bluuebunny/crossref_metadata_2025_split huggingface dataset:
Well‐being indicators in community‐dwelling elders with dementia
Authors: Alvarez Loreli , Acosta‐Castillo Gilberto Isaac , Sosa‐Ortiz Ana Luisa 
Published: December 2020

AbstractBackgroundDue to the high impact of dementia it is a priority to focus on the well‐being of those with this condition, enabling participation, inclusion and better functioning of people with this disease. In the research context it’s increasing the interest on documenting the needs reported by those living with dementia. The aim of this study was to describe well‐being indicators in people living with dementia to construct a composite measure of needs for this group.MethodWe analyze data from the cohort of the 10/66 Dementia Research Group in Mexico.ResultsOur sample consisted in 180 community‐dwelling elders with dementia. There were more women than men, with an average age of 80.8 (7.1) years, 52% had no formal education and 48.3% lived in rural areas. We selected 14 indicators of three dimensions of well‐being (physical health, psychological health and social resources) previously reported in literature. To build a composite measure of well‐being, scores of 0‐2 were assigned to each of the variables studied according to the benefit they represented for the elderly. Our composite measure has a total score of 22 with low scores indicating poor well‐being. We selected the 25th and 75th percentiles to classify subjects in three groups of well‐being (low, moderate, high). Those with higher showed less problems in eyesight, hearing and appetite problems; experience pain less frequently and had fewer comorbidities than the other two groups (low or moderate well‐being); highest well‐being group had less neuropsychiatric symptoms(NPS) and higher global cognitive scores; they attend more frequently to religious services, social activities and need no care according to their informant. The distributions of sleep problems, living alone, contact with relatives and disability showed no difference between the groups (Table1).ConclusionOur results show that people with higher well‐being have better physical and psychological health and more social resources compared with those classified with moderate and low well‐being. With our composite measure we can identify needs and possible areas to improve living well in community dwelling dementia patients.
Quantification of small vessel disease in frontal and parietal white matter, genu and splenium
Authors: McAleese Kirsty E. , Dugger Brittany N. , Mifflin Kelsey , Attems Johannes , Jin Lee‐Way , DeCarli Charles 
Published: December 2020

AbstractBackgroundCerebral small vessel disease (SVD) encompasses progressive fibrosis/hyalinosis of the small arteries (lipohyalinosis) and arterioles (arteriolosclerosis) of the white matter (WM) resulting in ischemic WM damage. SVD is commonly assessed using a broad semi‐quantitative (SQ) criterion. We implemented sclerotic index (SI) assessment to quantitatively assess vessel wall thickness in small arteries and arterioles separately in four regions known to exhibit WM changes.MethodThe cohort consisted of 75 cases from the University of California Davis Alzheimer’s Disease Centre Biorepository, neuropathological diagnosed as controls (n=18), intermediate Alzheimer’s disease neuropathologic change (n=13), definite Alzheimer’s disease (n=33), or cerebrovascular disease (n=11). H&E sections that included frontal and parietal WM, genu, or splenium were SQ assessed for SVD and images of small arteries (150‐800μm diameter) and arterioles (40‐150μm diameter) were captured. SI assessment was performed, and mean SI scores were calculated for arteries, arterioles, and an overall total.ResultAge was not associated with any SQ or SI measure in any region (p>0.106). SI and SQ scores of both arteries and arterioles were highly correlated in all regions (rho >0.551, p<0.0001) validating the SI method. Arteriole‐SI was significantly higher than artery‐SI in both WM regions (p<0.0001) and this was consistent cross controls and disease groups (all p<0.03). Regarding the whole cohort, frontal and parietal WM total‐SI was significantly higher than artery‐SI (P<0.0001) and significantly lower than arteriole‐SI (P<0.0001). Intragroup comparisons between frontal and parietal WM revealed no differences in artery‐ or arteriole‐SI scores (overall cohort p>0.76; subgroups p>0.112), and comparisons between genu and splenium also revealed no difference in arteriole‐SI (overall cohort p>0.41; subgroups p>0.34).ConclusionSVD‐associated vessel fibrosis is uniform between the anterior and posterior WM. Separate assessment of arteries and arterioles should be considered given arteriolosclerosis results in more severe vessel occlusion and maybe clinically relevant to ischemic WM changes. A combined SVD assessment may lead to under‐ or overestimation of disease severity.
Transcriptional endophenotypes predicting genetic risk of dementia in Mexican Americans
Authors: Almeida Marcio A ,   South Texas Diabetes and Obesity Institute
Published: December 2020

AbstractBackgroundDementias are heterogeneous age‐associated neurodegenerative disorders generally included in the broad term, Alzheimer’s disease and related dementias (ADRD). ADRD affects individuals of all ethnicities, but Hispanic individuals show a 1.5‐fold higher risk when compared to non‐Hispanic whites. ADRD is a complex phenotype where both genetic and environmental causal components play significant roles. The identification of early ADRD biomarkers is important and we propose to discover novel non‐invasive endophenotypes using high dimensional multiomic data in an existing Mexican American cohort. The 2000 Mexican American participants are members of large families from the GOBS (Genetics of Brain Structure and Function Study) project from which extensive phenotypic data is available.MethodWe applied a mean‐based endophenotype ranking value (ERV) method tailored for relatively rare diseases and extended pedigrees. A set of 70 GOBS subjects were diagnosed as ADRD cases. The estimated heritability is high (h2= 0.75, p = 2.6×10‐5) supporting a major role for genes influencing ADRD risk. The ADRD cases have 363 1st, 2nd, 3rd, and 4th degree relatives currently not suffering from dementia. To identify transcriptional endophenotypes that are genetically correlated with ADRD, we contrasted this group of relatives to 839 unaffected individuals without affected relatives. We constructed a genetic risk vector and tested its correlation to the expression level of each gene. (Figure 1).ResultWe tested the validity of our proposal by limiting ourselves to a set of 113 genes previously associated with ADRD. We observed a clear enrichment for significant effects over that expected under the null hypothesis (p=3.3×10‐10). Several cytokine genes (TNF, IL1B, and IL1A) exhibited reduced expression in relatives of cases versus controls (Table 1). Notably, the APBB1 gene showed increased expression in relatives of ADRD cases. This gene regulates the amyloid precursor protein playing a central role for ADRD development.ConclusionThe observed statistical enrichment of previously ADRD associated genes serves as a positive control for our approach. The ERV method is especially powerful for rare diseases when large human families are available. Candidate genes identified will be extensively annotated to aid the detection of relevant early ADRD genes highly correlated with ADRD risk.
A comparison of cerebral small vessel disease severity between autopsy cohorts in the northeast of England and Sacramento County in California, USA
Authors: McAleese Kirsty E. , Dugger Brittany N. , Mifflin Kelsey , Jin Lee‐Way , Attems Johannes , DeCarli Charles 
Published: December 2020

AbstractBackgroundCerebral small vessel disease (SVD) encompasses progressive fibrosis/hyalinosis of the small arteries and arterioles of the white matter (WM) resulting in ischemic WM damage. Few studies have compared SVD between different cohorts. Using a sclerotic index (SI) measurement, we quantitatively assessed vessel wall fibrosis in the frontal and parietal WM of human brains donated to brain banks in the UK and the USA.Method64 cases from the University of California Davis (UCD) Alzheimer’s Disease Centre Biorepository and 55 cases from the Newcastle Brain and Tissue resource (NBTR) were included. Cases were neuropathological diagnosed as controls (UCD n=18; NBTR n=25), intermediate Alzheimer’s disease (AD) neuropathologic change (UCD n=13; NBTR n=4), and definite AD (UCD n=33; NBTR n = 26). In the UCD cohort, 49 identified racially as White, 9 as Black African American, 3 as Chinese and 1 as Indian Asian. All cases from the NBTR identified racially as White. Using H&E sections, images of approximately eight arteries/arterioles from the frontal and parietal WM were captured and SI assessment performed. Mean SI score was calculated per region, per cases.ResultNo intergroup differences in age were observed and age was not associated with SI score in either cohort. In the UCD cohort, race was not associated with neuropathological diagnosis (Chi‐sq = 8.39, p>0.211) and no differences were seen in SI scores between White and Black African Americans (p>0.69). Intergroup comparisons revealed that SI scores in both WM regions were significantly higher in the overall UCD cohort compared to the overall NBTR cohort (p>0.006) and this was consistent across controls (frontal p=0.0001; parietal p=0.045), intermediate AD neuropathological change (p=0.001), and AD (frontal p=0.001) cases.ConclusionSVD‐associated vessel occlusion is more severe in the USA cohort from Sacramento compared to the UK cohort from Newcastle. This may reflect differences in cardiovascular disease and lifestyle of individuals enrolled in the two brain donation programmes.
Elucidating the relationship between TGF‐β signaling and Alzheimer’s disease
Authors: Croft Cara L. , Liu Xuefei , Ryu Daniel H. , Ceballos‐Diaz Carolina , Tejeda Giancarlo , Marrero Marc , Moran Corey , Cruz Pedro E. , Ladd Thomas , Moore Brenda D. , Golde Todd E. 
Published: December 2020

AbstractBackgroundThe TGF‐β signaling pathway represents a complex family and network of ligands and receptors. A body of evidence suggests that in Alzheimer’s Disease this signaling network may be perturbed and could contribute to disease development and progression. Other studies have shown a role for TGF‐β signaling in both Aβ clearance and deposition, as well as, in neuroprotection and neurotoxicity. It remains to be determined precisely the contributions of TGF‐β signaling to mechanisms underlying Alzheimer’s disease and other dementias and whether targeting TGF‐β may lead to suitable novel therapies.MethodsTo interrogate the contributions of TGF‐β signaling to Aβ and tau pathology in AD we developed several recombinant adeno‐associated virus (rAAV) constructs to express TGF‐β family ligands and decoy receptors. APP overexpressing (TgCRND8) mice were injected with rAAVs at postnatal day 0 or after 3 months of aging to examine contributions of the TGF‐β family prior to and during Aβ deposition. We also examined how TGF‐β family ligands and decoy receptors affect the development of tau pathology in tau brain slice culture (BSC) models.ResultsWe have successfully expressed TGF‐β family ligands and decoy receptors to determine their contributions to Aβ clearance and deposition in vivo in APP overexpressing mice, as well as, effects on tau pathology in ex vivo tau BSC models. Stimulating and blocking TGF‐β signaling cascades appears to have opposing effects on AD‐relevant pathology. Using this rAAV approach we can rapidly dissect how complex signaling cascades may contribute to the progression and development of human AD and how targeting these pathways may be therapeutically rewarding.ConclusionsThese findings suggest that interventions targeting TGF‐β signaling may be a novel therapeutic approach to AD. This data also enforces that pathways involved in immune function can have significant effects on the healthy and diseased brain and should be explored further in order to understand the development and progression of AD. Using a systems approach (NIH U01AG046139) we identified perturbed networks regulating innate immunity in the AD brain and have now validated how intervening with TGF‐β signaling may provide therapeutic benefit.
Electroencephalography (EEG) reveals a decrease in speed of animacy processing in mild cognitive impairment and an alteration in neural response patterns
Authors: Karimi Hamed , Marefat Haniye , Khanbagi Mahdiyeh , Kalafatis Chris , Vahabi Zahra , Razavi Seyed‐Mahdi Khaligh 
Published: December 2020

AbstractBackgroundElectroencephalography (EEG) has been commonly used to measure the brain alterations in the early stages of Alzheimer's Disease. However, the reported measures are limited to the univariate changes, including activation level and frequency bands. To look beyond the activation level, we used a task‐based EEG and applied multivariate pattern analysis (MVPA) to study the changes in the pattern of information processing.MethodWe recruited 18 participants with mild cognitive impairment (MCI), and 22 age‐matched healthy controls (HC). We acquired EEG data from all participants, while they were doing the integrative cognitive assessment (ICA) test (Khaligh‐Razavi et al., 2019). ICA is a rapid visual categorization task, in which participants are presented with a sequence of natural images of animals and non‐animals, and are asked to respond as quickly and accurately, whether images contained an animal. To analyze the EEG data, we took advantage of MVPA techniques to measure how accurately EEG signals can discriminate between brain representations of animals and non‐animals.ResultUnivariate analysis showed a significant decline in the activation level of the right temporal lobe in MCI compared to HC. In the left parietal lobe, we found that the pattern of EEG responses to the presented visual stimuli was significantly different between HC and MCI, in the absence of any difference in their level of activation. Furthermore, we found that animacy information (animal vs. non‐animal categorization) emerges later in the brain of patients with MCI (t = 67 ms ± 33 SE of mean; p‐value ≤ 0.03) compared to HC.ConclusionWe demonstrated that in addition to the level of activation (i.e., mean ERP response), the pattern of EEG responses to visual stimuli also carries information about the status of the disease. In particular, we see that in some of the brain areas where the mean activation shows no difference between HC and MCI, patterns of EEG responses are significantly different and can be used to discriminate MCI from HC. Furthermore, the results also suggest a delay or impairment in the speed of processing animacy information in MCI patients.
11C‐PBR28 brain PET imaging with lipopolysaccharide challenge for the study of microglia function in Alzheimer’s disease
Authors: Salardini Arash , Hillmer Ansel T , Mecca Adam P , Hashemi‐Aghdam Arsalan , Laltoo Emily , Savoia Sarah , O'Dell Ryan S , Harris Joanna E , Godek Tyler A. , Nabulsi Nabeel B , Lim Keunpoong , Ropchan Jim R , Huang Yiyun , Cosgrove Kelly , Carson Richard E , Strittmatter Stephen M , van Dyck Christopher H 
Published: December 2020

AbstractBackgroundThe study of neuroimmune function in Alzheimer’s disease (AD) has been challenging, partly because the underlying mechanisms are still incompletely understood. Here we present the results of a novel imaging study in human subjects to assess microglial activity in cognitively normal (CN) participants compared to participants with mild cognitive impairment (MCI) or mild dementia (MD) due to AD.MethodThis pilot study used positron emission tomography (PET) imaging with the radioligand 11C‐PBR28, which is specific for the 18 kDa‐translocator protein (TSPO), a marker sensitive to acute immune effects of lipopolysaccharide (LPS). The 11C‐PBR28 volume of distribution (VT) was measured from two scans, one at baseline and a second at 180 minutes after intravascular administration of lipopolysaccharide (LPS‐ 0.4 ng/Kg). We calculated microglia activation reserve index (MARI) as the proportional increase in binding of 11C‐PBR28, 180 minutes after the administration of the LPS: MARI = [(VT,LPS‐VT,Baseline)/ VT,Baseline] x 100.ResultsCN participants had a significantly higher global cerebral MARI of 35% (SD 13%, n=5) compared to the AD group (MARI=15%, SD 15%, n=5, p=0.030). We found no significant differences between global 11C‐PBR‐28 VT at baseline in CN participants compared to the AD group. MARI values correlated with clinical dementia rating (CDR) ‐ sum of boxes (CDR‐SB) score (R2=0.55, p=0.013), but not with MOCA scores. Conversely baseline 11C‐PBR‐28 VT correlated with MOCA scores (R2=0.44, p=0.025) but not CDR‐SB. TSPO gene polymorphism (high vs. medium affinity binding) did not make a difference in the response pattern. Measurements of serum cytokines indicated that the response differences between the two groups were central and not related to the peripheral immune response.ConclusionOur experiment presents preliminary human data on reduced brain microglial activity in AD.. Our novel method provides a unique opportunity to test the dynamic response of microglia in vivo. However, further investigations with larger sample sizes are required for better understanding of the role of microglia in AD.
For the sake of informed participation: Development of two audio‐visual aids for informed consent to a dementia prevalence study through participatory action research
Authors: Fadda Marta , Fiordelli Maddalena , Ibnidris Aliaa , Albanese Emiliano 
Published: December 2020

AbstractBackgroundThe limits of traditional informed consent are well known. Its goal should be to support individual autonomy and provide assurance that potential research participants are neither deceived nor coerced. For these reasons, they should be designed to give potential research participants control over the amount of information they receive and the opportunity to rescind consent already given. However, most informed consent forms are excessively long and use a technical jargon that is hard to understand for lay people. As part of an epidemiological study on dementia and its impact, we set out to develop two visual aids for informed consent (a video and a printed infographic) through participatory action research.MethodWe conducted four focus groups with people aged 65 or older and resident in the Italian‐speaking Canton of Switzerland (N=30). Participants were shown a preliminary version of the visual aids and were asked to provide feedback on information quality and appeal (speed, duration, color, font etc.). Focus groups were tape‐recorded, transcribed and analyzed to inform refinement of the visual aids before each subsequent focus group.ResultThe two visual aids complied with good clinical practice (GCP) guidelines of informed consent. We adapted the videos to the participants’ demand for lower speed and longer duration. We re‐arranged information according to a question‐and‐answer format displayed within the same graphical sequence. Information deemed too complex by participants was simplified using an advanced readability assessment tool (READ–IT), which combines traditional raw text features with lexical, morpho‐syntactic and syntactic information.ConclusionParticipatory action research is crucial for the development of tailored tools to support informed consent in epidemiological research. Further research is warranted to test if compared to traditional informed consents, the use of audio‐visual aids developed with potential participants to epidemiological research promotes research participation, and in a better informed fashion.
Association of brain amyloid accumulation and glucose hypometabolism with cognition domain of language
Authors: Huang Qi , Ren Shuhua , Huang Lin , Li Junpeng , Jiang Donglang , Wang Ying , Guan Yihui , Guo Qihao , Xie Fang 
Published: December 2020

AbstractBackgroundAmyloid is the main pathology for Alzheimer’s disease (AD), amyloid and glucose metabolism alternation are very important to investigate the progress of Alzheimer’s disease. However, not so many results were reported in Chinese population. In this study, we try to figure out the brain structure, function alternation and brain network alternation in Chinese subjective cognitive decline (SCD), mild cognition impairment (MCI) and Alzheimer’s disease (AD) from the data of Chinese preclinical Alzheimer’s disease (C‐PAS), which is initiated by us.Method200 participants were enrolled in this study, including 93 normal cognition (NC) healthy volunteers, 37 SCD, 34 MCI and 36 AD patients.6 types of neuropsychological tests from 3 cognitive domains and MMSE, Moca B were performed. FDG and amyloid PET (18F‐Flortabetapir) were conducted in these participants. 18F‐FDG and 18F‐Flortabetapir PET images were coregistered to the individual structural MRI images and then spatially normalized into MNI space.To assess the regional pattern of the 4 groups, one‐way ANOVA followed by two sample t test for post hoc analysis were performed, The statistical level was set at p<0.05 with FDR[hq1] correction and a minimum cluster extent Ke>20 voxels.ResultsIn Chinese population, changed glucosemetabolism were present in Superior temporalcortex, inferior temporal cortex, superior occipital cortex, precuneus, frontal cortex, supra‐marginal gyrus, anterior cingulate cortex, insula in a multiple comparison of AD MCI, SCD, and NC. And amyloid plaque were found in temporal cortex, frontal cortex, middle occipital cortex, inferior parietal cortex, insular, lingual gyrus, calcarine fissure and surrounding cortex, cingulate gyrus, fusiform gyrus, gyrus rectus, angular gyrus in these participants. Most of these changes were from AD patients, but slight hypometabolism, and amyloid accumulation were found among NC, SCD, MCI.ConclusionCortex and cingulate gyrus were the main regions for amyloid accumulation and glucose hypometabolism for Chinese AD patients. However, slight change was observed in NC, SCD, MCI participants.