bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal changes in the brain language system as amyloid accumulates
Authors: Reinartz Mariska , Gabel Silvy , Schaeverbeke Jolien , Luckett Emma Susanne , Van Laere Koen , Sunaert Stefan , Dupont Patrick , Vandenberghe Rik 
Published: February 2022

AbstractBackgroundLanguage dysfunction is common in Alzheimer disease (AD). There is increasing interest in the preclinical phase of AD. Here we tested longitudinally how activity in the associative‐semantic language network, measured with task‐based fMRI, changes in relation to increases in amyloid load, measured with 18F‐flutemetamol and 11C‐PIB. The main hypothesis was that an increase in amyloid would be associated with changes in activity in left or right posterior superior temporal sulcus (STS) and/or medial temporal gyrus (GTm).MethodA cohort of 35 cognitively intact older adults (mean age=65.4; range: 52‐78 years, 54.3% APOE‐ε4) participated who all received a task‐based fMRI and amyloid PET in 2009‐2011 and a repeat scan for both modalities in 2016‐2017. As primary analysis, we examined how longitudinal change in amyloid, measured using Centiloids (CL), relates to longitudinal activation change in the posterior temporal nodes of the associative‐semantic language network. The left and right posterior STS and GTm were defined as regions of prior interest using the Fan Brainnetome atlas, based on prior studies in amnestic mild cognitive impairment (MCI) and clinically probable AD using the same functional paradigm (Nelissen et al., 2007; Vandenbulcke et al., 2007; Adamczuk et al., 2016). Within this VOI, significance was determined based on SPM12 small volume correction. As a secondary analysis, we also performed a voxelwise whole‐brain analysis with a FWE whole‐brain corrected threshold <0.05. We also examined how the change in amyloid and the change in fMRI activation related to changes in offline language measures.ResultIn the right posterior STS, the change in response amplitude during the associative‐semantic versus the visuoperceptual task showed a positive correlation with the change in amyloid load (x=51 mm, y=‐31 mm, z=5 mm; Z=3.47, Pcorr=0.010; Fig. 1). The change in response amplitude also correlated with longer offline confrontation naming reaction times (RT; r=0.42, P=0.035; Fig. 2). In addition, in the whole‐brain analysis we observed a decrease in response in the right inferior frontal sulcus with increasing amyloid load (x=3 mm, y=20 mm, z=56 mm; Z=4.64, Pcorr=0.021).ConclusionThis study confirms the central role of the posterior STS as area of predilection in the earliest stages of AD.
A hippocampal hyperactivity signature observed in cognitively normal APOE4 carriers using deep learning for functional enhancement of structural brain MRI scans
Authors: Nuriel Tal , Guo Jia 
Published: February 2022

AbstractBackgroundAlzheimer’s disease (AD) affects millions of Americans and represents a significant and growing public health crisis. Despite this fact, there are currently no approved disease‐modifying therapies that are able to slow or prevent AD pathogenesis. One important reason for this is that most AD drug trials were performed on patients who had already begun to show significant cognitive decline, which is already well after the accumulation of AD pathology begins. For this reason, there is an urgent need to identify biomarkers that can help to identify which individuals will eventually develop AD, prior to the occurrence of irreversible pathological damage in the brain.MethodIn order to aid in these efforts, we have developed a novel deep‐learning method called DeepC, which is capable of extracting functional information from structural MRI scans. This functional extraction is performed with the help of prior training of the model with Gadolinium contrast‐enabled functional MRI scans, which allows DeepC to identify and amplify existing tissue/blood contrast information that is already embedded within T1w structural MRI scans, but which is otherwise imperceptible to the human eye. As an initial test of this DeepC method, we have analyzed the functional signals from publicly available T1w MRI scans in the ADNI database, focusing on APOE4 carriers and non‐carriers who were cognitively normal at the time of the scans.ResultWe observed increased "activity" in multiple brain regions of cognitively normal APOE4 carriers versus non‐carriers. Importantly, we observed a distinct "hyperactivity" signature in the hippocampus of the APOE4 carriers, which is consistent with previous studies. Furthermore, this hippocampal "hyperactivity" was also significantly correlated with the presence of other AD biomarkers present in these individuals.ConclusionWe believe that this DeepC method may represent an important new biomarker tool that will allow clinicians and clinical trials to better identify at‐risk individuals long before the pathological effects of AD become irreversible. In addition, we believe that the functional data uncovered from these structural MRI scans can also be utilized to further inform us on the mechanisms responsible for AD pathogenesis, especially with regards to APOE4 carriers.
Psychosocial effects of Corona virus measures on (pre‐)dementia patients during 2nd lockdown
Authors: Bakker Els D , Van Maurik Ingrid S , Mank Arenda , Zwan Marissa D , van den Buuse Susanne , van den Broeke Jennifer R , Gillissen Freek , van de Beek Marleen , Lemstra Evelien , van den Bosch Karlijn A , van Leeuwenstijn Mardou , Bouwman Femke H , Scheltens Philip , van der Flier Wiesje M 
Published: February 2022

AbstractBackgroundThe COVID‐19 pandemic poses enormous social challenges, especially during lockdown. Recently, the second lockdown started in the Netherlands. We aimed to investigate and compare the psychosocial effects of corona measures during lockdown in memory clinic (pre‐)dementia patients and their caregivers.MethodDuring second lockdown, n=137 symptomatic patients (age=67.7±6.54, 36.5%F, MMSE = 24.4±4.7; n=82 dementia, n=55 MCI), n=244 cognitively normal (age=63.6±7.56, 38.9%F, MMSE = 28.8±1.18; SCD) and n=198 caregivers of Alzheimer Center Amsterdam completed a survey on psychosocial effects of corona. Questions related to loneliness, worries for faster cognitive decline, psychological and behavioral problems. In a subset of patients (n=169) and caregivers (n=38) we were able to compare their answers to answers on a similar survey completed during first lockdown (May 2020).ResultIn total, n=17 (4.5%) patients [n=3 (2.2%) symptomatic, n=14 (5.7%) cognitively normal] and n=8 (4%) caregivers reported a positive test result for COVID‐19. Over one‐third of caregivers reported worries for faster cognitive decline [n=76 (38%)] and behavioral problems [n=70 (35%)] in patients. Feelings of loneliness were experienced by n=23 (17%) symptomatic patients, n=44 (18%) cognitively normal and n=50 (25%) caregivers. One quarter of patients [n=78 (25%)] reported more depressive feelings during lockdown [n=27 (20%) symptomatic, n=51 (21%) cognitively normal]. More feelings of fatigue were reported by n=23 (17%) symptomatic patients, n=46 (19%) cognitively normal, and n=67 (34%) caregivers. Comparing results to those obtained during the first lockdown, feelings of loneliness [Χ2=26.4, p<.001 in patients, Χ2=10.3, p<.001 in caregivers] and anxiety [Χ2=25.9, p<.001 in patients, Χ2=6.69, p=.010 in caregivers] increased. During second lockdown, less feelings of apathy [Χ2=13.0, p<.001], but more depressive feelings [Χ2=27.6, p<.001] were reported in patients compared to first lockdown. Caregivers were more worried for memory decline in patients during second lockdown [Χ2=4.09, p=.043].ConclusionCompared to first lockdown, feelings of loneliness, anxiety, worries for faster cognitive decline and depressive feelings increased in second lockdown. A noticeable part of (pre‐)dementia patients and caregivers report feelings of loneliness, worries for faster cognitive decline, psychological and behavioral problems in second lockdown. These psychosocial effects are more frequently reported by caregivers than patients.
Glucose metabolism changes in cerebellar tonsils as an early predictor of cognitive decline
Authors: Dartora Caroline Machado , Koole Michel , da Silva Ana Maria Marques 
Published: February 2022

AbstractBackgroundMild cognitive impairment (MCI) is associated with an increased risk of dementia, but imaging biomarkers are not clearly related to the likelihood of developing cognitive decline. This preliminary study aims to investigate the brain glucose metabolic PET imaging patterns in subjects that are cognitively unimpaired older adults (CUI) and those who convert to MCI within two years.MethodCUI subjects with 18F‐FDG PET and MR images were selected from the ADNI study. Two groups were separated in our research: (i) 36 stable CUI subjects during a minimum of 5 years; (ii) 12 subjects initially cognitively unimpaired (preCONV) that convert to MCI within two years (posCONV). Static 18F‐FDG PET images were co‐registered with the correspondent MR image and normalized to MNI space with an 8 mm Gaussian filter. A normalized whole‐brain (WB) mask was determined. Each PET was normalized by its WB mean value. Image analysis was performed using SPM 12, with proportional scaling and age‐corrected. Groups have no difference in age (79.5±5)y and years of education (15.8±3)y. Brain glucose hyper‐ and hypometabolism were evaluated between groups (CUI versus preCONV, CUI versus posCONV) and longitudinally (preCONV versus posCONV).ResultThe cluster analysis (p(unc)≤0.001) of CUI subjects when compared to preCONV shows brain glucose hypometabolism in the cerebellar tonsil and putamen regions, and infero‐medial temporoparietal lobe, and hypermetabolism in the left parietal and right temporal and frontal lobes. CUI shows hypometabolism compared to posCONV in regions of the left and right cerebellar tonsil, culmen, frontal lobe, Brodmann Area (BA) 6 and midbrain, and hypermetabolism in the parietal lobe, including the precuneus and BA39. No differences are found between preCONV and posCONV.Just hypometabolism in cerebellar tonsil in CUI compared to preCONV and posCONV survived correction for multiple comparisons (cluster p(FWE)≤0.05), showing a possible involvement in the cognitive decline beginning. Recent evidence suggests the cerebellum's involvement in the regulation of cortical areas associated with cognition as an abnormal structure in cingulo‐cerebellar circuitry (Walsh K., PARKER, K.L., 2018).ConclusionBeyond brain regions of altered glucose metabolism in cognitive decline like parietotemporal regions, cerebellar tonsil shows changes that could indicate early conversion of cognitively unimpaired older adults to MCI.
The troubles and needs of family caregivers of older adults with moderate to severe dementia
Authors: Leng Minmin 
Published: February 2022

AbstractBackgroundTo investigate the troubles and needs of family caregivers of older adults with moderate to severe dementia.MethodA total of 401 family caregivers from Beijing, Tianjin and other regions were recruited to complete a self‐designed questionnaire.ResultThe top 5 safety risks among older adults with moderate to severe dementia were irritating cough (30.2%), falls (28.4%), outreach (27.2%), lost (19.0%), and fall of bed (12.2%). The main troubles reported by family caregivers were daily care (82.5%) and coping with psychological and behavioral problems (51.9%). The top five support needs were instruction on psychological adjustment skills (88.5%), skills to cope with psychological and behavioral problems (75.8%), daily care skills (73.1%), safety risk prevention skills (72.8%), case management and referral services (70.8%). The top five ways to access support services were online training (86.5%), online counseling (86.0%), face‐to‐face counseling (84.0%), handbooks (78.8%) and community‐based lectures (74.6%).ConclusionFamily caregivers have a variety of needs in the long‐term care of older adults with dementia. It is suggested to establish a needs‐led care support service system for family caregivers that integrates skills instruction, education and training and care services by online and off‐line approaches.
Cross‐sectional comparison of psychosocial and executive function outcomes between low and high adherers of the MIND diet in a sample of middle‐aged Latinos
Authors: Soto Yuliana , Guzman Jacqueline , Aguiñaga Susan 
Published: February 2022

AbstractBackgroundIt is estimated the number of Latinos with Alzheimer’s disease (AD) will reach 3.5 million by 2060.1 Evidence suggests that lifestyle factors, such as adhering to diets like the Mediterranean‐type diet and the Mediterranean‐DASH Intervention for Neurodegenerative Delay (MIND) diet may be associated with lower risk of AD2, improved cognition3, and better psychosocial outcomes.4 The purpose of the present study was to compare psychosocial outcomes and executive function (EF) between low and high adherers of the MIND diet in middle‐aged Latinos.MethodA cross‐sectional study was conducted to assess MIND diet adherence, cognition, and psychosocial outcomes of middle‐aged Latinos. The MIND Diet consists of 15 food groups, 10 healthy food items and 5 unhealthy food items. Adherence to the MIND diet was assessed using the 114‐item Block 2005 Food Frequency Questionnaire.5 Frequency of consumption of each food item was assigned a score of 0,.5, or 1, scores ranged between 0‐15. MIND diet scores were dichotomized between low‐adherers (< 8.5) and high‐adherers (≥ 8.5). NIH Toolbox was used to assess psychosocial outcomes (stress, depressive symptoms, general life satisfaction, and loneliness). EF was measured as a composite score of the Trail Making6, Stroop7, Symbol Digit Modalities8, and word fluency9 cognitive tests. One‐way analysis of variance (ANOVA) was conducted to compare psychosocial outcomes and EF between low and high adherers.ResultData from 61 participants (Mage=58.6±8.7, MMMSE=27.93 ±2.28, 67% female) indicates that high‐adherers self‐reported significantly higher general life satisfaction (F[1,58] =11.16, p=.001, MSE=382.05, η
2=0.19) and lower stress levels (F[1,58]=3.88, p=.05, MSE=146.25, η
2=0.06). However, no significant differences between low and high adherers were detected for depressive symptoms, loneliness, or EF.ConclusionFindings suggest that middle‐aged Latinos adhering to the MIND diet exhibit lower levels of stress and higher general life satisfaction. However, no difference was detected in depressive symptoms and EF. Future interventions should consider culturally‐tailoring the MIND diet to increase adherence and acceptability of it to improve psychological distress and cognitive function among middle‐aged Latinos to reduce the risk of AD.
Association between cancer treatment and progression of all‐cause dementia
Authors: Fowler Mackenzie E , Kennedy Richard E , Wright Nicole C , Irvin Marguerite R , Triebel Kristen L , Rocque Gabrielle B 
Published: February 2022

AbstractBackgroundCancer treatments have been associated with cancer‐related cognitive impairment (CRCI). CRCI exhibits symptoms similar to those experienced with dementia syndromes, and could result from the cancer itself or as a consequence of cancer therapies. No studies have examined the potential effect of cancer treatments on cognition in dementia.MethodElectronic health record data from the University of Alabama at Birmingham were extracted July 2003 to February 2020. Baseline cognition and cognitive progression on the Alabama Brief Cognitive screener (ABCs) among dementia patients based on receipt of various cancer treatments were evaluated using adjusted linear mixed effects models.ResultHormone therapies were associated with faster decline on the ABCs compared to other treatments (b: ‐1.39, 95% CI: ‐2.73, ‐0.04). Similar results were seen for hormone therapies compared to neither hormone nor immunotherapy (b: ‐1.55, 95% CI: ‐3.02, ‐0.08). No cognitive differences were detected for other cancer treatments.ConclusionHormone therapies may lead to faster cognitive decline in cancer survivors who develop dementia later in life. Larger studies of long‐term effects of cancer therapies are needed to allow for stratification by cancer type and cancer staging and evaluate modification by race and socioeconomic status.
Altered brain functional connectivity and cardiovascular and metabolic risk factors in middle‐aged and older adults
Authors: Rashid Barnaly , Schwab Nadine A. , Carlyle Becky C. , Terpstra Melissa , Bookheimer Susan Y. , Ances Beau M. , Salat David H. , Arnold Steven E. 
Published: February 2022

AbstractBackgroundMetabolic and cardiovascular dysfunction accelerates biological aging and increases risk for many diseases, including Alzheimer's disease (AD) and AD‐related dementias (ADRD). The cumulative negative effects that the body and brain sustain due to the exposure to metabolic (e.g., insulin resistance, dyslipidemia), cardiovascular (e.g., blood pressure), and immune (e.g., C‐reactive protein) risk factors (i.e., MCI‐RFs) have been associated with increased vulnerability to cognitive decline later in life. This project examined whether the functional connectivity (FC) measures of core brain networks are altered due to MCI‐RFs, and how such alterations may relate to cognitive functioning.MethodResting fMRI scans were collected in 217 participants (aged 36‐90+ years) of the Human Connectome Project Aging study, and preprocessed using FreeSurfer’s standard stream. Using a seed‐based approach functional maps of the default mode network (DMN), amygdala, and hippocampus seeds were created. The vertex‐wise partial correlation (i.e., FC) measures to the seeds (i.e., correlation between mean seed time series and all other brain voxels’ time series, later transformed onto cortical surface) were computed and used for further group‐level analyses. Connectomes were evaluated in relation to a MCI‐RF index (higher index score corresponds to greater risk) including measures of body mass index, insulin and glucose, lipids, blood pressure, renal function, nutritional parameters and C‐reactive protein. Cognition was assessed using a multi‐domain composite index (CCI) encompassing aspects of general cognition, memory, processing speed, and executive functioning.ResultWith increasing age, all three networks showed reductions in network integrity with loss of both within‐network and between‐network functional connections in regions outside of the task‐positive network hubs. After correcting for age effects, associations between FC and MCI‐RF index were mostly observed in the DMN and amygdala. Increased MCI‐RF was associated with reduced negative connectivity (i.e., loss of between‐network connections) in amygdala map, suggesting less regulated networks. Associations with CCI were observed across all three networks’ FC maps but mostly in the amygdala.ConclusionOur findings suggest that MCI‐RFs impact brain network organization, and that connectivity in the amygdala network might be a key to the interface between metabolic, cardiovascular and immune dysfunction and cognition.
Synaptic PET imaging using [11C]UCB‐J in frontotemporal dementia
Authors: Clarke Mica TM , Mansur Ayla , Rizzo Gaia , Passchier Jan , Lewis Yvonne , Evans Karleyton C , Chen Laigao , Schwarz Adam J. , Takano Akihiro , Gunn Roger N , Cash David M , Rabiner Eugenii A. , Rohrer Jonathan D ,   MINDMAPS Consortium
Published: February 2022

AbstractBackgroundA number of pathophysiological mechanisms are associated with neurodegeneration, including synaptic dysfunction and/or loss. Novel radiotracers which enable the quantification of synaptic proteins in vivo have not previously been explored in frontotemporal dementia (FTD). We used [11C]UCB‐J PET to measure the density of synaptic vesicle protein 2A (SV2A) in FTD.MethodSix participants with behavioural variant FTD (mean age 61.8, SD 5.4) and 17 cognitively normal participants (63.7, 12.5) underwent 90‐minute dynamic acquisition PET scans following injection of [11C]UCB‐J, with metabolite corrected arterial input function. Thirteen regions of interest (ROIs) were defined on individual MR images using the CIC anatomical atlas. Regional density was evaluated using the regional VT normalised to the VT in the centrum semiovale (DVR‐1). Groups were compared using Mann‐Whitney tests with Bonferroni correction for multiple comparisons. W‐scores were computed from the 17 controls, with age and gender as covariates, to compare the magnitude of group differences in regional volumes versus [11C]UCB‐J distribution. Volumes were expressed as a percentage of total intracranial volume. A w‐score of <‐1.65 was considered abnormal.ResultWe found significant reductions in regional density of SV2A in FTD compared to controls in multiple cortical and subcortical regions: frontal, temporal, parietal, insula, anterior cingulate and posterior cingulate cortices (all 0.001), as well as the hippocampus, amygdala, thalamus and cerebellum (all 0.001). The w‐score analysis revealed significant reductions in SV2A density in FTD in all 13 ROIs, with the greatest reduction in the anterior cingulate (‐4.2), and in volume in 8 ROIs, with the greatest reduction in the temporal lobe (‐6.4). The magnitude of SV2A density loss was greater than the magnitude of volume loss in most ROIs (9/13), and there was more variability in the reduction in volume than there was in SV2A density (SD range [11C]UCB‐J 0.7‐2.1, volume 1.4‐3.9).ConclusionSignificant reductions in [11C]UCB‐J distribution indicate reduced synaptic density in disease‐relevant regions in FTD, which surpass reductions in volume. This suggests that [11C]UCB‐J PET imaging could be a sensitive biomarker of synaptic dysfunction in FTD, with future studies focused on its relationship with symptoms and whether it becomes abnormal before symptom onset.