bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spike S1 peptide associated neuroinflammatory and cytokine induction is associated with modified behavior in in vivo models
Authors: Paidi Ramesh Kumar , Pahan Kalipada 
Published: December 2023

AbstractBackgroundCoronavirus disease (COVID‐19), a severe acute respiratory syndrome coronavirus 2 (SARS CoV‐2) is a damaging illness leading to severe health crisis and economic crisis worldwide. Numerous brain complication has been reported in COVID‐19 patients and surprisingly has persisted after COVID‐19 infection recovery in patients. The underlying mechanism are not clear. So far, there is no proper therapeutic strategy against COVID‐19 and its complications on the brain.MethodInitially we validate the effect of recombinant Spike S1 in A5339 cells (Paidi, Jana et al. 2021, Paidi, Jana et al. 2021, Paidi, Jana et al. 2021) and as well as mouse primary astrocyte cultures, in terms of cytokine induction and neuroinflammatory markers. In the current study, mice were administered recombinant spike S1 intranasally for 14 days. Initially we evaluated the physiological and behavioral alteration for 12 days. SARS‐CoV‐2 binds to angiotensin‐converting enzyme 2 (ACE2) for entering host cells, we so investigate the lung histology and its cytokine induction. Further, we evaluate the cytokine and neuroinflammatory levels in the brain, and its relevance to behavioral modifications in the mouse.ResultIn the present study, Spike S1 treatment prominently elevate the cytokine levels and inflammatory markers in invitro models. Intranasal intoxication of C57/BL6 mice with recombinant SARS‐CoV‐2 spike S1 led to fever, increase in IL‐6 in the lungs and brain. We found that the impairment in spatial learning memory functions and motor disabilities, mimic some of the important symptoms of COVID‐19. Our studies show Spike S1 induced cytokine levels in lungs and as well as in the brain.ConclusionOur results suggest a simple, but reliable means of developing a Spike S1 mediated in vivo model which exhibits severe lung pathology and reinforce the validity of this animal model to study COVID‐19 pathogenesis and potential therapies.
Keywords
Spike S1, COVID‐19; IL‐6; Cognitive functions; Motor disabilities, Cytokine induction;
Conceptual saliency: Core and peripheral semantic knowledge in Alzheimer’s disease
Authors: Ulep Maileen G. , Lienard Pierre 
Published: December 2023

AbstractBackgroundSemantic memory impairment in Alzheimer’s disease (AD) is indicative of an actual degradation of semantic knowledge – the conceptual and factual knowledge necessary to engage with others and the physical world – rather than merely to a retrieval deficit. Historically, studies in semantic knowledge in AD have relied on predetermined sets of stimuli to probe knowledge. The analysis presented here compares the contents, sequences and organization of lists of salient concepts generated by 19 patients at the mild to moderates stages AD and by 15 age‐matched cognitively normal control individuals by means of a free‐listing task, for two semantic categories, living kinds and man‐made objects. The free elicitation by participants prevents the imposition of a priori ideas by the experimenter, which might not correspond to the native knowledge of the specific cultural group studied.MethodData collection starts with the ‘demarcation’ of a domain of knowledge X by a sample of participants who are being asked to write the names of as many items as they can conjure up, which they think belong to that domain X. Terms that appear earlier, or with higher frequency, on free‐lists indicate high consensus among respondents (i.e., the concept is an important component of the category); those items are considered as more salient in the domain under investigation.ResultEvidence of knowledge devolution is detected in the lists of participants with AD for both semantic categories. However, the core conceptual information and central aspects of the structuration of those knowledge domains are preserved to an extent. The peripheral conceptual knowledge is showing the greatest disease impact.ConclusionThe study starts the investigation of the aspects of living kinds and artefactual categorial knowledge especially resilient as neurodegeneration sets. Semantic knowledge holds the information about what one knows. Its integrity is critical in daily functioning, and interactions with others and the world at large. Because semantic memory supports various aspects of daily life, it is a prime candidate for therapeutic targets that can lead to meaningful outcomes for both patients and their care partners.
Categorical reasoning in Alzheimer’s disease: What is preserved?
Authors: Ulep Maileen G. , Lienard Pierre 
Published: December 2023

AbstractBackgroundSemantic knowledge impairment appears to be a robust early indicator of Alzheimer’s disease (AD) pathology. The disruption of semantic cognition has been detected in preclinical AD. We investigate the ability of patients with mild to moderate AD to categorize items belonging to two semantic domains critical in daily life, living kinds and artefacts.MethodThe categorial reasoning competence of 12 patients with AD and 16 age‐matched normal controls, in the semantic domains of living kinds and man‐made objects are compared by means of an unconstrained pile‐sorting experiment. The participants are left to decide how to lump a list of items, hence, to select organizational schemes of their choosing. Unconstrained pile‐sorting has the potential to better reveal the most salient concepts and principles that orient the classificatory decisions of the participants.ResultThe experimental findings highlight both preserved and disrupted abilities. Important structural principles organizing knowledge in both semantic categories seem to remain well preserved and to still drive patients’ core reasoning. Patients and controls do differ in the specific contents of their piles, even though the number of piles generated by each group does not diverge. Patients with AD were less systematic in their categorization strategies than control participants. The performance of patients displays evidence of a broad weakening of conceptual associations at levels of categorizations requiring finer details.ConclusionEarly deviations in cognitive performance of individuals with AD from cognitively normal adults might only appear when careful analyses of contents are conducted. To our knowledge, it is the first study to use this task as developed in cognitive anthropology to investigate semantic knowledge in AD. We propose that the detection of early deviations in performance of patients with AD might be enhanced by the combination of detailed analysis of contents and a quantitative approach.
Akinetic Mutism and Cognitive‐Affective Syndrome caused by unilateral PICA infarction
Authors: Han Jeong Ho , Yang Youngsoon , Choi Eun Joo 
Published: December 2023

AbstractBackgroundAkinetic mutism (AM) is characterized by sparse volitional motor and speech activation with reasonably preserved arousal and vigilance functions. Akinetic mutism, the most severe of these disorders, is most commonly associated with bilateral hemispheric pathology, although unilateral lesions may produce this condition as well.MethodCase: Our patient is a 42‐year‐old right handed man who presented to the emergency department with an acute onset of akinetic mutism. His family described him as a calm and intelligent individual with a good cultural knowledge level and without any evident cognitive abnormality before he suddenly experienced akinetic mutism. On examination, he was alert but produced no spontaneous speech and had only rare, spontaneous movement of his arm and leg. With repeated prompting, he followed single‐step commands.ResultMagnetic resonance imaging demonstrated an infarction in the distribution of the left posterior inferior cerebellar artery. During the course of 7 days, as the patient became more interactive, he demonstrated normal language function. As he became more communicative, cognitive impairment became apparent. Neuropsychological evaluation were performed after approximately 12 days after onset because of the impossibility of test administration during the acute phase. Impaired performances were evident on executive function testing with difficulties in planning, abstract reasoning, set‐shifting and perseveration. Furthermore, attention disorders and memory dysfunction were mild observed and were probably due to the poor ability of planning and organization. Language tests revealed mild deficits in the semantic sphere with paraphasia, anomia and circumlocutory expressions. During psychometric testing, the patient presented agitated and anxious behavior with affective air hunger and episodes of crying. Brain SPECT were performed after approximately 14 days after onset. Brain SPECT demonstrated hyporperfusion in Lt. cerebellar and frontal cortex.ConclusionThe syndrome of akinetic mutism is typically the result of bilateral hemispheric injury, usually involving the anterior cingulate gyri. Other locations for lesions producing akinetic mutism include the thalami, globus pallidus, internal capsule, and frontal white matter. We describe a man with akinetic mutism and cognitive impairment due to an ischemic stroke in the distribution of the left PICA.
Association between topographic distribution of dilated perivascular spaces and Alzheimer’s disease pathologies measured by 18F‐florbetaben and PI‐2620 PET
Authors: Booncharoen Kittithatch , Thanapornsangsuth Poosanu , Sarutikriangkri Yuthachai , Likitjaroen Yuttachai , Thanprasertsuk Sekh 
Published: December 2023

AbstractBackgroundDilated perivascular spaces (DPVS) has been hypothesized to be implicated in the development and/or progression Alzheimer’s disease (AD). However, evidence of a relationship between its topographic distribution and burden of AD pathologies has not been well‐established. We thus aimed to evaluate whether beta‐amyloid (Aβ) and tau burdens measured in positron emission tomography (PET) are associated with topographic distribution of DPVS.MethodFifty‐one patients with amnestic mild cognitive impairment or mild dementia due to possible AD were recruited. Aβ burden was measured as Centiloid (CL) scale from 18F‐florbetaben PET. Burden of tau on regions comprising Braak stage III‐IV of neurofibrillary pathology (Braak H, et al. 2006) was measured as standardized uptake value ratio (SUVR) from tau tracer PI‐2620 PET. DPVS were assessed in the basal ganglia (BG‐DPVS) and in the subcortical white matter (WM‐DPVS) in T1‐sequences of brain MRI. DPVS severities were rated by an established 4‐point semiquantitative score and were then classified as high degree (score>2) or low degree (score≤2) (Martinez‐Ramirez, et al. 2013). The patients were further categorized into 3 groups including patients with higher, equal, and lower score of BG‐DPVS compared to WM‐DPVS (BG>WM, BG = WM, and BG<WM, respectively) (Thanprasertsuk, et al. 2014). Multivariate analyses controlling for age, sex, and MoCA score were applied to ensure independent relationships of DPVS to Aβ‐CL and tau‐SUVR.ResultPatients with high degree of WM‐DPVS (n = 18), compared to ones with the low degree (n = 33), had higher burdens of both Aβ‐CL (median[IQR], 74.29[55.90‐102.02] versus 35.06[11.34‐57.57], p<0.001) and tau‐SUVR (1.46[1.24‐2.15] versus 1.16[1.07‐1.49], p = 0.001). Based on DPVS category, there were differences in both Aβ‐CL (p = 0.001) and tau‐SUVR (p = 0.009) among the BG>WM (n = 20), BG = WM (n = 13), and BG<WM (n = 18) groups, with apparently high disease‐specific pathologies of AD in the BG<WM group (Aβ‐CL = 74.29[46.60‐105.20], and tau‐SUVR = 1.50[1.24‐2.14]). There were no differences in Aβ‐CL and tau‐SUVR between patients with low and high degree of BG‐DPVS.ConclusionOur results suggest that WM‐DPVS is associated with the deposition of Aβ and tau in AD patients, while BG‐DPVS appears to have less substantial association.
Progranulin gene mutation of frontotemporal dementia in China: A case report and literature review
Authors: Chu Min , Nan Haitian , Jiang Deming , Liu Li , Wu Liyong 
Published: December 2023

AbstractBackgroundProgranulin (GRN) mutations of Frontotemporal dementia (FTD) were rarely reported in China. This study was to report one novel GRN mutation and summarize the genetic and clinical features of patients with GRN mutations in China.MethodComprehensive clinical, genetic, and neuroimaging examinations were conducted on a 58‐year‐old patient who was diagnosed with semantic variant primary progressive aphasia. A literature review was also conducted and the clinical and genetic features of patients with Progranulin mutations in China were summarized.ResultMarked lateral atrophy and hypometabolism on the left‐side frontal, temporal and parietal lobes of the patient were found on neuroimages, and amyloid and tau positron emission tomography ruled out pathological protein deposition. A novel heterozygous 45‐bp deletion (c.141414_1444delCCCTTCCCCGCCAGGCTGTGTGCTGCGAGGATCGCCAGCACTGCT) was identified through Whole Exon Sequencing of the patient’s genomic deoxyribonucleic acid. Nonsense‐mediated messenger ribonucleic acid decay was implicated in the degradation of the mutated messenger ribonucleic acid, and it was defined as pathogenic by American College of Medical Genetics and Genomics guidelines. In the literature review, we found Chinese reports of 13 patients with Progranulin mutations. A 1.2%–2.6% prevalence, an early disease onset and a female predominance were reported in Chinese patients with GRN mutations.ConclusionOur findings expand the mutational profile of Progranulin mutations in China and provide a basis for potential treatments for Progranulin.
A study of sleep quality, cognitive impairment and functional abilities in patients with dementia
Authors: Yadav Beer Bahadur , Prakash Om 
Published: December 2023

AbstractBackgroundSleep quality is affected with cognitive impairment and functional ability in patients with dementia.MethodThirty patients with dementia and thirty normal controls were studied. Subjects were evaluated for global cognitive impairment using Hindi Mental State Examination (HMSE) and activities of daily living using Everyday Ability scale for India (EASI). Dementia severity was assessed using Clinical Dementia Rating scale (CDR). A comprehensive sleep‐wake profile was obtained using a set of questionnaires Semi‐Structured Sleep Performa and Pittsburgh Sleep Quality Index (PSQI).ResultPatients were matched for age and gender. The severity of cognitive impairment (r value‐0.62, p<0.01) and functional ability (r value 0.59, p<0.01) was proportional to the poor sleep quality index.ConclusionSleep‐wake profile was altered in patients with dementia. This study helps to provide insights into sleep disturbances association with degree of cognitive impairment and degree of functional ability.
No Interaction Between BDNF Val66Met and APOE ε4 on PET‐Based Amyloid and Tau Measurements
Authors: Shaw Alannah , Malek‐Ahmadi Michael H. , Devadas Vivek , Wang Qi , Su Yi , Reiman Eric M. 
Published: December 2023

AbstractBackgroundThe interaction between the BDNF Val66Met gene and APOE ε4 gene on Alzheimer’s disease (AD) pathology is not fully understood. We aimed to determine how this interaction impacts PET based amyloid and tau measurements, hippocampal volume, and auditory verbal learning tests (AVLT) performance in cognitively unimpaired (CU) older adults.MethodData from 216 participants were used in this analysis. For the whole data set, the mean age was 75.56 ± 7.52 years, mean education was 16.82 ± 2.40 years, and 55% of the participants were female (118 females and 98 male). Linear regression models that adjusted for age, sex, education, were used to quantify main effects and interactions between APOE ε4 carrier status and BDNF Val66Met carrier status. Outcome measures included AV‐45 SUVR, tau meta‐ROI, hippocampal volume, AVLT Delayed Recall, and AVLT Total Recall.ResultThere was a main effect on APOE ε4 carrier status on amyloid load (β = 0.11, 95% CI (0.04, 0.17), p = 0.001), but no main effect for BDNF on amyloid load (β = ‐0.003, 95% CI (‐0.06, 0.06) p = 0.91). The interaction between APOE ε4 carrier status and BDNF Met carrier status was not significant (β = 0.03, 95% CI (‐0.07, 0.13), p = 0.58). There was no main effect on APOE ε4 carrier status on tau load (β = 0.003, 95% CI (‐0.06, 0.06), p = 0.93). There was also no main effect on BDNF on tau load (β = ‐0.0006, 95% CI (‐0.05, 0.05), p = 0.98) and the interaction between APOE ε4 carrier status and BDNF Met carrier status was not significant (β = 0.03, 95% CI (‐0.06, 0.12), p = 0.49). There were no significant main effects or interactions on hippocampal volume and cognitive measures.ConclusionThis cross‐sectional study found no significant interaction between APOE ε4 carrier status and BDNF met carrier status on measures of amyloid and tau load as well as hippocampal volume and cognition. These findings cast doubt on the BDNF Met allele’s role in moderating AD‐related pathological changes.
Test‐retest validity of light reflex pupillometry in a memory clinic cohort
Authors: Gramkow Mathias H. , Clemmensen Frederikke Kragh , Waldemar Gunhild , Hasselbalch Steen G. , Frederiksen Kristian Steen 
Published: December 2023

AbstractBackgroundThe pupillary light reflex and the contributing cerebral functions can be objectively assessed using a pupillometer. Light reflex pupillometry (LRP) has been found to be altered in Alzheimer’s disease (AD) and has potential as a diagnostic aid in this disease as a novel biomarker. Little is known about the variability of LRP in patients seen in memory clinics (including patients with AD). We aimed to quantify the test‐retest validity of LRP in these patients to elucidate possible pitfalls in using pupillometry and to ascertain the feasibility of implementing this clinical tool in a memory clinic setting.MethodIn total, 50 patients under diagnostic evaluation in a tertiary memory clinic will be included in the present study. Patients suspected of a neurodegenerative disease are included on the day of a scheduled lumbar puncture (LP). We measure the LRP at baseline (day of LP), 3‐14 days after LP, and 21‐35 days post‐LP using a research grade pupillometer (PLR‐3000, NeurOptics®). Spaghettiograms of measurements will be presented and the intraclass correlation coefficient from a two‐way mixed effects model will be calculated for the eight pupillometric variables provided by the PLR‐3000: Baseline pupil diameter, peak constriction diameter, change in pupillary size, average and maximum constriction velocity, average dilation velocity and T75 (time to reach 75% of baseline pupil diameter after peak constriction). We will study possible influencing factors that could affect the test‐retest variability by studying subgroups of patients based on diagnosis, disease severity, cerebrospinal fluid Aβ‐42, concurrent eye disease and medication.ResultAs of January 2023, 24 patients (9 female) have completed follow‐up. The mean age of patients is 72 years (range 63‐79). Half of the patients were diagnosed with Alzheimer’s disease (MCI or mild dementia). Our preliminary results show moderate‐good test‐retest reliability of most pupillometric variables.ConclusionLight reflex pupillometry may be a promising new bedside biomarker for AD. The present study generally demonstrated a moderate‐good test‐retest reliability of LRP in a memory clinic population. The study contributes to the foundation for an exploration of the tool for diagnostic purposes in various diseases, including Alzheimer’s disease.
Vascular dysfunction in behavior‐variant frontotemporal dementia
Authors: Chu Min , Jiang Deming , Qu Miao , Wu Liyong 
Published: December 2023

AbstractBackgroundThe vascular disturbance was recently found in a postmortem study of frontotemporal dementia (FTD), but whether vascular dysfunction exists in the early stage of FTD remains elusive. The study aimed to explore whether there was evidence of vascular dysfunction in FTD and its relationship with central neurodegeneration and the clinical outcome.MethodTwenty patients with behavior frontotemporal dementia (bvFTD) were enrolled and underwent assessment of peripheral plasma vascular markers, positron emission tomography/magnetic resonance imaging, and neuropsychological examinations. Group difference was tested using the student’s t‐test and Mann‐Whitney U test. Partial correlation analysis was implemented using age and sex as covariates to explore the association between peripheral vascular markers, neuroimaging, and clinical measures.ResultAll four factors including matrix metalloproteinases‐1(MMP‐1), matrix metalloproteinases‐3 (MMP‐3), Osteopontin, and pentraxin‐3 are increased in the FTD group. The plasma level of MMP‐1 was negatively correlated with the gray matter metabolism of the prefrontal cortex (r = ‐0.5119, p = 0.0210) and the anterior cingulate cortex (r = ‐0.4685, p = 0.0269). MMP‐3 was negatively correlated with the gray matter metabolism of the anterior temporal cortex (r = ‐0.4650, p = 0.0388). Pentraxin‐3 was negatively correlated with age at sampling (r = ‐0.5024, p = 0.0240) and age at onset (r = ‐0.5693, p = 0.0088). No other significant associations were found in other vascular cytokines and clinical measures.ConclusionThe vascular disturbance was found in patients with bvFTD and associated with the disease‐specific neurodegeneration pattern, indicating vascular dysfunction and perturbance of the BBB participation in the pathogenesis of FTD. The vascular pathway might be a promising target for future potential therapy.