bluuebunny/crossref_metadata_2025 huggingface dataset:
Cancer Type and Dementia Diagnosis in Community Dwelling African Americans
Authors: Anderson Loretta R. , Pollack Andrew A.
Published: December 2023

Background

Cancer and dementia have been reported to have an inverse relationship, suggesting those with cancer may have decreased risk of subsequent dementia, and those with dementia may have a decreased risk of subsequent cancer diagnosis (Zablocka, 2021). However, emerging evidence challenges this idea. A paucity of research exists examining these associations in African Americans, who are twice as likely as whites to develop dementia (Barnes, 2022). Our objective was to examine the association between different types of cancer and dementia risk in community dwelling African Americans.

Methods

Using data from the 2011 National Health and Aging Trends Study (NHATS), a nationally representative sample of Medicare beneficiaries aged 65 and older, we examined the association between cancer type and dementia diagnosis in community dwelling African Americans (n = 1529). Multinomial logistic regression models examined the association between cancer type and dementia diagnosis, controlling for age, sex, and education, as well as anxiety, depression, diabetes, heart disease, and stroke.

Results

Results showed 2.6% of African Americans reported a kidney disease diagnosis, representing 208,107 older adults. Fully adjusted models revealed that African Americans with kidney cancer are over 5 times as likely to have a dementia diagnosis compared to African Americans without kidney cancer [OR: 5.48, p<0.05 (95% CI: 1.24, 24.20]). Other types of cancer (skin, breast, prostate, bladder, ovarian, colon, and “other”) were not significantly associated with increased odds of dementia diagnosis.

Conclusion

Results show a strong association between kidney cancer and dementia diagnosis in older African Americans, but not other types of cancer. Further research in this area may elucidate reasons for increased dementia risk in African Americans.
Inflammatory and metabolic responses in the aging rat brain
Authors: de Souza Débora Guerini , da Rocha Andreia Silva , Almeida Roberto Farina , Peixoto Guilherme G. Schu , Salles Giovanna Bortoluzzi , Oliveira Ana Cristina Laydner Joly , Limberger Christian , de Bastiani Marco Antônio , Greggio Samuel , Venturin Gianina Teribele , da Costa Jaderson Costa , Souza Diogo O. , Zimmer Eduardo R.
Published: December 2023

Background

The brain is an energetically demanding organ that mostly relies on glucose oxidation to sustain its sophisticated networks. Transcriptomic studies suggest metabolic‐related genes are downregulated in the aging brain but inflammation‐related genes are highly upregulated. Astrocytes are key mediators of brain inflammation and metabolism. Yet, the relationship between inflammatory signals and energy substrates consumption in the aging brain remains unclear. To address this question, we investigated the response of the young and aged rat brain metabolism to a nonsteroidal anti‐inflammatory (NSAID) drug.

Method

Five young adults (4 mo), and five aged (24 mo) male Wistar rats were scanned using positron emission microtomography with 18F‐fluorodeoxyglucose ([18F]FDG‐PET). Scans were done under basal conditions or after three‐day treatment with 5mg/kg ketoprofen (i.p.), an NSAID known to cross the blood‐brain barrier. Standard uptake values ratios (SUVr, pons as reference) were calculated for the main brain regions. Synaptosome and total mitochondria preparations from the cortex had their oxygen consumption rates measured in an Oroboros Instrument, using a SUIT protocol. Results were analyzed by t‐test, with statistical significance P < 0.05.

Result

Under basal conditions, glucose uptake showed no differences between young and aged rats. After ketoprofen treatment, clusters of glucose hypermetabolism appeared in the cortex and hippocampus of the adult but not the aged brain. Synaptosomal and mitochondrial preparations did not present differences in ATP‐linked, maximal, or leak respiration between groups under basal conditions. However, aged synaptosomes (t = 3.417, p = 0.0112) and total mitochondria (t = 3.131, p = 0.0166) presented higher respiratory coupling ratios.

Conclusion

We previously showed that [18F]FDG‐PET signal highly depends on astrocyte function. The lack of response to ketoprofen in aged rats may be related to astrocyte dysfunction in aging. As a counter‐response to the aging process, the brain mitochondria are highly coupled, keeping the system as efficient as necessary. Our findings indicate that brain metabolism might not be coupled to inflammation in the aged rat brain. Still, we identified a remarkable plasticity of the mitochondria, which can sustain physiological responses despite the aging process.
Sex and age dependent effects of gut microbiota manipulation in AppSAA mouse model of Alzheimer disease
Authors: Kaur Harpreet , Singh Surjeet , Tooley Andrew , O'Connell Kristen MS , Kaczorowski Catherine C.
Published: December 2023

Background

Population based studies indicate that women are at significantly greater risk of developing Alzheimer’s disease (AD) than men. Gut microbiome is involved in the pathogenesis of AD however sex specific (/differential) effect of gut microbiome manipulation is not well understood.

Method

To determine the effect of sex and age on the impact of gut microbiota manipulation on cognitive outcomes, 3‐4 months old male and females AppSAA mice (AD) were treated with probiotics (for 8 weeks) and antibiotics for (10‐days) along with C57BL/6J and hApp as controls. Based on our previous studies, probiotic had beneficial effects on younger AD females and had no effect on males. To understand if gut bacteria are directly involved in eliciting these differential effects, we collected the stool samples from AD females treated with probiotic (VSL#3) and did fecal microbiota transplantation (FMT) in younger and older male and female AD mice. Neurobehavioral testing was performed including Open field task (OFT), Y‐Maze, Contextual fear conditioning (CFC) and Novel object recognition. Brain and intestine samples were collected for biochemical and molecular characterization.

Result

In OFT, AppSAA mice travelled more distance as compared to C57BL/6J, and treating AppSAA mice with probiotic or antibiotic resulted in increased distance traveled. Antibiotic mice also showed less freezing in CFC task when compared to controls. Overall, FMT mice had a trend towards lower mean speed and distance travelled on Y‐maze with no significant change in memory functions. That said, the AppSAA mice at 5‐6 months of age showed no significant memory deficits as assessed using CFC and Y‐maze, and will need to be aged further to assess the effect of antibiotics and FMT on cognitive deficits.

Conclusion

Treating AppSAA mice with probiotic or FMT (samples from probiotic treated females to AD young and old animals) had effects on motor behavior, but no effects in terms of memory functions. This lack of change is not surprising, as AD mice at early age did not demonstrate a behavioral phenotype compared to controls. Currently, we are doing biochemical analysis to elucidate if FMT influenced brain pathology (inflammation or Aβ) in AD mice.
Cognitive and muscle health, and related amino acid kinetics in older adults with Mild Cognitive Impairment, and the effect of comorbidities
Authors: De Wandel Sofie M , Deutz Nicolaas EP. , Engelen Marielle PKJ
Published: December 2023

Background

Recent studies suggest cognitive decline and reduced muscle health is associated with the presence of comorbidities. Our objective is to identify whether the presence of comorbidities in older adults affects muscle health (mass and function) and related protein and amino acid (AA) kinetics differently when Mild Cognitive Impairment is present.

Method

We selected older adults (127 with comorbidities (Charlson comorbidity index (CCIS>0)) and120 without comorbidities (CCIS = 0) from the MEDIT database. These were stratified into MCI and non‐MCI based on their Montreal Cognitive Assessment (MoCA) score. Health history obtained by interview, body composition by DEXA, and habitual dietary intake by 3‐day food record, . Mood (depression) assessed by questionnaire, and cognitive function by MoCA and battery. Muscle function measured by handgrip dynamometry. Postabsorptive protein and AA kinetics analyzed by pulse administration of 18 stable isotopes of AAs and tracer enrichments/concentrations by LC‐MS/MS to calculate whole‐body production (WBP) of these AAs. Statistics by ANCOVA to examine effects of MCI, CCIS, and MCI*CCIS interaction, with covariates Sex, BMI, and Age. Significance was set as p<0.05.

Result

Presence of MCI was associated with lower cognitive and muscle function and lean mass (all p<0.05). There were no differences in lean mass between CCIS and healthy counterparts (all p>0.05). CCIS subjects had higher depression score (p<0.05), performed worse on Stroop test (p = 0.0124) and had lower muscle function (p<0.05). Furthermore, CCIS subjects had higher plasma concentrations of glutamate (p = 0.0115), and isoleucine (p = 0.0071) compared to healthy counterparts. CCIS subjects had higher WBP of phenylalanine (p = 0.032), tryptophan (p = 0.0143), and isoleucine (p = 0.035), and higher net protein breakdown (PHE>>TYR) (p = 0.0758). There was no MCI*CCI interaction for lean mass, dietary intake, or mood. MCI with comorbidities had higher moca scores (p = 0.0037), stroop test performance (p = 0.0592) and muscle function compared to healthy counterparts (all P<0.05). MCI*CCI interactions showed MCI with CCIS had lower BCAA concentrations.

Conclusion

Presence of comorbidities affects mood, cognitive function, muscle health, and metabolism in older adults independent of MCI. The presence of comorbidities in MCI should be considered when designing nutritional based intervention trials.
A novel Caenorhabditis elegans model of Alzheimer’s Disease
Authors: Bajuszova Viktoria , Cohen Netta , Johnston Jamie
Published: December 2023

Background

Alzheimer’s disease (AD) is the most prevalent form of neurodegenerative disease, characterised by the presence of Aβ plaques and neurofibrillary tangles, mediating memory impairments due to loss of neurons and impairments in neuronal plasticity. The most common model to study the toxic effects of Aβ in AD are transgenic rodents. However, these animals develop cognitive impairments and suffer. Thus, to reduce and replace the rodent animals used to study these toxic effects, we are developing a C. elegans neuronal model of human Aβ1‐42 with a posterior co‐injection marker to allow multi‐colour neuronal imaging without interference from the fluorescence of the co‐injection marker. To achieve this we generated a transcriptional reporter of the antimicrobial peptide gene clec‐60, as the expression of this gene under normal conditions is solely in the posterior intestine.

Method

Constructs containing ultra pan‐neuronal Aβ reporter and the clec‐60p::cemOrange co‐injection marker were generated via gateway cloning and micro‐injected into wild type C. elegans. To confirm expression of the co‐injection marker is restricted to posterior intestine confocal images were taken of the injected strains. To confirm presence of Aβ in the neurons, fixed C. elegans were antibody stained using the 4G8 primary and goat anti mouse 488 secondary antibody.

Result

We generated the Aβ strain with the clec‐60 fluorescent marker, however, upon expression of the human Aβ1‐42 in the C. elegans nervous system we observed expression of the fluorescently tagged clec‐60 in the neurons. The presence of the Aβ in the neurons was confirmed with the antibody staining.

Conclusion

Expression of human Aβ1‐42 changes and increases the expression of the innate immunity antimicrobial peptide clec‐60 indicating C. elegans perceive Aβ as a pathogen and elevate innate immune peptide upon its expression.
Differential spatial transcriptome profile of the hippocampal formation of protected PSEN1 E280A familial Alzheimer’s disease cases
Authors: Villalba‐Moreno Nelson David , Littau Jessica Lisa , Amri Yassir El , Lopera Francisco , ‐Lanau Andres Villegas , Glatzel Markus , Quiroz Yakeel T. , Arboleda‐Velasquez Joseph F , Sepulveda‐Falla Diego
Published: December 2023

Background

We have described two cases with ∼ 30 years of delayed disease onset among carriers of PSEN1 mutation E280A, suffering from familial Alzheimer’s disease (FAD). One case was homozygous for the ApoE Christchurch (hApoEch) mutation. This case showed sparse hyperphosphorylated tau (pTau) pathology in several cortical areas. The second case was heterozygous for the RELN‐COLBOS mutation and was globally affected by severe pTau and amyloid beta pathology, with evidence of localized cellular protection in the entorhinal cortex (EC). Here we used digital spatial profiling (DSP) transcriptomics to characterize the hippocampal formation of FAD protected cases and identify possible molecular mechanisms of protection.

Methods

In depth morphological characterization of the EC together with identification of thirteen different regions of interest (ROIs) were performed in Formalin‐fixed paraffinized 3 mm thick slides taken from the hippocampal formation (Fig. 1A) of the RELN‐COLBOS FAD case, the hApoEch FAD case, three FAD cases, and three sporadic Alzheimer’s cases (SAD). Slides were immunostained for NeuN and GFAP for morphological ROIs identification and processed for localized transcriptome analyses using the GeoMX DSP platform from Nanostring. Obtained data was processed for quality control, dimensionality reduction and differential gene expression (DGE) analyses.

Results

Dimensionality reduction of transcriptomic data obtained from all ROIs and studied cases showed a distinctive distribution of ROIs belonging to both protected cases (Fig. 1B). Furthermore, DGE was observed in all sampled ROIs. ROIs such as hippocampal white matter or dentate gyri showed a higher number of differentially expressed genes due to a more homogeneous cellular composition of the ROIs (Fig. 1C). Also, EC and dentate gyrus from FAD protected cases showed distinctive molecular signatures compatible with excitatory neuronal pathways (Fig. 1D). Complementary morphological analyses showed increased neuronal density in the supragranular region of the EC in the RELN‐COLBOS FAD protected case, specifically in neuronal layer II.

Conclusion

Our results suggest that regardless of the protective gene conferring protection to FAD, the EC is one key protected structure with distinctive regional transcriptomic profiles suggesting the preservation of neuronal function in this region and hinting towards a possible therapeutic target in the protection against Alzheimer’s disease.
Palliative care in Autosomal Dominant Alzheimer’s disease due to PSEN1‐E280A genetic variant in Colombia
Authors: Márquez Isabel C , Tabares Maria Alejandra , Henao Paola Gallo , Londoño Luisa , Castaño Karen , Pabon Manuela , Upegui Maria , Gómez Manuela , Quintero Juan Felipe , Rassi Sofia , Vasquez Daniel , Zuluaga Maria , Aguillon David , Krikorian Alicia , Vargas John Jairo , Madrigal Lucia , Lopera Francisco
Published: December 2023

Background

Autosomal Dominant Alzheimer’s disease (ADAD) is a subtype of AD in which the symptoms begin before age 65. ADAD is an important subtype of AD as it affects people at productive and reproductive age, has a genetic origin in most of the cases and is one of the 10 causes of years lost to disability (YDLs) (1). Colombia has the largest kindred family with ADAD due to PSEN1‐E280A genetic variant, we aimed to characterize the palliative care need in a subsample of individuals from these families.

Methods

We performed an analytical observational study with one year follow‐up, data obtained from visit 1 (V1) is shown in this first report. Carriers of PSEN1‐E280A variant and GDS/FAST score above 4 were included. NECPAL and Edmonton surveys were conducted to the main carer to assess the need for palliative care and the frequency of symptoms. A complete medical evaluation was also performed.

Results

36 patients were included in V1. Median age was 53, most of the individuals were women (63.89%), lived in urban areas (88.89%) and the most common level of education was elementary‐middle school (47.22%). Clinical variables are listed in Table 2. Results of the poisson regression showed that dysphagia, pressure ulcers, asthenia perceived by the main carer, not being surprised if the patient died in the following 12 months (Surprise question of NECPAL scale), functional decline, use of medical services (2 visits in the past year), PAINAD scale and GDS/FAST scale were associated with the need for palliative care when adjusted by number of persons involved in caring, type of carer, hours of care per week and caregiver training.

Conclusion

ADAD is a neurodegenerative disease that requires follow‐up by palliative care services. The health perception of the main carer should be taken into consideration when deciding the need for palliative care in these patients.
Relationship between APOE risk score and myelin in Alzheimer’s disease
Authors: Schulz Nicholas R , Yang Kao Lee , Oh Jennifer M. , Kang Theresa J , Randall Allison M , Davenport‐Sis Nancy J , Deming Yuetiva , Van Hulle Carol A. , Betthauser Tobey J , Dean Doug C , Johnson Sterling C , Alexander Andrew L , Bendlin Barbara B
Published: December 2023

Background

Postmortem brain tissue analysis suggests that apolipoprotein E (APOE) ε4 is associated with lower brain myelination (Blanchard et al. 2022). However, in vivo evidence for this association is lacking. Here, we examined the relationship between APOE genotype and myelin content in the brain using multicomponent relaxometry (mcDESPOT) imaging and an APOE neuropathologic risk score (Deming et al, 2023).

Methods

121 cognitively unimpaired participants from the Wisconsin Alzheimer’s Disease Research Center and the Wisconsin Registry for Alzheimer’s Prevention completed at least one mcDESPOT MRI scan and were APOE genotyped. Myelin content was quantified using mcDESPOT‐derived myelin water fraction (MWF) maps. Amyloid positivity was determined using CSF Aβ42/Aβ40 or a [C‐11]PiB PET scan. Cutoffs for amyloid positivity was a CSF Aβ42/Aβ40 ratio of <0.046 (Van Hulle et al, 2020) or a global PiB DVR threshold >1.19 (Betthauser et al, 2020). MWF maps were registered to MNI space and smoothed with an 8mm FWHM kernel. We conducted a voxel‐wise regression analysis to determine the relationship between APOE risk and myelin content. Covariates included age, age difference between MRI and amyloid acquisition, gender, race, amyloid status, APOE by amyloid status interaction, and APOE by gender interaction. We followed up these analyses examining specific brain regions implicated in AD. All analyses were corrected for multiple comparisons.

Results

Participant characteristics are shown in Table 1. Voxel‐wise analysis indicated that MWF was negatively associated with age in the superior longitudinal fasciculus and small regions of the brainstem (Figure 1). MWF was not associated with APOE risk, gender, or race. ROI analysis showed a significant APOE by amyloid status interaction in the left (β = 0.006, p‐value = 0.035) and right cingulum (β = ‐0.013, p‐value = 0.037; Table 2). However, these interactions did not survive FDR correction.

Conclusion

These findings suggest that myelin content decreases with age. Although APOE ε4 increases risk for developing AD dementia, it was not associated with brain myelin content in this cohort. In preclinical participants harboring amyloid pathology, APOE risk may impact myelin content although our findings did not survive FDR correction. More research is needed to fully elucidate this relationship.
Cortical microstructural MRI for detection of early target engagement in AD drug trials: post‐hoc analysis of exploratory outcomes from a Phase 1b safety study for XPro1595 in AD
Authors: Pope Parris , Ridgway Gerard R , Barnum CJ , Torso Mario , Chance Steven A , Tesi RJ
Published: December 2023

Background

Evidence in support of the amyloid cascade hypothesis for Alzheimer’s disease (AD) suggests that pathological amyloid‐beta (Aβ) is initially associated with synaptic hyperactivity and accumulates in an activity dependent fashion. These findings are corroborated by longitudinal data from cohort studies with Aβ‐PET imaging, wherein Aβ accumulates first in gray matter (GM) cortices associated with the default‐mode network (DMN) before spreading in a semi‐hierarchical pattern to different neocortical regions as the disease progresses (Mattsson et al. 2019). Mapping brain regions most frequently affected by Aβ pathology at different stages of disease may provide a framework for investigation of new drug entities targeting other components of Aβ toxicity using less invasive imaging modalities. The hypothesis here is that indicators of disease specific, tissue‐level treatment effects should be first detectable in brain regions most frequently affected by active pathology.

Method

XPro1595 is a selective, brain penetrant neutralizer of soluble TNF with potent anti‐neuroinflammatory effects recently assessed for safety and pharmacological activity in a small, open‐label phase‐1b dose finding study (NCT03943264) in patients with AD. Clinical trial results for patients (n = 9) with analyzable dMRIs who completed 12‐weeks of treatment with XPro1595 [0.3 mg/kg; n = 3) or (1.0 mg/kg; n = 6)] met criteria for post‐hoc analysis. Exploratory outcomes included the novel cortical diffusivity measurement PerpPD+. PerpPD+ represents the diffusion components perpendicular to cortical GM minicolumns, indicates microscopic disruption when increased, and has proven more sensitive than standard volumetrics to changes in indicators of synaptic function, neuroinflammation and neurodegeneration across the AD continuum.

Result

Mean MMSE scores at baseline were 23.7 (SD = 2.5) and 15.8 (SD = 7.0) in the low‐dose and high‐dose groups, respectively, indicating varying degrees of severity. Week‐12 results showed decreases in bilateral PerPD+ at the whole brain level and in multiple GM cortices documented in the literature with the highest frequency of early (precuneus, isthmus cingulate, posterior cingulate, insula, and lateral and medial orbitofrontal) and late (lingual, pericalcarine, paracentral, precentral, and postcentral) Aβ accumulation (Figures1‐2).

Conclusion

Cortical diffusivity measurements related to minicolumnar microstructure may provide an opportunity for noninvasive detection of early, disease specific, tissue‐level target engagement in clinical trials for investigational new drugs in AD.
Working and episodic memory trajectories over time following bilateral oophorectomy in early midlife women
Authors: Gravelsins Laura , Reuben Rebekah , Brown Alana , Gervais Nicole J , Almey Anne , Duchesne Annie , Karkaby Laurice , Perovic Mateja , Witt Suzanne Tyson , Classon Elisabet , Lykke Nina , Theodorsson Elvar , Lundqvist Elisabeth Åvall , Kjølhede Preben , Engström Maria , Jacobson Michelle , Bernardini Marcus , Foulkes William , Page‐Gould Elizabeth , Hampson Elizabeth , Einstein Gillian
Published: December 2023

Background

Early ovarian hormone deprivation due to bilateral salpingo‐oophorectomy (BSO; ovarian and fallopian tube removal) is a risk for late‐life AD, but estradiol replacement therapy (ERT) may be protective (Rocca et al., 2007). Working and episodic memory decrements have been observed without ERT soon after surgery (Sherwin et al., 1988) and on average 5 years post‐BSO in midlife compared to premenopausal controls (Gervais et al., 2020). Unknown is whether memory continues to decrease over time in early midlife, a critical period for understanding cognitive trajectories that presage AD. We investigated memory changes in early midlife over time post‐BSO, and whether those taking ERT had different trajectories than those without.

Method

Participants with BSO taking ERT (BSO+ERT: M
age = 44.5y; n = 71) were compared to those not taking ERT (BSO: M
age = 43.2y; n = 55), recruited from Toronto and Montreal, Canada, and Linköping, Sweden, and completed up to four yearly visits. Episodic memory was evaluated using Logical Memory Task (LM) percent forgetting and Rey Auditory Verbal Learning Test (RAVLT) total learning. Working memory was assessed using Spatial Working Memory Task (SPWM) trial 1 errors, Digit Ordering Task (DOT) errors, and Digit Span Backward Task (DSB) span length. Multilevel models were used to examine whether ERT influenced memory over time post‐BSO and disaggregate within‐ and between‐person effects. Estimated marginal means (Aiken and West, 1991) were calculated to delineate significant interactions.

Result

There were no significant changes over time post‐BSO on LM or RAVLT. The DSB showed significant within‐ and between‐person effects; the BSO group showed decreases in span length over time post‐BSO, while the BSO+ERT group showed increases and had significantly longer span lengths at seven years post‐BSO and beyond (Fig.1A&B). The SPWM Task showed a significant within‐person effect; the BSO group had stable errors over time post‐BSO, while the BSO+ERT group had working memory improvements and made fewer errors (Fig.1C).

Conclusion

Findings suggest that immediate verbal episodic memory declines we observed previously may stabilize. They also reveal that without ERT, most women have working memory declines post‐BSO. These data support ERT administration post‐BSO for working memory preservation. If ERT is contraindicated, cognitive training or lifestyle interventions may mitigate working memory declines.
SPIN90 Deficiency Ameliorates Amyloid ß Accumulation by Regulating APP Trafficking in AD Model Mice
Authors: Kim Sung Hyun
Published: December 2023

Background

Alzheimer’s disease (AD), a common form of dementia, is caused in part by the aggregation and accumulation in the brain of amyloid ß (Aß), a product of the proteolytic cleavage of amyloid precursor protein (APP) in endosomes. Trafficking of APP, such as surface‐intracellular recycling, is an early critical step required for Aβ generation. Less is known, however, about the molecular mechanism regulating APP trafficking. This study investigated the mechanism by which SPIN90, along with Rab11, modulates APP trafficking, Aβ motility and accumulation, and synaptic functionality

Method

This study utilized live‐imaging technology with molecular, cellular and 5xFAD model mice system.

Result

Brain Aβ deposition was lower in the progeny of 5xFAD‐SPIN90KO mice than in 5xFAD‐SPIN90WT mice. Analysis of APP distribution and trafficking showed that the surface fraction of APP was locally distinct in axons and dendrites, with these distributions differing significantly in 5xFAD‐SPIN90WT and 5xFAD‐SPIN90KO mice, and that neural activity‐driven APP trafficking to the surface and intracellular recycling were more actively mobilized in 5xFAD‐SPIN90KO neurons. In addition, SPIN90 was found to be cotrafficked with APP via axons, with ablation of SPIN90 reducing the intracellular accumulation of APP in axons. Finally, synaptic transmission was restored over time in 5xFAD‐SPIN90KO but not in 5xFAD‐SPIN90WT neurons

Conclusion

The interaction of SPIN90 and Rab11 is implicated in Aβ production through the regulation of APP trafficking.
Brief Continuous Recognition Task for Early Alzheimer Detection and Tracking
Authors: Ashford John Wesson
Published: December 2023

Background

Alzheimer’s Disease (AD) affects memory processing in the brain. An important aspect of AD assessment and study is memory testing, which can be done with excellent efficiency using a Continuous Recognition Test (CRT). A CRT was designed for online administration to provide 25 unique, complex, interesting images, which were initially presented for up to 3 seconds, and 25 repeated images, which required a response to indicate recognition (takes about 90 seconds). The images include 5 from each of 5 categories, from a set of 3,000 images, ensuring that a broad spectrum of memory is interrogated. The selected images are culturally neutral, and the instructions are provided in 120 languages, so the test is comparable across most countries, and performance is not affected by racial, cultural, or ethnic variations. The test is engaging and has been taken by many individuals over 100 times and by several individuals over 1,000 times. Two studies have compared this test with the Montreal Cognitive Assessment (MoCA) (in China and Netherlands) and found that this test performed at least as well.

Method

Data was examined from over a million CRT administrations from 3 sources: at the URL: www.memtrax.com, including over 18,000 unique users recruited by a French company (HAPPYneuron, INC), over 200,000 unique users from free access, and over 90,000 unique users from a free recruitment program (www.brainhealthregistry.org, part of the Alzheimer’s Disease Neuroimaging Initiative). Response time data was available for every image of each CRT, and the 3 populations were evaluated for HITs (correct recognitions), Correct Rejections (CRs, not responding to a new image), and response time to HITs (RT), including average RTs.

Result

Analyses indicated that 97% of individuals, across sites who scored better than chance (65% correct), performed better than 80% correct. Percent HITs and CRs and RTs showed a dichotomy with HITs (recognitions) correlating with RT (an AD dysfunction), while a separate group had fewer correct rejections (response disinhibition) and RT inconsistency, presumably related to fronto‐temporal dementia (clinical observation). Statistical analysis provides precision of impairment estimation.

Conclusion

A CRT can be used for early AD screening, memory assessment, and progression tracking.
Facial emotional recognition in patients with dementia, part of the ReDLat study
Authors: Moreno Maria Jose , Garcia Deissy Milena , Buitrago Carlos Felipe , Forero Laura Valentina , Rivera Carlos , Reyes Pablo A , Matallana Diana
Published: December 2023

Background

The social domain impairments associated with Alzheimer’s disease and frontotemporal lobar degeneration have been linked to basic neurocognitive processes such as visual emotion identification through facial expressions.

Method

In this study, we explore the recognition of seven basic emotions presented in the Mini‐SEA test in a sample of 84 Colombian individuals with dementia (32 with Alzheimer’s Disease and 30 with Frontotemporal Dementia) and compare it with 22 healthy participants from the RedLat study.

Result

The results of the behavioral performance show a lower performance in people with dementia compared to healthy subjects, however, no significant differences are reported between the patient group (AD and FTD).

Conclusion

These findings may be associated with the clinical heterogeneity of the evaluated subjects.

References:

Couto, B., Manes, F., Montañés, P., Matallana, D., Reyes, P., Velasquez, M., … Ibáñez, A. (2013). Structural neuroimaging of social cognition in progressive non‐fluent aphasia and behavioral variant of frontotemporal dementia. Frontiers in Human Neuroscience, 7. https://doi.org/10.3389/fnhum.2013.00467

Hot, P., Klein‐Koerkamp, Y., Borg, C., Richard‐Mornas, A., Zsoldos, I., Paignon Adeline, A., … Baciu, M. (2013). Fear recognition impairment in early‐stage Alzheimer’s disease: When focusing on the eyes region improves performance. Brain and Cognition, 82(1), 25‐34. https://doi.org/10.1016/j.bandc.2013.02.001
¿Frontotemporal dementia or Alzheimer’s disease? Phenotypic variability in a large family with neurodegenerative disorders
Authors: Garcia Deissy Milena , Buitrago Carlos Felipe , Moreno Maria Jose , Forero Laura Valentina , Triviño Cristian , Lopez Greizy , Duran Clemencia , Reyes Pablo A , Gelvez Nancy , Matallana Diana
Published: December 2023

Background

The frontal variant of Alzheimer’s disease is characterized by behavioral changes and executive deficits in the early stages. This phenotype is similar in the behavioral variant of frontotemporal dementia, hindering the clinical diagnosis. The aim of this study is to describe the profile of cognitive, behavioral and motor disorders in a family with an autosomal dominant inheritance pattern of early‐onset dementia.

Method

Five cases of affected individuals of a Colombian family are presented. We conducted an interdisciplinary clinical evaluation involving different specialties including geriatric, neurology, psychiatry, neuropsychology, and genetics. After each individual evaluation, a consensus was reached among the specialists to define the diagnosis.

Result

In all cases, reported age of onset was before 60 years old. Three out of four cases met criteria for severe dementia and the remaining case presented Mild Cognitive Impairment (MCI). In two cases, the first symptoms reported were memory and planification problems that affected daily life activities. Nevertheless, at the formal evaluation, predominant changes at the executive functions and social cognition were found. In the other two cases, given the severity of the alterations, the evaluation was limited to the analysis of the clinical history, and it is suspected to be cases of linguistic variants of FTD.

Conclusion

Intrafamilial phenotypic variability was described in this family. This variability in the presentation of the disease phenotype could guide the clinical diagnosis.

References:

Ossenkoppele, R., Singleton, E. H., Groot, C., Dijkstra, A. A., Eikelboom, W. S., Seeley, W. W., … & Pijnenburg, Y. A. (2022). Research criteria for the behavioral variant of Alzheimer disease: a systematic review and meta‐analysis. JAMA neurology, 79(1), 48‐60.

Musa, G., Slachevsky, A., Muñoz‐Neira, C., Méndez‐Orellana, C., Villagra, R., González‐Billault, C., … & Lillo, P. (2020). Alzheimer’s disease or behavioral variant frontotemporal dementia? Review of key points toward an accurate clinical and neuropsychological diagnosis. Journal of Alzheimer’s disease, 73(3), 833‐848.
A Modified Quasi‐Classical Analysis to Capture the Effects of Strong Interaction in Open QED Lattices
Authors: Tiwari Tarush , Shrivastava Kuldeep K , Roy Dibyendu , Singh Rajeev
Published: December 2023

The role of optical nonlinearity in light propagation through two different 1D open QED lattices is investigated, namely a chain of qubits with direct coupling between the nearest neighbors and a chain of connected resonators to each of which a qubit is side‐coupled. Using the more accurate truncated Heisenberg‐Langevin equations method, a reduction of light transmission with increasing intensity in these lattices is shown due to effective photon–photon interactions and related photon blockade mediated by nonlinearity in qubits. In contrast to the direct‐coupled qubits, a revival in the light transmission is found in the side‐coupled qubits at relatively higher intensities due to saturation of qubits by photons. In absence of bulk dissipation, it is found that the standard quasi‐classical analysis fails to capture the reduction in light transmission due to effective photon–photon interaction. A systemic method is devised to modify the quasi‐classical analysis to give much better results.
Effects of cross‐linked networks on dielectric properties of epoxy resins based on molecular dynamics
Authors: Wang Yifang , Du Boxue , Kong Xiaoxiao , Li Xiaolong
Published: December 2023

In this paper, three epoxy resin systems commonly used in power equipment are prepared to obtain cross‐linked networks with structural differences. The relationship between microscopic structures and dielectric properties of epoxy resins is investigated and discussed. Experimental results show that the polarization and conductance losses are inhibited in the anhydride‐cured systems with methyl groups. The molecular dynamics (MD) simulation shows that rigid anhydride structures (such as methyl groups) play a major role in reducing the local segment mobility and increasing the free volume at cross‐linking points. The decrease in local segment mobility has been confirmed by the decrease of mean square displacement (MSD) at the cross‐linking points, which is consistent with the change of measured polarization and conductance loss. In the glassy state, the dielectric properties of different anhydride‐cured systems can be reflected by local MSD at the cross‐linking points. At high temperatures near the glass transition temperature, both the free volume and network mobility increase significantly, which reflects the increased dielectric relaxation strength and conductance loss. The understanding of the structure–property relationships could provide a theoretical foundation for epoxy modification in a controlled manner for power equipment applications.
Higher 1‐year mortality on rest days in patients with acute coronary syndromes and decompensated heart failure—A SPUM‐ACS sub‐study
Authors: Matter Michael A. , Candreva Alessandro , Stähli Barbara E. , Heg Dik , Klingenberg Roland , Räber Lorenz , Windecker Stephan , Rodondi Nicolas , Nanchen David , Mach François , Gencer Baris , Ruschitzka Frank , Matter Christian M. , Templin Christian
Published: December 2023

Background

Acute coronary syndromes (ACS) occurring on rest days have been associated with higher mortality, but the current literature remains inconsistent in this regard. This study included ACS patients presenting with acute decompensated heart failure (ADHF) investigating the relationship between time of coronary catheterization and outcomes.

Methods

Analyses were performed from the prospective, multicentric Special Program University Medicine Acute Coronary Syndromes and Inflammation (SPUM‐ACS) Cohort. Patients were divided into two groups according to time of coronary catheterization on either workdays (Monday, 00:00 to Friday, 23:59) or rest days (Saturday, 00:00 to Sunday, 23:59 and public holidays). ADHF was defined by Killip Class III or IV upon presentation. Patients were followed over 1 year.

Results

Out of 4787 ACS patients enrolled in the SPUM‐ACS Cohort, 207 (4.3%) presented with ADHF. 52 (25.1%) and 155 (74.9%) patients underwent coronary angiography on rest days or workdays, respectively. Baseline characteristics were similar among these groups. ACS patients with ADHF showed increased 1‐year mortality on rest days (34.6% vs. 17.4%, p‐value = 0.009). After correction for baseline characteristics, including the GRACE 2.0 Score, rest day presentation remained a significant predictor for 1‐year mortality (adjusted hazard ratio = 2.42 [95% confidence interval: 1.14–5.17], p‐value = 0.022).

Conclusions

One‐year all‐cause mortality was high in ACS patients with ADHF and doubled for patients admitted on rest days. The present data support the association of a rest day effect and long‐term patient survival and indicate a need for further investigations.
Rise up: Career empowerment, adaptability and resilience during a pandemic
Authors: Grabarski Mirit K. , Mouratidou Maria
Published: December 2023

The present article examines employee resilience during the COVID‐19 pandemic, which created a major career disruption and a psychological strain for many individuals worldwide. Resilience is an essential psychological resource for coping with setbacks and maintaining mental health. Using a time‐lagged survey design, we test a theoretical model that links career empowerment, a motivational cognitive construct, with resilience, mediated by career adaptability. Our findings support these hypotheses. In addition, we investigate the moderating role of neuroticism and authentic leadership in the relationship between the career empowerment and career adaptability. Findings show that while authentic leadership moderates this relationship, the hypothesis regarding neuroticism was not supported. Our research provides insights regarding resilience during crisis, which has both theoretical and practical implications.
Preparation and Characterization of Nanocomposite Perovskite Cathode Materials La0.3Sr0.7Fe0.4Ti0.6O3‐δ (LSFT) for Low‐Temperature SOFCs with Incorporation of Graphene Oxide (GO)
Authors: Ahmad Khalil , Abbas Ghazanfar , Ahmad M. Ashfaq , kazim Zafarullah , Munir Tariq
Published: December 2023

The porous and mixed ionic electronic cathode conductor plays a vital role in the efficient working of low‐temperature solid oxide fuel cells. Perovskite composite cathode material La0.3Sr0.7Fe0.4Ti0.6O3‐δ (LSFT) is synthesized using the sol–gel method. Graphene oxide (GO) is integrated in 1 and 1.5 wt.% into the perovskite LSFT cathode to use as a cathode for low‐temperature solid oxide fuel cell (LT‐SOFC). Crystal structure analysis is studied by XRD and the crystalline size of samples is determined in the range of 103–73 nm. SEM analysis is used to characterize homogeneous and porous morphology. The FTIR spectral analysis is examined for proposed nanocomposite cathode materials. The electrical conductivities are carried out by four probe method in air atmosphere in the temperature range 300–600 °C and enhanced conductivity is obtained 7 Scm−1 for LSFT‐1.5 wt.% GO sample. For the same sample, a minimum value of area‐specific resistance (ASR) of 0.02 Ωcm2 is obtained. The performance of three‐layer fuel cells is tested by supplying H2 fueled at the anode and oxygen at the cathode terminal of the cell and peak power density is determined to be 362 mWcm−2 for GO incorporated fuel cell. The prepared cathode can be proposed as a potential candidate for low‐temperature solid oxide fuel cells.
A Thermoresponsive Lead‐Free Organic‐Inorganic Hybrid Perovskite as a Dielectric Switch
Authors: Ou‐yang Yuliang , Li Lutao , Wang Chen , Zou Guifu , Huang Chao‐Ran
Published: December 2023

Thermochromic perovskites, renowned for their tunable bandgap, high absorption coefficient, and reversible color changes, emerge as promising candidates for applications in smart windows. These advancements not only have the potential to enhance occupant comfort but also contribute significantly to reducing energy consumption in buildings. Here, we present a two‐dimensional lead‐free organic‐inorganic hybrid perovskite [Cyclobutylammonium]2CuCl4 which shows phase transitions from C2/c to P21/c to P21/c space group at 319.5 K and 348.8 K, respectively. Accompanying these transitions is a fascinating, reversible thermochromic behavior that is dependent on the phase structure. This behavior manifests as a vibrant sequence transitioning from yellow to brown and finally to a slightly dark brown. Most importantly, the demonstrated ability to switch stably between high and low dielectric states indicates the enormous potential of this material as a dielectric switch. This non‐toxic thermoresponsive perovskite, characterized by its appropriate transition temperatures, reversible phase structure‐dependent thermochromism, and stable dielectric switching behavior, is expected to generate significant interest within the fields of thermoresponsive and dielectric switching materials. The integration of these features not only positions this perovskite as a noteworthy subject of scientific inquiry but also opens avenues for practical applications in diverse fields.
Visible‐Light Mediated Tandem Oxidation–Organocatalyzed Aromatic C−S Bond Functionalization: Synthesis of 2‐(Benzo[b]thiophen‐2‐yl)benzenesulfonamide Derivatives
Authors: Venkateswarlu Derangula , Murugesh Venkatesh , Sridhar Balasubramanian , Prakash Singh Surya
Published: December 2023

Herein, we demonstrated a visible light mediated tandem oxidation–organo catalyzed C−S bond functionalization protocol for the cleavage of aromatic C−S bond. The investigation encompassed the functionalization of C−S bonds within sulfones, sulfoxides, and aliphatic sulfide derivatives. However, the process of functionalizing the C−S bond in aromatic sulfides remains uncertain. The presented protocol demonstrates the C−S bond functionalization on benzo[b]benzo[4,5]thieno[2,3‐d]thiophene derivative and amines including primary and secondary amines as well. A radical mediated mechanism was proposed for the tandem oxidation–organocatalyzed C−S bond functionalization protocol.
Assessing the asymmetric volatility linkages of energy and agricultural commodity futures during low and high volatility regimes
Authors: Rezitis Anthony N. , Andrikopoulos Panagiotis , Daglis Theodoros
Published: December 2023

This study investigated the volatility linkages between energy and agricultural futures, including possible causes for these comovements, such as external macroeconomic and financial shocks during low and high volatility regimes. A combination of Markov‐switching regressions and quadrivariate VAR–DCC–GARCH and VAR–BEKK–GARCH modeling revealed that external shocks have an asymmetric effect on the relationship of these assets with higher cross‐correlations reported during high volatility regimes. This comovement effect outweighs the substitution effect between energy and agricultural products. Furthermore, the quadrivariate VAR–BEKK–GARCH model provides strong evidence of a bidirectional price volatility spillover between the agricultural and energy markets during periods of high volatility. Overall, the results suggest that energy futures can be effectively used for hedging in a portfolio comprising agricultural futures (and vice versa), while a combination of macroeconomic and financial index futures can serve as an effective hedging tool in investment portfolios comprising both energy and agricultural commodities.
Price monotonicity violations during stock market crashes: Evidence from the SSE 50 ETF options market
Authors: Luo Xingguo , Ryu Doojin , Tao Libin , Ye Chuxin
Published: December 2023

This study empirically tests whether price violations, as defined by Bakshi, Cao, and Chen (2000), show different patterns in response to market shocks. Specifically, we analyze the Chinese options market during a period covering a stock market crash and a series of trading restrictions in the Chinese derivatives markets. Our results confirm the significant changes of the defined violations in the face of unexpected shocks, and more importantly, we interpret such variations from the perspective of information spillovers. Our findings suggest that the stock market crash prompts informed traders in the Chinese options market to frequently adjust their positions on put options, exacerbating the misunderstandings and overreactions to new information. Further, the regulatory shock in the derivatives markets diminishes the efficiency of information incorporation for both options and spot markets but does not affect the dominance of the Chinese options market in price discovery.