bluuebunny/crossref_metadata_2025_split huggingface dataset:
A case of progressive multifocal leukoencephalopathy with HIV positivity
Authors: Yu Yingxin 
Published: December 2020

AbstractBackgroundWe report a case of progressive multifocal leukoencephalopathy with HIV positive. We analyzed her epidemiology, clinical manifestation, neuroimaging and laboratory test.MethodThe patient was a 36‐year‐old right‐handed man with 4 months of left upper limb numb, 2 months of left limbs weak. 4 months ago, he felt cold on her left upper limb without any reason.3 months agohe suddenly couldn’t recognize his routine home way for several minutes. 2 months ago, he felt dizzy and weak on his left upper limb. He was considered as cervical spondylosis without recover after massage. His brain MRI showed his right frontal and parietal cortex ischemic, right thalamus, corona radiata and callosum ischemic infarction (subacute stage), and posterior angel of bilateral ventricles demyelination. The focus weren’t enhanced on brain enhancement MRI. He got treatment according to cerebral infarction and didn’t relieve. His blood test results showed decreased white cells, red cells and platelet count. His CSF test was normal. His serum NMDA, AQP4 antibody were all negative.1 months ago, he began to have fever and could relieve after cortisone. He couldn’t get better after antiviral therapy according to viral encephalitis. His bilateral vision suddenly got blind. His PET‐CT scan was normal. He didn’t relieve after immune globulin. His nervous system examination showed his cognitive function deceased, left central facial paralysis and left limbs upper motor neuron paralysis. His bilateral light reflex was normal. However both of his eyes couldn’t react on light. His bone marrow aspiration was normal. Finally, he got HIV test and the result was positive. His CSF and urine of JC virus PCR test were 1000000copies/ml and 2000copies/ml.ResultHe was diagnosed as progressive multifocal leukoencephalopathy and HIV infection. 1 month later, he was dead.ConclusionThe syndromes of this case became worse and worse, but he couldn’t get right diagnose and treatment. His brain MRI image seems like ischemic stroke. The most important HIV test was done at the final stage. This case gave us a lesson and we should keep mind on HIV test.
Brahmi (Bacopa Monnieri) for dementia due to Alzheimer’s disease: Systematic review and meta‐analysis protocol
Authors: Vishnu Venugopalan Y. , Padma Vasantha , Basheer Aneesh , Gupta Anu , Kirubakaran Richard 
Published: December 2020

AbstractBackgroundBacopa Monnieri or Brahmi is a herb belonging to plant family Scrophulariaceae whose medicinal properties have been reported in Indian traditional medicine (Ayurveda) literature for treatment of anxiety, intellect and memory disorders. Even though there is good quality preclinical evidence on utility of Brahmi, peer‐reviewed published data on the use of the Brahmi in Alzheimer’s disease (AD) and MCI‐AD is limited. Most of the research on Brahmi are methodologically weak in design and a systematic review of the existing literature will give us the best available evidence to undertake future research including a multicentre randomised controlled trial comparing Brahmi and Choline‐esterase inhibitors.MethodPrimary objective is to determine the clinical efficacy and safety of Brahmi in people with mild, moderate or severe dementia due to AD and MCI‐AD. Secondary objective is to compare the efficacy and safety of different doses of Brahmi. We will include RCTs and quasi‐RCTs, regardless of publication status or language, that have compared Brahmi with placebo or a choline esterase inhibitor in persons with AD and MCI‐AD, irrespective of any duration of intervention including cross‐over trials. We will include individuals diagnosed with dementia due to AD or MCI‐AD according to ICD‐10, DSM IV/DSM V, NINCDS‐ADRDA or Duboi’s criteria. Brahmi of any formulation and dose given for any duration will be the intervention. Placebo or any Choline esterase inhibitor at standard doses given for AD and MCI‐AD will be the comparator.ResultThe outcomes that will be assessed are 1) Cognitive function (2) Activities of daily living 3) Behavioural disturbance 4) Clinical global impression 4) Quality of life 5) Dependency 6) Death 7) Acceptability of treatment as measured by withdrawal from trial 8) Safety as measured by the incidence of adverse effects leading to withdrawal 9) Safety as measured by the overall incidence of adverse effects. Subgroup analysis include 1) Mild, moderate and severe dementia, and those with MCI‐AD 2)Duration of intervention 3) Different doses of BacopaConclusionThis systematic review and meta‐analysis will bring out the current best available evidence regarding efficacy and safety of Brahmi in treatment of AD and MCI‐AD
Population prevalence of autosomal dominant Alzheimer’s disease: A systematic review
Authors: Potter Richard R , Long Alexandra P , Lichtenstein Maya L 
Published: December 2020

AbstractBackgroundAlzheimer's disease is the leading cause of dementia, accounting for >50% of cases. Autosomal dominant Alzheimer's Disease (ADAD) is estimated to account for approximately 1% of AD cases. Current estimates of ADAD prevalence have largely been drawn from subjects already diagnosed with dementia, thus representing a biased sample. This study aimed to perform a systematic review investigating ADAD prevalence through currently available epidemiological studies to determine whether a more accurate estimation of population prevalence can be made.MethodA systematic review was performed. Medline, Pubmed, Web of Science, and ClinicalKey were used to locate studies pertaining to ADAD prevalence (mutations of PSEN1, PSEN2 and APP). Search terms: (Autosomal Dominant or Familial or Early Onset) and (Alzheimer’s or Dementia) and (Prevalence or Epidemiology). Inclusion criteria: Humans of any age and gender, studies after 1985, and studies available in English from any country. Exclusion criteria: case reports, case series, clinical trials, cohort studies, studies that focused on ApoE or less established genes, and studies that focused on diseases besides Alzheimer’s Disease. Two independent reviewers conducted all levels of screening, data abstraction, and quality appraisal with a third arbitrator to settle discrepancies.ResultsThe search identified 2,047 titles; 650 duplicates were discarded. From the remaining 1397 titles, 147 abstracts were identified for further review. Based on predetermined criteria, 19 studies were fully reviewed and included in the study. Prevalence ranged from 0.00‐71.54%. 10 studies took samples from clinic populations, 6 specifically from a community of people diagnosed with dementia, and 3 took samples in a unique manner. 9 of the 19 studies targeted only early‐onset AD. None of the studies performed a true population prevalence without enriching or limiting the sample.ConclusionThere is large variability in prevalence estimates of ADAD in the literature, which appears related to sample selection and methodological differences. Understanding how these prevalence estimates were obtained is important, since it informs us that, to our knowledge, a true population prevalence of ADAD does not currently exist. To develop a more accurate population prevalence of ADAD, future studies may benefit from less biased genetic screening of a population.
Reduced awareness of cognitive decline is associated with brain amyloid load in asymptomatic elderly individuals at risk for AD: A longitudinal study
Authors: Cacciamani Federica , Sambati Luisa , Houot Marion , Habert Marie‐Odile , Dubois Bruno , Epelbaum Stéphane 
Published: December 2020

AbstractBackgroundIt has recently been proposed that the awareness of cognitive decline (ACD) may already be slightly reduced in the preclinical phase of AD, in the presence of subtle cognitive changes. This is a recent field of research, and the few studies available do not allow to appreciate the actual evolution of ACD in the pre‐dementia phases of AD. The present study describes the longitudinal trajectory of an index of ACD (ACDI) over 3 years in a cohort of cognitively‐normal elderly, its association to AD biomarkers, as well as its impact on cognitive scores’ evolution.Method314 elderly memory complainers, as just as many study‐partners, were followed‐up for 3 years. Brain glucose metabolism and amyloid load were assessed at baseline; screening cognitive tests were performed every 6 months, and a comprehensive neuropsychological evaluation every 12 months. The ACDI was based on the subject‐informant discrepancy on a questionnaire evaluating the subject’s cognitive decline. We performed a Latent Class Linear Mixed Model (LCLMM) to identify different trends of evolution of the ACDI over time, and Generalized Linear Mixed Models to analyse the impact of the baseline ACDI on the evolution of cognitive scores.ResultThe LCLMM identified three classes of subjects sharing similar longitudinal trajectories of the ACDI. Most subjects (76.8%) have accurate ACD (Class 2), and have been considered as the reference group. 18.95% of subjects showed heightened ACD (“worried‐well” individuals). They were comparable to subjects with accurate ACD in terms of AD biomarkers. 4.25% of the sample showing low ACD had higher amyloid burden than the reference group, and were mostly men. The GLMM found no overall effect of baseline ACDI on the evolution of the cognitive scores.ConclusionThe study of ACD in AD, its evolution and correlates is a topic of growing interest, as it is, notably, a piece of the larger understanding of the pre‐dementia phases of AD. This can be useful for a timely diagnosis of AD, and for the selection of populations to be included in clinical trials.
Cognitive performance and complex functionality in a population with mild cognitive impairment and vascular damage
Authors: Guajardo Maria Elena , Söderlund Maria Elvira , Pagotto Vanina , Schapira Marcelo , Seinhart Daniel Bernardo , Labos Edith 
Published: December 2020

AbstractBackgroundSmall vessel disease is a frequent cause of vascular damage, observed on magnetic resonance imaging and increased with age.(Pantoni, Poggesi & Inzitari,2007) One scale to assess vascular damage that correlates with cognitive measures is Fazekas scale.(Fazekas, Chawluk, et.al. 1987). Vascular damage can have an impact on cognitive and functional performance.MethodCross‐sectional study with prospective recruitment of patients 65 years or more, evaluated in the Geriatric Section, Italian Buenos Aires Hospital. Patients with MCI and brain MRI were included. All subjects were evaluated with a complete neurocognitive battery, and functional scales (complex activities of daily living: EFE). Patients were divided in 3 categories of vascular brain damage according to the MRI in Fazekas (F) group: 0‐1, 2 and 3. Bivariate analysis and multivariable analysis was performed. Odds ratio (OR) and confidence intervals 95% (CI) were informed.Result346 patients were included, women 71.7%, mean age: 77.9 (ds 6.1). Fazekas (F) categories: F0‐1: 229 (66.2%), F 2: 79 (22.8 %) y F 3: 38 (11.0 %). Patients with hippocampus atrophy (HA)119 (46.1%).There were no differences in the presence of comorbidities between the 3 categories of Fazekas. Patients with F3 were older (table1). In cognitive profile, patients with F3 showed greater impairment in executive functions and episodic memory than patients with F2 and F0‐1 (table2); in functional profile, patients with F3 showed greater impairment in complex functionality than patients with F2 and F 0‐1 (table 2). Fazekas categories were an independent factor associated with the impairment of the EFE (F3 OR 2.53 CI1.05‐6.11 p= 0.039 ) (Figure 1) and with the free memory delayed recall impairment (F3 OR: 2.84 CI 1.09‐7.43 p= 0.033) (Figure 2)ConclusionThe results obtained show a functional cognitive profile in patients with MCI and its associations with vascular damage. Severe vascular damage was independently associated with: 1) the deterioration of complex activities of daily living as a manifestation of executive impairment and 2) the deterioration of free memory delayed recall by compromise executive control processes that is critical for to maintain, code and retrieve long time memories.
Deep multilayer brain proteomics identifies molecular networks and Netrin‐1 accumulation in Alzheimer’s disease progression
Authors: Bai Bing , Wang Xusheng , Li Yuxin , Chen Ping‐Chung , Yarbro Jay M. , Beach Thomas G. , Peng Junmin 
Published: December 2020

AbstractBackgroundAlzheimer’s disease (AD) displays a long asymptomatic stage prior to development of dementia. Identification of molecular alterations during AD progression would provide insight into temporal alterations associated with AD.MethodAD stage‐associated molecular networks were characterized by mass spectrometry in 90 frontal cortical tissue samples in five groups, including controls with low/high amyloid plaque and tau tangle pathology (LPC and HPC, respectively), cases with high Aβ pathology and slight mild cognitive impairment (MCI), late‐stage AD with high plaque/tangle pathology, and samples with progressive supranuclear palsy (PSP). We additionally performed whole proteome comparisons between human AD and the 5XFAD and Tau P301S mouse models. Protein targets implicated as altered by AD progression in the proteomic analyses were validated by affinity assays and immunostaining in human tissue and mouse models.ResultsAD stage‐associated molecular networks were characterized by profiling 14,513 proteins and 34,173 phosphosites in human brain with mass spectrometry, highlighting 173 protein alterations in 17 pathways. In total 16,128 proteins in 5xFAD and wild‐type mouse cortex were profiled, and share 97, 89, and 169 protein alterations with HPC, MCI, and AD, respectively, whereas Tau P301S mice share less than 15 protein alterations with each group. Neither mouse model shares more than 15 non‐tau phosphopeptide alterations with each AD sub‐group, although Tau P301S shares up to 78 phospho‐Tau peptides with human AD. During validation of proteins implicated in the proteome characterization, Netrin‐1 levels were found to increase in AD stage progression by immunoblotting but was not augmented in any other neurodegenerative disease cases tested. Additionally, affinity assays demonstrated a direct Aβ‐Netrin‐1 interaction, and immunostaining demonstrated Netrin‐1 and amyloid plaque colocalization in human AD and 5X‐FAD brain tissues, but not in Tau P301S.ConclusionOur proteomic analyses reveal altered proteins in AD and related mouse models. Human‐mouse comparisons suggest 5xFAD mice resemble symptomatic AD and that Tau P301S mice reproduce only AD‐related Tau phosphorylation. Netrin‐1 accumulates in AD, shows direct Aβ binding, and colocalizes with amyloid plaques in human AD and mouse 5XFAD brain tissue, and may be vital to AD pathogenesis. These results provide novel insights into AD‐associated proteins and pathways.
Volumetric multispectral optoacoustic tomography of beta‐amyloid deposits in whole mouse brain
Authors: Ni Ruiqing , Dean‐Ben Xose Luis , Rudin Markus , Shi Gloria , Chen Zhenyue , Mu Linjing , Nitsch Roger M. , Razansky Daniel , Klohs Jan 
Published: December 2020

AbstractBackgroundThe abnormal deposition of fibrillar beta‐amyloid deposits in the brain is one of the major histopathological hallmarks of Alzheimer’s disease. Currently 3D imaging using positron emission tomography for plaque visualization is of a limited resolution (1 mm) in relation to the size of mouse brain in widely used AD models.MethodWe developed a novel high‐resolution non‐invasive volumetric multi‐spectral optoacoustic tomography (vMSOT) of 100 mm resolution using amyloid probe AOI987 to visualize amyloid‐beta distribution in arcAβ and APP/PS1 transgenic mouse models of cerebral amyloidosis. Immunohistochemical staining was performed with AOI987, anti‐Aβ antibody 6E10 and fibrillar amyloid conformation antibody OC on mouse brain sections.Result
In vivo vMSOT detects higher Aβ load in the cortex, hippocampus and thalamus of arcAβ mice, and in the cortex of APP/PS1 mice compared to non‐transgenic littermates, corresponding with immunohistochemical staining results in mouse brain sections. Confocal microscopy showed co‐localization of AOI987, 6E10 and OC to parenchymal and cerebral amyloid angiopathy in brain tissue sections from arcAb and APP/PS1 mice, thus verifying the specificity of the vMSOT amyloid imaging approach.ConclusionWe demonstrate a new high‐resolution in vivo 3D amyloid imaging platform across the murine brain in animal models of AD pathology, which facilitates mechanistic studies and the monitoring of putative treatments targeting Aβ.
Verbal and non‐verbal auditory comprehension tests in early diagnosis of Alzheimer's disease
Authors: Fang Ting , Wu Zhong ting , Xiao Jun , Ye Fang 
Published: December 2020

AbstractBackgroundThe purposes of this study are to correlate auditory comprehension impairment with AD early development and to evaluate the verbal and non‐verbal auditory comprehension tests for early diagnosis of AD.MethodThe 24 healthy controls (HC), 30 amnestic mild cognitive impairment (aMCI) and 27 mild AD (mAD) patients were recruited. The verbal (yes‐or‐no question, listening identification and oral instruction) and non‐verbal (sound categorization, emotion judgment, beat judgement, sound naming) auditory comprehension tests were adapted to evaluate the diagnostic ability of auditory comprehension. The receiver operating characteristic curves were used to analyze the diagnostic values.ResultAll tests except for yes‐or‐no question presented moderate or higher level of positive correlation in the scores with Mini‐Mental State Examination (MMSE) and Montreal Cognitive Assessment (MOCA), among which sound naming and oral instruction were the best. Statistical analysis identified a significant difference of sound naming and verbal auditory comprehension tests in aMCI group compared with the HC group. In addition, the mAD group exhibited statistically significant difference in sound categorization, sound naming, beat judgement and oral instruction when compared with the other two groups. Oral instruction sound categorization and naming benefited better in early diagnosis than the other subtests.ConclusionThe impairments of auditory comprehension emerge early in AD, or even aMCI patients, which worsen with the progression of the disease. The tests of sound categorization, sound naming and oral instruction exhibited better discriminative values, which might be beneficial for the early diagnosis of AD.
Mapping the contributing factors of depression in community elders
Authors: Zhao Lei , Yiu Brian , Lam Bonnie Y.K. , Biesbroek J. Matthijs , Luo Yishan , Shi Lin , Mok Vincent C.T. , Wong Adrian 
Published: December 2020

AbstractBackgroundThe contributing factors of depressive symptoms in elderlies are not known quite well. This study aims to investigate the clinical and neuroimaging risk factors of depression in community elderlies.MethodClinical risk factors (Table 1) and MRI scans (including T1‐weighted (T1W), T2‐weighted, FLAIR, diffusion tensor imaging (DTI)) were acquired from 609 stroke‐ and dementia‐free elderlies. T1W images were processed with AccuBrain to quantify volumes of brain anatomical structures (Table 2). White matter hyperintensities (WMHs) were automatically delineated using AccuBrain with manual correction when needed. The generated WMH masks were projected to standard space to calculate regional WMH volumes (Table 2). Other small vessel disease features, including lacunes, cerebral microbleed and enlarged perivascular spaces (EPVS) were visually rated (Table 2). Peak width of skeletonized mean diffusivity (PSMD) was calculated on DTI sequence. These imaging features and clinical variables were used to predict geriatric depression scale (GDS) with support vector regression (SVR). We compared three prediction models here: (1) with clinical variables as predictors, (2) with imaging features as predictors, and (3) with the combination of clinical and imaging features as predictors. Different feature selection methods were attempted. Statistical inference was performed with permutations to investigate the significance of individual contributing factors.ResultRepresentative characteristics of the participants were shown in Table 3. For the prediction of GDS, Model 2 with imaging features was inferior to Model 1 with clinical variables (p<0.001), and Model 3 that combined both types of features did no better than Model 1 (p=0.031). In the statistical inference for Model 1 and Model 2, the significant individual risk factors (p<0.01) included clinical variables such as disturbance of gait, hypertension and frequent urine (Table 4), and imaging features such as the WMH volumes within right superior cerebellar peduncle, retrolenticular part of internal capsule and cingulum (Table 5).ConclusionCombining clinical variables and MRI‐based features did not achieve better prediction of GDS than using either type of features alone. WMH in specific regions may have more independent contribution to depression than other MRI‐based imaging features. These findings may help to understand the risk factors of depression in community elderlies.
A preclinical model for modulation and characterisation of neuropsychiatric disturbances in Alzheimer’s disease
Authors: Clement Amalie , Wiborg Ove , Stensballe Allan , Asuni Ayodeji A. 
Published: December 2020

AbstractBackgroundThe events that direct the shift from asymptomatic to symptomatic Alzheimer’s disease (AD) have yet to be fully characterized, however the consensus is that neuropsychiatric disturbances (NPDs) play a significant role in this. Most AD patients (80‐97%) experience at least one NPD at least once during their disease, nevertheless recognizing and treating NPDs remain a major challenge due to the poor understanding of the underlying pathology. Inflammation is thought to contribute to NPD development and ultimately exacerbate AD pathology. In AD, sleep disturbances drive neuroinflammation processes, precede clinical symptoms, and increase the risk of developing AD. Neuroinflammation can also be associated with more server NPDs and is linked to faster cognitive decline and worse prognosis. Contrary to memory and learning, which is reasonably well modelled in transgenic animals, robust preclinical models for NPDs are still lacking. We hypothesis that circadian disruption combined with chronic mild stress can introduce sleep disturbances, alter phenotypic behavior, and exacerbate AD‐related neuropathology in a common mouse model of AD.MethodWe introduced socio‐environmental stress and circadian disruption to APPPS1 and wildtype (WT) littermates, to investigate NPD‐like behavior and changes in the proteome and transcriptome.ResultThis approach altered normal circadian rhythm activity patterns and induced subtle NPD‐like behavior in both WT and APPPS1 mice. Furthermore, these conditions changed normal transcription of clock genes, particularly transcription levels of Cry1, Per1 and Per2 were changed in WT and APPPS1 mice. β‐amyloid plaque load was elevated in prefrontal cortex of APPPS1 mice and we observed changes in the hippocampal proteome of APPPS1 and WT compared to WT and APPPS1 mice under normal conditions.ConclusionAlthough further characterization of the model is needed, we believe the model presented here can increase our understanding of the circuits responsible for NPD development in AD. This may hold the key to developing better treatments for NPDs and thus improving the quality of life for both AD patients and caregivers.