Elderly Controls Research Articles

Attention Network Dysfunctions in Lewy Body Dementia and Alzheimer’s Disease

Background: Attention deficits are notable in Lewy body dementia (LBD) and in Alzheimer’s disease (AD). In this study, we combined functional magnetic resonance imaging (fMRI) and electroencephalograph (EEG) to detect neural correlates of attention dysfunctions in LBD and AD. Methods: We recruited 33 patients with LBD, 15 patients with AD and 19 elderly healthy controls. The participants performed the modified Attention Network Task (ANT) to investigate the attention dysfunctions. Results: We found that LBD had alerting attention deficits and AD showed apparent orienting attention dysfunctions, while LBD and AD maintained relatively normal executive/conflict attention. Based on source-level EEG analyses, LBD had frontal-central deficits for alerting attention while AD showed inferior frontal and precentral impairments for orienting attention. In addition, the insular and inferior frontal areas were hyper-activated in LBD and AD for executive/conflict attention. Apart from these areas, LBD showed activity in the complementary temporal-central-occipital network for the modified ANT task. Furthermore, the oscillational sources for the ANT effects indicated that the alpha and theta bands were partly impaired in dementia patients. Conclusions: In summary, using source-localised EEG, we found that attention dysfunctions in LBD and AD engaged different neural networks.

Potential mechanism of CARD16 protein action and susceptibility to sepsis in the elderly infected population: Through transcriptome analysis of blood

As global aging accelerates, the super-elderly population is at higher risk of infectious diseases, especially sepsis, a condition that may be associated with declining immune system function and abnormal inflammatory responses. The aim of this study was to investigate the role of CARD16 protein in sepsis susceptibility in the elderly population and its potential mechanism, and to reveal the expression characteristics of CARD16-related genes through blood transcriptomic analysis. Transcriptome sequencing was conducted on peripheral blood samples obtained from patients suffering from senile sepsis, along with samples from a healthy elderly control group. To examine the differences in gene expression, bioinformatics techniques were employed to compare the expression levels of CARD16-related genes between the two groups. Additionally, a comprehensive analysis was performed on the downstream inflammatory pathways and cytokines that are regulated by CARD16.The findings from the transcriptome analysis indicated that the expression of CARD16 was markedly upregulated in the cohort of patients experiencing hypersenile sepsis. This upregulation was associated with an increase in a variety of pro-inflammatory factors. Further network analysis suggested that CARD16 may potentiate the inflammatory response by modulating the NF-κB signaling pathway, which could consequently heighten the patients' vulnerability to sepsis.In comparison to the healthy elderly control group, the levels of anti-inflammatory genes in the super-elderly cohort were found to be significantly diminished. This observation points to a notable imbalance in immune regulation, further emphasizing the altered immune response in individuals with senile sepsis.

Age-related and age-independent complications in atrial fibrillation ablation: insights from the Japan ablation registry

Abstract Background The growing prevalence of atrial fibrillation (AF) has intensified the focus on managing this condition in the elderly. Catheter ablation, a popular treatment option, requires more detailed examination due to limited data on its efficacy and risks in this age group. Aim To identify the types of complications of AF ablation correlated with advanced age and to differentiate them from age-independent complications. Method We conducted a prospective analysis of 170,017 AF ablation procedures from the Japan ablation registry, conducted across 482 facilities between 2017 and 2020. Complications in patients aged 80 and above (elderly group, n=14,389) were compared with those under 80 (control group, n=155,628). The overall complication rate was 2.77%, with a higher occurrence in the elderly group (elderly group vs. control group, 3.62% vs. 2.69%, p<0.001). Notably, the elderly experienced more cardiac tamponade/pericardial effusion (0.95% vs. 0.6%, p<0.001), symptomatic cerebral infarction or transient ischemic attacks (0.27% vs. 0.15%, p=0.001), and sick sinus syndrome (0.31% vs. 0.05%, p<0.001). While in-hospital mortality in the elderly group was relatively low (0.16%), it was significantly higher compared to the control group (0.06%, p<0.001). However, incidences of other complications like puncture-site complications (0.49% vs. 0.42%, p=0.28), non-puncture-site bleeding, esophagus-related complications (0.22% vs. 0.22%, p=0.72), and phrenic nerve palsy (0.44% vs. 0.43%, p=0.69) showed no significant age-related differences. Conclusion Elderly patients undergoing AF ablation are at a higher risk of overall complications, with particular susceptibility to cardiac tamponade/pericardial effusion, symptomatic cerebral infarction/transient ischemic attacks, and sick sinus syndrome. This highlights the need for careful monitoring of these specific complications in the elderly. Additionally, it is noteworthy that the risk of certain complications appears to be independent of age.

Apolipoprotein B gene expression and regulation in relation to Alzheimer’s disease pathophysiology

Apolipoprotein B (APOB), a receptor-binding protein present in cholesterol-rich lipoproteins, has been implicated in Alzheimer's disease (AD). High levels of APOB-containing low-density lipoproteins (LDL) are linked to the pathogenesis of both early-onset familial and late onset sporadic AD. Rare coding mutations in the APOB gene are associated with familial AD, suggesting a role for APOB-bound lipoproteins in the central nervous system.This research explores APOB gene regulation across the AD spectrum using four cohorts: BRAINEAC (elderly control brains), DBCBB (controls, AD brains), ROSMAP (controls, MCI, AD brains), and ADNI (control, MCI, AD clinical subjects). APOB protein levels, measured via mass spectrometry and ELISA, positively correlated with AD pathology indices and cognition, while APOB mRNA levels showed negative correlations. Brain APOB protein levels also correlated with cortical Aβ levels.A common coding variant in the APOB gene locus affected its expression but didn't impact AD risk or brain cholesterol concentrations, except for 24-S-hydroxycholesterol. Polymorphisms in the CYP27A1 gene, notably rs4674344, were associated with APOB protein levels. A negative correlation was observed between brain APOB gene expression and AD biomarker levels. CSF APOB correlated with Tau pathology in presymptomatic subjects, while cortical APOB was strongly associated with cortical Aβ deposition in late-stage AD.The study discusses the potential link between blood-brain barrier dysfunction and AD symptoms in relation to APOB neurobiology. Overall, APOB's involvement in lipoprotein metabolism appears to influence AD pathology across different stages of the disease.

Cardiovascular and fracture events analysis and intervention strategies in patients undergoing parathyroidectomy with secondary hyperparathyroidism.

Chronic kidney disease (CKD), especially end-stage renal disease (ESRD), is the most common cause of secondary hyperparathyroidism (SHPT), and SHPT is the most severe complication of ESRD. This study aimed to analyze the influencing factors of cardiovascular and fracture events in patients with SHPT which are the leading causes of death in patients with CKD, and provide a reference for selecting patients for whom surgery is more suitable. Patients who underwent parathyroidectomy (PTX) for SHPT at The First Affiliated Hospital, Zhejiang University School of Medicine from September 2021 to April 2024 were selected as the study object, with the inclusion and exclusion criteria as followed. They were divided into rural and urban residents for comparison as a cross-sectional study. The study evaluated the comorbidities, socioeconomic status, and postoperative complications diagnosed by radiography of patients undergoing surgery for SHPT. A total of 119 patients were included, among whom, 71 were from rural areas and 48 were from urban areas. Compared with urban residents, rural residents had poorer economic conditions, a longer interval from disease onset to PTX, and a higher incidence of cardiovascular and fracture events and concurrent nephrolithiasis, all of which were statistically significant. Multivariate analysis indicated that place of residence, age, and duration of uremia were independent risk factors of cardiovascular/fracture events. Medical staff in ESRD outpatient clinics should pay attention to patients with SHPT. ESRD patients should have better surveillance especially for rural, elder and poor phosphorus control patients, and promptly assess surgical intervention measures.

Classification of Alzheimer’s Disease and Frontotemporal Dementia Using Electroencephalography to Quantify Communication between Electrode Pairs

Accurate diagnosis of dementia subtypes is crucial for optimizing treatment planning and enhancing caregiving strategies. To date, the accuracy of classifying Alzheimer’s disease (AD) and frontotemporal dementia (FTD) using electroencephalogram (EEG) data has been lower than that of distinguishing individuals with these diseases from healthy elderly controls (HCs). This limitation has impeded the feasibility of a cost-effective differential diagnosis for the two subtypes in clinical settings. This study addressed this issue by quantifying communication between electrode pairs in EEG data, along with demographic information, as features to train machine learning (support vector machine) models. Our focus was on refining the feature set specifically for AD-FTD classification. Using our initial feature set, we achieved classification accuracies of 76.9% for AD-HC, 90.4% for FTD-HC, and 91.5% for AD-FTD. Notably, feature importance analyses revealed that the features influencing AD-HC classification are unnecessary for distinguishing between AD and FTD. Eliminating these unnecessary features improved the classification accuracy of AD-FTD to 96.6%. We concluded that communication between electrode pairs specifically involved in the neurological pathology of FTD, but not AD, enables highly accurate EEG-based AD-FTD classification.

Deformation-based morphometry applied to FDG PET data reveals hippocampal atrophy in Alzheimer’s disease

Cerebral atrophy is a key finding in patients with dementia and usually determined on MRI. We tested whether cerebral atrophy can be imaged with FDG PET by applying deformation-based morphometry (DBM). We retrospectively identified 26 patients with a biomarker-supported clinical diagnosis of Alzheimer’s disease (AD) who had received FDG PET on a fully-digital PET/CT system and structural MRI and compared them to 13 healthy elderly controls (HEC). We performed DBM with FDG PET data (FDG-DBM). As a reference standard for determining atrophy we used voxel-based morphometry of MRI data (MRI-VBM). For conventional analysis of hypometabolism, scaled FDG PET scans (reference: brain parenchyma) were compared between groups. Receiver operating characteristic (ROC) analyses were performed. ROI read-outs were tested for associations with cognitive test performance. FDG-DBM showed abnormalities in AD mainly in the bilateral hippocampi. Similarly, MRI-VBM showed hippocampal atrophy. By contrast, conventional FDG PET analysis revealed reduced bilateral temporo-parietal FDG uptake (all p < 0.05, FWE-corrected). FDG-DBM measures of the hippocampus significantly separated AD from HEC with an AUC of 0.81; MRI-VBM achieved an AUC of 0.87; the difference between the two ROC curves was not significant (p = 0.40). Whereas FDG uptake of the hippocampus did not separate AD from HEC, FDG uptake of the Landau Meta-ROI achieved an AUC of 0.88. Verbal memory was significantly associated with FDG-DBM measures of the hippocampus (p = 0.009), but not of the Landau Meta-ROI (p > 0.1). The opposite held true for conventional FDG uptake (p > 0.1 and p = 0.001, respectively). Hippocampal atrophy in AD can be detected by applying DBM to clinical, fully-digital FDG PET. It correlates with cognitive performance and might constitute a biomarker of neurodegeneration that is complementary to conventional FDG PET analysis of regional hypometabolism.

Right anterior insula ASL hypoperfusion as a diagnostic biomarker of prodromal and mild dementia with Lewy bodies: preliminary evidence using a Bayesian approach.

Identifying and validating a biomarker with high specificity in early-stage dementia with Lewy bodies (DLB) using a feasible method is crucial to enhance the current suboptimal diagnostic procedure. Previous research revealed abnormalities, including hypoperfusion in the right anterior insular cortex at group level, in prodromal DLB. Exploring hypoperfusion of the right anterior insula, at an individual-level and assessing its relevance as a potential imaging biomarker in early DLB, has, to our knowledge, not been investigated. Our preliminary study aims to assess the feasibility of the technique and to provide a methodological framework for further investigation. We assessed the feasibility and accuracy of the hypoperfusion of the right anterior insula per arterial spin labelling magnetic resonance imaging (ASL-MRI) as a diagnostic biomarker in early DLB and provided rough estimates of its sensitivity and specificity. Defining the region of interest based on previous research, we established the biomarker as the hypoperfusion of the right anterior insula. Discriminative and analytical performances were assessed in comparison to a control group of treatment-resistant depression patients. Bayesian diagnostic reasoning was employed to assess the biomarker diagnostic usability in early DLB in two scenarios: healthy elderly controls and mild cognitive impairment. Additionally, we updated probabilities by integrating data from the Mayo-clinic cognitive fluctuations scale and real-time quaking-induced conversion (RT-QuIC) α-synuclein data. Lastly, a whole-brain perfusion analysis of DLB patients was conducted to identify further brain regions with discriminative abilities. We successfully replicated the right anterior insular hypoperfusion (RAI-Hypo) in all DLB patients at the individual level. The overall sensitivity of the biomarker was 96%, and the specificity was 92%. Bayesian testing revealed the biomarker's highest performance in early-stage DLB with cognitive fluctuations, showcasing a diagnostic potential associated with a high precision and moderate accuracy. In a cognitively non-impaired population, the RAI-Hypo showed a limited usability and lacked in selectivity to qualify as a screening tool. The exploratory whole-brain analysis revealed perfect discriminative capacities in the bilateral anterior insulae and the left inferior parietal lobule. Further studies are needed to confirm our preliminary results. If performance is maintained in subsequent studies and is compared to a more suitable control population, the proposed biomarker may be eventually sufficient to discriminate early-stage DLB from non-DLB.

Dementia with Lewy bodies and gait neural basis: a cross-sectional study

BackgroundDementia with Lewy Bodies (DLB) is responsible for cognitive-behavioural disorders but also for gait disorders. The latter are thought to be related to parkinsonism, but the neural bases of these disorders are not well known, especially in the early stages. The aim of this study was to investigate by volumetric Magnetic Resonance Imaging the neuronal basis of gait disorders in DLB patients, compared to Healthy Elderly Controls and Alzheimer’s Disease patients.MethodsClinical examination with motor assessment including 10-meter walking speed, one-leg balance and Timed Up and Go test, a comprehensive neuropsychological evaluation and 3D brain Magnetic Resonance Imaging were performed on 84 DLB patients, 39 Alzheimer’s Disease patients and 22 Healthy Elderly Controls. We used Statistical Parametric Mapping 12 to perform a one-sample t-test to investigate the correlation between each gait score and gray matter volume (P ≤ 0.05 corrected for family-wise error).ResultsWe found a correlation for DLB patients between walking speed and gray matter decrease (P < 0.05, corrected for family-wise error) in caudate nuclei, anterior cingulate cortex, mid-cingulate cortex, hippocampi, supplementary motor area, right cerebellar cortex and left parietal operculum. We found no correlation with Timed Up and Go test and one-leg balance.ConclusionGait disorders are underpinned by certain classical regions such as the cerebellum and the supplementary motor area. Our results suggest there may be a motivational and emotional component of voluntary gait in DLB subjects, underpinned by the cingulate cortex, a spatial orientation component, underpinned by hippocampi and suggest the involvement of brain processing speed and parkinsonism, underpinned by the caudate nuclei.Trial registrationThe study protocol has been registered on ClinicalTrials.gov. (NCT01876459) on June 12, 2013.

Neuroinflammation Parallels 18F-PI-2620 Positron Emission Tomography Patterns in Primary 4-Repeat Tauopathies.

Preclinical, postmortem, and positron emission tomography (PET) imaging studies have pointed to neuroinflammation as a key pathophysiological hallmark in primary 4-repeat (4R) tauopathies and its role in accelerating disease progression. We tested whether microglial activation (1) progresses in similar spatial patterns as the primary pathology tau spreads across interconnected brain regions, and (2) whether the degree of microglial activation parallels tau pathology spreading. We examined in vivo associations between tau aggregation and microglial activation in 31 patients with clinically diagnosed 4R tauopathies, using 18F-PI-2620 PET and 18F-GE180 (translocator protein [TSPO]) PET. We determined tau epicenters, defined as subcortical brain regions with highest tau PET signal, and assessed the connectivity of tau epicenters to cortical regions of interest using a 3-T resting-state functional magnetic resonance imaging template derived from age-matched healthy elderly controls. In 4R tauopathy patients, we found that higher regional tau PET covaries with elevated TSPO-PET across brain regions that are functionally connected to each other (β = 0.414, P < 0.001). Microglial activation follows similar distribution patterns as tau and distributes primarily across brain regions strongly connected to patient-specific tau epicenters (β = -0.594, P < 0.001). In these regions, microglial activation spatially parallels tau distribution detectable with 18F-PI-2620 PET. Our findings indicate that the spatial expansion of microglial activation parallels tau distribution across brain regions that are functionally connected to each other, suggesting that tau and inflammation are closely interrelated in patients with 4R tauopathies. The combination of in vivo tau and inflammatory biomarkers could therefore support the development of immunomodulatory strategies for disease-modifying treatments in these conditions. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Exploring the effects of combining health qigong and dance on working memory in middle-aged and elderly women: A preliminary investigation

ObjectiveCognitive decline represents a critical clinical and public health issue that adversely affects the quality of life for older patients and their families. This concern was exacerbated by the reduced engagement in outdoor activities among seniors during the COVID-19 pandemic, presenting substantial challenges to aging societies. The objective of this study was to investigate the impact of health qigong combined with Tibetan dance on working memory in middle-aged and elderly women, and to determine its potential as a preventive strategy against cognitive disorders. MethodsA pilot study was conducted to compare the effects of a Health Qigong exercise intervention with those of everyday life and sports routines. The primary outcome measure was working memory assessed using a 2-Back working memory task research paradigm. Between July and September 2021, a total of 33 women were divided into four groups: two middle-aged groups (N = 18, with 8 women in the experimental group and 10 in the control group) and two elderly groups (N = 15, with 7 in the experimental group and 8 in the control group). Participants in the experimental groups underwent a 10-week intervention, consisting of three 60-min sessions per week. Each session included a warm-up, Health Qigong combined with Tibetan dance, and a cool-down. Throughout the study, all participants continued their daily routines. Response times and error rates were analyzed using a mixed-design repeated-measures analysis of variance. ResultsA simple effects analysis revealed that Health Qigong combined with Tibetan dance significantly enhanced 2-Back response time and error rate in the middle-aged group. In contrast, the 2-Back error rate significantly increased in the elderly control group that did not receive the intervention (p < 0.05). ConclusionHealth Qigong demonstrates beneficial effects on middle-aged and elderly women. Combining Health Qigong with dance may serve as a preventive measure against cognitive disorders. This pioneering study conducted during the COVID-19 pandemic, assesses the new possibility of Health Qigong and dance, with the objective to offer more diverse indoor exercise options for middle-aged and elderly women.

Connectivity based on glucose dynamics reveals exaggerated sensorimotor network coupling on subject-level in Parkinson’s disease

PurposeWhile fMRI provides information on the temporal changes in blood oxygenation, 2- [18F]fluoro-2-deoxy-D-glucose ([18F]FDG)-PET has traditionally offered a static snapshot of brain glucose consumption. As a result, studies investigating metabolic brain networks as potential biomarkers for neurodegeneration have primarily been conducted at the group level. However, recent pioneering studies introduced time-resolved [18F]FDG-PET with constant infusion, which enables metabolic connectivity studies at the individual level.MethodsIn the current study, this technique was employed to explore Parkinson’s disease (PD)-related alterations in individual metabolic connectivity, in comparison to inter-subject measures and hemodynamic connectivity. Fifteen PD patients and 14 healthy controls with comparable cognition underwent sequential resting-state dynamic PET with constant infusion and functional MRI. Intrinsic networks were identified by independent component analysis and interregional connectivity calculated for summed static PET images, PET time series and functional MRI.ResultsOur findings revealed an intrinsic sensorimotor network in PD patients that has not been previously observed to this extent. In PD, a significantly higher number of connections in cortical motor areas was observed compared to elderly control subjects, as indicated by both static PET and functional MRI (pBonferroni−Holm = 0.027), as well as constant infusion PET and functional MRI connectomes (pBonferroni−Holm = 0.012). This intensified coupling was associated with disease severity (ρ = 0.56, p = 0.036).ConclusionMetabolic connectivity, as revealed by both static and dynamic PET, provides unique information on metabolic network activity. Subject-level metabolic connectivity based on constant infusion PET may serve as a potential marker for the metabolic network signature in neurodegeneration.

The potential of five c-miRNAs as serum biomarkers for Late-Onset Alzheimer’s disease diagnosis: miR-10a-5p, miR-29b-2-5p, miR-125a-5p, miR-342-3p, and miR-708-5p

The nervous system is rich in miRNAs, indicating an important role of these molecules in regulating processes associated with cognition, memory, and others. Therefore, qualitative and quantitative imbalances involving such miRNAs may be involved in dementia contexts, including Late-Onset Alzheimer’s Disease (LOAD). To test the viability of circulating miRNAs (c-miRNAs) as biomarkers for LOAD, we proceed accordingly to the following reasoning. The first stage was to discover and identify profile of c-miRNAs by RNA sequencing (RNA-Seq). For this purpose, blood serum samples were used from LOAD patients (n = 5) and cognitively healthy elderly control group (CTRL_CH) (n = 5), all over 70 years old. We identified seven c-miRNAs differentially expressed (p ≤ 0.05) in the serum of LOAD patients compared to CTRL_CH (miR-10a-5p; miR-29b-2-5p; miR-125a-5p; miR-342-3p, miR-708-5p, miR-380-5p and miR-340-3p). Of these, five (p ≤ 0.01) were selected for in silico analysis (miR-10a-5p; miR-29b-2-5p; miR-125a-5p; miR-342-3p, miR-708-5p), for which 44 relevant target genes were found regulated by these c-miRNAs and related to LOAD. Through the analysis of these target genes in databases, it was possible to observe that they have functions related to the development and progress of LOAD, directly or indirectly connecting the different Alzheimer’s pathways. Thus, this work found five promising serum c-miRNAs as options for biomarkers contributing to LOAD diagnosis. Our study shows the complex network between these molecules and LOAD, supporting the relevance of studies using c-miRNAs in dementia contexts.

Investigation of hemispheric asymmetry in Alzheimer’s disease patients during resting state revealed by fNIRS

Alzheimer's disease (AD) is characterized by the gradual deterioration of brain structures and changes in hemispheric asymmetry. Meanwhile, healthy aging is associated with a decrease in functional hemispheric asymmetry. In this study, functional connectivity analysis was used to compare the functional hemispheric asymmetry in eyes-open resting-state fNIRS data of 16 healthy elderly controls (mean age: 60.4 years, MMSE (Mini-Mental State Examination): 27.3 ± 2.52) and 14 Alzheimer's patients (mean age: 73.8 years, MMSE: 22 ± 4.32). Increased interhemispheric functional connectivity was found in the premotor cortex, supplementary motor cortex, primary motor cortex, inferior parietal cortex, primary somatosensory cortex, and supramarginal gyrus in the control group compared to the AD group. The study revealed that the control group had stronger interhemispheric connectivity, leading to a more significant decrease in hemispheric asymmetry than the AD group. The results show that there is a difference in interhemispheric functional connections at rest between the Alzheimer's group and the control group, suggesting that functional hemispheric asymmetry continues in Alzheimer's patients.

Subcortical tau is linked to hypoperfusion in connected cortical regions in 4-repeat tauopathies.

Four-repeat (4R) tauopathies are neurodegenerative diseases characterized by cerebral accumulation of 4R tau pathology. The most prominent 4R tauopathies are progressive supranuclear palsy (PSP) and corticobasal degeneration characterized by subcortical tau accumulation and cortical neuronal dysfunction, as shown by PET-assessed hypoperfusion and glucose hypometabolism. Yet, there is a spatial mismatch between subcortical tau deposition patterns and cortical neuronal dysfunction, and it is unclear how these two pathological brain changes are interrelated. Here, we hypothesized that subcortical tau pathology induces remote neuronal dysfunction in functionally connected cortical regions to test a pathophysiological model that mechanistically links subcortical tau accumulation to cortical neuronal dysfunction in 4R tauopathies. We included 51 Aβ-negative patients with clinically diagnosed PSP variants (n = 26) or corticobasal syndrome (n = 25) who underwent structural MRI and 18F-PI-2620 tau-PET. 18F-PI-2620 tau-PET was recorded using a dynamic one-stop-shop acquisition protocol to determine an early 0.5-2.5 min post tracer-injection perfusion window for assessing cortical neuronal dysfunction, as well as a 20-40 min post tracer-injection window to determine 4R-tau load. Perfusion-PET (i.e. early window) was assessed in 200 cortical regions, and tau-PET was assessed in 32 subcortical regions of established functional brain atlases. We determined tau epicentres as subcortical regions with the highest 18F-PI-2620 tau-PET signal and assessed the connectivity of tau epicentres to cortical regions of interest using a resting-state functional MRI-based functional connectivity template derived from 69 healthy elderly controls from the ADNI cohort. Using linear regression, we assessed whether: (i) higher subcortical tau-PET was associated with reduced cortical perfusion; and (ii) cortical perfusion reductions were observed preferentially in regions closely connected to subcortical tau epicentres. As hypothesized, higher subcortical tau-PET was associated with overall lower cortical perfusion, which remained consistent when controlling for cortical tau-PET. Using group-average and subject-level PET data, we found that the seed-based connectivity pattern of subcortical tau epicentres aligned with cortical perfusion patterns, where cortical regions that were more closely connected to the tau epicentre showed lower perfusion. Together, subcortical tau-accumulation is associated with remote perfusion reductions indicative of neuronal dysfunction in functionally connected cortical regions in 4R-tauopathies. This suggests that subcortical tau pathology may induce cortical dysfunction, which may contribute to clinical disease manifestation and clinical heterogeneity.

Speed-dependent modulations of muscle modules in the gait of people with radiographical and asymptomatic knee osteoarthritis and elderly controls: Case-control pilot study

This study investigates the muscle modules involved in the increase of walking speed in radiographical and asymptomatic knee osteoarthritis (KOA) patients using tensor decomposition. The human body possesses redundancy, which is the property to achieve desired movements with more degrees of freedom than necessary. The muscle module hypothesis is a proposed solution to this redundancy. While previous studies have examined the pathological muscle activity modulations in musculoskeletal diseases such as KOA, they have focused on single muscles rather than muscle modules. Moreover, most studies have only examined the gait of KOA patients at a single speed, leaving the way in which gait speed affects gait parameters in KOA patients unclear. Assessing this influence is crucial for determining appropriate gait speed and understanding why preferred gait speed decreases in KOA patients. In this study, we apply tensor decomposition to muscle activity data to extract muscle modules in KOA patients and elderly controls during walking at different speeds. We found a muscle module comprising hip adductors and back muscles that activate bimodally in a gait cycle, specific to KOA patients when they increase their walking speed. These findings may provide valuable insights for rehabilitation for KOA patients.

A murine model of hypertensive heart disease in older women.

We propose a new mouse (C57Bl6/J) model combining several features of heart failure with preserved ejection fraction encountered in older women, including hypertension from Angiotensin II infusion (AngII), menopause, and advanced age. To mimic menopause, we delayed ovariectomy (Ovx) at 12 months of age. We also studied the effects of AngII infusion for 28 days in younger animals and the impact of losing gonadal steroids earlier in life. We observed that AngII effects on heart morphology were different in younger and adult mice (3- and 12-month-old; 20 and 19% increase in heart weight. P<0.01 for both) than in older animals (24-month-old; 6%; not significant). Ovariectomy at 12 months restored the hypertrophic response to AngII in elderly females (23%, p=0.0001). We performed a bulk RNA sequencing study of the left ventricle (LV) and left atrial gene expression in elderly animals, controls, and Ovx. AngII modulated (|Log2 fold change| ≥ 1) the LV expression of 170 genes in control females and 179 in Ovx ones, 64 being shared. In the left atrium, AngII modulated 235 genes in control females and 453 in Ovx, 140 shared. We observed many upregulated genes associated with the extracellular matrix regulation in both heart chambers. Many of these upregulated genes were shared between the ventricle and the atrium as well as in control and Ovx animals, namely for the most expressed Ankrd1, Nppb, Col3a1, Col1a1, Ctgf Col8a1, and Cilp. Several circadian clock LV genes were modulated differently by AngII between control and Ovx females (Clock, Arntl, Per2, Cry2, and Ciart). In conclusion, sex hormones, even in elderly female mice, modulate the heart's hypertrophic response to AngII. Our study identifies potential new markers of hypertensive disease in aging female mice and possible disturbances of their cardiac circadian clock.

Employ the 5H Model, Evaluate its Efficacy, And Illustrate the Change in Elderly Depression Levels and Symptoms

Introduction: Age-related disorders include mental health. This reduction in intergenerational cohesion and filial responsibilities has caused older people's dissatisfaction, sadness, and grief. Depression and dementia impair elderly people worldwide by taking away their independence and autonomy. Methodology: The authors use the experimental approach to implement the 5H model, evaluate its efficacy, and show the change in depression levels and symptoms in Quang Ngai's elderly. The author chose 26 senior persons from Truong Quang Trong Ward and 23 from Tinh Thien Village to engage in the intervention study. The semi-experimental study compared N=60 samples (Experimental Group=30 and Control Group=30). The elderly control group receives conventional therapy according to the local program, whereas the experimental group receives community intervention. The GDS-15 and ICD-10 examined the intervention's efficacy. Results: This study found that I mild depression had a significant change post-intervention; (ii) the mean score of depression through 2 assessments (GDS-15 scale and ICD-10 clinical assessment) both showed a significant reduction; (iii) females tended to change more than males; (iv) elderly aged 60-70 were easier to change than those over 80 years old; and (v) community-based psychosocial therapy had a significant impact on depression. Conclusion: Considering the aforementioned favourable results, the Quang Ngai city depression prevention intervention program for the elderly is practical and can reduce symptoms, severity, and reverse depression. Hence, the model is applicable across Quang Ngai City.

고령자의 디지털기기 이용 효능감과 디지털정보 역량의 관계에서 사회적 자본의 조절효과

Objectives The purpose of this study is to understand the effect of the elderly's efficacy in using digital devices on digital information capabilities and to empirically analyze the moderating effect of social capital on this effect. Methods To this end, the second data of the 2022 Digital Information Gap Survey surveyed by the Korea Intelligence Information Society Agency were used, and the data of a total of 2,300 elderly people aged 55 or older were used. The analysis was conducted as follows using the IBM SPSS 26.0 statistical program. First, descriptive statistical analysis such as frequency, percentage, mean, standard deviation, skewness, and kurtosis was used to find out the distribution of survey respondents. Second, Pearson's moment correlation coefficient was analyzed to confirm the correlation between major variables. Third, multiple regression analysis was performed to analyze the moderating effect. Results The results derived through the analysis are as follows. First, it was found that the elderly's efficacy in using digital devices had a positive effect on digital information capabilities. Second, it was found that social capital had a positive effect on digital information capabilities. Third, it was found that the social capital of the elderly controls the relationship between the efficacy of using digital devices and digital information capabilities. Conclusions In this study, it was confirmed that social capital plays a control and buffer role in the effect of the elderly's efficacy in using digital devices on digital information capabilities. Based on the research results of this study, interest in social capital that controls the efficacy of using digital devices and digital information capabilities, and measures to strengthen them were discussed.

Gut Microbiota Composition Correlates with Disease Severity in Myelodysplastic Syndrome.

The myelodysplastic syndrome (MDS) is a heterogeneous group of clonal disorders of hematopoietic progenitor cells related to ineffective hematopoiesis and an increased risk of transformation to acute myelogenous leukemia. MDS is divided into categories, namely lineage dysplasia (MDS-SLD), MDS with ring sideroblasts (MDS-RS), MDS with multilineage dysplasia (MDS-MLD), MDS with excess blasts (MDS-EB). The International Prognostic Classification System (IPSS) ranks the patients as very low, low, intermediate, high, and very high based on disease evolution and survival rates. Evidence points to toll-like receptor (TLR) abnormal signaling as an underlying mechanism of this disease, providing a link between MDS and immune dysfunction. Microbial signals, such as lipopolysaccharides from gram-negative bacteria, can activate or suppress TLRs. Therefore, we hypothesized that MDS patients present gut microbiota alterations associated with disease subtypes and prognosis. To test this hypothesis, we sequenced the 16S rRNA gene from fecal samples of 30 MDS patients and 16 healthy elderly controls. We observed a negative correlation between Prevotella spp. and Akkermansia spp. in MDS patients compared with the control group. High-risk patients presented a significant increase in the genus Prevotella spp. compared to the other risk categories. There was a significant reduction in the abundance of the genus Akkermansia spp. in high-risk patients compared with low- and intermediate-risk. There was a significant decrease in the genus Ruminococcus spp. in MDS-EB patients compared with controls. Our findings show a new association between gut dysbiosis and higher-risk MDS, with a predominance of gram-negative bacteria.