Šarkinaitė, Milda

Purpose: Subcutaneous fat accumulation has been linked to adverse brain health outcomes. This study examines the relationship between thigh muscle mass, subcutaneous fat distribution, and brain structure in elderly adults. It explores how body composition affects cortical thickness in brain regions linked to cognitive function. Methods or Background: Fifty-four healthy elderly individuals underwent imaging of the right thigh and brain using a 3T Siemens Avanto MRI system. Muscle and subcutaneous fat cross-sectional areas (CSA) were measured at 50% and 20% of thigh length, with the muscle-to-fat ratio calculated at the 50% mark. Cortical thickness was assessed through brain volumetric analysis using Freesurfer 7.4.1 software. Results or Findings: Significant positive correlations (r ≥ 0.2, p ≤ 0.05) were found between the muscle-to-fat ratio and cortical thickness in the left cerebellum, cuneus, and transverse temporal cortex, in the right entorhinal cortex, inferior temporal cortex, postcentral gyrus, superior temporal cortex, and the banks of the superior temporal sulcus (BANKSSTS). Additionally, significant negative correlations (r ≤ -0.2, p ≤ 0.05) were observed between subcutaneous fat CSA at 50% of thigh length and cortical thickness in the left cuneus and entorhinal cortex, in the right BANKSSTS, postcentral gyrus, and superior temporal cortex. Additionally, subcutaneous fat CSA at 20% of thigh length was inversely correlated with cortical thickness in the left cuneus and right BANKSSTS (r ≤ -0.2, p ≤ 0.05). Conclusion: Our findings demonstrate that increased thigh muscle mass correlates with greater cortical thickness in cognitive regions, while elevated subcutaneous fat is linked to reduced thickness. These results highlight the role of body composition in maintaining brain health in the elderly and underscore the importance of muscle mass in mitigating age-related cortical decline. Limitations: With only 54 participants, the study's findings may lack generalizability.

In this randomized controlled trial, we assessed the neuroprotective effect of a 12-week resistance training (RT) program on executive control and cortical thickness of the prefrontal, temporal, parietal, and central cortex, regions prone to structural decline in individuals with mild cognitive impairment (MCI).

Background / Objective The study aimed to investigate the impact of different types of exercise on brain morphology in healthy males. Specifically, two exercise groups were compared with a control group over a 12-week period, focusing on High Intensity Resistance Training (HIRT) and Blood Flow Restriction (BFR) training. Methods Seventeen participants underwent 12 weeks of HIRT, while 18 participants underwent BFR training. Fifteen males comprised the control group. Brain MRIs were conducted before and after the training period. Brain volumetric changes were analyzed using Freesurfer 7.4.1 software, and white matter integrity was assessed through DTI using ExploreDTI software. Results Significant volumetric changes were observed in the HIRT group post-training compared to the control group, with specific regions including the left hippocampal head, body, and surrounding areas showing notable changes (p<0.05). In contrast, the BFR group did not exhibit significant volumetric changes post-training. Regarding white matter integrity, the HIRT group demonstrated a significant difference in the FA value of the whole brain (p<0.05), particularly in the hippocampal regions. The BFR group did not show a similar significant change in FA values. Conclusions The findings suggest that High Intensity Resistance Training has a significant impact on brain morphology, particularly in the hippocampal regions and overall brain volume. In contrast, Blood Flow Restriction training did not result in significant changes in brain morphology post-training. Further research is warranted to delve deeper into the observed differences and understand the underlying mechanisms driving these effects.

Physical exercise is suggested to promote hippocampal neuroplasticity by increasing circulating neurotrophic and anti-inflammatory factors. Our aim was to explore the interplay between the effect of progressive resistance exercise on blood biomarker levels, hippocampal neurometabolite levels and hippocampal volume in older adults with a low compared to a high risk of mild cognitive impairment (MCI). Seventy apparently healthy male/female older adults (aged 60-85 years old) were randomly allocated to a 12 week lower limb progressive resistance or no intervention, stratified for low (< 26/30) or high (≥ 26/30) Montreal Cognitive Assessment (MoCA) score, indicating MCI risk. Outcome measures were blood levels of insulin-like growth factor-1 (IGF-1), interleukin-6 (IL-6) or kynurenine (KYN); hippocampal total and subfield volumes of the cornu ammonis 1 (CA1) and 4 (CA4), subiculum, presubiculum, and dentate gyrus measured with magnetic resonance imaging (MRI); and hippocampus neurometabolites including total N-acetylaspartate (NAA), myo-inositol (mIns), and total creatine (Cr) measured with proton magnetic resonance spectroscopy (1H-MRS). We evaluated the intervention effect, cognitive status effect, their interaction and the bivariate relationship between exercise-induced changes between the outcome measures. Higher kynurenine levels (p = 0.015) and lower subiculum volumes (p = 0.043) were found in older adults with high MCI risk compared to older adults with low MCI risk. Exercise-induced CA1 volume changes were negatively correlated with hippocampal tNAA/mIns level changes (r = -0.605, p = 0.006). This study provides valuable insight in the multifactorial processes related to resistance training in older adults with low or high MCI risk.

We implemented a multimodal approach to examine associations between structural and neurochemical changes that could signify neurodegenerative processes related to mild cognitive impairment (MCI). Fifty-nine older adults (60–85 years; 22 MCI) underwent whole-brain structural 3T MRI (T1W, T2W, DTI) and proton magnetic resonance spectroscopy (1H-MRS). The regions of interest (ROIs) for 1H-MRS measurements were the dorsal posterior cingulate cortex, left hippocampal cortex, left medial temporal cortex, left primary sensorimotor cortex, and right dorsolateral prefrontal cortex. The findings revealed that subjects in the MCI group showed moderate to strong positive associations between the total N-acetylaspartate to total creatine and the total N-acetylaspartate to myo-inositol ratios in the hippocampus and dorsal posterior cingulate cortex and fractional anisotropy (FA) of WM tracts crossing these regions—specifically, the left temporal tapetum, right corona radiata, and right posterior cingulate gyri. In addition, negative associations between the myo-inositol to total creatine ratio and FA of the left temporal tapetum and right posterior cingulate gyri were observed. These observations suggest that the biochemical integrity of the hippocampus and cingulate cortex is associated with a microstructural organization of ipsilateral WM tracts originating in the hippocampus. Specifically, elevated myo-inositol might be an underlying mechanism for decreased connectivity between the hippocampus and the prefrontal/cingulate cortex in MCI.

Synopsis: There is known relationship between hippocampal volumes and major depressive disorder (MDD), but the links between hippocampal volumes and suicidality remain unclear. If the hippocampus could be used as a biomarker of suicide attempts, it could be useful for prevention. In this study we compared hippocampal volumes between suicide attempters (SA) with MDD (n=21), SA without MDD (n=26) and healthy controls (HC) (n=59). Surface-based morphometry (Freesurfer) analysis was used to evaluate the volumes of gray matter. Although hippocampal volumes did not differ significantly between SA with and without MDD, both right (p=0.007) and left (p=0.006) hippocampi in SA with MDD and in SA without MDD (p=0.011; p=0.004) were reduced comparing them with HC. In SA with MDD analysis revealed the subregional deformations of the right subiculum (p=0.002) and CA1, CA3, CA4 subfields in the right (p=0.006; p=0.025; p=0.005) and left (p=0.015; p = 0.010; p=0.003) hippocampi. Similar volume changes of left CA4 (p=0.007) and CA1, CA3 in both right (p=0.007; p=0.019) and left (p=0.028; p=0.028) hippocampi were found in SA without MDD. Regardless of depressive disorder, atrophy is seen in both groups of suicide attempters and it is more noticeable than in the group of healthy controls. Both suicide groups showed similar hippocampal changes. Therefore, suicidality causes hippocampal changes on its own and can be distinguished from depressive disorder.

Objective Neuroimaging in general, and proton magnetic resonance spectroscopy in particular are used as diagnostic tools for neurodegenerative disease. It is expected that structural and neurochemical alterations in the brain may reflect different aspects of the same pathology. Nonetheless, associations between neuroanatomical structural changes and neurochemical changes in the brain are underexplored. In this presentation we will introduce a multimodal approach to discuss associations between structural and neurochemical changes that could signify neurodegenerative processes related to mild cognitive impairment (MCI). We combined multiple MRI scanning techniques to examine these associations and discuss them in the context of routine MRI imaging as it is implemented in daily practice. Moreover, these combined neuroimaging features will be discussed in relation to pathological conditions that may be related to onset of disease such as systemic inflammation or neuroinflammation.Methods74 older adults (60-85y) underwent whole brain structural 3T MRI (T1W, T2W, DTI) and proton magnetic resonance spectroscopy (1H-MRS). 1H-MRS post-processing software packages were compared. The regions of interest for 1H-MRS measurements were dorsal posterior cingulate cortex (DPCC), left hippocampal cortex (HPC), left medial temporal cortex (MTC), left primary sensorimotor cortex (SM1), and right dorsolateral prefrontal cortex (DLPFC). Spectra from the aforementioned regions were acquired using a PRESS sequence (TR/TE = 2000/30 ms) with excitation water suppression. LC Model was used to quantify water referenced levels of N-acetyl aspartate (NAA), choline (Cho), myo-inositole (mIns) and their ratios to creatine (Cr). Only spectra with linewidths less than 0.1 ppm and signal to noise ratios (SNR) greater than 5 were included in the statistical analyses. DTI images were checked for artefacts by an experienced neuroradiologist. Tractography was performed using the Siemens “syngo.via” workstation (Siemens Healthineers, Erlangen, Germany). Circular voxels (1 cm radius) were manually placed on the regions of interest. The software automatically calculated the median values of fractional anisotropy, and number of tracts. For anatomical reference, a high-resolution T1W 3D structural image was acquired for all participants at each scanning site. Spearman correlation coefficients were used to evaluate relationships between NAA/Cr, Cho/Cr and mIns/Cr ratios in the five regions and DTI measures. Mann-Whitney test was used to examine group differences in neurometabolites and white matter structural properties between MCI and healthy controls. Peripheral inflammation was assessed with serum interleukin-6 and kynurenine, measured with ELISA and were used in a regression model to examine associations between neurometabolic expressions of neuroinflammation (i.e., elevated mIns/Cr and Cho/Cr) and blood biomarkers of peripheral inflammation. Results Findings from correlation analysis revealed a trend showing that an increased level of hippocampal mIns/Cr was negatively related to decreased FA in the left external capsule of MCI patients (r = -0.399) which was not seen in non-MCI (r = 0.02). Contrarily, higher levels of hippocampal Cho/Cr were negatively related to lower FA in non-MCI (r = -0.455, p = 0.033) but not in MCI (r = 0.120). No associations were found between metabolites in the two other brain locations and FA. Overall, these observations may suggest that biochemical integrity of the left hippocampus is associated with microstructural organization of ipsilateral WM tracts connecting the hippocampus with temporal and prefrontal cortex. Elevated serum kynurenine levels were associated with signs of neuroinflammation, specifically in the DLPFC (Cho/Cr, β = 0.297, p = 0.02) and MTC (Cho/Cr, β = 0.418, p= 0.003). In addition, we found a negative correlation between IL-6 and measures of neural density in the MTC [NAA/Cr (β = -0.407, p = 0.011); and a positive correlation with Cho/Cr (β = 0.442, p=0.007)] in the same region. However, no association were observed between Kynurenine/ IL-6 and DTI measures. Conclusions Our observations suggest that decreased microstructural organization of the left external capsule could be related to local neuro-inflammation in the hippocampus. Our exploratory regression analysis showed associations between neurometabolic biomarkers and blood biomarkers of peripheral inflammation. There were no associations between peripheral inflammatory biomarkers and white matter structure. Overall, these findings suggest that elevated glial cell activity as expressed by elevated mIns/Cr might be an underlying mechanism for decreased connectivity between hippocampus and prefrontal/cingulate cortex that could lead to cognitive decline and potentially to neurodegenerative diseases. One possible cause of neurodegenerative processes that seems to have been overlooked in the research of normal aging is low-grade neuroinflammation. Pro-inflammatory processes have long been argued to play a role in conditions associated with cognitive decline and neurodegeneration in the normal aging process. However, only a limited number of studies have attempted to measure both peripheral and central biomarkers of inflammation and examined their interrelationship. Our results suggest that serum kynurenine may be used as a peripheral inflammatory marker that is associated with neuroinflammation and potentially neurodegeneration. Further research is needed to confirm these observations. Brief description of the abstract We examined links between biochemical status, brain structural properties and biomarkers of peripheral inflammation in order to establish a neurobiological model of aging. Our observations suggest that biochemical integrity of the left hippocampus is associated with microstructural organization of ipsilateral WM tracts connecting the hippocampus with temporal and prefrontal cortex.

Purpose Mild cognitive impairment (MCI) refers to individuals not yet fulfilling the criteria of Alzheimer disease (AD) but who have impaired cognitive functions compared to other adults their age while activities of daily living remain intact [1]. It has been shown that about 60% of people with diagnosis of MCI progress to dementia in a 5-year period [2,3]. Loss of hippocampal volume is widely used as a biomarker of neurodegeneration in early stage of AD as it is one of the first sites where morphological changes occur [4]. However, volumetric declines due to MCI may not differ from those seen during the normal course of cognitive aging. Nevertheless, neuroimaging studies have demonstrated that the progression of hippocampal atrophy in patients with MCI is a highly precise to predict progression to AD [5]. Earlier studies have indicated that clinical features cross-sectionally correlate with regional or whole brain atrophy using magnetic resonance imaging (MRI) [6,7]. The Montreal Cognitive Assessment (MoCA) is brief screening tool for MCI and extensively used in a variety of contexts [8]. Despite wide application, neuroanatomical correlates associated with cognitive functions on the MoCA remain unclear. The purpose of our study was to examine whether lower scores on MoCA test would predict greater atrophy of the hippocampus and its subfields in MCI patients. Methods and materialsParticipants55 participants were chosen for this study consisting of 28 subjects with MCI (years range 60-80) and 27 cognitively intact older adults (years range 60-75). Participants with MCI were diagnosed using ICD-10 and Petersen criteria [2]. Exclusionary criteria for both groups included diagnosis of dementia, and/or MoCA score ≤16, MRI evidence of brain pathology such as tumor, stroke, or significant trauma, multiple sclerosis, psychiatric illness, history of drug abuse or alcoholism, and MRI contraindications. All participants signed an informed consent document prior to assessment. The study was approved by the local Medical Ethics Committee for Biomedical Research (No. BE-10-7). Neuropsychological testing Neuropsychological testing was done using MoCA which assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. The total possible score is 30 points; a score of 26 or above is considered normal [8].Magnetic resonance examination and volumetric analysis Magnetic resonance scans were performed using 3T scanner with a 32-channel receiver head coil. A high-resolution T1W structural image (TR = 2200 ms, TE = 2.48 ms, 0.9 mm slice thickness) was used to acquire a 3D magnetization prepared gradient echo. Volumetric analysis of hippocampus (both right and left) was performed using FreeSurfer v7.1.1 (Harvard, MA, USA, http://surfer.nmr.mgh.harvard.edu/). Hippocampal segmentation included hippocampal tail, subiculum head and body, cornu ammonis (CA)1 head and body, CA3 head and body, CA4 head and body, hippocampal fissure, presubiculum head and body, parasubiculum, molecular layer of hippocampus proper (ML-HP) head and body, granule cell and molecular layer of the dentate gyrus (GC-ML-DG) head and body, fimbria, hippocampal-amygdala transition area (HATA), whole hippocampal body, whole hippocampal tail and whole hippocampus (Figure 1). The participants in our study were divided into 2 groups. The first group included MCI patients with MoCA scores ≤25 (MCI ≤25) and healthy controls (HC) with MoCA scores ≥26 (HC ≥26). The second group consisted of MCI patients with MoCA scores ≤24 (MCI ≤24) and HC with MoCA scores ≥27 (MCI ≥27). Demographic characteristics of subjects are shown in Figure 2. Fig. 2 [...]. Selecting MoCA cutoff of 24 for MCI patients revealed statistically significant loss of volume in various hippocampal subfields compared to cognitively intact adults with MoCA scores ≥ 27 (Figure 3). Fig. 3 [...]. Hippocampal volume differences were not present when cutoffs of 25 for MCI patients and 26 for older adults with no MCI were selected (all p ≥ 0.05). Figure 3 presents only statistically significant volume differences of hippocampus and its subfields which became evident when MoCA cutoff of 24 for MCI and 27 for HC was selected. Conclusion MoCA cutoff score of 25 is usually considered to separate patients with MCI from cognitively intact older adults. However, the relationship between MoCA performance and structural brain changes is not fully understood. In our study reduced volume of hippocampus and its subfields became evident when MoCA cutoffs for MCI patients and older adults without MCI were set at 24 and 27, respectively. This could suggest that a cutoff score of 25 may not be sensitive enough to detect structural volumetric differences in hippocampus as a result of MCI.

Purpose In Coronavirus 2019 disease has wide range of neurological manifestation from mild like anosmia and ageusia to severe acute infarcts, intracranial hemorrhage, encephalitis. [1,2]. Neuroimaging studies in COVID 19 revealed inflammatory, cerebrovascular, and neurometabolitic abnormalities [3]. Neurometabolitic changes was reported only in patients with severe COVID -19 clinical symptoms, but to our knowledge no study examined neurometabolitic alternations from pre-to post COVID-19 in brains of the same subjects. The purpose of our study was to examine the diagnostic value of brain neurometabolites in determining neurological complications in mild COVID-19. Methods and materials Whole brain MRI images and 1H-MRS of the left hippocampus were collected at baseline and after recovery (Figure 1), Fig 1. [...], from three elderly individuals (aged 63-68 years) who had a COVID-19 infection with mild symptoms (Figure 2). Fig 2. [...]. Spectroscopic imaging measures were contrasted to their baseline (pre-COVID-19) measures and were compared with values for Minimal Detectable Change at 95% (MDC95) and 90% (MDC90) confidence from a group of six elderly (aged 60-79 years) without COVID-19 that participated in the same study. Comparisons were also made with pre-to-post alterations of the spectroscopic measures from 9 healthy age-matched individuals that underwent 12 weeks of resistance training. The study was approved by the local Medical Ethics Committee for Biomedical Research (No. BE-10-7). Results We observed a reduction of glutamate-glutamine (Glx) from baseline in Patients 1 and 2 (≥ 42.0 %) and elevation of myo-inositol (mIns) and N-acetyl-aspartate (NAA) in Patient 3 (≥ 36.4%); see Figure 3 and Figure 4. Fig 3. [...], Fig 4. [...]. All three patients had small focal hyperintense lesions in subcortical or periventricular regions prior to their COVID-19 infection. One patient (patient 3) also had hemosiderin deposit in the left peritrigonal area. The lesions were detectable by T2W/FLAIR and SWI, both in the baseline and in the post-COVID-19 scanning sessions and were not found to be worsened by the infection (Figure 5). Fig 5. [...]. Conclusion This study is the first pilot study were pre- and post-COVID-19 spectroscopic measures were available. Mild COVID-19 infection was associated with development of local neuroinflammation and reduced glutamate levels in the hippocampus. Our 1H-MRS findings may have clinical value for explaining chronic neurological and psychological complaints in COVID-19 long-haulers. Generalization of the present findings should be made with caution due to small sample size and inclusion of mild COVID-19 patients.

RATIONALE AND OBJECTIVES: Pro-inflammatory processes have been argued to play a role in conditions associated with cognitive decline and neurodegeneration, like aging and obesity. Only a limited number of studies have tried to measure both peripheral and central biomarkers of inflammation and examined their interrelationship. The primary aim of this study was to examine the hypothesis that chronic peripheral inflammation would be associated with neurometabolic changes that indicate neuroinflammation (the combined elevation of myoinositol and choline), brain gray matter volume decrease, and lower cognitive functioning in older adults. MATERIALS AND METHODS: Seventy-four older adults underwent bio-impedance body composition analysis, cognitive testing with the Montreal Cognitive Assessment (MoCA), blood serum analysis of inflammatory markers interleukin-6 (IL-6) and kynurenine, magnetic resonance imaging (MRI), and proton magnetic resonance spectroscopy ((1)H-MRS) of the brain. Neurometabolic findings from both Tarquin and LCModel (1)H-MRS post-processing software packages were compared. The regions of interest for MRI and (1)H-MRS measurements were dorsal posterior cingulate cortex (DPCC), left hippocampal cortex (HPC), left medial temporal cortex (MTC), left primary sensorimotor cortex (SM1), and right dorsolateral prefrontal cortex (DLPFC). RESULTS: Elevated serum kynurenine levels were associated with signs of neuroinflammation, specifically in the DPCC, left SM1 and right DLPFC, and signs of neurodegeneration, specifically in the left HPC, left MTC and left SM1, after adjusting for age, sex and fat percentage (fat%). Elevated serum IL-6 levels were associated with increased Glx levels in left HPC, left MTC, and right DLPFC, after processing the (1)H-MRS data with Tarquin. Overall, the agreement between Tarquin and LCModel results was moderate-to-strong for tNAA, tCho, mIns, and tCr, but weak to very weak for Glx. Peripheral inflammatory markers (IL-6 and kynurenine) were not associated with older age, higher fat%, decreased brain gray matter volume loss or decreased cognitive functioning within a cohort of older adults. CONCLUSION: Our results suggest that serum kynurenine may be used as a peripheral inflammatory marker that is associated with neuroinflammation and neurodegeneration, although not linked to cognition. Future studies should consider longitudinal analysis to assess the causal inferences between chronic peripheral and neuroinflammation, brain structural and neurometabolic changes, and cognitive decline in aging.