Age Healthy Controls Research Articles

Amnestik hafif kognitif bozuklukta beyaz cevher değişiklikleri: yolak tabanlı uzamsal istatistik çalışması

Purpose: To compare white matter (WM) structural alterations between the subjects with amnestic mild cognitive impairment (MCI) which is a transitional state to Alzheimer's Disease (AD) and healthy elderly controls.
 Methods: Diffusion tensor imaging (DTI) scans of 20 subjects with amnestic MCI and 20 healthy control groups who are matched by age, gender, and education with the MCI group between 2011 and 2016 were examined by in this retrospective study. WM structural integrity was analyzed using tract based spatial statistics (TBSS) for voxel-based differences in fractional anisotropy (FA) between the two groups. 
 Results: Fractional anisotropy was found significantly lower in the forceps minor, the body and genu of the corpus callosum, the right anterior thalamic radiation, the right cingulum, the right inferior fronto-occipital fasciculus, the right superior longitudinal fasciculus, and the right superior corona radiata in the MCI group than the control group. 
 Conclusion: TBSS analysis is a promising method to examine structural WM integrity. These findings suggested that the DTI measurements may be useful for the detection of preclinical changes in AD.

Heritable defects in telomere and mitotic function selectively predispose to sarcomas.

Cancer genetics has to date focused on epithelial malignancies, identifying multiple histotype-specific pathways underlying cancer susceptibility. Sarcomas are rare malignancies predominantly derived from embryonic mesoderm. To identify pathways specific to mesenchymal cancers, we performed whole-genome germline sequencing on 1644 sporadic cases and 3205 matched healthy elderly controls. Using an extreme phenotype design, a combined rare-variant burden and ontologic analysis identified two sarcoma-specific pathways involved in mitotic and telomere functions. Variants in centrosome genes are linked to malignant peripheral nerve sheath and gastrointestinal stromal tumors, whereas heritable defects in the shelterin complex link susceptibility to sarcoma, melanoma, and thyroid cancers. These studies indicate a specific role for heritable defects in mitotic and telomere biology in risk of sarcomas.

Povezanost dužine trajanja bolesti i primenjene terapije sa metaboličkim sindromom kod pacijenata obolelih od sistemskog eritemskog lupusa

Aim. The aim of the paper was to examine the impact of disease duration and administered therapy on the development of metabolic syndrome (MetS) in patients with systemic lupus erythematosus (SLE). Material and methods. This study involved 55 patients (50 females and 5 males) with the diagnosis and 49 healthy controls of similar age. MetS was defined according to modified NCEP-ATP III diagnostic criteria, and obesity was defined by body mass index BMI > 30. Results. In the group of SLE patients with MetS, there were 23 individuals (41.82%). In the control group, there were 10 (20.4%) patients with MetS. There were significantly more SLE patients with MetS in comparison to the controls (p = 0.04). Duration of the disease in the group with MetS was longer in comparison to those without MetS, but it was not statistically significant (15.35 ± 10.26 vs 10.44 ± 7.88, p = 0.073). The study confirmed that there is a moderate association (CC = 0.355) between disease duration and number of MetS parameters, however, this dependency was not statistically significant (p = 0.439). In the group without MetS, there were statistically more patients treated with antimalarial drugs monotherapy (p = 0.023). It has been found that the patients with MetS were treated with corticosteroid therapy longer than those without MetS, but it was not statistically significant (153.57 ± 103.34 vs 114.75 ± 83.32, p = 0.129). Conclusion. Patients with longer SLE duration have more often MetS. It has been shown that, statistically, more patients without MetS were treated with antimalarial drugs monotherapy, and that long-term CS use, in our study, was not associated with higher incidence of MetS.

Evaluation of Ventilatory Functions in Hypothyroid Patients

Introduction Respiratory muscle weakness is proportional to the degree of thyroid function and is reversible by replacement therapy with thyroxine. Aim To evaluate the changes in pulmonary functions in newly diagnosed hypothyroid patients as compare with healthy controls by spirometry and to observe the improvement in pulmonary functions after hormone replacement therapy. Patients and methods A total of 30 newly diagnosed hypothyroid patients and 30 healthy controls of age between 18 to 50 years of either sex were included in our study. Clinical criteria and biochemical tests were registered, and spirometry was done. Results Approximately 17% of the hypothyroid patients were normal, whereas 33% had mild restrictive lung impairment and the rest 50% had moderate to severe restrictive impairment on spirometry. Conclusion On comparing the hypothyroid patients with normal healthy person of same age group through spirometer, the ventilatory functions were diminished and these pulmonary functions improved after levothyroxine therapy for 6 months but could not reach the normal healthy values. A spirometric evaluation should be considered in hypothyroid patients, even in the absence of respiratory illness.

Evaluation of changes in corneal endothelium in chronic kidney disease a cross sectional study

Chronic kidney disease is a growing global health concern that affects approximately 10 percent of overall worldwide people. High blood pressure and diabetes account for around two-thirds of all cases of chronic kidney disease worldwide. Because the kidneys and eye grow at about the same embryonic period, around the 4th week to 6th week of pregnancy, there is a strong link connecting kidney problems and eye problems. Hence the aim of the study was to carry out evaluation of changes in corneal endothelium in chronic kidney disease. The study included three categories of patients, each with twenty five patients. Stage 5 CKD patients on dialysis were placed in Category A, non-dialyzed stage three and four CKD patients were placed in category B, and healthy controls of matching age were placed in category C. They had their whole blood composition evaluation, concentration of blood urea, concentration of serum creatinine, and concentration of blood sugar levels checked as well. Both eyes were inspected and measurement of important parameters like endothelial cell density in cornea, measurement of coefficient of variation (CV percent), measurement of percentage of hexagonally (Hx percent), measurement of central corneal thickness (CCT), and measurement of average size of cells was carried out using a non-contact variant of specular microscope (TOPCON SP 300P) utilizing. Topcon Cell Count Software. Endothelial cell density changed significantly in kidney disease patients compared to controls. In our study, we discovered a substantial difference in CV, hexagonality, and mean cell size across the three groups, indicating polymegathism and pleomorphism in these cells. It was observed that participants who were recently diagnosed with CKD and dialysis commenced recently had a higher central corneal thicknesses than those who had been on hemodialysis for a long time. Patients with long-term illness, on the other hand, had thinner corneas, indicating adaptive alterations. Due to morphological abnormalities in the corneal endothelium caused by CKD, such as pleomorphism and polymegathism, patients with CKD may be more susceptible to endothelial damage. This necessitates extra precaution in patients having CKD undergoing intraocular surgery.

Bacterial DNAemia in Alzheimer's Disease and Mild Cognitive Impairment: Association with Cognitive Decline, Plasma BDNF Levels, and Inflammatory Response.

Microbial dysbiosis (MD) provokes gut barrier alterations and bacterial translocation in the bloodstream. The increased blood bacterial DNA (BB-DNA) may promote peripheral- and neuro-inflammation, contributing to cognitive impairment. MD also influences brain-derived neurotrophic factor (BDNF) production, whose alterations contribute to the etiopathogenesis of Alzheimer's disease (AD). The purpose of this study is to measure BB-DNA in healthy elderly controls (EC), and in patients with mild cognitive impairment (MCI) and AD to explore the effect on plasma BDNF levels (pBDNF), the inflammatory response, and the association with cognitive decline during a two-year follow-up. Baseline BB-DNA and pBDNF were significantly higher in MCI and AD than in EC. BB-DNA was positively correlated with pBDNF in AD, plasma Tumor necrosis factor-alpha (TNF-α), and Interleukin-10 (IL-10) levels in MCI. AD patients with BB-DNA values above the 50th percentile had lower baseline Mini-Mental State Examination (MMSE). After a two-year follow-up, AD patients with the highest BB-DNA tertile had a worse cognitive decline, while higher BB-DNA levels were associated with higher TNF-α and lower IL-10 in MCI. Our study demonstrates that, in early AD, the higher the BB-DNA levels, the higher the pBDNF levels, suggesting a defensive attempt; BB-DNA seems to play a role in the AD severity/progression; in MCI, higher BB-DNA may trigger an increased inflammatory response.

Classification of mild cognitive impairment based on handwriting dynamics and qEEG

Subtle changes in fine motor control and quantitative electroencephalography (qEEG) in patients with mild cognitive impairment (MCI) are important in screening for early dementia in primary care populations. In this study, an automated, non-invasive and rapid detection protocol for mild cognitive impairment based on handwriting kinetics and quantitative EEG analysis was proposed, and a classification model based on a dual fusion of feature and decision layers was designed for clinical decision-marking. Seventy-nine volunteers (39 healthy elderly controls and 40 patients with mild cognitive impairment) were recruited for this study, and the handwritten data and the EEG signals were performed using a tablet and MUSE under four designed handwriting tasks. Sixty-eight features were extracted from the EEG and handwriting parameters of each test. Features selected from both models were fused using a late feature fusion strategy with a weighted voting strategy for decision making, and classification accuracy was compared using three different classifiers under handwritten features, EEG features and fused features respectively. The results show that the dual fusion model can further improve the classification accuracy, with the highest classification accuracy for the combined features and the best classification result of 96.3% using SVM with RBF kernel as the base classifier. In addition, this not only supports the greater significance of multimodal data for differentiating MCI, but also tests the feasibility of using the portable EEG headband as a measure of EEG in patients with cognitive impairment.

Free water imaging in healthy brain aging and first signs of brain pathology

AbstractBackgroundBrain aging is associated with cerebral small vessel disease (SVD). Recently, it was suggested that SVD is mainly driven by increases of extracellular free water (FW). The aim of the present study was to examine the association of FW, conventional and FW‐corrected diffusion tensor imaging (DTI) parameters (fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD)) with aging. The second aim was to determine if differences in FW and DTI parameters exist between individuals with first signs of pathology and healthy elderly controls regarding metrics that are not associated with age.MethodWe examined 87 healthy elderly (age: M = 66.34, SD = 9.82) and 87 individuals with first signs of cerebral pathology (age: M = 68.14, SD = 9.18) of the Austrian Stroke Prevention Family Study. Individuals with first signs of cerebral pathology were defined as having WMH score >1, presence of lacunes and/or microbleeds. FW in global normal appearing white matter (NAWM) as well as conventional and FW‐corrected DTI parameters were used in correlation analyses to assess their association with age. ANOVA adjusted for multiple comparison was used to determine the differences in FW and FW‐corrected DTI metrics between individuals with initial signs of SVD and healthy controls.ResultFW in NAWM as well as non‐FW‐corrected DTI were significantly associated with age in the total sample and both stratified groups (range of |r|: 0.24‐0.49). No correlation between FW‐corrected DTI measures and age were found. Differences between individuals with and without first signs of pathology were only identified for FW in NAWM.ConclusionThe association between uncorrected conventional DTI parameters and age is mainly driven by the amount of FW, calling for caution when interpreting uncorrected DTI scores. In contrast, FW appears to be a sensitive marker at very early, clinically silent, signs of SVD.

UK Biobank imaging adapted for a real‐world memory clinic sample

AbstractBackgroundThe Oxford Brain Health Centre (BHC) provides real‐world research data, aligned with the UK Biobank imaging study (UKB), routinely captured in a clinical service from patients under‐represented in dementia research. In this work we present how we 1) adapted the UKB MRI acquisition protocol to be suitable for memory clinic patients, 2) modified the imaging analysis pipeline to extract measures that are in line with radiology reports and 3) compare measures from BHC patients to the biggest brain MRI study in the world (ultimately 100,000 participants).MethodAdaptations of the UKB acquisition protocol for BHC patients include dividing the scan into core and optional sequences to improve patients’ tolerance. We adapted the UKB structural MRI analysis pipeline to extract quantitative measures from the scans, taking into account the characteristics of a memory clinic population (e.g. high level of white matter hyperintensities, WMH, causing misclassifications in tissue‐type segmentation). We compared the measurements extracted from the scans to visual ratings from radiology reports and to reference distributions derived from UKB data.ResultOf the 108 BHC attendees since August 2020 (average age 78.5 years, range 65‐101 years, 50.9% female), 100 (92.6%) completed the clinical scans, 100 (92.6%) consented to use of data for research, and 69 (63.9%) consented to additional research sequences, demonstrating that the protocol is well tolerated. Modified tissue‐type segmentation improved grey matter volume estimation, which showed stronger correlation with visual ratings of global atrophy after correction (r=‐0.34; p=0.001) than with the original analysis pipeline (r=‐0.31; p=0.002). Correlations between hippocampal volumes and MTA scale (r(L)=‐0.59, r(R)=‐0.71) and between WMH volume and Fazekas scale (r=0.78) were also significant (p<0.001). Because UKB participants are younger than memory clinic patients, additional scans on elderly healthy controls are planned to improve reference distributions to detect pathological deviations. Measures from BHC patients within UKB age range are comparable to those from UKB participants, with several patients falling in the lower percentiles.ConclusionWe adapted UKB research imaging for clinical practice. Current and future work aims to integrate automated quantitative measures in the radiology reports and evaluate their clinical utility.

Different Types of Chronic Inflammation Engender Distinctive Immunosenescent Profiles in Affected Patients.

Immunosenescence encompasses a spectrum of lymphocyte phenotypic alterations. The aim of the study was to evaluate immunosenescent effect of two different forms of chronic inflammation, Systemic Lupus Erythematosous (SLE), a systemic autoimmune disease, and End-Stage Kidney Disease (ESKD), a chronic inflammatory disorder. Certain lymphocyte surface molecules, including CD31, CD45RA, CCR7, CD28, CD57, for T, and IgD, CD27 for B lymphocytes, were analyzed by flow cytometry in 30 SLE and 53 ESKD patients on hemodialysis (HD), and results were compared to 31 healthy controls (HC) of similar age, gender, and nationality. Significant Lymphopenia was evident in both SLE and ESKD-HD patients, compared to HC, affecting B cells 75.4 (14.4−520.8), 97 (32−341), and 214 (84−576) cells/μL, respectively, p < 0.0001, and CD4 cells 651.2 (71.1−1478.2), 713 (234−1509), and 986 (344−1591) cells/μL, respectively, p < 0.0001. The allocation of B cell subpopulations was remarkably different between SLE and ESKD-HD patients. SLE showed a clear shift to senescence (CD19IgD-CD27−) cells, compared to ESKD-HD and HC, 11.75 (10)% vs. 8 (6) vs. 8.1 (10), respectively. Regarding T lymphocytes, Central Memory CD8 cells predominated in both SLE and ESKD-HD patients compared to HC, 53 (50)%, 52 (63), and 24 (64)%, respectively, while ESKD-HD but not SLE patients also had increased expression of CD4CD28− and CD8CD28− cells. In conclusion, both diseases are followed by significant lymphopenia; however, the senescent phenomenon affects the B lymphocyte compartment in SLE patients and T lymphocytes in ESKD-HD patients.

Disrupted topological organization of the motor execution network in Wilson's disease.

There are a number of symptoms associated with Wilson's disease (WD), including motor function damage. The neuropathological mechanisms underlying motor impairments in WD are, however, little understood. In this study, we explored changes in the motor execution network topology in WD. We conducted resting-state functional magnetic resonance imaging (fMRI) on 38 right-handed individuals, including 23 WD patients and 15 healthy controls of the same age. Based on graph theory, a motor execution network was constructed and analyzed. In this study, global, nodal, and edge topological properties of motor execution networks were compared. The global topological organization of the motor execution network in the two groups did not differ significantly across groups. In the cerebellum, WD patients had a higher nodal degree. At the edge level, a cerebello-thalamo-striato-cortical circuit with altered functional connectivity strength in WD patients was observed. Specifically, the strength of the functional connections between the cerebellum and thalamus increased, whereas the cortical-thalamic, cortical-striatum and cortical-cerebellar connections exhibited a decrease in the strength of the functional connection. There is a disruption of the topology of the motor execution network in WD patients, which may be the potential basis for WD motor dysfunction and may provide important insights into neurobiological research related to WD motor dysfunction.

Galectin-9: A novel promoter of atherosclerosis progression

Background and aimsAtherosclerosis is widely accepted to be an inflammatory disease driven by lipid accumulation and leukocyte recruitment. More recently, galectins, a family of β-galactoside binding proteins, have been shown to play a role in leukocyte recruitment among other immunomodulatory functions. Galectin (Gal) −9, a tandem repeat type galectin expressed by the endothelium in inflammatory environments, has been proposed to promote leukocyte recruitment. However, the role of Gal-9 in the context of monocyte recruitment remains elusive. Methods and ResultsHere, we characterise the immunomodulatory role of Gal-9 in context of atherosclerosis. We show that ApoE−/−Gal-9−/− mice have a significantly reduced aortic plaque burden compared to their ApoE−/− littermate controls after 12 weeks of high fat diet. RNA sequencing data from two independent studies reveal Lgals9 expression in leukocyte clusters isolated from murine atherosclerotic plaques. Additionally, soluble Gal-9 protein induces monocyte activation and a pro-inflammatory phenotype in macrophages. Furthermore, we show that immobilised recombinant Gal-9 acts as capture and adhesion molecule for CD14+ monocytes in a β2-integrin and glycan dependent manner, while adhesion of monocytes to stimulated endothelium is reduced when Gal-9 is knocked down. Gal-9 also facilitates enhanced recruitment of leukocytes from peripheral arterial disease (PAD) patients compared to healthy young and aged controls. We further characterise the endothelium as source of circulating Gal-9, which is increased in plasma of PAD patients compared to healthy controls. ConclusionsThese results highlight a pathological role for Gal-9 as promoter of monocyte recruitment and atherosclerotic plaque progression, making it a novel target in the prevention of plaque formation and progression.

Effects of Pharmacological Treatments in Alzheimer's Disease: Permutation Entropy-Based EEG Complexity Study.

Alzheimer's disease (AD) is a neurodegenerative brain disease affecting cognitive and physical functioning. The currently available pharmacological treatments for AD mainly contain cholinesterase inhibitors (AChE-I) and N-methyl-D-aspartic acid (NMDA) receptor antagonists (i.e., memantine). Because brain signals have complex nonlinear dynamics, there has been an increase in interest in researching complexity changes in the time series of brain signals in individuals with AD. In this study, we explore the electroencephalographic (EEG) complexity for making better observation of pharmacological therapy-based treatment effects on AD patients using the permutation entropy (PE) method. We examined EEG sub-band (delta, theta, alpha, beta, and gamma) complexity in de-novo, monotherapy (AChE-I), dual therapy (AChE-I and memantine) receiving AD participants compared with healthy elderly controls. We showed that each frequency band depicts its own complexity profile, which is regionally altered between groups. These alterations were also found to be associated with global cognitive scores. Overall, our findings indicate that entropy measures could be useful to show medication effects in AD.

Hyperconnectivity matters in early-onset Alzheimer's disease: a resting-state EEG connectivity study

ObjectivesThe aim of this study was to differentiate individuals with early-onset Alzheimer's disease (EOAD) and identify differences of functional connectivity in resting-state EEG between individuals with EOAD and late-onset AD (LOAD) in comparison with both healthy young and elderly individuals. MethodsForty EOAD and 56 LOAD patients were included along with 51 demographically matched young, and 54 elderly healthy individuals as controls to the EOAD and LOAD groups. Four minutes of resting-state EEG were recorded during the eyes-closed condition. The absolute value of imaginary coherence (ICoh) was measured for connectivity. The maximum values of ICoh were measured at delta (0.5-3.5 Hz), theta (4-7.5Hz), alpha (8-13 Hz), alpha-1 (8-10 Hz), alpha-2 (10.5-13 Hz), beta (13-30 Hz), beta-1 (13-20 Hz), and beta-2 (20.5-30 Hz) frequency bands. ResultsIndividuals with EOAD showed higher coherence values in all frequency bands than LOAD patients. Compared to young healthy controls (YHC), EOAD had increased ICoh values in theta and beta-2 bands, whereas LOAD had lower ICoh values in the alpha-1 band than elderly healthy controls (EHC). Lastly, patients with EOAD demonstrated negative moderate correlations between language domains and beta-1 ICoh values. ConclusionTo the authors’ knowledge, this is the first study evaluating coherence alterations among early-and late-onset AD patients and the diagnostic value of coherence measures. It was suggested that EOAD patients had more severe pathological changes compared with LOAD.

Deep learning-based classification of healthy aging controls, mild cognitive impairment and Alzheimer’s disease using fusion of MRI-PET imaging

Automated detection of dementia stage using multimodal imaging modalities will be helpful for improving the clinical diagnosis. In this study, we develop the Inception-ResNet wrapper model in differentiating the healthy controls (HC), mild cognitive impairment (MCI), and Alzheimer’s disease (AD) using conjoint magnetic resonance imaging (MRI) and positron emission tomography (PET) scans. We use T1-weighted MR and PET images of individuals aged between 42 and 95 years, including HC, MCI and AD patients. We first perform 3D tissue segmentation of MR images after skull striping. The atlas-based segmented MR image tissue is fused with PET image. Then we transform PET images from RGB to HSI color space and apply fusion of MRI with PET images using two-dimensional Fourier and discrete wavelet transform (DWT) and then reconstruct the MR-PET fused image using inverse Fourier and DWT methods. After the fusion of MRI and PET imaging modalities, we used 60 % training, 20 % for validation and the remaining 20 % as a test set using various convolutional neural networks. We found the proposed model as the best classifier with an accuracy of 95.5 %, 94.1 % and 95.9 % in classifying HC vs MCI, MCI vs AD and AD vs HC respectively when compared to the existing methods. We conclude that the proposed deep learning model has potential in automated classification of healthy and dementia stages using combined MRI and PET modalities with good performance.

The relationship of biochemical factors related to calcium metabolism with temporomandibular disorders

ObjectiveThe aim of this study is to investigate the relationship between calcium metabolism-related biochemical factors (alkaline phosphatase, vitamin D, parathyroid hormone (PTH), calcium, phosphorus and magnesium), and temporomandibular joint (TMJ) disk displacement with reduction (DDWR). Materials and MethodsThis prospective observational study included patients with temporomandibular disorders (TMDs) (n = 50) and healthy controls (n = 50) of similar age and sex. The diagnosis of TMJ DDWR was made using the diagnostic criteria for temporomandibular joint disorders (DC/TMD). Both groups were compared in terms of serum alkaline phosphatase, 25 (OH) vitamin D, PTH, calcium, magnesium, and phosphorus levels. P<0.005 was accepted as a significant difference. ResultsThere was no significant difference between the groups in terms of age, gender, and body mass index (BMI). Calcium levels of patients with TMD were statistically significantly lower than control patients (p<0.05). While there was no significant difference between the two groups in terms of mean VIT D, the number of people with severe Vit D deficiency (<10 ng) in the TMD group was significantly higher than in the control group (p<0.05). There was no statistically significant difference between the groups in terms of serum alkaline phosphatase, magnesium, phosphorus and PTH levels. ConclusionThe differences in serum calcium and vitamin D levels seen in the study indicate that biochemical factors related to calcium metabolism may be associated with TMJ DDWR. These results suggest that calcium and vitamin D deficiency should be evaluated and corrected in patients with TMD.

Metabolomic Signatures of Autism Spectrum Disorder.

Autism Spectrum Disorder (ASD) is associated with many variations in metabolism, but the ex-act correlates of these metabolic disturbances with behavior and development and their links to other core metabolic disruptions are understudied. In this study, large-scale targeted LC-MS/MS metabolomic analysis was conducted on fasting morning plasma samples from 57 children with ASD (29 with neurodevelopmental regression, NDR) and 37 healthy controls of similar age and gender. Linear model determined the metabolic signatures of ASD with and without NDR, measures of behavior and neurodevelopment, as well as markers of oxidative stress, inflammation, redox, methylation, and mitochondrial metabolism. MetaboAnalyst ver 5.0 (the Wishart Research Group at the University of Alberta, Edmonton, Canada) identified the pathways associated with altered metabolic signatures. Differences in histidine and glutathione metabolism as well as aromatic amino acid (AAA) biosynthesis differentiated ASD from controls. NDR was associated with disruption in nicotinamide and energy metabolism. Sleep and neurodevelopment were associated with energy metabolism while neurodevelopment was also associated with purine metabolism and aminoacyl-tRNA biosynthesis. While behavior was as-sociated with some of the same pathways as neurodevelopment, it was also associated with alternations in neurotransmitter metabolism. Alterations in methylation was associated with aminoacyl-tRNA biosynthesis and branched chain amino acid (BCAA) and nicotinamide metabolism. Alterations in glutathione metabolism was associated with changes in glycine, serine and threonine, BCAA and AAA metabolism. Markers of oxidative stress and inflammation were as-sociated with energy metabolism and aminoacyl-tRNA biosynthesis. Alterations in mitochondrial metabolism was associated with alterations in energy metabolism and L-glutamine. Using behavioral and biochemical markers, this study finds convergent disturbances in specific metabolic pathways with ASD, particularly changes in energy, nicotinamide, neurotransmitters, and BCAA, as well as aminoacyl-tRNA biosynthesis.

Impaired Facial Emotion Recognition and Gaze Direction Detection in Mild Alzheimer's Disease: Results from the PACO Study.

Facial emotion recognition (FER) and gaze direction (GD) identification are core components of social cognition, possibly impaired in many psychiatric or neurological conditions. Regarding Alzheimer's disease (AD), current knowledge is controversial. The aim of this study was to explore FER and GD identification in mild AD compared to healthy controls. 180 participants with mild AD drawn from the PACO study and 74 healthy elderly controls were enrolled. Participants were asked to complete three socio-cognitive tasks: face sex identification, recognition of facial emotions (fear, happiness, anger, disgust) expressed at different intensities, and GD discrimination. Multivariate analyses were conducted to compare AD participants and healthy controls. Sex recognition was preserved. GD determination for subtle deviations was impaired in AD. Recognition of prototypically expressed facial emotions was preserved while recognition of degraded facial emotions was impacted in AD participants compared to controls. Use of multivariate analysis suggested significant alteration of low-expressed fear and disgust recognition in the AD group. Our results showed emotion recognition and GD identification in patients with early-stage AD compared to elderly controls. These impairments could be the object of specific therapeutic interventions such as social cognition remediation or raising awareness of primary caregivers to improve the quality of life of patients with early AD.

Plasma microRNAs as potential biomarkers in early Alzheimer disease expression

The microRNAs (miRNAs) are potential biomarkers for complex pathologies due to their involvement in the regulation of several pathways. Alzheimer Disease (AD) requires new biomarkers in minimally invasive samples that allow an early diagnosis. The aim of this work is to study miRNAS as potential AD biomarkers and their role in the pathology development. In this study, participants (n = 46) were classified into mild cognitive impairment due to AD (MCI-AD, n = 19), preclinical AD (n = 8) and healthy elderly controls (n = 19), according to CSF biomarkers levels (amyloid β42, total tau, phosphorylated tau) and neuropsychological assessment. Then, plasma miRNAomic expression profiles were analysed by Next Generation Sequencing. Finally, the selected miRNAs were validated by quantitative PCR (q-PCR). A panel of 11 miRNAs was selected from omics expression analysis, and 8 of them were validated by q-PCR. Individually, they did not show statistically significant differences among participant groups. However, a multivariate model including these 8 miRNAs revealed a potential association with AD for three of them. Specifically, relatively lower expression levels of miR-92a-3p and miR-486-5p are observed in AD patients, and relatively higher levels of miR-29a-3p are observed in AD patients. These biomarkers could be involved in the regulation of pathways such as synaptic transmission, structural functions, cell signalling and metabolism or transcription regulation. Some plasma miRNAs (miRNA-92a-3p, miRNA-486-5p, miRNA-29a-3p) are slightly dysregulated in AD, being potential biomarkers of the pathology. However, more studies with a large sample size should be carried out to verify these results, as well as to further investigate the mechanisms of action of these miRNAs.

Abstract IA030: A population-based, whole genome sequencing approach to mapping the genetic basis of mesenchymal malignancies

Abstract Cancer genetics has to date focused on epithelial malignancies, identifying multiple histotype-specific pathways underlying cancer susceptibility. Sarcomas are rare malignancies predominantly derived from embryonic mesoderm. To identify novel pathways specific to mesenchymal cancers, whole genome germline sequencing was performed on 1,644 sporadic cases, and 3,205 matched healthy elderly controls. Using an extreme phenotype design, a combined rare variant burden and ontologic analysis identified two new sarcoma-specific pathways involved in mitotic and telomere functions. Variants in centrosome genes are linked to malignant peripheral nerve sheath and gastrointestinal stromal tumors, while heritable defects in the shelterin complex link susceptibility to sarcoma, melanoma and thyroid cancers. These studies indicate a specific role for heritable defects in mitotic and telomere biology in risk of sarcomas. Citation Format: David M. Thomas. A population-based, whole genome sequencing approach to mapping the genetic basis of mesenchymal malignancies [abstract]. In: Proceedings of the AACR Special Conference: Sarcomas; 2022 May 9-12; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(18_Suppl):Abstract nr IA030.