bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical versus neuropathological diagnosis in an ADRC sample: Factors impacting diagnostic concordance rates
Authors: Neugroschl Judith , Sewell Margaret , Haas Mikayla , Radler Keith , Purohit Dushyant , Grossman Hillel , Zhu Carolyn W. , Sano Mary 
Published: December 2020

AbstractBackgroundImproving clinical diagnostic accuracy and refining criteria is challenging in dementia research. To explore our ADRC’s diagnostic accuracy, a QI project was initiated to identify potential systemic areas affecting our center’s performance.MethodClinical consensus diagnoses were compared to the neuropathological findings of 68 ADRC brain bank participants between 2008‐2017. Concordance level (full, partial, discordant) was assigned by three authors (MS, JN, and HG) with input from our neuropathologist (DP). Fisher's exact test was used to examine concordance and Clinical Dementia Rating (CDR), race, age at death, education, number of visits, time between last visit and death, onset age, and depression.ResultsParticipants were 56% female, 88% non‐Hispanic white, education 14.6+/3.9 (range 2‐22), age of onset 71+/‐11 (range 47‐93), age at death 82.5+/‐10.4 (range 52‐102), CDR sum of boxes 12.8+/‐6.5, CDR Global 2.2+/‐1.03, number of follow‐up visits 2.5+/‐2.8, one visit only 40%, 56% had a visit within 18 months before death ( range 0‐132 months). Depression was present in 28%. Primary clinical diagnosis at death was 82.4% AD, 7.4% normal, 4.4% MCI, 2.9% DLB and 3% other. 88% were fully or partially concordant (clinical diagnosis matched at least one neuropathological diagnosis). Of the 8 discordant cases, 2 had no identifiable neuropathology despite dementia; 2 had tauopathies; 1 was an AD/FTD mismatch. Three who were >92yo had no clinical diagnosis but exhibited AD pathology. For partially concordant cases where the second diagnosis was mismatched, it was most frequently DLB (80%). Concordance rate was not associated with any of the above clinical/demographic variables except for CDR and race (p < 0.05). Regarding CDR, 5/8 (63%) discordant cases had a CDR of 0.5 (mild symptoms); the other three had a CDR of 3 (severe dementia). 3/8 minority cases were discordant but two had diagnoses currently only available at autopsy.ConclusionConsistent with the literature, the most common error was either missing DLB when present or diagnosing it when absent. No systemic issues were identified that contributed to inaccuracies.
Mild behavioral impairment checklist differentiates normal controls and MCI in a well‐characterized sample
Authors: Sewell Margaret , Neugroschl Judith , Zhu Carolyn W. , Krystal Hannah , Thepmankorn Parisa , Velasco Nelly , Martin Jane , Sano Mary 
Published: December 2020

AbstractBackgroundNeuropsychiatric symptoms (NPS) are common early signs of cognitive impairment and dementia. The Mild Behavioral Impairment (MBI) Checklist was created to capture these symptoms. Our objective was to use the MBI to measure NPS in non‐demented normal and MCI research participants and to identify associations among MBI and other established clinical and demographic measures.MethodsADRC participants with MCI (N=52) or NC (N=84) completed the MBI. The MBI’s 34 yes/no questions assess decreased motivation, emotional dysregulation, impulse dyscontrol, social inappropriateness, and abnormal perception/thought content. ‘Yes’ answers were ranked in severity on a Likert scale of 1 (Mild) to 3 (Significant). Responses were summarized to create global (range 0‐102, with lower scores representing fewer symptoms) and domain scores which were compared in MCI/NC groups. Correlations were run by diagnostic group for the MBI and the demographic and clinical variables. Multivariable regression models examined the relationship between MBI total and diagnosis after controlling for participant characteristics.ResultsThe characteristics of our total sample were: (mean±SD) age=76.6±8.2, 64% female, 56.4% non‐Hispanic white, 26.3% Hispanic,17.3% non‐Hispanic black, and education 15.3±4.1 years. As regards demographics, there were no statistical differences between NC and MCI. In the MCI group, the MOCA (lower), GDS, NPIQ, FAQ (higher) were all significantly different from the NC group (all p<0.05). MBI total was significantly higher in the MCI group (mean MCI 11.7±15.9, NC 5.2±8.0 p<0.001). MBI domain scores were significantly higher as well (all p<0.01) except for impulse control (p=0.07). For both the MCI and NC groups, MBI‐total was significantly negatively correlated with education and positively with depression in the past 2 years as well as current GDS (all p<0.05). In multivariate regression analyses these significant associations remained.ConclusionControlling for demographic factors and comorbidities, MBI scores are significantly different between normal controls and those with MCI.
NIA genetics of Alzheimer’s disease data storage site (NIAGADS): Update 2020
Authors: Vogel Briana , Kuzma Amanda B. , Valladares Otto , Greenfest‐Allen Emily , Klamann Conor , Issen Heather , Gangadharan Prabhakaran , Katanic Zivadin , Zhao Yi , Qu Liming , Lin Han‐Jen , Moon Michelle K. , Leung Yuk Yee , Naj Adam C. , Stoeckert Christian J. , Schellenberg Gerard D. , Wang Li‐San 
Published: December 2020

AbstractBackgroundNIAGADS is a national genetics data repository that facilitates access of genotypic data to qualified investigators for the study of the genetics of late‐onset Alzheimer’s disease (AD) and other neurological diseases. Collaborations with large consortia and centers such as the Alzheimer’s Disease Genetics Consortium (ADGC), Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, the Alzheimer’s Disease Genome Sequencing Project (ADSP), and the Genome Center for Alzheimer’s Disease (GCAD) allow NIAGADS to lead the effort in managing large AD datasets that can be easily accessed by the research community and utilized to their fullest extent.MethodNIAGADS is supported by National Institute on Aging (NIA) under a cooperative agreement (U24 AG041689). All data derived from NIA funded AD genetics studies are expected to be deposited in NIAGADS or another NIA approved site. NIAGADS manages a Data Sharing Service (DSS) that facilitates the deposition and sharing of genomic data and association results with approved users in the neurodegenerative research community. In addition, researchers are able to freely use the NIAGADS Genomics Database to search annotation resources that link published AD studies to AD‐relevant sequence features and genome‐wide annotations.ResultAs of January 2020, NIAGADS houses 67 datasets (23 added in 2019) with >59,000 samples and nearly 34 billion genotypes. Qualified investigators can retrieve ADSP sequencing data with ease and flexibility through the NIAGADS DSS. The ADSP and other contributing studies have completed whole exome sequencing (WES) of 20,630 subjects and whole‐genome sequencing (WGS) of 4,750 subjects. Raw WES and WGS files, quality controlled VCF files, and phenotype data files are available via qualified access. The next planned dataset release will occur in late 2020 and will contain an additional 13,136 genomes jointly genotype called with the first release of 4,750 genomes, totaling about 17,886 genomes.ConclusionNIAGADS is a rich resource for AD researchers, with the goal of facilitating advances in Alzheimer’s genetics research. By housing datasets from multiple projects and institutions, NIAGADS enables AD researchers to be more efficient in meeting their research goals. Datasets, guidelines, and new features are available on our website at https://www.niagads.org.
A newly developed amnestic subjective cognitive decline questionnaire shows high internal consistency and inter‐rater reliability
Authors: Flores‐Vazquez Juan Francisco , Acosta‐Castillo Gilberto Isaac , Contreras‐López José Juan , Cruz‐Contreras Cecilia , Aleman André , Enriquez‐Geppert Stefanie , Sosa‐Ortíz Ana Luisa 
Published: December 2020

AbstractBackgroundSubjective cognitive decline (SCD) represents a state in which a participant perceives a decline in cognitive functions, yet standardized psychological tests remain within expected performance compared to age‐ and education‐matched controls. SCD is growingly recognized as a risk state for mild cognitive decline (MCI), and eventually, dementia. In this study, we introduce a newly developed Amnestic Subjective Cognitive Decline questionnaire (aSCDq), an instrument with four screening and five severity items (Table 1). We present preliminary internal consistency and inter‐rater reliability results.MethodWe analyzed the clinimetric data from 52 older adults (age 67.2 ±4.4 years), 9 diagnosed with amnestic Mild Cognitive Impairment (MCI), 16 with amnestic Subjective Cognitive Decline (aSCD), and 27 healthy older adults (HOA). We used polychoric correlation matrixes in a principal component analysis to assess the internal consistency of the four screening items, and to analyze the correlation between subject and informant response in all items.ResultHigh internal consistency was found regarding the four screening items, resulting in a single component with an eigenvalue of 3.3, and 0.83 explained variance. High inter‐rater correlations in all screening items were found (1: 0.9, 2: 0.8, 3: 0.5, 4: 0.7), with more variable correlations demonstrated in severity items (s1: 0.3, s2: 0.5, s3: 0.7, s4: 0.9, s5: 0.6). Higher scores (i.e. worst memory complaints) were consistently reported by subjects in HOA and aSCD groups, and by informants in the MCI group.ConclusionBased on these preliminary results, the aSCDq has been shown to be a consistent and reliable tool to determine aSCD in older adults. The inter‐rater differences are slight but consistent with previous literature. For a full validation of this instrument, a higher number of participants will be necessary.
Baseline cognitive assessment in the Life After 90 Study: A racially/ethnically diverse cohort of people age 90 and older
Authors: Petrosyan Diana , Demos Asmeret , Ganzon Czarina , Popovich Oksana , Gaied Reham , Johal Sharan , Corrada Maria M.M. , Kawas Claudia H. , Whitmer Rachel A. , DeCarli Charles 
Published: December 2020

AbstractBackgroundThe prevalence of Alzheimer’s disease and related disorders increase with age and is particularly high among the growing segment of oldest‐old (≥90 years). Despite considerable research in this area, a significant gap still exists in the epidemiology of these diseases among ethnic minorities.The LifeAfter90 Study is an ongoing prospective study of long‐term members of Kaiser Permanente Northern California Health Care System (KPNC) older than 90 without a diagnosis of dementia in their medical records. The study aims to explore racial differences in the incidence of cognitive impairment, identify its determinants, and understand the pattern of brain pathologies in an oldest old population of Blacks, Asians, Hispanics and Whites (enrollment goal=800). This abstract presents descriptive analyses of the first 383 participants enrolled.MethodParticipants receive clinical assessments every 6 months including collection of health history, physical and neurological examination, Clinical Dementia Rating Scale (CDR), Modified Mini‐Mental State Exam (3MS), Functional Activities Questionnaire (FAQ) and Short Physical Performance Battery (SPPB).ResultMost individuals had normal cognition (55.4%), were female (63.4%) and white (42.3%) at a mean age of 93.6 years at enrollment (Table). Participants reported their health as generally good, although 11% had dementia at initial evaluation. Individuals with dementia were significantly older. No association was identified between race/ethnicity and cognitive status. Higher education (≥high school diploma) was more common among the normal cognition (NC) group. Participants with mild cognitive impairment and dementia had significantly lower SBBP scores (5.7 and 3.7 respectively) compared to people with NC (6.8). Functional scores due to cognitive difficulties showed the same trend across level of cognitive ability. Surprisingly, vascular disease was more prevalent among individuals with NC (Table). Logistic regression analysis that included age, race/ethnicity, gender, education and SPPB scores, found a high sensitivity and specificity for dementia (ROC=0.96) based on 3MS and cognitive FAQ (Figure).ConclusionThe oldest old are a select group of the growing population who may escape major illnesses or delay their onset toward the end of life. Preliminary analysis of this population identifies discrepancies of great importance to be further explored once the enrollment is completed.
The FNAME yields equivalent results differentiating amnestic mild cognitive impairment from subjective cognitive decline and healthy controls in Mexico and the Netherlands
Authors: Flores‐Vazquez Juan Francisco , Van der Kolk Iris , Contreras‐López José Juan , Cruz‐Contreras Cecilia , Stegeman Rutger A. , del Pilar Andrés‐Benito María , Acosta‐Castillo Gilberto Isaac , Aleman André , Sosa‐Ortíz Ana Luisa , Enriquez‐Geppert Stefanie 
Published: December 2020

AbstractBackgroundThe Face‐Name Associative Memory Exam (FNAME) has been shown to detect memory deficits early in the spectrum of Alzheimer’s disease. In this study, we used a newly developed and further extended version of the FNAME, to evaluate the discriminating ability of this test in amnestic cognitive decline (aMCI), amnestic subjective cognitive decline (aSMD), and healthy controls (HC) in two different cultures, namely Mexico and the Netherlands.MethodParticipants were recruited in two sites, in Mexico (n= 69) and the Netherlands (n= 55). The mean age of the subjects was 69.3 ±6 years, and the mean years of education 15.5 ±5 years. In this study we used a newly extended version of the FNAME that was developed in both countries concurrently. A total of 42 aMCI, 43 aSCD, and 32 HC were assessed. We used a mixed model ANOVA, with the factors FNAME (7 subtests), GROUPS (aMCI, aSCD, HC), and the SITES (Mexico, the Netherlands) and post hoc t‐tests.ResultCrucially, a high interaction of FNAME x GROUPS was revealed. Subsequent t–tests showed that the FNAME was able to detect differences between aMCI and aSCD/HC. No significant differences were observed between aSCD and HC. The three‐way interaction’s effect was non‐significant (F= 1.7, p= 0.07). As expected, we found a significant main effect of FNAME (F= 228.4, p< 0.001) demonstrating differences of demands of the subtests (e.g., recall, recognition), as well as a main effect of GROUPS (F= 2.1, p= 0.02). A two‐way interaction of FNAME x SITES was similarly revealed (F= 2.95, p< 0.001), reflecting a difference regarding the performance between sites.ConclusionThis newly adapted and extended version of the FNAME test is able to differentiate aMCI subjects from aSCD and EC both in Mexico and in the Netherlands. Further studies should focus on better understanding the differences in performance in these countries.
Integrity of the blood‐brain barrier and changes in the microvasculature during the progression of Alzheimer’s disease in the 3XTG‐AD model
Authors: Islas‐Hernandez Azul , Garcia‐Delatorre Paola 
Published: December 2020

AbstractBackgroundThere is evidence that vasculature failures are related with the development of Alzheimer´s. Between 60 and 90% of patients with AD present with pathologies of cerebrovascular disease. The blood brain barrier (BBB) is a highly selective, semipermeable chemical and structural barrier that ensures a stable internal environment in the brain. BBB dysfunction was initially identified in animal models for AD, and confirmed in patients. To date it is not clear how it originates. Physically, BBB endothelial cells are bound by tight junction complexes (TJ), formed by plasma membrane proteins, such as ocludins and claudins and cytoplasmic scaffolding proteins, such as ZO1. The study of changes in the expression of TJ proteins in a 3xTg‐AD mouse model at different ages will allow us to determine if damage to the BBB occurs before the appearance of amyloid‐β plaques.MethodThe animal's brain (3xTg‐AD mice of 9 and 13 months) is removed. Subsequently, the microvasculature is precipitated by density‐dependent centrifugation through the use of a solution with dextran, managing to separate the cerebral parenchyma and the myelin from the microvasculature. Once the microvessels are obtained, we incubate with anti‐ZO‐1, claudin‐5 and ocludin fluorescent primary antibodies and secondary antibodies (Alexas 488 and 546) and Hoechst 33342. Isolated microvessels are mixed with a fluorescent mounting medium (Fluoromount), mounted on slides and covered with a coverslip. Once mounted, they are scanned with a confocal laser scanning microscope.ResultWe found a decrease in the expression of tight junction proteins in 3xTg‐AD mice of 13 months compared to the same model but at 9 months and also compared to control animals. Morphological differences were also observed in the microvessels of the animals 3xTg‐AD in comparison with the WT and between the animals of 9 and 13 months, with morphological damage being more evident in the older animals.ConclusionThis could be telling us that the BBB is compromised. We still have to analyze the association between this decrease in TJ proteins and the accumulation of beta‐amyloid, in addition to analyzing it at earlier ages in order to establish from what age these changes in this murine model are measurable.
Pain and behavioral subgroups among nursing home patients with worsening cognition: A latent transition analysis
Authors: Forrester Sarah N. , Jesdale William , Morrison Reynolds , Lapane Kate L. 
Published: December 2020

AbstractBackgroundPrevalence estimates of pain in nursing home patients with dementia range from 40% ‐ 60% however pain among those who have difficulty with self‐report such as those with dementia is often missed. Pain scales may miss some key indicators of pain such as aggressive behavior (physical and verbal) and rejection of care, particularly among those who have cognitive difficulties. The purpose of this study was to utilize measurements of staff‐assessed pain, agitated and reactive behavior, functional status, and symptoms of depression to uncover non‐traditional pain subgroups.MethodThe Minimum Data Set 3.0 contains information on the health and functional status of every nursing home resident in Medicare/Medicaid certified nursing homes in the United States. Only patients who had staff assessed pain at admittance, 3 months, and 6 months, and thus were unable to self‐report pain, were included in the analysis (n = 26,816). Latent class analysis was used first to classify subgroups of pain, depression, functional status, and behavioral symptoms and then latent transition analysis was used to measure if and how patients moved between these subgroups at 3 and 6 months given if their cognition (measured by the Cognitive Performance Scale) got worse or had no change/got better.ResultThe latent class analysis revealed 5 classes: behavioral plus depression, functional, physical, behavioral, and low classes. At all time‐points the functional class was the most prevalent (∼28%) and the behavioral plus severe depression was the least prevalent (∼8%). Among those with worsening cognition, pain manifesting as behavioral symptoms in addition to depression remained largely unchanged in the first three months but partially transitioned to a subgroup characterized by physical dependence or remained the same by 6 months. Among the same group, pain manifesting as behavioral symptoms without depression largely stayed the same from admittance to month 3 with some movement to the behavioral plus depression and physical subgroups and largely stayed in the behavioral class by month 6.ConclusionThis may indicate that pain manifesting as behavioral symptoms is not being properly treated among those with worsening cognitive function.
Aβ‐potentiated and Aβ‐independent age‐related opacity changes in the lens of the eye in wild‐type and APPswe transgenic mice
Authors: Moncaster Juliet A. , Minaeva Olga , Goldstein Lee E. 
Published: December 2020

AbstractBackgroundThe lens of the eye is composed of crystallin proteins. These proteins have been shown to interact with Aβ in particular in Alzheimer’s disease. Crystallin proteins undergo various post‐translational modifications during aging that disrupt the normal functioning of these proteins resulting in protein aggregation and light scattering. We expand on our previous work and investigated here the aging effect on lens opacity in an Aβ‐independent (wild‐type mice) and Aβ‐potentiated (Alzheimer’s disease transgenic mice [APPswe]) environment.MethodMice were bred, maintained and genotyped at Boston University. Mice were sacrificed at ages 8‐35 months, perfused with phosphate buffer saline, lenses were isolated and imaged under two different sources of light using a D70 digital Nikon camera and a Zeiss stereophotomicroscope.ResultWild‐type aged mice demonstrated light scattering and opacities in two distinct regions of the lens in aged mice compared to younger mice. Moreover, APPswe aged mice showed increased scattering in the outer layer compared to wild‐type aged mice.ConclusionTwo distinct light scattering regions of the lens are affected during aging involving Aβ‐potentiated mechanisms in APPswe mice and Aβ‐independent mechanisms in wild‐type mice.
Effect of carbamylated erythropoietin FC fusion protein (CEPO‐FC) on learning and memory impairment and hippocampal apoptosis induced by intracerebroventricular administration of streptozotocin in rats
Authors: Moosavi Maryam , Hooshmandi Etrat , Javadpour Pegah , Maghsoudi Nader , Katinger Hermann , Ghasemi Rasoul 
Published: December 2020

AbstractBackgroundIntracerebroventricular (ICV) administration of streptozotocin (STZ) has been used as a metabolic model of sporadic Alzheimer’s disease (AD). Erythropoietin (EPO) possesses neuroprotective and memory‐improving effects, which might be advantageous in treating different characteristics of AD. Nevertheless, the hematopoietic effect of EPO has hindered its application as a neuroprotective agent. Previous studies have shown that a new Epo derivative called carbamylated Erythropoietin‐Fc (CEPO‐Fc), yield noticeable neuroprotective effects without affecting hematopoiesis. In this study, the neuroprotective effects of CEPO‐Fc on icv‐STZ induced memory impairment and hippocampal apoptosis were examined.MethodAdult male Wistar rats weighing 250‐300 g were used. STZ was administered on days 1 and 3 (3 mg/kg in divided doses/icv), and CEPO‐Fc was administered at the dose of 5000 IU/ip/daily during days 4‐14. The animals were trained in Morris water maze during days 15‐17, and the memory retention test was performed on the 18th day. Following behavioral studies, the animals were sacrificed and their hippocampi isolated to determine the amounts of cleaved caspase‐3 (the landmark of apoptosis).ResultThe results showed that CEPO‐Fc treatment at the dose of 5000 IU/kg/ip was able to prevent the learning and memory deficit induced by icv‐STZ. Western blot analysis revealed that STZ prompted the cleavage of caspase‐3 in the hippocampus while pretreatment with CEPO‐Fc significantly reduced the cleavage of this protein.ConclusionCollectively, our findings suggest that CEPO‐Fc could restore STZ‐induced learning and memory impairment as well as apoptosis in the hippocampal region in a rat model of sporadic AD induced by icv‐STZ.