bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel type of amyloid‐beta plaques identified in early‐onset AD
Authors: Boon Baayla D.C. , Bulk Marjolein , Jonker Allert J. , Popovic Marko , Walter Jochen , Kumar Sathish , Natte Remco , van der Weerd Louise , Bouwman Femke , Van de Berg Wilma D.J. , Hoozemans Jeroen J.M. , Rozemuller Annemieke J.M. 
Published: December 2020

AbstractBackgroundThe clinical presentation of Alzheimer’s disease (AD) including age at onset, is remarkably heterogeneous. In previous research, we showed that inflammation is differently distributed between typical and atypical AD (Boon et al., 2018). In addition, distinct Aβ deposits in AD pathology are recognized. These deposits are called plaques when located in brain parenchyma or cerebral amyloid angiopathy (CAA) when located in the cerebral vessels. Recently, we described a novel Aβ plaque‐type, referred to as ‘the coarse‐grained plaque’. In this study, we evaluate its clinical relevance and perform in‐depth morphological characterization.MethodThe coarse‐grained plaque’s presence was investigated in the frontal cortex of Aβ‐pathology‐positive cases (N=74), including non‐demented controls (n=15), early‐onset (EO)AD (n=38), and late‐onset (LO)AD (n=21), using a semi‐quantitative approach. Main plaque characteristics were compared to other well‐defined Aβ deposits; the classic cored plaque, the cotton wool plaque, and CAA. In‐depth characterization was done by studying the coarse‐grained plaque’s Aβ isoform (Aβ40, Aβ42, AβN3pE, and pSer8Aβ) composition, neuroinflammatory component, and vascular association using immunohistochemistry and 3D confocal laser scanning microscopy imaging.ResultThe plaque was only observed in cases with clinical symptoms, it was more prominent in EOAD (95%) than in LOAD (66%) and was associated with a homozygous ApoE4 status (Figure 1). The coarse‐grained plaque showed a multi‐cored Aβ morphology and was seen in the proximity of CAA‐affected sulci. Its predominant Aβ40 composition was distinct from other plaques, but showed similarities to that of CAA (Figure 2A). 3D imaging revealed a unique hollow Aβ40‐shell structure (Figure 2B) with microglia in Aβ‐devoid holes (Figure 3). Furthermore, the plaque’s immunoreactivity for the CAA‐Type 1 specific marker norrin suggests – although having a different morphology ‐ a close etiological relation with CAA.ConclusionThe coarse‐grained plaque is a clinically relevant Aβ deposit as it occurs only in clinical AD and is more frequent in early‐onset cases. The plaque is strongly associated with neuroinflammatory and vascular changes. Differences in presence of coarse‐grained plaque among AD subtypes, contributes to the compiling evidence that also pathophysiology in AD is heterogeneous.
Differentiating among stages of cognitive impairment: Comparisons of versions two and three of the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set (UDS) neuropsychological test battery
Authors: Dodge Hiroko H , Goldstein Felicia C , Wakim Nicky I , Gefen Tamar , Teylan Merilee , Kukull Walter A , Barnes Lisa L , Giordani Bruno , Hughes Timothy M , Kramer Joel H , Loewenstein David A , Marson Daniel C , Mungas Dan M , Sachs Bonnie , Salmon David P. , Steenland Kyle , Parker Monica W , Welsh‐Bohmer Kathleen A , Morris John C , Weintraub Sandra ,   National Alzheimer's Coordinating Center
Published: December 2020

AbstractBackgroundNational Institute on Aging (NIA)‐funded Alzheimer’s Disease Centers in the United States have been using a standardized neuropsychological test battery as part of the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set (UDS) since 2005. Version 3 (V3) of the UDS was implemented in 2015 and included several changes to its neuropsychological battery, replacing the previous version [Version 2 (V2)]. The current study compares the V3 and V2 neuropsychological batteries with respect to their ability to distinguish among categories of cognitive impairment captured by the Clinical Dementia Rating (CDR) global scores representing either no cognitive impairment (CDR=0), questionable or mild cognitive impairment (CDR=0.5) or mild stage of dementia (CDR=1.0).MethodData from the NACC UDS V2 and V3 neuropsychological batteries were examined. There were 16,935 unique subjects from V2 and 5022 unique subjects from V3 aged 60 years and older with CDR global score ≤ 1. To reduce the influence of practice effects, only data from their first assessment was used. To control for inequalities in sample sizes between V2 and V3, we identified an approximately equal number of subjects from V2 within each CDR group. Receiver Operating Characteristics Area under Curve (ROC‐AUC) in differentiating stages of cognitive impairment were compared and optimal cut‐points based on Youden’s J scores were calculated.ResultROC‐AUCs from all of the V3 neuropsychological tests were comparable in their ability to differentiate CDR global scores with the corresponding tests in V2, despite the fact that V3 participants included more subjects at earlier stage of CDR 0.5. UDS V3 composite scores yielded similar ROC‐AUCs to the best performing individual test within each domain, while the Montreal Cognitive Assessment (MoCA) total score yielded higher ROC‐AUCs than any individual MoCA index scores. Racial differences in differentiating between CDR=0 and CDR=0.5 were also found.ConclusionA nonproprietary suite of neuropsychological tests in UDS V3 provided similar discriminative ability to tests in UDS V2 to distinguish categories of cognitive impairment. Optimal cut‐points calculated in this study will be useful for clinical diagnosis.
Amyloid (a), tau (t) and voxel‐based morphometry (n) correlates of visual memory performance
Authors: Arias Jaime Fernandez , Pascoal Tharick A. , Benedet Andréa Lessa , Therriault Joseph , Kang Min Su , Savard Melissa , Mathotaarachchi Sulantha , Lussier Firoza Z. , Tissot Cecile , Gauthier Serge , Rosa‐Neto Pedro 
Published: December 2020

AbstractBackgroundThe Aggie Figures Learning Test (AFLT) is a memory test that was designed to be a visual analogue of the Rey Auditory Verbal Learning Test (RAVLT). Previous studies have found associations between tau and amyloid PET and brain volume and RAVLT scores. However, to date, no study has explored the associations between these markers and AFLT scores. We aimed at exploring such associations.MethodsStructural MRI, amyloid PET ([18F]‐NAV4694) and tau PET ([18F]‐MK6240) were acquired for 161 individuals. We conducted analyses on two sub‐samples. Demographic data is shown on Tables 1 and 2. MRI were segmented into probabilistic grey (GM) and white (WM) maps, non‐linearly registered to the ADNI template using Dartel and smoothed with an 8mm FWHM gaussian kernel. Voxel‐wise linear regression models were applied, using VoxelStats, with AFLT sub‐scores as dependent variables and either tau and amyloid binding or Voxel‐Based Morphometry as predictors. We corrected for sex, Apoe genotype, age and years of education.ResultsWe found negative associations between tau binding and AFLT total (trials 1‐5) and AFLT delayed recall (DR) scores in the MTL and temporo‐occipital cortices, as well as in some of their WM tracts. These associations were stronger for the total scores and, in both cases, in the right hemisphere. For the amyloid biomarker, associations with AFLT total and AFLT DR scores were negative in right ventromedial PFC, right posterior thalamus and basal ganglia. In this case, strongest associations are reported between amyloid burden and AFLT DR scores. Finally, we found positive associations between AFLT total and DR scores and VBM in the fusiform gyrus bilaterally.ConclusionsResults resemble previously reported findings on associations between RAVLT and tau, amyloid and brain volume estimates. Our findings are also in line with initial reporting of patients with right hemisphere damage having difficulties with AFLT tasks (Madjan, et al. 1996). In addition, relationships with tau tend to be more posterior, while relationships with amyloid were shown to be more anterior. Further analyses based on diagnostic categories are needed to explore how these associations change with pathology.
Dynamic network connectivity alteration predicts cognitive decline in Alzheimer’s disease spectrum
Authors: Wang Qing , He Cancan , Xie Ming Chun 
Published: December 2020

AbstractBackgroundBrian network integrity plays a pivotal role in the regulation of high‐order cognitive function and emotion for human brain. Disrupted functional coupling within‐ and between resting‐state networks (RSNs) are selectively vulnerable for neurodegenerative disease, such as Alzheimer’s disease. However, dynamic network alteration and its molecular pathological basis following the disease course in the AD spectrum still remain unclear. Currently, we integrated a new method combination of large‐scale network analysis and canonical correlation analysis (CCA) to explore dynamic spatiotemporal patterns within‐ and between RSNs and their significance in the AD spectrum.MethodWe analyzed data from the Alzheimer’s Disease Neuroimaging Initiative 1, GO and 2 datasets. A total of 160participants (59 cognitively normal (CN) participants, 49 patients with early mild cognitive impairment (EMCI), 28 patients with late mild cognitive impairment (LMCI) and 24 AD patients) completed fMRI scan, 3T MRI brain scan, CSF biomarkers and genes which strongly tied to AD risk detection and cognitive function assessment (MMSE and ADAS‐Cog scores). We studied group differences in within‐ and between RSNs. For cognitive function, genes and biomarkers, we did canonical correlation analysis between gene scores, cognitive scores , the biomarker levels and network variables across disease spectrum.ResultWe identified that all RSNs represented the increase connectivity within networks by enhancing inner cohesive ability, while seven out of ten RSNs were characterized by the decreased connectivity between networks, which indicates weaken connector ability among networks from the early stage to dementia. This dichotomous mode presenting large‐scale dynamic network abnormality was significantly correlated with the levels of molecular biomarkers (amyloid‐β, Tau, p‐Tau), cognitive performance, as well as accumulating effects of AD‐related ten genetic risk factors. This study implicated that spatiotemporal pattern of large‐scale network connectivity failure was not cascading, but represented a bouncing mode with the progression of cognitive decline. Taken together, we identified the determinants of the spread of disrupted network incoherence, molecular correlates, and summative effects of genetic variants on the RSNs.ConclusionThese findings provide novel insights for better understanding the mechanism underlying large‐scale network disruption linking molecular biomarkers and phenotypic variations in the AD spectrum.
Modifiable risk factor possession patterns of dementia in elderly with mild cognitive impairment: A 4‐year longitudinal study
Authors: Katayama Osamu , Lee Sangyoon , Bae Seongryu , Makino Keitaro , Shinkai Yohei , Chiba Ippei , Harada Kenji , Shimada Hiroyuki 
Published: December 2020

AbstractBackgroundWe clarified modifiable risk factor patterns of dementia in elderly patients with mild cognitive impairment (MCI) and determined the relationship between retention patterns and reversion from MCI over a 4‐year follow‐up.MethodParticipants were 5104 older adults who completed the National Center for Geriatrics and Gerontology‐Study of Geriatric Syndromes (NCGG‐SGS) examinations in August 2011–February 2012; 3095 (60.6%) completed the second‐wave cognitive examination in August 2015–August 2016. Among the longitudinal data, missing values were imputed for 789 community‐dwelling people who were aged ≥65 years (mean age, 72.0±5.4 years; 368 men and 421 women) with MCI and classified them as “reverters” and “nonreverters.” Longitudinal analysis was performed after missing values resulting from dropout were imputed. Nine modifiable risk factors at baseline—namely, less education, hearing loss, hypertension, obesity, smoking, depression, physical inactivity, social isolation, and diabetes—were classified in latent class analysis. In subsequent binomial logistic regression analysis, reversion status was the dependent variable (the nonreverters served as a reference group) and cluster membership the independent variable.ResultOf the 461 participants for whom data were not imputed, 234 (50.8%) reverted from MCI to normal cognitive status. Reversion rate among the 789 participants for whom we imputed data was 30.9%. The modifiable risk factors among participants with MCI were classified into five patterns: low‐risk, psychosocial, health behavior, educational, and smoking factors. According to logistic regression analysis, people with low‐risk factors were more likely to revert from MCI to normal cognitive status than were patients with the other factors (P<.05).ConclusionWe formulated five patterns of modifiable risk factors among elderly people with MCI. Participants with low‐risk factors were more likely to recover from MCI than participants with the other factors. These results may provide useful information for designing interventions to prevent cognitive decline and dementia in individuals with MCI.
AD biomarker stability for stored CSF based on immunoassay results
Authors: Vandijck Manu , Bastard Nathalie Le , Persson Staffan , Zetterberg Henrik , Blennow Kaj , Kostanjevecki Vesna 
Published: December 2020

AbstractBackgroundDiagnosis of Alzheimer’s Disease (AD) is currently more often based on a clinical assessment combined with biomarker data. For AD, four core cerebrospinal fluid (CSF) biomarkers have been identified and levels are determined on measurements with various immunoassays (INNOTEST, Lumipulse, Elecsys, etc.). Each assay has its own concept (technology, antibodies, protocol) and performance characteristics.The Alzheimer’s Association Quality Control (AA‐QC) program lead by the University of Gothenburg aims to monitor the inter‐laboratory variation for immunoassays for CSF biomarkers using a set of CSF samples (2 round specific & 1 longitudinal), periodically measured at participating sites.Biomarker levels over time of the longitudinal QC CSF sample (2016QC‐L) on the different immunoassays can be interpreted to assess long‐term stability. This is relevant given that CSF samples are often stored in a biorepository as part of a study cohort for future assessment of (new) biomarkers.MethodIn the AA‐QC program, immunoassays for the different AD CSF core biomarkers (Aβ1‐42, Aβ1‐40, total‐Tau, and pTau181) from different suppliers are tested three times per year with 2016QC‐L. The average result per immunoassay for this sample since round 22 (October 2016) till round 31 (October 2019) were analyzed, considering round 22 as start of storage.ResultFor all four CSF biomarkers, the coefficient of variation (CV) per immunoassay obtained over all round averages was below 10% (except one). The CVs ranged from 2% to 10% for Aβ1‐42, 1% to 8% for Aβ1‐40, 1% to 17% for total‐Tau, and 1% to 9% for pTau181, indicating relatively stable concentration assignment over time, despite the use of different batches. For each biomarker, no consistent trend in analyte concentration over all immunoassays in function of time was observed.ConclusionFor the CSF sample analyzed, AD core biomarkers are stable over the follow‐up period of 36 months. The results of the different immunoassays all show a comparable behavior of the analyte concentration over time. These results from Clinical Chemistry practice confirm the long‐term stability of the core CSF biomarkers, lending further support for their use in clinical research studies and therapy monitoring in clinical trials, where stored samples are often analyzed in batch at end‐of‐study.
A case of amyotrophic lateral sclerosis with frontotemporal dementia manifested as naming and sentence comprehension disorder
Authors: Zhang Yuan , Yang Bo , Chen Qidong , Shi Jiong , Xu Jun 
Published: December 2020

AbstractBackgroundApproximately half of the patients with motor neuron disease (MND) will develop frontotemporal dysfunction. Most of case reports showed a strong association between amyotrophic lateral sclerosis (ALS) and behavioral variant frontotemporal dementia (bvFTD) and mostly presented as FTD at the onset, while the relationship between ALS and primary progressive aphasia (PPA) has not been fully understood.MethodA patient suspected to be ALS‐PPA admitted to Beijing Tiantan Hospital, Capital Medical University in January 2020. We want to describe this case to summarize its clinical characteristics.ResultThe patient is 70 years old,female, illiteracy and with severe hearing impairment. She developed bulbar paralysis manifestations like hoarseness, dysarthria and dysphagia without obvious mental, character and behavior changes in the course of the disease.Both upper limbs tendon reflex was hyperactive and lower limbs tendon reflex was decreased. Sucking reflex existed. Neuropsychological test suggested dementia, impaired naming and sentence comprehension. Electromyography suggested neurogenic changes around the upper and lower extremities. Magnetic resonance imaging showed symmetrical anomaly signal of bilateral basal ganglia, where manifested as low metabolism on PETCT. Amyloid β (1‐42) was elevated, the total protein Tau was reduced and the phosphorylated tau protein was normal in cerebrospinal fluid.ConclusionALS‐PPA is a relatively rare disease. Sometimes maybe genetic and pathological examinations are required for diagnosis.
Power and functional connectivity of alpha oscillations in mild cognitive impairment: A systematic review and meta‐analysis
Authors: Lejko Nena , Larabi Daouia I , Herrmann Christoph S , Aleman André , Ćurčić‐Blake Branislava 
Published: December 2020

AbstractBackgroundAlzheimer’s disease (AD) is sometimes preceded by a less severe decline in cognitive abilities called mild cognitive impairment (MCI). Having affordable and non‐invasive biomarkers of MCI would ease diagnosis, improve prognosis, and open up possibilities to delay the transition to AD. One potential biomarker is alpha oscillations measured with electroencephalography (EEG) that have been found to differ between cognitively intact older adults (OA) and people with AD. To find whether these changes can already be detected in MCI, we reviewed studies that compared alpha power and functional connectivity in people with MCI and OA, in people with MCI and people with AD, and in people with MCI who progress to AD and those who do not.MethodWe searched for records published until 24 January 2020 using search terms “mild cognitive impairment” AND (eeg OR oscillations). 65 studies were included in the review. We conducted four random effects meta‐analyses. We compared resting state power in people with MCI and OA in the full alpha band (∼ 8‐12 Hz; k=5; n=198 MCI, 258 OA), in lower alpha frequencies (∼ 8‐10 Hz; k=5; n=196 MCI, 203 OA), and in upper alpha frequencies (∼ 10‐12 Hz; k=5; n=131 MCI, OA 139). We also compared resting state power in the full alpha band in people with AD and people with MCI (k=6; n=481 AD, 499 MCI).ResultIn the full alpha band, resting state power was lower in people with AD than in people with MCI (ES=‐0.30, 95% CI=‐0.51, ‐0.10, p=0.003), and in people with MCI than in OA (ES=‐1.49, 95% CI=‐2.69, ‐0.29, p=0.02). Reviewing the literature showed that resting state alpha power is lower in people with MCI who eventually progress to AD than in those who do not. During task performance, alpha activity changed less in people with MCI than in OA. Studies that compared functional connectivity between the three groups reported inconsistent results.ConclusionLower resting state alpha power, that has been found in people with AD can, though to a lesser degree, also be detected in people with MCI, especially those who are on a trajectory towards AD.
The Mini Linguistic State Examination (MLSE): A standardised tool to classify and monitor primary progressive aphasia
Authors: Patel Nikil , Peterson Katie A. , Ralph Matthew L. , Rowe James B. , Patterson Karalyn , Cappa Stefano , Ingram Ruth , Garrard Peter 
Published: December 2020

AbstractBackgroundLanguage assessment is critical in the diagnosis of patients with neurodegenerative diseases, in particular those presenting with progressive speech and language impairment such as the primary progressive aphasias (PPA). Current diagnostic criteria identify three main variants of PPA based on clinical and neuroimaging features: semantic variant PPA ‐ characterised by dramatically reduced ability to understand the meaning of words and objects; nonfluent variant PPA – featuring problems with the grammatical and phonetic aspects of language production; and logopenic variant PPA – characterised by a striking inability to repeat spoken sentences. Most currently utilised assessments of the heterogeneous language profiles of PPA are time‐consuming and not readily comparable across languages. Improved tools to screen, diagnose, and monitor these conditions will be essential to progress in the characterisation and treatments for brain diseases underlying PPAs. The aim of the current project is to develop and fully validate English and Italian versions of an abbreviated language assessment instrument, the Mini Linguistic State Examination (MLSE), which will be able to detect the differing patterns of linguistic deficit that characterise the three variants of PPA with complete equivalence between English and Italian versions.MethodsParticipants completed the MLSE test which included tasks of picture naming, word and sentence repetition, word and sentence comprehension, semantic association, reading, writing, and picture description.ResultsData were used to present contrasting characteristics of the MLSE performance in 61 patients with PPA (20 PNFA, 17 SD, and 24 LPA), and a matched control group (40 controls; aged: 45‐75 years).ConclusionsThe MLSE will provide a much‐needed short clinical tool to classify and monitor PPA. Additionally, the MLSE will be a template for further language‐specific versions.