-
Alzheimer's Research & Therapy May 2024Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β (Aβ) plaques, neurofibrillary tau tangles, and neurodegeneration in the brain parenchyma....
Blood biomarkers of neurodegeneration associate differently with amyloid deposition, medial temporal atrophy, and cerebrovascular changes in APOE ε4-enriched cognitively unimpaired elderly.
BACKGROUND
Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β (Aβ) plaques, neurofibrillary tau tangles, and neurodegeneration in the brain parenchyma. Here, we aimed to (i) assess differences in blood and imaging biomarkers used to evaluate neurodegeneration among cognitively unimpaired APOE ε4 homozygotes, heterozygotes, and non-carriers with varying risk for sporadic AD, and (ii) to determine how different cerebral pathologies (i.e., Aβ deposition, medial temporal atrophy, and cerebrovascular pathology) contribute to blood biomarker concentrations in this sample.
METHODS
Sixty APOE ε4 homozygotes (n = 19), heterozygotes (n = 21), and non-carriers (n = 20) ranging from 60 to 75 years, were recruited in collaboration with Auria biobank (Turku, Finland). Participants underwent Aβ-PET ([C]PiB), structural brain MRI including T1-weighted and T2-FLAIR sequences, and blood sampling for measuring serum neurofilament light chain (NfL), plasma total tau (t-tau), plasma N-terminal tau fragments (NTA-tau) and plasma glial fibrillary acidic protein (GFAP). [C]PiB standardized uptake value ratio was calculated for regions typical for Aβ accumulation in AD. MRI images were analysed for regional volumes, atrophy scores, and volumes of white matter hyperintensities. Differences in biomarker levels and associations between blood and imaging biomarkers were tested using uni- and multivariable linear models (unadjusted and adjusted for age and sex).
RESULTS
Serum NfL concentration was increased in APOE ε4 homozygotes compared with non-carriers (mean 21.4 pg/ml (SD 9.5) vs. 15.5 pg/ml (3.8), p = 0.013), whereas other blood biomarkers did not differ between the groups (p > 0.077 for all). From imaging biomarkers, hippocampal volume was significantly decreased in APOE ε4 homozygotes compared with non-carriers (6.71 ml (0.86) vs. 7.2 ml (0.7), p = 0.029). In the whole sample, blood biomarker levels were differently predicted by the three measured cerebral pathologies; serum NfL concentration was associated with cerebrovascular pathology and medial temporal atrophy, while plasma NTA-tau associated with medial temporal atrophy. Plasma GFAP showed significant association with both medial temporal atrophy and Aβ pathology. Plasma t-tau concentration did not associate with any of the measured pathologies.
CONCLUSIONS
Only increased serum NfL concentrations and decreased hippocampal volume was observed in cognitively unimpaired APOEε4 homozygotes compared to non-carriers. In the whole population the concentrations of blood biomarkers were affected in distinct ways by different pathologies.
Topics: Humans; Female; Male; Aged; Biomarkers; Atrophy; Middle Aged; Apolipoprotein E4; tau Proteins; Positron-Emission Tomography; Amyloid beta-Peptides; Magnetic Resonance Imaging; Neurofilament Proteins; Temporal Lobe; Alzheimer Disease; Heterozygote; Glial Fibrillary Acidic Protein; Aniline Compounds; Thiazoles
PubMed: 38762725
DOI: 10.1186/s13195-024-01477-w -
Scientific Reports May 2024Metacognitive systematic bias impairs human learning efficiency, which is characterized by the inconsistency between predicted and actual memory performance. However,...
Metacognitive systematic bias impairs human learning efficiency, which is characterized by the inconsistency between predicted and actual memory performance. However, the underlying mechanism of metacognitive systematic bias remains unclear in existing studies. In this study, we utilized judgments of learning task in human participants to compare the neural mechanism difference in metacognitive systematic bias. Participants encoded words in fMRI sessions that would be tested later. Immediately after encoding each item, participants predicted how likely they would remember it. Multivariate analyses on fMRI data demonstrated that working memory and uncertainty decisions are represented in patterns of neural activity in metacognitive systematic bias. The available information participants used led to overestimated bias and underestimated bias. Effective connectivity analyses further indicate that information about the metacognitive systematic bias is represented in the dorsolateral prefrontal cortex and inferior parietal cortex. Different neural patterns were found underlying overestimated bias and underestimated bias. Specifically, connectivity regions with the dorsolateral prefrontal cortex, anterior cingulate cortex, and supramarginal gyrus form overestimated bias, while less regional connectivity forms underestimated bias. These findings provide a mechanistic account for the construction of metacognitive systematic bias.
Topics: Humans; Parietal Lobe; Magnetic Resonance Imaging; Male; Dorsolateral Prefrontal Cortex; Female; Metacognition; Young Adult; Adult; Brain Mapping; Memory, Short-Term; Learning; Prefrontal Cortex; Judgment
PubMed: 38762635
DOI: 10.1038/s41598-024-62343-1 -
Prague Medical Report 2024An 82-year-old woman with COPD presented to the emergency department with cough, increasing sputum production, wheezing, and worsening shortness of breath for two weeks....
An 82-year-old woman with COPD presented to the emergency department with cough, increasing sputum production, wheezing, and worsening shortness of breath for two weeks. On imaging studies, the patient was found to have a right upper lobe spiculated nodule and an endobronchial lesion with near total occlusion of the right lower lobe bronchus with sub-segmental atelectasis. Bronchoscopy with EBUS-TBNA of subcarinal and right hilar lymph nodes revealed lung cancer with clear cell phenotype. Given the predominance of clear cell morphology, the diagnosis of metastatic renal or ovarian cancer was entertained. However, there was no evidence of renal or ovarian lesions on the PET-CT scan, ruling out the possibility. Salivary gland type lung cancer (STLC), which is responsible for less than 1% of all lung cancer cases in adults, was also considered. The two distinct STLCs that may have similar morphologic appearances are hyalinizing clear cell carcinoma (HCCC) and mucoepidermoid carcinoma (MEC). The other type of tumour in the lung that demonstrates a clear cell phenotype is perivascular epithelioid cell neoplasms or PEComa, which are mesenchymal in origin. Immunohistochemical staining was strongly positive for p63, CK5/6, CK7, CK-LMW, and negative for TTF-1, Napsin A, p16, and CK20. Additional staining, including HMB-45, S-100, and mucicarmine, were also negative. Next-generation sequencing for the salivary gland fusion panel, including EWSR1-ATF1 fusion and EWSR1 gene rearrangement for HCCC and MAML2 gene rearrangements for MEC, was negative. She was diagnosed with non-small cell lung cancer favouring squamous cell carcinoma with clear cell phenotype, a rare entity.
Topics: Humans; Female; Lung Neoplasms; Aged, 80 and over; Diagnosis, Differential; Adenocarcinoma, Clear Cell; Bronchoscopy
PubMed: 38761046
DOI: 10.14712/23362936.2024.12 -
Neuropsychologia May 2024Key unanswered questions for cognitive neuroscience include whether social cognition is underpinned by specialised brain regions and to what extent it simultaneously...
Key unanswered questions for cognitive neuroscience include whether social cognition is underpinned by specialised brain regions and to what extent it simultaneously depends on more domain-general systems. Until we glean a better understanding of the full set of contributions made by various systems, theories of social cognition will remain fundamentally limited. In the present study, we evaluate a recent proposal that semantic cognition plays a crucial role in supporting social cognition. While previous brain-based investigations have focused on dissociating these two systems, our primary aim was to assess the degree to which the neural correlates are overlapping, particularly within two key regions, the anterior temporal lobe (ATL) and the temporoparietal junction (TPJ). We focus on activation associated with theory of mind (ToM) and adopt a meta-analytic activation likelihood approach to synthesise a large set of functional neuroimaging studies and compare their results with studies of semantic cognition. As a key consideration, we sought to account for methodological differences across the two sets of studies, including the fact that ToM studies tend to use nonverbal stimuli while the semantics literature is dominated by language-based tasks. Overall, we observed consistent overlap between the two sets of brain regions, especially in the ATL and TPJ. This supports the claim that tasks involving ToM draw upon more general semantic retrieval processes. We also identified activation specific to ToM in the right TPJ, bilateral anterior mPFC, and right precuneus. This is consistent with the view that, nested amongst more domain-general systems, there is specialised circuitry that is tuned to social processes.
PubMed: 38759780
DOI: 10.1016/j.neuropsychologia.2024.108904 -
Antimicrobial Agents and Chemotherapy May 2024Treatment of infection presents significant challenges, exacerbated by the emergence of macrolide-resistant strains that necessitate the use of multiple antimicrobials...
Treatment of infection presents significant challenges, exacerbated by the emergence of macrolide-resistant strains that necessitate the use of multiple antimicrobials in combination and carry the potential for significant toxic effects. Select dual beta-lactam combinations, with or without beta-lactamase inhibitors, have been shown to be highly active . Herein, we describe a 6-year-old child with underlying mild bilateral lower lobe cylindrical bronchiectatic lung disease who developed pulmonary infection and was treated with a multi-drug regimen including two β-lactam antibiotics, achieving both early clinical and microbiological cure. This case highlights the potential benefit of dual β-lactam therapy for the treatment of drug-resistant infection.
PubMed: 38757973
DOI: 10.1128/aac.00319-24 -
Brain Communications 2024The brain network of speech fluency has not yet been investigated via a study with a large and homogenous sample. This study analysed multimodal imaging data from 115...
The brain network of speech fluency has not yet been investigated via a study with a large and homogenous sample. This study analysed multimodal imaging data from 115 patients with low-grade glioma to explore the brain network of speech fluency. We applied voxel-based lesion-symptom mapping to identify domain-specific regions and white matter pathways associated with speech fluency. Direct cortical stimulation validated the domain-specific regions intra-operatively. We then performed connectivity-behaviour analysis with the aim of identifying connections that significantly correlated with speech fluency. Voxel-based lesion-symptom mapping analysis showed that damage to domain-specific regions (the middle frontal gyrus, the precentral gyrus, the orbital part of inferior frontal gyrus and the insula) and white matter pathways (corticospinal fasciculus, internal capsule, arcuate fasciculus, uncinate fasciculus, frontal aslant tract) are associated with reduced speech fluency. Furthermore, we identified connections emanating from these domain-specific regions that exhibited significant correlations with speech fluency. These findings illuminate the interaction between domain-specific regions and 17 domain-general regions-encompassing the superior frontal gyrus, middle frontal gyrus, inferior frontal gyrus and rolandic operculum, superior temporal gyrus, temporal pole, inferior temporal pole, middle cingulate gyrus, supramarginal gyrus, fusiform gyrus, inferior parietal lobe, as well as subcortical structures such as thalamus-implicating their collective role in supporting fluent speech. Our detailed mapping of the speech fluency network offers a strategic foundation for clinicians to safeguard language function during the surgical intervention for brain tumours.
PubMed: 38756538
DOI: 10.1093/braincomms/fcae153 -
Case Reports in Pulmonology 2024Lung sequestration is a subtype of congenital lung malformations; it is infrequently diagnosed in adults and is a rare cause of hemoptysis. The typical management of...
BACKGROUND
Lung sequestration is a subtype of congenital lung malformations; it is infrequently diagnosed in adults and is a rare cause of hemoptysis. The typical management of symptomatic lung sequestration is usually surgical, though intra-arterial embolization is becoming an acceptable alternative. . We report a case of a 36-year-old female patient who presented for an acute onset of hemoptysis. CT chest showed an intralobar sequestration of the right lower lobe lung segment. In addition to the sequestration, the chest imaging also revealed a number of associated abnormalities including double superior vena cava communicating through a bridge, absence of brachiocephalic venous trunk, cardiac dextroposition, and agenesis of the right middle lobe. . The transarterial embolization was selected for being mini-invasive and effective. It successfully controlled the bleed and led to complete regression of the sequestered lung on the follow-up CT chest several months later.
CONCLUSION
Successful management and complete regression are possible with mini-invasive intra-arterial embolization of lung sequestration. Although it is not uncommon to have associated congenital cardiopulmonary abnormalities with lung sequestration, however the exceptional abnormalities described in this case have never been reported before.
PubMed: 38756205
DOI: 10.1155/2024/1428495 -
NMC Case Report Journal 2024To improve optic nerve function in a patient with progressive visual dysfunction, performing early decompressive and debulking surgery for a metastatic tumor located in...
To improve optic nerve function in a patient with progressive visual dysfunction, performing early decompressive and debulking surgery for a metastatic tumor located in the optic canal is essential. The endoscopic endonasal approach could be a practical and effective alternative for lesions in the inferomedial part of the optic canal. A 66-year-old man with a right visual eye field deficit had multiple lesions in the pineal gland, occipital lobe, and right inferomedial optic canal. The optic nerve was distorted by a tumor compressing against the falciform ligament. Although a systemic examination suggested the presence of primary lung cancer, the patient only complained of progressive visual impairment in the right eye. We planned surgery with endoscopic transethmoidal and transsphenoidal approaches to restore visual function and make a pathological diagnosis. During the procedure, we drilled the sella floor, tuberculum sellae, and optic canal and successfully removed the tumor underneath the dura mater. The patient's visual function improved rapidly following surgery, and no complications were observed, such as cerebrospinal fluid leakage. After confirming the pathological diagnosis, the patient subsequently received whole-brain radiotherapy. The endoscopic endonasal skull base approach to the optic canal region could be a practical alternative for treating symptomatic metastatic tumors.
PubMed: 38756143
DOI: 10.2176/jns-nmc.2023-0203 -
Neuroscience and Biobehavioral Reviews May 2024Limb apraxia is a motor disorder frequently observed following a stroke. Apraxic deficits are classically assessed with four tasks: tool use, pantomime of tool use,... (Review)
Review
Limb apraxia is a motor disorder frequently observed following a stroke. Apraxic deficits are classically assessed with four tasks: tool use, pantomime of tool use, imitation, and gesture understanding. These tasks are supported by several cognitive processes represented in a left-lateralized brain network including inferior frontal gyrus, inferior parietal lobe (IPL), and lateral occipito-temporal cortex (LOTC). For the past twenty years, voxel-wise lesion symptom mapping (VLSM) studies have been used to unravel the neural correlates associated with apraxia, but none of them has proposed a comprehensive view of the topic. In the present work, we proposed to fill this gap by performing a systematic Anatomic Likelihood Estimation meta-analysis of VLSM studies which included tasks traditionally used to assess apraxia. We found that the IPL was crucial for all the tasks. Moreover, lesions within the LOTC were more associated with imitation deficits than tool use or pantomime, confirming its important role in higher visual processing. Our results questioned traditional neurocognitive models on apraxia and may have important clinical implications.
PubMed: 38754714
DOI: 10.1016/j.neubiorev.2024.105720 -
PloS One 2024Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive and fatal neurodegenerative diseases for which at present no cure is available. Despite the extensive... (Comparative Study)
Comparative Study
Understanding the relationship between cerebellum and the frontal-cortex region of C9orf72-related amyotrophic lateral sclerosis: A comparative analysis of genetic features.
BACKGROUND
Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive and fatal neurodegenerative diseases for which at present no cure is available. Despite the extensive research the progress from diagnosis to prognosis in ALS and frontotemporal dementia (FTD) has been slow which represents suboptimal understanding of disease pathophysiological processes. In recent studies, several genes have been associated with the ALS and FTD diseases such as SOD1, TDP43, and TBK1, whereas the hexanucleotide GGGGCC repeat expansion (HRE) in C9orf72 gene is a most frequent cause of ALS and FTD, that has changed the understanding of these diseases.
METHODS
The goal of this study was to identify and spatially determine differential gene expression signature differences between cerebellum and frontal cortex in C9orf72-associated ALS (C9-ALS), to study the network properties of these differentially expressed genes, and to identify miRNAs targeting the common differentially expressed genes in both the tissues. This study thus highlights underlying differential cell susceptibilities to the disease mechanisms in C9-ALS and suggesting therapeutic target selection in C9-ALS.
RESULTS
In this manuscript, we have identified that the genes involved in neuron development, protein localization and transcription are mostly enriched in cerebellum of C9-ALS patients, while the UPR-related genes are enriched in the frontal cortex. Of note, UPR pathway genes were mostly dysregulated both in the C9-ALS cerebellum and frontal cortex. Overall, the data presented here show that defects in normal RNA processing and the UPR pathway are the pathological hallmarks of C9-ALS. Interestingly, the cerebellum showed more strong transcriptome changes than the frontal cortex.
CONCLUSION
Interestingly, the cerebellum region showed more significant transcriptomic changes as compared to the frontal cortex region suggesting its active participation in the disease process. This nuanced understanding may offer valuable insights for the development of targeted therapeutic strategies aimed at mitigating disease progression in C9-ALS.
Topics: Humans; Amyotrophic Lateral Sclerosis; C9orf72 Protein; Cerebellum; Frontal Lobe; Female; Male; Middle Aged; MicroRNAs; Aged; Frontotemporal Dementia
PubMed: 38753768
DOI: 10.1371/journal.pone.0301267