bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of presentation modality on cognitive test performance for adults with hearing loss
Authors: Goodwin Maria V , Hogervorst Eef , Maidment David W 
Published: December 2021

AbstractBackgroundThere is a growing body of evidence demonstrating hearing loss in middle‐aged and older adults is independently associated with an increased risk of developing cognitive‐decline and dementia. Verbal memory is one of the most common functions to decline early in Alzheimer’s disease, the most common form of dementia Whilst the exact mechanisms underlying this association remain unclear, poorer test performance may reflect an overarching sensory deficit, as, for instance, most verbal memory tests are predominantly delivered auditorily. Therefore, this study aimed to investigate whether different modes of presentation (i.e., visual, or auditory) influence verbal memory screening test performance in those who failed a hearing screener.MethodThe study was conducted via online video‐conferencing due to the COVID‐19 pandemic. Participants (N= 63) completed a validated hearing screener, which was a digit‐in‐noise test delivered via the hearWHO smartphone application. Three cognitive tests were also administered: (1) the Modified Telephone Interview for Cognitive Status (TICS‐M), presented auditorily; (2) the Hopkins Verbal Learning Test (HVLT), presented visually; and (3) a verbal fluency task as a control. All tests have been used as dementia screening tests.ResultSeparate ANCOVAs revealed that, when controlling for age, gender, and education level, adults who failed the hearing screener performed more poorly on the TICS‐M compared to individuals who passed (p<.001). No differences between hearing groups were found for the other cognitive tests administered (p≥ .132).ConclusionThis study provides support for the notion that the presentation mode of cognitive tests may account for some of the deficits observed in older adults with hearing loss. As such, researchers and clinicians should be mindful of the sensory deficits experienced by individuals when interpreting cognitive test performance, to avoid the overestimation of cognitive deficits and dementia in adults with hearing loss.
Modeling AD‐related metabolic impairments in the TgF344‐AD rat model
Authors: Hernandez Abbi Lynn (R) , Ding Sarah L , Simley Alexis L , McMahon Lori L , Carter Christy S 
Published: December 2021

AbstractBackgroundAlzheimer’s disease (AD) not only affects cognition and neuropathology, but has several other facets capable of negatively impacting quality of life, including impaired metabolic function, which is present in ∼80% of cases. However, the influence of metabolism is seldom considered when utilizing rodent models of AD, particularly in conjunction with cognitive impairment and neuropathology. Therefore, we characterized metabolic and cognitive status of the TgF344‐AD rat model first presented in Cohen et al. in 2013.MethodAged (20‐26 mo) female rats were utilized. Metabolic health was characterized through body composition analysis, food consumption quantification, insulin and glucose tolerance tests and hypothalamic p‐AKT/AKT response to insulin. Cognition was assessed through object discrimination tasks, including novel object discrimination, working memory/object discrimination and working memory/biconditional association tasks. This series of increasingly complex behavioral tasks requires proper function of individual brain regions, as well as integration of information across these regions, in which AD‐related pathology is commonly observed.ResultAD rats required significantly more trials before reaching criterion performance across several tasks, including a working memory/object recognition task and a working memory/biconditional association task. However, there were no group differences in ability to perform a simple object discrimination, demonstrating all rats were able to participate procedurally, therefore differences in performance can be attributed to cognitive impairment. AD rats had significantly more body fat than WT, and lost significantly less weight than their wild type (WT) counterparts while relocating to our colony, despite consistent food consumption across groups. Moreover, glucose appears to be rapidly degraded in AD rats relative to WT controls, indicating significant differences in metabolic function across genotypes.ConclusionTogether, these data indicate that not only do we observe genotype‐specific deficits in cognitive function, but also that the transgenic rats metabolize their energy sources in different ways than WT littermates. The long range projection neurons required to support task acquisition are more metabolically costly than locally projecting neurons, and thus most likely affected by the impaired metabolic function in this rats. Therefore, treatments targeting these metabolic deficits may help prevent or ameliorate AD‐related cognitive decline.
The association between proactive semantic interference and blood sugar levels
Authors: Sosa Jaylene , Amaya Alexandra C , Gonzalez‐Jimenez Christian J , Gorman Katherine , Leal Eduardo , Kitaigorodsky Marcela , Curiel Rosie E , Loewenstein David 
Published: December 2021

AbstractBackgroundGlucose levels, together with hemoglobin A1c (HA1c), have been associated with reduced cognitive performance, particularly on executive functioning and memory measures. Numerous studies using the Loewenstein‐Acevedo Scales for Semantic Interference and Learning (LASSI‐L) have demonstrated that proactive semantic interference (PSI) and failure to recover from PSI (frPSI) are sensitive to early cognitive changes present in the preclinical stages of Alzheimer's disease (AD).MethodThe aim of the present study was to examine the association between PSI, frPSI, blood glucose levels, and hemoglobin A1c (HA1c) among cognitively normal middle‐aged adults. Seventy‐five adults (Age: 50.8 ± 6.67; Education: 16.23 ± 2.93; Sex: 68% female) without psychological disorders, substance use disorders, or previous cognitive diagnoses were recruited as part of a memory and aging study. Sixty‐seven participants identified as White (89%) and eight as African American (11%). They were fluent in English and/or Spanish and were tested in their dominant and preferred language (65% English, 35% Spanish), as assessed by the Language Experience and Proficiency Questionnaire. All participants underwent a neuropsychological evaluation and administration of the Clinical Dementia Rating Scale (CDR); all were diagnosed as cognitively normal by trained neuropsychologists. Participants fasted six to eight hours prior to providing a blood sample. Comparisons were made between participants using t‐tests and Chi‐square tests. An additional Spearman correlation was used to determine the relationship between the variables. Blood glucose and HA1c levels were compared to LASSI‐L scores, including the number of words correctly recalled and the number of intrusion errors (IE) on the PSI (List B Cued Recall 1) and frPSI (List B Cued Recall 2) trials.ResultThere was no significant association between glucose and the LASSI‐L Scales. However, higher HA1c levels were correlated with lower intrusion errors sensitive to proactive semantic interference.ConclusionOur findings are inconsistent with previous research, as an increase of blood glucose and HA1c levels have been formerly found to lead to reduced cognitive performance. Based on these findings, further investigations are warranted to better understand the associations between HA1C levels, proactive semantic interference, and varying cognitive domains.
Accelerated epigenetic aging in adults with Down Syndrome in the Argentine population
Authors: Clas Giulia Solange , Fernández Elmer A. , Vázquez Juan Carlos Guillermo , Pertierra Lucia , Guimet Nahuel Magrath , Tapajoz Fernanda , Helou Belén , Itzcovich Tatiana , Kennedy Micaela Barbieri , Martinetto Horacio , Sevlever Gustavo , Allegri Ricardo Francisco , Surace Ezequiel 
Published: December 2021

AbstractBackgroundLife expectancy of individuals with Down Syndrome (DS) is currently 60 years. From age 40 they have an increased risk of dementia and almost all of them have histopathological features of Alzheimer's disease (AD) in their brains. Also, it is known that the ε4 allele of the APOE gene and the R47H variant of TREM2 increase the risk of AD. DS is also associated with a group of clinical manifestations of accelerated aging. DNA methylation‐based biomarkers of ageing (epigenetic clocks) can be assessed by different models. It is known that DNA methylation age (DNAm) has a positive correlation with chronological age in disomic individuals while DS subjects exhibit an age acceleration effect in blood and brain.MethodWe determined the DNAm age of a cohort of seven participants with chromosome 21 trisomy (confirmed by G‐banding karyotyping). Median age was 49 years. Their cognitive status was assessed by clinical and neuropsychological evaluations. AD risk variants in APOE and TREM2 were analyzed by RFLP‐PCR. DNAm age was assessed in peripheral blood leukocytes, using the Illumina 850K platform. We used the Horvath’s epigenetic clock, based on the DNAm levels of 353 specific CpG sites.ResultFive participants exhibited the ε3/ε3 genotype in APOE and two of them the ε3/ε4 genotype. We did not observe the R47H risk variant in TREM2 in this group. Five participants showed a significant biological age acceleration and one participant’s DNAm age was similar to his chronological age. Of note, one participant showed a deceleration in the DNAm age. This participant also had multiple myeloma. It is known that the DNA methylation profile of multiple myeloma cells differs from normal plasma cells. On the other hand, we did not find a trend towards a greater presence of the risk allele ε4 or cognitive impairment in participants with a significant DNAm age acceleration.ConclusionThe majority participants presented an acceleration in their biological age, but this fact was not correlated with a greater presence of the risk allele ε4 or cognitive impairment. This is the first dataset of DNA methylation ages of a cohort of people with Down Syndrome in Latin America.
Comparison of latent cognitive reserve markers and a latent marker score in Alzheimer’s disease
Authors: Ersoezlue Ersin , Rauchmann Boris‐Stephan , Perneczky Robert ,   Alzheimer’s Disease Neuroimaging Initiative
Published: December 2021

AbstractBackgroundThe cognitive reserve (CR) hypothesis explains inter‐individual differences in the association between observed cognitive function and estimated neurodegenerative burden. Latent CR marker approach were suggested as a promising method to estimate cognitive reserve. We aimed to compare different CR marker approaches and test a clinical latent CR marker score.MethodAmyloid‐β (Aβ)‐negative and cognitively normal participants were included as healthy controls (HC) and Aβ‐positive and clinically impaired participants were included as AD spectrum (ADS) from the AD Neuroimaging Initiative (ADNI) study as two separate CSF data‐only discovery and a PET data‐only replication cohorts. A latent CR marker factor (CRM‐Factor) was obtained as the latent global cognitive domain score (gCDS) through a principal component analysis remaining after accounting for neuropathological burden and demographic variables. A residual CR marker (CRM‐Residual) was calculated as residualized gCDS in a multilinear regression analysis. We then estimated a CR marker score (CRM‐Score) as predictions from a multiple regression model with CRM‐Factor as dependent variable and demographics, total Mini‐Mental State Examination score and binarized biomarker status as predictors. Markers have been derived at baseline. We tested the moderation of each CR marker on the individual trajectories of memory decline in separate linear mixed models.ResultHigher years of education were predicted by the CR markers when tested separately. CRM‐Residual levels were strongly associated with CRM‐Factor, while CRM‐Residual was moderately associated with CRM‐Factor and CRM‐Score. In linear mixed models, patients in ADS with higher CR revealed a slower memory decline, mainly in preclinical AD.ConclusionOur results support the operational value and effectivity of the latent CR marker approach. We defined a novel latent CR Marker Score that may be operationalized in independent cohorts without conducting a data‐driven analysis. In line with previous studies, latent CR markers estimated differences in cognitive trajectories predominantly in the MCI stage. Our marker score approach can offer a standardized clinical scoring for simple, cohort‐independent and effective estimation the individual CR in clinical and epidemiological studies, making a better individual risk assessment and estimating therapeutic effects to strengthen the CR.
Whole Exome Sequence Study of Mild Cognitive Impairment in African and European Americans; the Atherosclerosis Risk in Communities‐Neurocognitive Study
Authors: Mahmud Shamsed , Mei Hao , Tin Adrienne , Bressler Jan , Pruett William A , Fornage Myriam , Huang Juebin , Boerwinkle Eric , Mosley Thomas H , Simino Jeannette 
Published: December 2021

AbstractBackgroundMild cognitive impairment (MCI) encompasses cognitive deficits beyond normal aging that minimally impact daily functioning. Uncovering the genetic architecture of MCI, which can progress to Alzheimer’s disease in some individuals, may facilitate the development of lifestyle and pharmacologic interventions to minimize cognitive impairment or prevent dementia. We conducted a whole exome sequence study of MCI in 1,144 African American (AA) and 3,358 European American (EA) participants aged 67‐90 years from the Atherosclerosis Risk in Communities‐Neurocognitive Study.MethodsFor both single‐variant and gene‐based tests, we employed seqMeta to perform race‐stratified analyses of functional (nonsynonymous, splicing, stopgain, stoploss, or frameshift) variants in each sex alone and both sexes combined. Models were adjusted for age, sex (except sex‐stratified models), field center, and population substructure (the first ten principal components). Logistic regression models were fit on autosomal single‐variants with minor allele frequency (MAF) ≥0.01 while SKAT‐O, T1 burden, and SKAT (beta weights and MAF ≤ 0.05) gene‐based tests were conducted. The significance and suggestive p‐value thresholds were 1.13E‐06 and 2.27E‐05 for single‐variant tests and 2.81E‐06 and 5.63E‐05 for gene‐based tests, respectively, after Bonferroni correction.ResultsThe analysis sample contained 993 MCI cases and 3,509 cognitively normal participants; Table 1 contains the count for each race and sex subgroup. One significant (p‐value=1.06E‐7) single‐variant association (chr6:51712759:T:C in PKHD1) was detected in AA males (Figure 1). This variant had MAF=0.025 in AA males but was monomorphic in EA males. Four significant gene‐based associations with minor allele counts (MAC) ≥ 10 were discovered: CDC27 in AA females (SKAT‐O p‐value=6.63E‐07), C19orf18 in AA males (SKAT‐O p‐value=1.26E‐07), SLC16A10 in EA males and females combined (SKAT p‐value=1.90E‐06), and ZNF804A in EA females (T1 p‐value=2.69E‐07). Twenty‐three suggestive single‐variant and gene‐based associations with MAC ≥ 10 were identified (Figure 2).ConclusionsMCI‐associated genes have diverse biological functions including cell division, sodium‐independent transportation of amino acids, and zinc finger binding. Our findings imply that the genetic underpinnings of MCI may differ by race and sex. External replication of our findings, as well as investigations using large samples in consortia, will provide insight into the pervasiveness of sex‐specific genetic effects in dementia‐related traits.
The Interaction between Ventricle to Brain Ratio and Serum Klotho on Cognition in Older Adults at Risk for Alzheimer’s Disease
Authors: Czaplicki Alec M , Gaitán Julian M. , Bendlin Barbara B , Johnson Sterling C. , Asthana Sanjay , Dubal Dena B. , Okonkwo Ozioma C. 
Published: December 2021

AbstractBackgroundVentricle to brain volume ratio (VBR) may be associated with Alzheimer’s disease (AD) progression and is a robust correlate of cognition in AD. Klotho is a circulating protein positively associated with cognition. The purpose of this study was to evaluate whether serum klotho attenuates the adverse effect of higher VBR on cognition in older adults at risk for AD.MethodThis study included 359 cognitively unimpaired participants from the Wisconsin Alzheimer’s Disease Research Center and Wisconsin Registry for Alzheimer’s Prevention (mean age = 61.8 ± 6.5, 67% female). VBR was calculated from structural T1 MRI scans as the ratio of total ventricle volume to the sum of grey and white matter. Fasting venipuncture was conducted and analyzed for serum klotho. Neuropsychological examination was conducted for global cognition (PACC3) and composite scores were calculated for executive function, immediate learning, and delayed recall. Linear regression models were performed to assess the effect of VBR on cognition, accounting for APOE, gender, age, and time difference between MRI and serum klotho measurements. Next, models were fitted with an interaction for VBR x klotho. Follow‐up analyses, stratified by median age (63.2 years), assessed age‐specific effects.ResultHigher VBR predicted poorer delayed recall (β(SE)=‐6.3(3.1); p=.043), but not global cognition (β(SE)=‐4.9(3.0); p=.101), executive function (β(SE)=‐4.4(3.3); p=.178), or immediate learning (β(SE)=‐4.4(3.3); p=.185). Significant VBR x klotho interactions existed for global cognition (p=.024) and executive function (p=.009) whereby higher serum klotho attenuated the adverse effect of VBR. This effect was absent for immediate learning (p=.162) and delayed recall (p=.267). Among older participants, VBR predicted worse global cognition (β=‐7.4; p=.055), executive function (B=‐8.8; p=.048), and nearly delayed recall (β=‐8.1; p=.061), but not for immediate learning (p=.521). There were no effects among younger individuals (all p’s ≥ .203). Lastly, the VBR x klotho interaction on executive function was significant among older participants (p=.037).ConclusionSerum klotho may protect against the adverse effect of high VBR on cognition, particularly among older individuals.
Behavioural Effects of Aerial Parts of Alysicarpus glumaceus Vahl DC in Murine Models
Authors: Khan Ferhat , Abdulsalam Abdullateef , Saban Hafsat Abdullahi , Nazifi Abdullahi Balarabe , Sani Munir Ari , Shehu Aishatu , Olorukooba Amina Busola 
Published: December 2021

AbstractBackground
Alysicarpus glumaceus has been reported to be used in managing patients with neuropsychiatric disorders. This work aimed to determine the behavioural effects of aerial parts of Alysicarpus glumaceus in murine models.MethodThe behavioural effects of the drug extract was evaluated using elevated zero maze (EZM), stair case test (SCT) and the open field test (OFT) while beam walking was used to test for motor coordination deficit and stimulant activity in mice at doses of 500, 1000 and 1500 mg/kg using diazepam (0.05 mg/kg) as the standard and normal saline (NS) as the control.ResultsAll the test doses of the extract reduced the stretch attend posture and head dips as well as the number of rearing without significant decrease in the number of stairs climbed in the EZM and SCT respectively when compared to NS. In the OFT, Alysicarpus glumaceus extract increased the number of square crossing but it was insignificant (p>0.05). The extract at 1000 and 1500 mg/kg significantly (p<0.01) decreased the number of rearing; while at 500 mg/kg it significantly (p<0.001) decreased the number of rearing. At all the test doses used, there was no significant difference in time to reach the goal box and number of foot slips, however, mice given 500 mg/kg of the extract produced a significant (p<0.05) increase in time spent on the beam.ConclusionThe findings revealed that the aerial parts of Alysicarpus glumaceus possesses central nervous system depressant actions.
Unveiling Center‐Type Topological Defects on Rosettes of Lead Zirconate Titanate Associated to Oxygen Vacancies
Authors: Neckel Itamar T. , da Silva Francisco M. C. , Guedes Eduardo B. , Dias Carlos S. B. , Soares Marcio M. , Costa Carlos A. R. , Mori Thiago J. A. , Björling Alexander , Zakharov Alexei , Tolentino Helio C. N. 
Published: December 2021

AbstractUnderstanding the formation of topological defects in ferroelectric materials can provide access to their unusual physics, invaluable for possible applications of domain engineering in nanoelectronics. The present study shows the spontaneous formation of center‐type topological defects in lead zirconate titanate (PZT) films, characterized by a strong in‐plane radial electromechanical response on rosette‐like structures, as revealed by piezoelectric response force microscopy. Multi‐modal electron and X‐ray based techniques provide a comprehensive set of tools for delving at atomic scale the local chemistry, electronic, and crystalline structures. The elemental surface‐sensitivity of soft X‐ray absorption shows chemical segregation and drastic changes in the titanium electronic structure, which have been associated to oxygen vacancies, leading to a mechanism that describe the polarization symmetry on the rosettes. X‐ray nanofluorescence experiments revealed titanium segregation, corroborating with the absorption and low energy electron microscopy images. Taking advantage of a nanobeam, 2D nanodiffraction maps probed the complex microstructure of the domains, revealing its mosaicity and lattice strain at the nanoscale. This study highlights a complex topological structure and provides, by the simultaneous application of a set of analytical tools, a broad comprehension of the formation of center‐type ferroelectric topological defects in PZT.
Cation‐Tuning Induced d‐Band Center Modulation on Co‐Based Spinel Oxide for Oxygen Reduction/Evolution Reaction
Authors: Wang Zepan , Huang Jiahui , Wang Ling , Liu Yangyang , Liu Wenhui , Zhao Shenlong , Liu Zhao‐Qing 
Published: December 2021

AbstractAtomic substitutions at the tetrahedral site (ATd) could theoretically achieve an efficient optimization of the charge at the octahedral site (BOh) through the ATd‐O‐BOh interactions in the spinel oxides (AB2O4). Despite substantial progress having been made, the precise control and adjustment of the spinel oxides are still challenging owing to the complexity of their crystal structure. In this work, we demonstrate a simple solvent method to tailor the structures of spinel oxides and use the spinel oxide composites (ACo2O4/NCNTs, A=Mn, Co, Ni, Cu, Zn) for oxygen electrocatalysis. The optimized MnCo2O4/NCNTs exhibit high activity and excellent durability for oxygen reduction/evolution reactions. Remarkably, the rechargeable liquid Zn–air battery equipped with a MnCo2O4/NCNTs cathode affords a specific capacity of 827 mAh gZn−1 with a high power density of 74.63 mW cm−2 and no voltage degradation after 300 cycles at a high charging–discharging rate (5 mA cm−2). The density functional theory (DFT) calculations reveal that the substitution could regulate the ratio of Co3+/Co2+ and thereby lead to the modulation of the electronic structure accompanied with the movement of the d‐band center. The tetrahedral and octahedral sites interact through the Mn−O−Co, and the Co3+Oh of MnCo2O4 with the optimal charge structure allows a more suitable binding interaction between the active center and the oxygenated species, resulting in superior oxygen electrocatalytic performance.