bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum cortisol, cerebral amyloidosis, and neurodegeneration: A longitudinal study
Authors: Kim Jeongsim , Byun Min Soo , Lee Jun Ho , Yi Dahyun , Jeon So Yeon , Byeon Gihwan , Shin Seong A , Kim Yu Kyeong , Sohn Chul‐Ho , Lee Dong Young ,   the KBASE Research Group
Published: December 2020

AbstractBackgroundAlthough elevated blood cortisol has been repeatedly associated with Alzheimer`s disease (AD) and related cognitive decline, the pathological links underlying the association remain poorly understood. In this context, we aimed to investigate the relationship between serum cortisol and AD neuroimaging markers including amyloid beta protein (Aβ) deposition, tau deposition, AD‐signature region cerebral glucose metabolism (AD‐CM), AD‐signature region cortical thickness (AD‐CT), and adjusted hippocampal volume (HVa).MethodThis study was part of the of the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE), an ongoing prospective cohort study. A total of 503 middle‐aged and elderly adults, including cognitively normal adults and individuals with mild cognitive impairment and AD dementia, underwent comprehensive clinical and neuropsychological assessments, 11C‐Pittsburgh compound B (PiB)‐PET, 18F‐deoxyglucose (FDG)‐PET, MRI, and serum cortisol level quantification at baseline and 2 years later. A subset of subjects also received 18F‐AV‐1451 PET during the follow‐up evaluation.ResultAt baseline, a significant positive association was found between serum cortisol level and global cerebral Aβ deposition after controlling for the effects of potential confounders (i.e., age, sex, APOE4 status, cognitive status, vascular risk, and depression). In addition, cortisol level showed significant inverse association with AD‐CM even after controlling for global Aβ retention as well as the confounders. There was no significant relationship between cortisol and cerebral tau deposition. In regard of longitudinal changes of AD markers, baseline cortisol level also had significant positive association with increase of cerebral Aβ deposition over 2 years, but not with changes of any neurodegeneration markers.ConclusionThe findings indicate that high serum cortisol contribute to AD processes through pathological cerebral Aβ deposition. Additionally, cortisol appears to directly affect neurodegeneration in AD‐signature brain regions via Aβ‐independent mechanisms.
Improved centiloid robustness using non‐negative matrix factorization
Authors: Bourgeat Pierrick , Dore Vincent , Ames David , Martins Ralph N , Masters Colin L , Rowe Christopher C , Fripp Jurgen , Villemagne Victor LL ,   the AIBL Research Group
Published: December 2020

AbstractBackgroundCentiloid was introduced to harmonise Amyloid PET quantification across different tracers, scanners and analysis techniques. Unfortunately, Centiloid suffers from quantification disparities in longitudinal analysis when switching from different tracers or scanners. In this work, we aim to reduce such variability using a different analysis technique on the existing calibration data.MethodAll the PET images from the calibration dataset, along with 3658 PET images from the AIBL study were analysed using the recommended SPM pipeline. All the images were SUVR normalised using the whole cerebellum and skull stripped. The nomalised PiB images were decomposed into 6 components using non‐negative matrix factorisation (NMF). NMF is similar to a PCA decomposition but imposes that all components and associated coefficients remain positive. The NMF coefficients related to the first component were strongly correlated with global SUVR (R2 = 0.93), and were subsequently used as a surrogate for Aβ retention. The NMF coefficients were calibrated to Centiloid using the anchoring groups in the PiB calibration dataset. For each tracer of the calibration dataset, a NMF decomposition was computed, where the coefficients of the 1st component were fixed, and set to those of their corresponding PiB, hence forcing the 1st component of the NMF decomposition to match across tracers. All PET images from AIBL were subsequently decomposed using the computed NMF, and their coefficients transformed into Centiloids.ResultIn AIBL, the correlation between the standard Centiloid and the novel CentiloidNMF was high in each tracer with 0.93 in 11C‐PiB, 0.97 in 18F‐NAV, 0.96 in 18F‐FBB, 0.91 in 18F‐FLUTE and 0.86 in 18F‐AV45. The longitudinal consistency was assessed using average fitting error of a linear regression model applied to each subject with 3 or more timepoints, and also by measuring the number of subjects with longitudinal changes >20CL/year, which are physiologically implausible and likely caused by noise. The average fitting error was decreased by 15%, and the number of subjects with changes >20CL/year was halved from 41 to 20.ConclusionWe have proposed an image driven method to measure Centiloids. The method is highly correlated with standard Centiloids and reduces its longitudinal variability when switching scanners and tracers.
The electronic person specific outcome measure (ePSOM) programme: Overview and survey results
Authors: Saunders Stina , Sheehan Shane , Evans Alison , Luz Saturnino , Ritchie Craig W. , Terrera Graciela Muniz 
Published: December 2020

AbstractBackgroundThe ePSOM programme is a collaboration between the University of Edinburgh and Alzheimer’s Research UK. prompted by the recognition that outcome measures currently used in clinical trials in prodromal and preclinical neurodegenerative diseases do not capture the research participants’ views of effectiveness. This led to a 4‐stage programme. [1] Evidence review and programme methodology [2] Focus groups to identify key domains of importance to people at various degrees of neurodegenerative disease [3] National online survey and [4] App development which can be used as an outcome measure in trials. Here we present stage [3] of the programme.MethodThe online survey captured free text responses in 5 predefined domains. Self‐reported clinical details and sociodemographic data were captured to analyse responses by key variables whilst keeping the survey short (around 15 minutes). The survey received ethical approval and ran August – November 2019. Using clustering and natural language processing techniques we identified clusters of response by domain and across domains. A specific question about the steps individuals take to ‘maintain brain health’ was also included.Result5807 people completed the survey. Most were female (76.9%), married (63.4%) and living in an urban area (61.8%). The mean age in women was 57.35 (SD=13.8) and 62.88 (SD=13.08) in men. 73% had supported a relative with dementia but only 15.4% had sought help for their own brain health. On a 10‐point scale (10 = best level of health), the mean score for self‐rated brain health was 9.32 (SD=1.97). We consider that the population undertaking the survey was exactly as intended as a primary or secondary prevention population. Thirty distinct clusters of response were identified across all domain and will be presented. The most common activities undertaken to maintain brain health were ‘trying to keep brain active’ (86.6%) followed by ‘trying to keep physically active’ (70.8%).ConclusionThe survey was successful in capturing a large number of people from a population at higher risk of neurodegenerative disease. The respondents understood the objectives of the survey and relevant clusters and items emerged which will guide the 4th phase of App development.
Relationship between vestibular dysfunction and dementia in elderly patients: Peripheral vertigo or central vertigo
Authors: Lee Jong Yoon 
Published: December 2020

AbstractBackgroundRecent research suggests an association between vestibular impairment and dementia. Mild cognitive impairment (MCI) and dementia patients are associated with increased rate of vestibular loss. The vestibular system consists of the peripheral vestibular organs and the associated extensive vestibular cortical pathway. We investigate whether vertigo (peripheral vertigo or central vertigo) is correlated with an increased risk of dementia and clinical relevance of vertigo types to dementia.MethodFrom August 2019 to January 2020, 300 patients, aged ≥ 50 years and vertigo symptom were retrospectively enrolled. Multivariate a Multivariate analysis was performed for vertigo types that showed a significant difference between dementia and non‐dementia groups. First, we reviewed vertigo with previous diagnosed 177 dementia and 123 healthy controls, and the differences in vertigo types between these groups were examined. Second, the patients with vertigo were classified into 2 groups: peripheral (Acute vestibular neuritis, Meniere's disease, Benign paroxysmal positional vertigo, Autonomic related vertigo, and so on) or central (Stroke, Vertiginous migraine and Epilepsy vertigo) types. Third, dementia groups included AD, VaD and Mixed types. Finally, this study evaluated risk factors for vertigo in cognitive impairment patients.ResultAmong 177 dementia patients with a mean age of 75.30 years, 56 (31.63%) developed vertigo. The frequency of vertigo types (peripheral vertigo or central vertigo) was different in dementia with vertiginous patients compared to non dementia groups {peripheral: central 55.35% vs 44.64%; 81.30% vs 18.69}. In this study, total 56 vertigo patients were divided into two groups based on peripheral type (n = 31) or central type (n = 25). There was no significant difference in vertigo classification between peripheral and central according to dementia subtype. On the other hand, 121 individuals with dementia were not found symptom of vertigo. Among, 123 non dementia patients with vertigo, there were 100 of peripheral vertigo (81.30%) and 23 of central vertigo (18.69%).ConclusionThe classification of vertigo is different depending on dementia or not. The proportion of central vertigo has a tendency to increase with dementia groups. The findings of our study may provide direction for potentially useful diagnostic tests and vestibular‐targeted therapy such problem in dementia patients.
The validity of the good spirit, good quality‐of‐life tool for older Aboriginal Australians
Authors: Gilchrist Lianne , Bessarab Dawn , Douglas Harry , LoGiudice Dina , Ratcliffe Julie , Flicker Leon , Hyde Zoe , Smith Kate 
Published: December 2020

AbstractBackgroundEnhancing quality of life (QoL) is the primary goal of aged care services for older people with dementia. Despite this, there are no culturally appropriate QoL measures for older Indigenous peoples with or without dementia. This study aims to address this gap.MethodThe Good Spirit, Good Life (GSGL) tool was co‐developed with older Aboriginal Australians and services in Perth and Melbourne, Australia. Adaptations were made following face validity with Aboriginal participants with dementia or cognitive impairment. Quantitative data collected by Aboriginal researchers included demographic information, GSGL tool (12 items, total score 60), KICA Cog (Indigenous cognitive assessment), EQ‐5D‐5L (health‐related QoL tool), ICECAP‐O (generic wellbeing tool for older people), Geriatric Anxiety Inventory‐Short Form (GAI‐SF), KICA‐Dep (Indigenous depression scale), Aboriginal Resilience and Recovery Questionnaire (ARRQ‐25), and GSGL Carers version.Result120 Aboriginal people aged 45‐86 years participated in the GSGL validity study, 68% were women. The mean total GSGL score was 48.7/60. 11% of participants had cognitive impairment or dementia. GSGL internal (Spearman‐Brown 0.83, Cronbach’s alpha 0.75) and inter‐rater (ICC 0.69‐0.95) reliability was strong. Concurrent validity is supported by strong correlation with ICECAP‐O (Spearman’s Rho (ρ)=0.61, p<0.05). GSGL was weakly correlated with health‐related EQ‐5D‐5L (ρ=‐0.32, p<0.05). Known‐groups validity was supported by significant difference in GSGL scores between participants with (40%) and without anxiety (Student’s t test t=4.3, p<0.05) and with (44%) and without depression (t=4.1, p<0.05). GSGL scores did not differ significantly for participants with and without cognitive impairment. Following multivariate regression, resilience (β=0.55, 95%CI [0.39, 0.70]) and GAI‐SF score (β=‐0.22, [‐0.38, ‐0.06]) were associated with total GSGL score. There was significant difference in GSGL item scores (p<0.05; Hotelling’s T2 test), with the ‘Country’ item having the lowest mean score (3.05/5, p<0.05).ConclusionThe GSGL is a culturally valid tool for measuring quality of life in older Aboriginal Australians. Items are based on the quality of life priorities of Aboriginal Australians with and without dementia. Interventions targeted at building resilience and treating anxiety and depression may improve the quality of life of older Aboriginal Australians. More could be done by services and families to facilitate older people’s connection to Country.
The validation of the adapted Kimberley Indigenous Cognitive Assessment in a Brazilian indigenous community of older adults from Amazonas
Authors: Souza‐Talarico Juliana Nery , Carvalho Anna Paula , Nitrini Ricardo , Ferretti‐Rebustini Renata Eloah de Lucena , LoGiudice Dina , MD Brucki Sonia 
Published: December 2020

AbstractBackgroundDementia detection in indigenous populations, represents a challenge worldwide, due to the absence of culturally adapted cognitive tests. The Kimberley Indigenous Cognitive Assessment (KICA) was developed and validated to evaluate global cognitive performance in Aboriginal Australians. We aimed to determine reliability and validity of the KICA, and specificity and sensitivity in detecting cognitive impairment in a Brazilian indigenous community.MethodThe KICA was translated and back translated into Portuguese by independent translators. The translated version was revised by an experts committee and pre‐tested. Healthy indigenous older adults (n=123, Age mean=63.7, SD=±9.1; Education mean=1.5, SD±2.3) and indigenous patients with cognitive impairment (n=94; Age mean=65.0, SD±11.5; Education mean=1.1, SD±11.5) from Amazonas, Brazil, were administered the KICA and Mini‐Mental State Examination (MMSE). Cognitive impairment classification was based on the DSM‐IV and ICD‐10 criteria. The KICA reliability and validity was analyzed using Cronbach's alpha and Pearson correlation coefficient between KICA and MMSE scores. Sensitivity and specificity were calculated at several cutoff values and the area under the Receiver Operator Characteristic (ROC) curve was calculated.ResultThe KICA demonstrated moderate internal consistency (Cronbach's alpha coefficient=0.787) and was significantly correlated with MMSE scores (r=0.660; p<0.001; Pearson coefficient). The best equilibrium was at the cutoff value of 26/27 out of 39 showing 72% sensitivity and 73% specificity; the area under the ROC curve was 0.78 (95% CI: 0.72‐0.84).ConclusionOur results indicate that the KICA is a reliable tool and can be used for screening cognitive impairment in Brazilian indigenous with low education background.
Phenome‐wide associations with an Alzheimer’s disease genetic risk score in UK Biobank: Identifying early indicators of disease
Authors: Zimmerman Scott C , Ackley Sarah F , Brenowitz Willa D , Graff Rebecca E , Glymour M Maria 
Published: December 2020

AbstractBackgroundThere is a pressing need to identify early indicators of Alzheimer’s disease and Alzheimer’s disease‐related dementias (AD/ADRD) to understand the time course of disease and help target potential secondary prevention measures. A phenome‐wide association study (PHeWAS) could be used to rapidly screen numerous possible leading indicators of AD/ADRD based on phenotypes predicted by an Alzheimer’s Disease genetic risk score (ADGRS). We conducted a preliminary PheWAS to evaluate associations with an ADGRS, considering multiple phenotypic domains relevant to AD/ADRD.MethodWe calculated an ADGRS as a weighted sum of 23 previously identified AD‐related single nucleotide polymorphisms in individuals of European ancestry. We conducted a PheWAS of 373,225 UK Biobank participants of European ancestry aged 50‐69 years at enrollment. Using the open‐source tool PHEnome Scan ANalysis Tool (github.com/MRCIEU/PHESANT), we tested the ADGRS against 434 phenotypes: 183 neuroimaging, 100 cognitive, 84 mental health, 31 psychosocial, and 14 behavioral. PHESANT regresses the ADGRS on each phenotype adjusted for baseline age, sex, genotype chip, and 10 genetic ancestry principal components.ResultUsing a global Bonferroni threshold (p<1.15E‐4) significance criterion, we found 34 phenotype‐ADGRS associations. The three most significant associations were with cognitive functioning from a symbol digit substitution test: Duration to entering value (0.029, 95%CI=[0.023, 0.035]; p=2.58E‐06), number of matches made correctly (‐0.029, 95%CI=[‐0.035,‐0.022]; p=7.56E‐05), and number of matches attempted (‐0.028, 95%CI=[‐0.033,‐0.021]; p=2.63E‐08). Overall, 11 behavioral (69%), 21 cognitive (21%), 1 psychosocial (2%), and 1 mental health (2%) variables were significantly associated with the ADGRS. None of the neuroimaging variables were significant, but sample sizes were small (18,314‐20,827). Using category‐specific Bonferroni‐adjustments, 13 behavioral (81%), 23 cognitive (23%), 2 psychosocial (2%), and 2 mental health (2%) variables were significant.ConclusionIn a largely healthy and cognitively normal sample, the PheWAS identified cognitive assessments that may be leading indicators of AD/ADRD and identified novel associations of ADGRS with 1 mental health, 1 psychosocial, and 11 behavioral variables. PHeWAS using AD/ADRD genetic profiles may have potential for identifying early indicators of AD/ADRD.
FC gamma receptor activation is related to neuronal and microglial toxicity mediated by palmitic acid
Authors: Phitthayaphong Phansa , Kumfu Sirinart , Chattipakorn Siriporn C. , Chattipakorn Nipon 
Published: December 2020

AbstractBackgroundA high‐fat diet (HFD) rich in saturated fatty acid, particularly palmitic acid (PA), promotes pathophysiological changes in the brain. HFD induces cognitive impairment due to abnormal Alzheimer’s‐related protein production and increases the upregulation of hyperphosphorylation of Tau and Aβ peptides. Moreover, the progression of neuroinflammation and activated microglia were driven after HFD consumption. Activated microglia are able to eliminate abnormal proteins by using surface receptors called FcγR. These receptors have been found to mediate tissue injury within the CNS. However, the expression and activation of FcγRs, the presence of Alzheimer’s‐related proteins, proinflammatory cytokines as well as cell viability of neurons and microglia under PA exposure have not been investigated.MethodSH‐SY5Y, the human neuroblastoma cell line, and HMC3, the human microglia clone 3 cell line, were exposed to 200 and 400 µM of PA‐conjugated BSA. After 24 hours of exposure, Alzheimer’s‐related proteins, including Aβ, APP, BACE1, IDE, p‐Tau and Tau, as well as the production of proinflammatory cytokines composed of TNFα, IL‐1β and IL‐6, were investigated. FcγRs levels with signaling and cell viability were determined.ResultAfter exposure of PA‐conjugated BSA for 24 hours, SH‐SY5Y and HMC3 cells increased Alzheimer’s‐related protein production including Aβ, APP, BACE1, and decreased IDE. While p‐Tau/Tau ratio was increased only in SH‐SY5Y cells. Furthermore, both cell lines increased TNFα, IL‐1β and IL‐6 production after PA‐conjugated BSA exposure. Interestingly, an increase in FcγRs expression was only found in HMC3 cells, whereas FcγRs signaling significantly increased in both cell lines. The viability of SH‐SY5Y and HMC3 cells were decreased in a dose‐dependent manner with PA exposure.ConclusionPA increased Alzheimer’s‐related protein production, inflammation and FcγRs activation, which related to the presence of neuronal and microglial cell death. These findings suggest that the blockage of FcγRs should restrain further progression of Alzheimer’s pathology and neuroinflammation in HFD‐induced cognitive decline.
Texture of brain magnetic resonance images is associated with tau accumulation but not with amyloid accumulation in Alzheimer’s disease
Authors: Lee Subin , Kim Ki Woong 
Published: December 2020

AbstractBackgroundSpatial variations in signal intensity on magnetic resonance images (MRI), as measured by texture analysis, has been reported to be able to discriminate and predict progression to Alzheimer’s disease (AD). In this study, we investigated associations between the MRI signal intensity variations and hallmark AD pathologies (amyloid and tau accumulation).MethodStudy participants consisted of 151 subjects from the Alzheimer’s Disease Neuroimaging Initiative 3 who had a T1‐weighted image, AV45 positron emission tomography (PET), and AV1451 PET. We extracted texture features from each of five regions: entorhinal cortex, hippocampus, posterior cingulate cortex, precuneus, and superior frontal cortex. Cerebral amyloid burden was measured as standardized uptake value ratio (SUVR) in AV45 positron emission tomography (PET), and cerebral tau burden was measured as SUVR in AV1451 PET. We investigated associations between each texture feature and AD pathological measures in each of the regions by using linear regression, controlling for the effects of age and gender. We also compared texture features and AD pathological burden among in vivo Braak stage groups.ResultRegional texture were associated with regional tau burden but not with amyloid burden. Furthermore, the texture features that were associated with tau accumulation were different between regions with different cytoarchitecture. Significant group differences were observed for amyloid and tau accumulation, and certain texture features. Mean signal intensity showed an increasing trend across higher stage groups.ConclusionThis study suggests that brain MRI texture may reflect microstructural changes related to tau accumulation, and has potential as an early non‐invasive imaging marker of AD. This study was supported by a grant from the Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (grant no. HI09C1379 [A092077]).