bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV‐associated neurocognitive disorders (HAND) in a cART‐treated cohort of adults aged 50 and over in Kilimanjaro, Tanzania: The first longitudinal follow‐up study of HAND in an older population in sub‐Saharan Africa
Authors: Paddick Stella‐Maria , Holmes Sarah , Ranasinghe Sherika , Mukaetova‐Ladinska Elizabeta , Gray William K. , Urasa Sarah , Dekker Marieke , Dotchin Catherine , Kisoli Aloyce , Howlett William , Lewis Thomas , Kalaria Raj N. , Walker Richard 
Published: December 2020

AbstractBackgroundHIV‐associated neurocognitive disorders (HAND) are highly prevalent in Sub‐Saharan Africa (SSA), due to increasing life expectancy and availability of combination antiretroviral therapy (cART). These preliminary data represent the first longitudinal study of HAND in older cART‐treated adults in SSA with the aim of reporting prevalence and persistence of cognitive impairment, and neurocognitive profile.MethodWe investigated prevalence and incidence of HAND diagnosis and subtypes (asymptomatic neurocognitive impairment (ANI), minor neurocognitive disorder (MND) and HIV‐associated dementia (HAD), alongside neuropsychological profile and neurological symptom burden over 40 months in 253 HIV positive adults aged ≥50 attending a government clinic (2016‐2019). HAND diagnoses were reviewed annually by a consensus panel using Frascati criteria, based on detailed clinical assessment.ResultAt baseline (2016), 253 individuals underwent full assessment, of these, 185 were re‐evaluated in 2017, 181 in 2018 and 128 in 2019. 139 individuals had complete data 2016 ‐2018. The majority (68%) were female, median age at diagnosis was 51, and time since diagnosis 7.6 years. Almost all were receiving cART and were well‐managed (mn CD4 532.76. HAND prevalence was 47% in 2016 (n=253, 95.5% cART‐treated) and 49% in 2017 (one‐year incidence from those at risk 37%). Provisional follow‐up data indicates HAND prevalence of 62% in 2018 (n=172) and 54% in 2019 (n=128). Milder forms of HAND predominated, with evidence of reversibility. The predominant cognitive domains affected were both cortical and subcortical (executive function, motor speed, working memory, verbal memory (word list learning) and orientation) with visuoconstruction and language comprehension relatively spared. Both depression and neurological impairments were highly prevalent.ConclusionThis is the first longitudinal study of neurocognitive impairment in older adults living with HIV in SSA. Findings suggest cART and regular follow‐up are insufficient to prevent occurrence or progression of HAND, though the aetiology remains unclear. Both cortical and subcortical cognitive domains are affected suggesting the possibility of non‐HIV‐related neurodegenerative cognitive decline. If replicated in other SSA settings, HAND is likely to be a major cause of cognitive impairment in older people in SSA, despite cART treatment.
Correlation of insomnia on cognitive functions in perimenopausal and postmenopausal women
Authors: Rothenberg Kasia Gustaw , Bojar Iwona , Humieniuk Ewa , Raczkiewicz Dorota 
Published: December 2020

AbstractBackgroundSleep disturbances as well as cognitive dysfunction are s relatively common and disturbing phenomena in menopause. Little is known however how much cognitive and sleep dysfunctions overlap and influence each other in the population of women transitioning through the menopause.Method300, employed women aged 44‐66 were divided into 2 groups according to STRAW criteria: perimenopausal and postmenopausal group. Cognitive functions were assessed by CNS Vital Signs in the following domains: Complex Memory, Verbal Memory, Visual Memory, Psychomotor Speed, Reaction Time, Complex Attention, Cognitive Flexibility, Processing Speed, Executive Function, Simple Attention and Motor Speed. Neurocognitive Index (NCI) is automatically calculated based on: memory, psychomotor speed, reaction time, attention, and cognitive flexibility. Athens Insomnia Scale (8‐item scale, 0‐24 score range) was used to assess insomnia. The t‐test for two means in independent samples was used to compare and Pearson’s correlation coefficient r to correlate theseverity of insomnia and level of cognitive functions. The significance level was assumed at 0.05.ResultThe mean severity of insomnia in the total group of women in the study was 6.70±4.66, which indicates the border of normal range on average. Insomnia was present in 54 (18.00%) of women (Tab. 1). The examined postmenopausal women obtained a significant lower reaction time (87 scores, on average) than those perimenopausal (91 scores, on average) (Tab. 1). Severity of insomnia negatively correlated with the following cognitive functions: complex and visual memories and simple attention in the total group, i.e. the greater the severity of insomnia, the worse the complex and visual memories, and simple attention. Also, a negative correlation was foung between severity of insomnia and simple attention in perimenopausal but not postmenopausal women (Table 2).ConclusionThe more severe insomnia the worse complex memory, visual memory, and simple attention. In premenopausal group, insomnia corresponded in worsening in simple attention. The results obtained indicate the need for further studies in the area of modulation of the effect of insomnia on cognitive functions in peri‐ and postmenopausal women. This may be important for prophylaxis and treatment of cognitive disorders during perimenopausal transition.
Prevalence of cognitive frailty and associations with other frailty domains in a Spanish community‐dwelling sample
Authors: Facal David , Campos‐Magdaleno Maria , Navarro‐Pardo Esparanza , Pereiro Arturo X. 
Published: December 2020

AbstractBackgroundThe concept of cognitive frailty has been defined as the simultaneous presence of frailty and mild cognitive impairment in absence of dementia, although recent approaches has considered cognitive frailty as a distinct construct and has taken into account different domains of physical frailty (De Roeck et al., 2020). The aim of the present study is to analyze the prevalence of cognitive frailty in groups with different degrees of cognitive impairment.MethodA total of 285 community‐dwelling middle‐age and older adults, aged >50 years, from Galicia and Valencia (northwest and southeast of Spain respectively) participated. Cognitive function was assessed using MoCA test, and cognitive complaints with the Spanish version of the Everyday Memory Questionnaire. Participants were classified as objective cognitively impaired, cognitively unimpaired, and cognitively unimpaired with subjective cognitive complaints. Physical frailty criteria included: a) unintentional weight loss or lack of appetite in the last three months; b) self‐reported exhaustion, measured with the General Health Questionnaire‐12 question about affective state; c) weakness, measured with a dynamometer to determine handgrip strength; d) slow walking speed, measured through a timed‐up and go task; and e) low physical activity, measured with the reduced Spanish version of the Minnesota Leisure Time Physical Activity Questionnaire (VREM). Participants were classified as robust if they met none of the criteria, pre‐frail if they met 1 or 2 criteria, and frail if they met 3 or more criteria, corrected by gender and age.ResultsThe prevalence of frailty was 2.5% in the cognitively unimpaired group, 12.2% in the group with cognitive complaints, and 9.6% in the group with objective cognitive impairment (chi‐square=18.37;p<0.01) (Table 1). The co‐occurrence with physical frailty is more frequent with slow walking speed and, in the group with complaints, with self‐reported exhaustion.ConclusionThe prevalence of physical frailty was higher in both cognitive complaints and cognitive impairment groups, compared with the cognitively unimpaired group. The subjective cognitive complaints can play a relevant role in characterizing the relation between physical and cognitive impairments.
Alpha‐synuclein, ferroptosis and neurodegeneration: Investigating a complex relationship
Authors: Ganguly Upasana , Banerjee Anindita , Chakrabarti Sasanka 
Published: December 2020

AbstractBackgroundThe accumulation of brain iron in several neurodegenerative diseases like Alzheimer’s disease (AD) or Parkinson’s disease (PD) is well established both by ante‐mortem imaging studies and post‐mortem biochemical analysis of affected brain tissue. Thus, understanding the cytotoxic actions of iron in neurons or cells of neural origin would be important in elucidating the mechanisms of neurodegeneration in disorders like AD or PD. We have recently shown that cytotoxic action of iron in SH‐SY5Y cells (catecholaminergic human neuroblastoma cell line) is mediated by accumulated α‐synuclein which triggers mitochondrial dysfunction and cell death. The accumulation of α‐synuclein occurs as a result of decreased clearance from the cell as a result of oxidative inactivation of Parkin. In the current study we have further examined the role of oxidative stress in this process.MethodSH‐SY5Y cells were treated with ferrostatin‐1, liproxstatin‐1 and vitamin E (ferroptosis inhibitors) and then co‐incubated with 100‐400 μM Ferric ammonium citrate and analyzed for cell death (LDH assay and trypan blue assay), ROS generation (DCFDA assay), lipid peroxidation (MDA levels), reduced glutathione levels and α‐synuclein protein levels (western blotting). α‐synuclein silencing was performed by using commercially available siRNAs.ResultOur results show that iron induced an increased formation of reactive oxygen species (ROS) and malondialdehyde (MDA) along with a decreased level of reduced glutathione content in SH‐SY5Y cells, and these changes were associated with significant cell death. Co‐incubation of SH‐SY5Y cells with vitamin E, ferrostatin‐1 and liproxstatin‐1, prevented all the toxic actions of iron in our experimental system, and in addition these prevented iron‐induced accumulation of α‐synuclein . These results tend to imply that iron cytotoxicity in our system clearly resembles ferroptotic cell death, and it appears that α‐synuclein could be a key mediator in the latter process. Furthermore, knocking‐down α‐synuclein gene expression by specific siRNA resulted in a significant decrease in oxidative stress induced by iron in SH‐SY5Y cells.Conclusionα‐synuclein appears to have a dual role in enhancing oxidative stress as well as functioning as a mediator of oxidative damage to the cells. The implications of these results in neurodegeneration of AD and PD are obvious and need further exploration.
The use of Alzheimer CSF biomarkers in daily clinical practice
Authors: Escudero Joaquin V. , Ladron Gema , Satorres Encarnacion , Timoneda Pilar , Melendez Juan C. , Guarner Jerico 
Published: December 2020

AbstractBackgroundCurrently, there is a discrepancy regarding whether CSF biomarkers (BM) in Alzheimer’s Disease (AD) should be applied generally in daily clinical practice, performed in high‐level clinical centres, or reserved for research only. The main objective is to assess the influence of these BM on the diagnosis of AD in daily clinical practice, analyzing the change or maintenance of the etiological diagnosis after the performance of the test. As a secondary objective, the type of patients requested to take this test will be assessed. Finally, the concordance between the test request and the recommendations from literature (Shaw et al, 2018) will be analyzed.MethodThis is an observational and retrospective study of patients referred to our hospital’s neurology department for suspected cognitive or behavioral impairment. The patients underwent a CSF study between the years 2014‐2019. For the etiological diagnosis, the most widespread diagnostic criteria were applied at that time (DSM‐IV and NIAA). Main variable: change of pre‐test vs post‐test diagnosis. Secondary variables: concordance with the recommendations, sex, age, symptoms or signs, MMSE, GDS.Result102 patients were analyzed, 67.6 a ± 7.9 (49‐84), 53 % men, 75 % with memory loss and 33 % with neuro‐psychiatric symptoms. MMSE: 22 ± 5 (6‐30), GDS: 3 ± 1.2 (2‐6). There was a change in the etiological diagnosis in 39,2 % of the patients, especially when psychiatric disorder was the initial suspicion (34,2 %). There was a complete consistency with the recommendations from literatureConclusionThe profile of the patient requested for testing was young (compared to the usual age of cognitive disorder), with memory complaints or neuro‐psychiatric symptoms, in the early clinical stages of the disease. The agreement with the recommendations is total. Our change in diagnosis is similar to the one found in other series in literature (Tabaraud et al, 2011), and close to clinical trials using amyloid BM. Therefore, it is believed that CSF BMs are clearly useful in their application under real clinical practice conditions.
Population attributable fraction of dementia risk in individuals with reduced kidney function
Authors: Xu Hong , Garcia‐Ptacek Sara , Trevisan Marco , Evans Marie , Lindholm Bengt , Eriksdotter Maria , Carrero Juan Jesus 
Published: December 2020

AbstractBackgroundCommunity‐based studies regarding the association between chronic kidney disease and dementia risk are conflicting. In a large Swedish population‐based cohort, we explored the incidence and population attributable fractions (PAFs) of dementia risk in patients with chronic kidney disease (CKD).MethodIn the Stockholm CREAtinine Measurements (SCREAM) project, we studied the associations of baseline estimated glomerular filtration rate (eGFR) with the incidence of dementia among 329,822 residents of Stockholm, aged ≥65 years and with no prior history of dementia. The primary outcome was dementia incidence based on ICD‐10 codes or use of anti‐dementia drugs. Secondary outcomes were incidence of the dementia subtypes Alzheimer’s and vascular dementia. The association between eGFR and dementia risk was examined with Cox proportional hazards models. The weighted contributions of kidney disease (eGFR<60ml/min/1.73m2) and other plausible comorbidities to the risk of dementia were quantified using the population attributable fraction (PAF).Result18,983 cases of dementia (5.8% of participants) were detected throughout 1,185,304 person‐years. Dementia incidence rates (IR) were progressively higher with lower eGFR: from 6.56/1000 person‐years in persons with eGFR 90‐104ml/min to 30.28/1000 person‐years in those with eGFR<30ml/min). The HR of dementia risk was highest for the presence of CKD [eGFR<60ml/min; HR 1.54(1.28‐1.85)], followed by having a history of stroke [1.51(1.44‐1.58)], diabetes [1.23(1.18‐1.28)], atrial fibrillation [1.09(1.05‐1.14)], and myocardial infarction [1.07(1.01‐1.14)]. The presence of diagnosed hypertension and history of cancer [0.96(0.93‐0.99); and 0.87(0.84‐0.90) respectively] were associated with a lower dementia risk. Via PAF analyses we estimated that 11% [(95% CI (7‐14%)] of the dementia cases were attributed to eGFR<60 ml/min, followed by stroke [4% of cases attributed, 95%CI (4‐5%)] and diabetes [3% of cases, 95% CI (2‐3%)]. PAFs were around 1% for comorbidities such as atrial fibrillation and myocardial infarction. Risk magnitudes were stronger for vascular dementia than for Alzheimer. Sensitivity analyses across predefined strata or after excluding early events yielded similar results.ConclusionReduced kidney function is a strong risk factor for development of dementia, particularly vascular dementia. The proportion of dementia cases attributed to CKD is higher than that attributed to other dementia risk factors such as cardiovascular disease and diabetes.
Biochemical characterization of age‐related calcium‐cAMP‐PKA signaling dysregulation and its effect on tau pathology in rhesus monkey cortex
Authors: Leslie Shannon N. , Datta Dibyadeep , Wang Min , van Dyck Christopher H. , Arnsten Amy F. T. , Nairn Angus C. 
Published: December 2020

AbstractBackgroundEarly onset forms of Alzheimer’s disease (AD) are driven by rare dominantly inherited genes; however, the predominant form of the disease is sporadic and occurs later in life through an unknown etiology. Sporadic AD emerges after age 60‐65 and preferentially afflicts the association cortex. Thus, a better understanding of how age‐related changes in vulnerable brain regions relate to AD pathology is crucial to developing novel treatments for the disease. AD is characterized by two main pathological hallmarks, tau neurofibrillary tangles and amyloid‐beta plaques. Tau pathology correlates with cognitive decline while amyloid pathology does not. Thus, we focused on the role of age‐related signaling changes on tau pathology. Dysregulated calcium signaling has long been hypothesized to play a major role in age‐related vulnerability to AD1. Thus, we investigated the impact of aging on calcium signaling in the vulnerable dorsolateral prefrontal cortex (dlPFC) of rhesus monkeys, focusing on regulation of and by cAMP‐PKA signaling in relationship to tau pathology. Monkeys provide a unique opportunity to study higher order cognitive circuits unique to primates while still being able to probe molecular networks to a degree that is not possible in human post‐mortem samples. Overall, we found a significant age‐related dysregulation of calcium‐cAMP‐PKA signaling that strongly associated with early stage tau pathology in rhesus monkey dlPFC. (1) Khachaturian, Z. S. C Alzheimer’s & Dementia
13, 178‐182.e17 (2017)MethodPatterns of molecular signaling were assessed via western blot and immuno‐electron microscopy of monkey dlPFC in animals ranging from 8 to 28 years of age. Mechanistic studies of the relationship between intracellular calcium and tau phosphorylation were performed in rat primary cortical cultures.ResultWe observed a consistent pattern of calcium‐cAMP‐PKA dysregulation in the vulnerable dlPFC region of rhesus monkeys. We found a highly significant association between leaky ryanodine receptor calcium channels and early stage tau phosphorylation (pS214 and pS356). The link between these phosphorylation sites and intracellular calcium was validated through in vitro mechanistic studies.ConclusionAge‐related dysregulation of calcium‐cAMP in the dlPFC is associated with early stage tau pathology and may explain the vulnerability of these circuits to degeneration.
Amyloid pathology changes hippocampal GFAP‐positive astrocytes phenotype
Authors: Zimmer Eduardo R. , Bellaver Bruna , Ferreira Pamela C.L. , de Souza Débora Guerini , De Bastiani Marco Antônio 
Published: December 2020

AbstractBackgroundAstrocytes are physically intercalated with neurons and a single astrocyte simultaneously exchanges information with multiple neurons. In Alzheimer’s disease (AD), they seem to respond to pathology by becoming reactive, i.e. changing morphology and overexpressing specific proteins, such as the glial fibrillary acidic protein (GFAP). Astrocyte reactivity is one of the earliest brain changes in AD and may serve as a potential target for early diagnosis and treatment. Still, few astrocyte biomarkers have been investigated in AD and, though promising, further development is needed. Therefore, a better understanding of AD‐reactive astrocyte phenotypes is needed. Here, we aimed at evaluating hippocampal astrocytes phenotype in the presence of amyloid pathology in a transgenic AD‐like mice model. We hypothesize that hippocampal astrocytes will react to amyloid‐pathology by assuming a different phenotype when compared to their wild‐type (WT) littermates.MethodsHippocampal GFAP‐positive astrocytes data from 10 months‐old male and female PS2APP [Tg(Thy1‐APPSwe,Prnp‐PSEN2*N141I)152HLaoz]mice, which express human APP K670N/M671L and human presenilin 2 N141I mutations, and WT littermates (n = 5 per group) were obtained from GEO dataset(GSE129770) and used to evaluate differentially expressed genes (DEGs) and altered pathways/biological processes. In brief, raw fastq data reads were submitted to quality control assessment. Afterwards, we used the Salmon algorithm on high‐quality RNAseq samples. Finally, DEGs were evaluated using the DESeq2 method. Further data exploration included Gene Ontology (GO) functional evaluation. All RNAseq data analysis were performed using R/Bioconductor.ResultsPrincipal component analyses (PCA) clearly differentiated gene expression from P2APP and WT astrocytes (Figure 1A). We further identified 1140 up‐regulated and 646 down‐regulated genes in P2APP astrocytes compared to WT (Figure 1B‐C). Interestingly, cell‐to‐cell communication pathways were amongst the top 10 altered GO pathways (Figure 1D). Differences were considered statistically significant at P<0.05.ConclusionWe identified a striking gene expression signature in hippocampal astrocytes of a mice model presenting heavy load of amyloid‐β. Therefore, changes in astrocyte phenotype, which can impact astrocyte morphology, protein expression and function, may hold the key for the development of novel biomarkers and for advancing our understanding of AD pathophysiology.
Holocaust survivorship and late‐life cognitive performance in men with coronary heart disease
Authors: Weinstein Galit , Lutski Miri , Lital Keinan‐Boker , Goldbourt Uri , Tanne David 
Published: December 2020

AbstractBackgroundHolocaust victims experienced extreme physical and mental stress that could lead to prolonged deficits in psychological and physiological well‐being. Indeed, some evidence demonstrates a link between Holocaust exposure and higher incidence of post‐traumatic disorder as well as for cardiovascular morbidity and its risk factors, which in turn are associated with increased brain aging. Recent evidence points to increased dementia risk among Holocaust survivors compared to the general population, however data are limited. We aimed to examine whether exposure to Holocaust conditions is associated with cognitive function and decline in old age.MethodThe study sample included 351 individuals (mean age at baseline 56.7±6.5y) with coronary heart disease (CHD) who participated in the secondary prevention Bezafibrate Infarction Prevention trial in 1990‐1997. During 2004‐2008, these participants underwent a computerized cognitive assessment (mean age 71.8±6.5y). A second cognitive assessment was performed during 2011‐2013 (mean age 77.1±6.4y). Exposure to Holocaust conditions was based on self‐report at the second assessment. Linear regression and mixed‐effect models were conducted to evaluate the associations between Holocaust survivorship and subsequent cognitive performance and rate of decline while adjusting for potential confounders.ResultOf the total sample, 45 (12.8%) survived concentration camp/ghettos, 70 (19.9%) were Holocaust survivors who escaped concentration camps/ghettos, and 236 (67.2%) were not Holocaust survivors. After adjustment for potential confounders, concentration camp/ghetto survivors had poorer global cognitive performance and poorer attention (β=‐3.90; 95% CI:‐7.11;‐0.68 and β=‐4.11; 95% CI:‐7.83;‐0.38, respectively) compared to individuals who were not exposed to Holocaust conditions. In the longitudinal analysis, participants who reported being at concentration camps/ghettoes had increased cognitive decline in global performance and executive function (β=‐0.19; 95% CI: ‐0.37;‐0.008 and β=‐0.29; 95% CI: ‐0.53;‐0.06, respectively) compared to participants who were not Holocaust survivors. Lastly, those who were Holocaust survivors but not in concentration camps/ghettos had greater decline in attention (β=‐0.11; 95% CI: ‐0.21;‐0.01). Results remained unchanged after excluding individuals with prevalent stroke and dementia and after utilizing Inverse Probability Weighting to adjust for potential selection bias.ConclusionExposure to Holocaust conditions in early‐life may be linked with poorer cognitive function and greater cognitive decline decades later in old‐adults with (CHD).