo , Hashem Suhaib , Kaufman Carolyn S. , Cullum Munro , Kelley Brendan , Zhang Rong 
Published: February 2022

AbstractBackgroundThree AD Centers have joined together to study the regulation of cerebral perfusion at resting conditions using spontaneous time‐series data with a modeling methodology that previously yielded indications of reduced dynamic vasomotor CO2 reactivity in amnestic MCI patients [Marmarelis et al., J. Alzh. Dis. 56:89–105, 2017] and significant correlation of this reduction with functional impairment of the chemoreflex in these MCI patients [Marmarelis et al., J. Alzh. Dis. 75:1‐16, 2020]. The goal of this multi‐center study is to confirm these preliminary findings with larger cohorts of MCI patients, AD patients and age‐matched cognitively normal controls (NC), and to examine the time‐course of these impairments with longitudinal data over 5 years.MethodQuantitative results were obtained through dynamic modeling of the effects of spontaneous changes in arterial blood pressure (ABP) and end‐tidal CO2 (etCO2) upon cerebral blood flow velocity (CBFV) in the middle cerebral arteries measured via transcranial Doppler. The obtained subject‐specific input‐output predictive models were used to compute indices (physio‐markers) that quantify the Dynamic Vasomotor Reactivity (DVR) in each subject/patient and to compare differences between NC, and MCI/AD patients.ResultThe obtained DVR indices were significantly different for patients (9 MCI and 4 AD taken together due to small numbers) vs. 32 controls (p=0.026). Notably, the delineation between patients and controls improved (p=0.009) after a session of slow paced‐breathing (8 breaths/minute) that led to larger average DVR for controls and to reduction of inter‐subject variability of DVR indices. This is illustrated in Figure 1, where the average model‐predicted responses (representing the CBFV response to a unit‐step change of etCO2) are shown for 13 MCI/AD patients (red line) and 32 controls (blue line) before and after the paced‐breathing session. Further improvement in delineating patients from controls is achieved (p=9x10‐5) when the DVR indices from the two sessions were averaged for each subject/patient.ConclusionSignificantly lower DVR index under resting spontaneous conditions was observed in 13 MCI/AD patients relative to 32 NC before (p= 0.026) and after (p=0.009) slow paced‐breathing session. Averaging of the DVR indices obtained from data before and after paced‐breathing improved substantially this delineation (p=9x10‐5).
Technology use and attitudes among individuals with mild cognitive impairment and their care partners
Authors: Vickers Kayci L , Saurman Jessica L , Goldstein Felicia C 
Published: February 2022

AbstractBackgroundDuring the COVID‐19 pandemic, the shift toward telehealth has drastically increased providers’ need to quickly gauge patient comfort with various technologies, especially for older individuals exhibiting cognitive impairments. Existing measures require significant training for administration and scoring, and do not include many technologies in use by older adults (e.g., social media or common smart phone applications). The present study aimed to adapt the Everyday Technology Use Questionnaire (ETUQ) to be self‐administered by individuals with MCI and their Care Partners.MethodTwelve older adults with MCI (Mean Age= 74.1, SD= 8.4) and 10 Care Partners (Mean Age= 69.0, SD= 8.2) completed the 28‐item ETUQ and a Technology Attitudes Questionnaire (TAQ). The adapted ETUQ lists different technologies (e.g., television, smart phone, ride share apps). Participants were asked to rate their comfort using these technologies on a scale from 1 to 6, with higher ratings indicating greater comfort.ResultTotal scores in the MCI group ranged from 72 to 168 (Mean= 129.3, SD= 31.2) and in the Care Partners ranged from 137 to 162 (Mean= 149.2, SD=9.9). Independent samples t‐tests revealed a trend in ETUQ scores, wherein individuals with MCI reported lower overall comfort with technologies than care partners, t(13.6)= ‐2.09, p = .056. This represented a large effect size, d= 0.83. Items rated lower by individuals with MCI included: ride share apps (Lyft or Uber), Fitbit or activity trackers, social media (e.g., Facebook), Skype or video call, and WIFI routers. Analyses revealed no significant differences in age, attitudes toward technology or dependence on technology between groups.ConclusionThese results support the use of an adapted ETUQ for individuals with MCI and their care partners. Interestingly, these ratings suggest individuals with MCI feel less comfortable with complex technology than their care partners, possibly reflecting cognitive difficulties. Future directions include validation of the adapted ETUQ and correlation to real‐world behaviors through in‐home monitoring.
Data‐driven staging and subtyping of genetic frontotemporal dementia using multi‐modal MRI
Authors: McCarthy Jillian , Medina Yasser Iturria , Ducharme Simon ,   for the GENetic Frontotemporal dementia Initiative (GENFI)
Published: February 2022

AbstractBackgroundFrontotemporal dementia is a highly heterogeneous disorder and neurodegeneration begins years prior to symptom onset, complicating disease understanding and treatment. Here we used an unsupervised machine learning algorithm to identify disease sub‐trajectories in genetic frontotemporal dementia.MethodThe contrastive trajectory inference (cTI, available at neuropm‐lab.com/neuropm‐box.html) is a method to analyze temporal patterns in multi‐dimensional populational datasets, consisting of unsupervised feature selection, contrastive prinicipal component analysis and subject ordering to obtain individual disease severity scores and distinct subtypes. We applied the cTI to cross‐sectional MRI data (gray matter density, T1/T2 ratio, fALFF, gray matter fractional ansiotrophy and mean diffusivity) from 383 gene carriers (269 presymptomatic and 115 symptomatic) from the GENFI study (148 with C9orf72 expansions, 169 with GRN mutations, and 67 with MAPT mutations) and a control group of 253 non‐carriers. The cTI was applied to all modalities in combination and individually. We compared the obtained disease severity scores to the estimated years to onset (EYO; age ‐ mean age of onset in relatives), clinical, and neuropsychological test scores. cTI subtypes were compared to genetic variants, as gene variants have specific pathology and group‐level differences in neuroimaging.ResultThe cTI identified disease severity scores were significantly correlated with all clinical and neuropsychiatric tests (measuring behavioural symptoms, attention, memory, language, and executive function) for all modalities, in combination and individually, and for the EYO for all modalities except mean diffusivity. The combination of all modalities provided the best overall results (CBI: r = 0.581, p < 0.001; EYO: r = 0.321, p < 0.001) (figure 1). Among individual modalities, gray matter density performed best (CBI: r = 0.475, p < 0.001; EYO: r = 0.286, p < 0.001). The cTI did not recover the three genetic variants, instead assigning most gene carriers (> 80%) to subtype 1 (figure 2). The cTI distinguished non‐carriers from carriers (87% of non‐carriers are in subtype 2).ConclusionThe cTI can identify disease severity in a heterogeneous sample of genetic FTD using only neuroimaging metrics. It is unable to uncover genetic variants, suggesting that genetic variants may have similar neuroimaging features at early presymptomatic stages.
Baseline biomarker (tau PET) characteristics from TANGO: A phase 2 trial of gosuranemab (BIIB092) in early Alzheimer's disease
Authors: Racine Annie M. , Rajagovindan Raj , Collins Jessica A. , Kong Jessica , Li Yumeng , O'Gorman John , Jones Stephanie , Graham Danielle , Ratti Elena , Shulman Melanie 
Published: February 2022

AbstractBackgroundGosuranemab is a humanized monoclonal antibody that is hypothesized to neutralize extracellular tau and prevent the trans‐neuronal propagation of tau pathology across the brain. The TANGO study is an ongoing randomized, placebo‐controlled, global Phase 2 study evaluating safety and clinical efficacy of gosuranemab in individuals diagnosed with mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) or mild AD dementia. The TANGO study included two biomarker sub‐studies: cerebrospinal fluid (CSF) sub‐study and Tau positron emission tomography (PET) sub‐study; the baseline characteristics of the Tau PET sub‐study are described below.MethodTANGO enrolled 654 individuals aged 50‐80 years, diagnosed with MCI or mild AD, who were amyloid positive as assessed by amyloid PET or CSF testing. Approximately 350 patients enrolled in the longitudinal 18F‐MK‐6240 Tau PET sub‐study. Randomization was stratified by biomarker sub‐study participation among other factors. Baseline standardized uptake value ratio (SUVR) was measured in composite brain regions of interest (ROIs) corresponding to Braak I‐II, Braak III‐IV, and Braak V‐VI regions using superior‐eroded cerebellum as the reference region. Tau extent (percentage of supra‐threshold voxels within an ROI relative to reference region), an exploratory measure of the spatial extent of 18F‐MK‐6240 binding, was also investigated.ResultThe baseline demographics of the Tau PET sub‐study population were consistent with the overall TANGO study population including clinical stage (MCI vs. mild AD), age, gender, APOE4, and clinical scores. At baseline, average SUVR (±SD) was 1.92±0.6 in Braak I‐II, 1.90±0.7 in Braak III‐IV and 1.75±0.8 in Braak V‐VI composite ROIs. The Braak composite SUVRs were positively associated with disease stage (i.e. higher SUVR with increasing disease severity). Exploratory analyses of extent were supportive of the SUVR results.ConclusionAt study baseline, tau SUVR was highest in Braak I‐II, followed by Braak III‐IV, then Braak V‐VI. Cross‐sectionally, higher tau PET SUVR was associated with increasing disease severity and worse clinical scores, as expected. The TANGO Tau PET sub‐study will aid our understanding of gosuranemab’s effect on tau pathology and further inform on the value of tau PET in clinical trials.