bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating Aß42, P‐Tau and NFL as blood‐based biomarkers for diagnosis of Alzheimer’s disease in Pakistani population
Authors: Ahmed Tehniat F , Imtiaz Fauzia , Ahmed Affan , Zaman Uzma , Shahbaz Naila 
Published: December 2022

AbstractBackgroundOverlapping symptoms of different neurodegenerative dementias and heterogeneity in the presentation of Alzheimer’s disease (AD) pose a challenge to its diagnosis in clinics. The AT(N) research framework proposed by National Institute of Ageing‐Alzheimer’s Association in 2018 assigned its diagnosis a molecular construct. However, in Pakistan the diagnosis of AD still rests on clinical exclusionary approach. As an initial step towards establishing accessible and affordable biochemical diagnosis of AD in Pakistan, we for the first time investigated the plasma levels of Amyloid‐β42 (Aβ42), Phosphorylated tau (P‐tau) and Neurofilament light (NFL) in patients with Alzheimer’s Clinical Syndrome (ACS) and healthy controls (HC) from Pakistani population.MethodSubjects presenting with cognitive decline to neurology OPDs of two tertiary care hospitals of Karachi, Pakistan were recruited through convenience sampling after being diagnosed with ACS by the attending neurophysician. Following informed consent, demographic and lifestyle details, along with 5cc blood in EDTA tubes were obtained. Plasma was aliquoted and stored at ‐800C after centrifugation. For analysis it was thawed at 4°C and protein levels were measured through ELISA. Data of 28 subjects with ACS and 28 age‐matched healthy controls was analyzed using USCN Business Co. Ltd kits CE946Hu and SEE038Hu for Aβ42 and NFL respectively, and Bioassay Technology Laboratory kit E4844Hu for P‐tau.ResultThe only demographic variables associated with health status were education and depression status of the subjects (p=0.03 and 0.003 respectively). Mean values of NFL and P‐tau showed significant difference between ACS and control groups (p=0.003 and 0.006) while Aβ42 showed no significant difference (p=0.114). ROC analysis revealed that plasma P‐tau and NFL could significantly differentiate ACS from HC group (p=0.007 and 0.003) with AUC 0.717 and 0.735 respectively. Significant negative correlation with MMSE score of subjects was seen for both plasma P‐tau (r = ‐0.389; p=0.004) and NFL (r= ‐0.424; p=0.001) levels.ConclusionPlasma P‐tau and NFL hold promise for distinguishing AD patients from healthy controls. This is the first such study conducted in Pakistan. Larger, similar studies can help employ non‐invasive tests for AD screening in the country.
Tablet training at home for people with dementia and their caregivers during pandemic
Authors: Blekou Patra , Sakka Paraskevi , Zoi Panagiota , Kalligeros Nikolaos 
Published: December 2022

AbstractTechnology has provided some wonderful tools both for people with dementia and their caregivers by creating applications that empower seniors to live more actively and independently and remotely connect with family and friends.Since covid‐19 pandemic started, Alzheimer Athens has been offering to its members a wide range of digital services, providing online support, cognitive training, physical exercise programs, as well as opportunities to relax, socialize and have fun. However, in Greece, low level of digital literacy of elderly people with dementia and their caregivers have been key obstacles to the use of appropriate technological tools (PCs, tablets, smartphones etc.).To address this issue and explore the impact of tablet training on cognitive status, social engagement and quality of life, Alzheimer Athens has developed a 12‐month program of tablet training at home. The program started in August 2021 and will be completed in July 2022. In total, 120 people with dementia and their caregivers receive a free tablet and attend a series of 16 weekly workshops teaching basic skills allowing participants to feel confident using a tablet. Internet access is also provided free of charge for 12 months.Social isolation, loneliness, social support, and quality of life of participants were assessed before and after the intervention. Data on tablet use and attitudes toward technology tools were also collected. The overall experience of the 60 people with mild cognitive impairment and early dementia who participated in the first phase of tablet training intervention was extremely positive. The vast majority of them started using Alzheimer Athens digital services shortly after the training had been completed!Detailed results of the questionnaires used to assess all aspects of the intervention, will be reported at the end of it. We aspire our preliminary and very encouraging findings will help us develop more successful interventions utilizing new technologies and create better health outcomes for people with dementia in the future as we move into a post‐COVID‐19 world.
In‐season docosahexaenoic acid supplementation does not prevent white matter damage during a single American football season: Implications for neurodegeneration prevention
Authors: Raikes Adam C. , Hernandez Gerson D , Mullins Veronica A. , Wang Yiwei , Lopez Claudia M , Killgore William D. S. , Chilton Floyd , Brinton Roberta Diaz 
Published: December 2022

AbstractBackgroundRepetitive sub‐concussive head impacts (RSHIs) are common in American football, result in changes to white matter microstructural integrity, and are suggested as a potential risk factor for neurodegenerative diseases, including Alzheimer’s disease. RSHI‐induced white matter degradation may accelerate neurodegenerative processes, necessitating effective preventative and therapeutic approaches in this population. Prior studies indicate potential neuroprotective and remyelinating effects of docosahexaenoic acid (DHA). Here, we conducted a double‐blind, randomized, placebo‐controlled trial to assess the effects DHA supplementation during a National Collegiate Athletic Association football season on neuroimaging measures of white matter integrity.MethodThirty‐eight participants were randomized to treatment (6g DHA/EPA) or placebo (6g oleic/linoleic acid) group for seven months of five‐times‐per‐week supplementation. 27 participants completed the trial and had complete neuroimaging datasets (n = 16 placebo; n = 11 treatment). White matter integrity changes from preseason to immediately post‐season were quantified using voxel‐wise fractional anisotropy and diffusivity (mean, axial, radial) as well as deterministic tractography using quantitative anisotropy (QA). Gray matter volume as well as intra‐regional, edge‐wise, and network level functional connectivity were obtained as secondary measures along with serum neurofilament light (NfL) as a peripheral biomarker of axonal damage.ResultThere were no voxel‐wise, between‐group differences in voxel‐wise DTI analyses. Compared to placebo, the treatment group had increased QA in ascending corticostriatal fibers and decreased QA in long association and commissural fibers. Increased mean (ρ = 0.47), axial (ρ = 0.44), and radial (ρ = 0.51) diffusivity and decreased QA (ρ = ‐0.52) in the corpus callosum and bilateral corona radiata were correlated with increasing NfL levels during the season irrespective of treatment group. Default mode/frontoparietal network connectivity (g = 0.96, p = 0.024) was greater in the treatment group.ConclusionIn‐season DHA supplementation was insufficient to prevent or protect against axonal damage as it occurred during the season. However, there may be neuroprotective effects on functional connectivity despite structural damage. If RSHIs are a risk factor for future neurodegeneration, then alternative therapeutic merit further investigation. These present outcomes do not support the use of in‐season DHA supplementation as a preventive strategy to reduce brain injury resulting from collegiate football.AcknowledgementStudy funded by the Center for Innovation in Brain Science, University of Arizona. DHA provided by Pharmavite
Clinical features in prodromal disease: Comparing dementia with Lewy bodies with Alzheimer’s disease
Authors: Wyman‐Chick Kathryn A , Boeve Bradley F. , Weintraub Daniel , Armstrong Melissa J , O'Keefe Lauren R , Rosenbloom Michael H , Barrett Matthew J 
Published: December 2022

AbstractBackgroundDementia with Lewy bodies (DLB) is a common neurodegenerative disorder; however, DLB can be difficult to differentiate from Alzheimer’s disease dementia (AD), particularly in the early stages. Research criteria for prodromal DLB were published in 2020 and further studies are needed to validate and refine future clinical criteria.MethodWe analyzed data from the Uniform Data Set from the National Alzheimer’s Coordinating Center (NACC database is funded by NIA/NIH U01‐AG016976). Annual visits occurred across 39 Alzheimer’s Disease Research Centers between September 2005 and September 2021. We identified non‐demented participants [i.e., normal cognition, impaired‐not mild cognitive impairment (MCI) or MCI] at baseline who subsequently received a clinical diagnosis of DLB or AD. Core clinical features (CCF) for DLB (i.e., motor features, visual hallucinations, probable REM sleep behavior disorder (pRBD), cognitive fluctuations), and supportive neuropsychiatric features (NPF; anxiety, apathy, and depression) were assessed through clinical exam and informant responses up to five years prior to dementia diagnosis.ResultThe sample consisted of 160 participants with DLB and 480 age/sex‐matched (1:3) participants with AD at first visit with dementia diagnosis. There was no significant difference in the number of visits prior to dementia diagnosis. The AD group was more racially and ethnically diverse than the DLB group. At the time of diagnosis, DLB participants demonstrated greater functional impairment. Descriptive results indicate CCF and NPF are common in DLB up to five years prior to conversion to dementia; however, motor slowing and NPF were reported in over 20% of the AD participants within the prodromal phase. The presence of 2 or more CCF yielded the greatest AUC (0.786; 95% CI: 0.743, 0.830) in distinguishing DLB from AD one year prior to dementia diagnosis. Combinations of 1 or more CCF with 1, 2, or 3 NPF resulted in significantly lower AUCs (0.725, 0.651, 0.547, respectively) due to decreased specificity.ConclusionCCF and supportive NPF are common in the prodromal phase of DLB; however, parkinsonism and NPF also occurred in the prodromal AD group. Parkinsonism may provide lower discrimination than cognitive fluctuations, visual hallucinations, or pRBD in differentiating DLB from AD in the prodromal phase.
Selective inhibition of ACE‐2‐interacting domain of SARS‐CoV‐2 by AIDS peptide attenuates Spike S1 associated behavioral and neuronal inflammation in in vitro and in vivo models
Authors: Paidi Ramesh Kumar , Pahan Kalipada 
Published: December 2022

AbstractBackgroundCoronavirus disease 2019 (COVID‐19) is a serious contagious illness caused by the virus strain severe acute respiratory syndrome coronavirus 2 (SARS CoV‐2). Covid‐19 patients are suffered from various brain complications, but underlying mechanism is not clear. So far, there is no proper therapeutic strategy against Covid‐19 and its implications on the brain.MethodSince SARS‐CoV‐2 binds to angiotensin‐converting enzyme 2 (ACE2) for entering into host cells, to target COVID‐19 from therapeutic angle, we designed a hexapeptide corresponding to the ACE2‐interacting domain of SARS‐CoV‐2 (AIDS) that inhibits the association between receptor‐binding domain‐containing spike S1 and ACE‐2. Initially, we have validated the effect of AIDS peptide and the its role in Spike S1 associated neuroinflammatory alteration in mouse primary glia cultures. For in vivo, recombinant spike S1 was administered Intranasally for 14 days. Wild type and mutant AIDS peptide were administered post 5 days treatment of spike S1. Post two weeks treatment, we performed several behavioral assessment and biochemical evaluationResultIncreased INOS levels and microglia activation was observed by Spike S1 treatment in mice primary microglia. AIDS peptide prominently attenuates Spike S1 associated inflammatory markers in glia cultures. Intranasal intoxication of C57/BL6 mice with recombinant SARS‐CoV‐2 spike S1 led to fever, increase in IL‐6 in lungs as well as in brain, and impairment in spatial learning memory functions and motor disabilities, mimicking some of the important symptoms of COVID‐19. Intranasal treatment with wtAIDS, but not mAIDS, peptide reduced fever, enhanced locomotor functions and cognitive and memory functions in SARS‐CoV‐2 spike S1‐intoxicated mice. Our studies show wtAIDS peptide attenuates Spike S1 inducted cytokine levels in the brain.ConclusionOur results illustrated that, selective targeting of ACE2‐to‐SARS‐CoV‐2 interaction by wtAIDS may be beneficial for COVID‐19 associated memory and learning deficits via maintaining the cytokine levels
Physical activity reverted the increased risk of dementia associated with cardiovascular risk factors: findings a population‐based cohort study
Authors: Feter Natan , Dumith Samuel C , Leite Jayne S , Cunha Larissa , Rombaldi Airton 
Published: December 2022

AbstractBackgroundCardiovascular risk factors are associated with a higher risk of dementia. However, whether physical activity could revert this increased risk remains uncertain. We analyzed the effect of physical activity on the risk of dementia stratified by cardiovascular risk factors.MethodsData from baseline (2002‐2003) to wave 9 (2018‐2019) of the English Longitudinal Study of Ageing (ELSA) were analyzed (n = 6,021). The wave that dementia was first detected after baseline was defined as the event time. Self‐reported physical activity (inactive, low, moderate, high) at baseline was measured using a validated questionnaire. Smoking, excessive alcohol consumption, hypertension, diabetes, and obesity were analyzed as cardiovascular risk factors. Participants with simultaneous presence of 2+ risk factors were classified with a high cardiovascular risk for dementia. Socioeconomic, behavioral, and health variables were added in the Cox proportional hazard regression model as possible confounders. The incidence and the risk of dementia for physical activity, cardiovascular risk factors, and their interaction were calculated.ResultBetween baseline and wave 9, 6.21% (95% confidence interval [CI]: 5.63 to 6.85) of the participants were diagnosed with dementia. Participants with 2+ cardiovascular risk factors had a higher risk of dementia (hazard ratio [HR]: 1.31; 95%CI: 1.04, 1.63) than low‐risk adults. Physical activity level was inversely associated with the risk of incident dementia in participants who were smokers (p for linear trend = 0.027), had hypertension (p for linear trend = 0.015), and obesity (p for linear trend = 0.014). Low physical activity level (e.g., engaging in moderate‐intensity physical activity once per week) reduced the risk of dementia in participants with hypertension (HR: 0.41; 95%CI: 0.24, 0.70), and obesity (HR: 0.37; 95%CI: 0.21, 0.67). Physical activity attenuated the increased risk of incident dementia provoked by accumulated cardiovascular risk factors. High risk participants with low (HR: 0.51; 95%CI: 0.29, 0.88), moderate (HR: 0.38; 95%CI: 0.21, 0.67) and high (HR: 0.46; 95%CI: 0.22, 0.98) physical activity level had lower risk of dementia than the high risk, inactive group. Sensitivity analyses confirmed the above‐mentioned findings.ConclusionPhysical activity starting at moderate‐intensity activities once per week attenuated the increased risk of dementia associated with cardiovascular risk factors in older adults.
KDM6A expression is associated with a sex‐disease interaction in activated microglia
Authors: Brase Logan , Dunn Amy R , Dumitrescu Logan , Kaczorowski Catherine C. , Hohman Timothy J. , Karch Celeste M. , Harari Oscar , Benitez Bruno A. 
Published: December 2022

AbstractBackgroundThere is increasing evidence indicating sex‐specific patterns in disease manifestation and sex differences in the rates of cognitive decline and brain atrophy. Women are protected, relative to men, at the prodromal phases but later exhibit steeper cognitive decline and higher brain atrophy rates1. Sex‐related differences in AD‐associated genes are starting to emerge. The X‐linked gene, KDM6A, avoids X‐inactivation and the resulting elevation in expression confers resilience in women2. KDM6A is also dysregulated in disease associated microglia (DAM) in the 5XFAD mouse model3. We sought to identify if activated microglia was the effector cell type for the KDM6A resilience effect in the brain using single‐nucleus RNA‐seq (snRNA‐seq).MethodsUsing snRNA‐seq data from the parietal cortex of 56 pathologically confirmed control, sporadic AD (sAD), and autosomal dominant AD (ADAD) samples from the Knight ADRC and DIAN cohorts4, we applied a linear mixed model to confirm the female specific upregulation of KDM6A in the major brain cell types and their alternative transcriptional states. We then applied a sex‐AD interaction linear mixed model to identify the cell types and expression states that potentially contribute to disease resilience through KDM6A expression.Results
KDM6A is expressed in all major brain cell types, with the highest expression in oligodendrocytes, followed by endocytes, microglia, astrocytes, OPCs, and neurons (http://ngi.pub/SNARE/). All cell types showed increased KDM6A expression in females compared to males (oligo P=4.22×10‐15, microglia P=1.07×10‐41, astro P=1.30×10‐13, OPC P=2.55×10‐5, neuron P=7.55×10‐8). We identified a sex‐AD interaction in KDM6A expression within activated microglia (sAD P=9.12×10‐3; ADAD P=2.28×10‐3; Fig. 1), but no evidence in the overall DAM signature. Female sAD and ADAD samples showed higher expression compared to controls, while male sAD and ADAD samples had less expression than controls. Furthermore, we observed sex differences in KDM6A expression within transcriptional states of oligodendrocytes, OPCs, astrocytes and neurons. We are validating these results in additional generated data and publicly available data sets.ConclusionThese results suggest that the role of KDM6A in AD resilience could be mediated through activated microglia, but current data cannot rule out additional cell types as effectors in KDM6A resilience.
Long‐term care Facilities and Dementia. Development of a framework to assess design quality in healthcare structures for people with dementia
Authors: Mangili Silvia , Brambilla Andrea , Capolongo Stefano 
Published: December 2022

AbstractBackgroundLife expectancy has experienced rapid growth (from 77.6 to 81.3 years), resulting in an increase in Non‐Communicable Diseases (NCDs) and years lived with disability. One of those is dementia, with about 7 million people affected in Europe and the number is set to double by 2050. Those patients are complex due to the serious changes in the cognitive sphere, altering perceptions of the space. They are the most frequent users of healthcare facilities, but these structures often are not suitable to them. To this end, a rethinking is now urgent, and the use of Evidence‐Based Design (EBD) could be the way to create safe and suitable environments. This study aims to develop an evaluation framework of the main aspect in the design of a built environment for people with dementia.MethodThree analyses were conducted: systematic literature review, analysis of existing tools, and case study analysis. The first was conducted on scientific databases using meaningful keywords. In the second the assessment tools in the field of healthcare facilities used worldwide were analyzed. The third explored best practices of dementia architecture. The three analyses were compared to outline the main characteristics that the environment dedicated to the dementia patient must possess to be inclusive and prosthetic.ResultThe final union of results obtained from the analysis has allowed defining a set of requirements that the space must have to be prosthetic for the patient. Those findings have been identified by comparing the two analyses were then divided into three main macro‐areas (physical, cognitive, and social aspects) and 31 criteria. The results were also validated through the involvement of stakeholders and experts in the topic, both from architectural and medical field to establish the relationship between physical factors and patient outcomes.ConclusionThe framework is a starting point for the development of inclusive projects for people with dementia and cognitive disabilities because it is urgent to investigate which are the main aspects to be considered in the design and renovations of facilities to make them as much as possible therapeutic and prosthetic, creating places where the wellbeing of patients is the priority.
Cholinergic Hub Vulnerability in Typical and Atypical Alzheimer’s Disease Presentations
Authors: Murray Melissa E. 
Published: December 2022

AbstractBackgroundThe nucleus basalis of Meynert (nbM) is a critical hub that supplies cholinergic input throughout the cortex. Prior to even entorhinal cortex involvement, the nbM is observed to be vulnerable to tau pathology. Neuropathologic and neuroimaging studies provide strong evidence suggesting evaluation of nbM volume may be highly informative as an early biomarker of Alzheimer’s disease.MethodThe relevant AD biomarker literature with neuropathologic validation will be highlighted. Data will be provided from the FLorida Autopsied Multi‐Ethnic (FLAME) series of neuropathologically diagnosed AD cases. To enhance translational neuropathologic studies of the nbM, differences in neuronal density will be compared in the context of both typical and atypical (non‐memory) clinical presentations of AD using digital pathology to quantify nbM neurons in the postmortem tissue.ResultIn the FLAME series, we observed greater nbM neuronal loss in individuals with atypical clinical presentations (median=23/mm2) compared to typical AD dementia (median=26; p=0.002). Atypical clinical variants will be compared to provide a didactic learning experience, in addition to discussing the nbM’s influence on cortical tangle accumulation. Moreover, we will emphasize the paradoxical nature of greater nbM neuronal loss in young‐onset AD (median=21) compared to late‐onset AD (median=28; p<0.001).ConclusionEvaluation of cholinergic hub vulnerability may greatly inform our understanding of clinical heterogeneity in AD and provide key insight into early biomarker interpretation.