Authors:Solale Tabarestani, Mohammad Eslami, Mercedes Cabrerizo, Rosie E. Curiel, Armando Barreto, Naphtali Rishe, David Vaillancourt, Steven T. DeKosky, David A. Loewenstein, Ranjan Duara, Malek Adjouadi Abstract: With the advances in machine learning for the diagnosis of Alzheimer’s disease (AD), most studies have focused on either identifying the subject’s status through classification algorithms or on predicting their cognitive scores through regression methods, neglecting the potential association between these two tasks. Motivated by the need to enhance the prospects for early diagnosis along with the ability to predict future disease states, this study proposes a deep neural network based on modality fusion, kernelization, and tensorization that perform multiclass classification and longitudinal regression simultaneously within a unified multitask framework. This relationship between multiclass classification and longitudinal regression is found to boost the efficacy of the final model in dealing with both tasks. Different multimodality scenarios are investigated, and complementary aspects of the multimodal features are exploited to simultaneously delineate the subject’s label and predict related cognitive scores at future timepoints using baseline data. The main intent in this multitask framework is to consolidate the highest accuracy possible in terms of precision, sensitivity, F1 score, and area under the curve (AUC) in the multiclass classification task while maintaining the highest similarity in the MMSE score as measured through the correlation coefficient and the RMSE for all time points under the prediction task, with both tasks, run simultaneously under the same set of hyperparameters. The overall accuracy for multiclass classification of the proposed KTMnet method is 66.85 ± 3.77. The prediction results show an average RMSE of 2.32 ± 0.52 and a correlation of 0.71 ± 5.98 for predicting MMSE throughout the time points. These results are compared to state-of-the-art techniques reported in the literature. A discovery from the multitasking of this consolidated machine learning framework is that a set of hyperparameters that optimize the prediction results may not necessarily be the same as those that would optimize the multiclass classification. In other words, there is a breakpoint beyond which enhancing further the results of one process could lead to the downgrading in accuracy for the other. PubDate: 2022-05-06T00:00:00Z
Authors:Jinyoung Youn, Mansu Kim, Suyeon Park, Ji Sun Kim, Hyunjin Park, Jin Whan Cho Abstract: BackgroundDespite the clinical impact of levodopa-induced dyskinesia (LID) in Parkinson's disease (PD), the mechanism, especially the role of basal ganglia (BG), is not fully elucidated yet. We investigated the BG structural changes related to LID in PD using a surface-based shape analysis technique.MethodsWe recruited patients with PD who developed LID within 3 years (LID group, 28 patients) and who did not develop it after 7 years (non-LID group, 35 patients) from levodopa treatment for the extreme case-control study. BG structure volumes were measured using volumetry analysis and the surface-based morphometry feature (i.e., Jacobian) from the subcortical surface vertices. We compared the volume and Jacobian of meshes in the regions between the two groups. We also performed a correlation analysis between local atrophy and the severity of LID. Additionally, we evaluated structural connectivity profiles from globus pallidus interna and externa (GPi and GPe) to other brain structures based on the group comparison.ResultsThe demographic and clinical data showed no significant difference except for disease duration, treatment duration, parkinsonism severity, and levodopa equivalent dose. The LID group had more local atrophies of vertices in the right GPi than the non-LID group, despite no difference in volumes. Furthermore, the LID group demonstrated significantly reduced structural connectivity between left GPi and thalamus.ConclusionThis is the first demonstration of distinct shape alterations of basal ganglia structures, especially GPi, related to LID in PD. Considering both direct and indirect BG pathways share the connection between GPi and thalamus, the BG pathway plays a crucial role in the development of LID. PubDate: 2022-05-06T00:00:00Z
Authors:Ya Qing Zhang, Wen juan Zhang, Jin hao Liu, Wei zhong Ji Abstract: ObjectiveThis study aimed to investigate the effects of long-term hypoxic environment exposure on cognitive ability and neuroimaging characteristics in a highland population in China.MethodsHealth system workers in Maduo County (4,300 m above sea level) and Minhe County (1,700 m above sea level) were selected as research participants and divided into a high-altitude (HA) group and low-altitude (LA) group, respectively. Cognitive ability was assessed using the Montreal Cognitive Assessment (MoCA), Verbal Fluency Test (VFT), Symbol Digit Modalities Test (SDMT), Trail Making Test A and B (TMT), Digit Span Test (DST), and Rey Auditory Verbal Learning Test (RAVLT). All participants underwent a magnetic resonance imaging (MRI) scan, resting state functional MRI scan, and diffusion tensor imaging to clarify changes in regional gray matter (GM) volume, anisotropy index (FA), local consistency (ReHo), and low-frequency oscillation amplitude (ALFF).ResultsThe HA group had significantly lower MoCA, DST, VFT, RAVLT, and TMT scores compared to the control group. No significant differences were found in SDMT score. Furthermore, compared to the LA group, the HA group had significantly lower GM density of the left olfactory cortex, right medial orbital superior frontal gyrus, bilateral insula, left globus pallidus, and temporal lobe (left superior temporal gyrus temporal pole, bilateral middle temporal gyrus temporal pole, and right middle temporal gyrus). In terms of FA, compared with the LA group, the HA group had lower values for the corpus callosum, corpus callosum knee, bilateral radiative corona, and left internal capsule. The HA group had lower ALFF values of the left cerebellum, left putamen, left orbital inferior frontal gyrus, and left precuneus, but higher ALFF values of the left fusiform gyrus, bilateral inferior temporal gyrus, left orbital superior frontal gyrus and medial superior frontal gyrus, compared to the LA group. There was no significant group difference in ReHo values.ConclusionOur findings suggest that a chronic hypoxic environment can induce extensive cognitive impairment. Decreased GM density in multiple brain regions, damaged nerve fibers, and unbalanced neuronal activity intensity in different brain regions may be the structural and functional basis of cognitive impairment due to hypoxia. PubDate: 2022-05-06T00:00:00Z
Authors:Jingchun Liu, Caihong Wang, Jingliang Cheng, Peifang Miao, Zhen Li Abstract: Background and PurposeIncreased interhemispheric resting-state functional connectivity (rsFC) between the bilateral primary motor cortex (M1) compensates for corticospinal tract (CST) impairment, which facilitates motor recovery in chronic subcortical stroke. However, there is a lack of data on the evolution patterns and correlations between M1–M1 rsFC and diffusion indices of CSTs with different origins after subcortical stroke and their relations with long-term motor outcomes.MethodsA total of 44 patients with subcortical stroke underwent longitudinal structural and functional magnetic resonance imaging (MRI) examinations and clinical assessments at four time points. Diffusion tensor imaging was used to extract fractional anisotropy (FA) values of the affected CSTs with different origins. Resting-state functional MRI was used to calculate the M1–M1 rsFC. Longitudinal patterns of functional and anatomic changes in connections were explored using a linear mixed-effects model. Dynamic relationships between M1–M1 rsFC and FA values of the affected specific CSTs and the impact of these variations on the long-term motor outcomes were analyzed in patients with subcortical stroke.ResultsStroke patients showed a significantly decreased FA in the affected specific CSTs and a gradually increasing M1–M1 rsFC from the acute to the chronic stage. The FA of the affected M1 fiber was negatively correlated with the M1–M1 rsFC from the subacute to the chronic stage, FA of the affected supplementary motor area fiber was negatively correlated with the M1–M1 rsFC in the subacute stage, and FA of the affected M1 fiber in the acute stage was correlated with the long-term motor recovery after subcortical stroke.ConclusionOur findings show that the FA of the affected M1 fiber in the acute stage had the most significant correlation with long-term motor recovery and may be used as an imaging biomarker for predicting motor outcomes after stroke. The compensatory role of the M1–M1 rsFC enhancement may start from the subacute stage in stroke patients with CST impairment. PubDate: 2022-05-06T00:00:00Z
Authors:Min Liu, Jiang Li, Juan Li, Hui Yang, Qianqian Yao, Xiuzhu Zheng, Zheng Zhang, Jian Qin Abstract: BackgroundThe pathophysiological mechanism of cognitive impairment by osteoporosis in type 2 diabetes mellitus (T2DM) remains unclear. This study aims to further investigate the regional spontaneous brain activity changes of patients with diabetic osteoporosis (DOP), and the correlation between abnormal brain regions and bone metabolites.MethodsA total of 29 subjects with T2DM were recruited, including fourteen patients with DOP and thirteen patients without osteoporosis (Control group). Based on the resting-state functional magnetic resonance imaging (rs-fMRI) datasets acquired from all the subjects, a two-sample t-test was performed on individual normalized regional homogeneity (ReHo) maps. Spearman correlation analysis was performed between the abnormal ReHo regions with the clinical parameters and Montreal Cognitive Assessment (MOCA) scores.ResultsIn the DOP group, we demonstrated the significantly increased ReHo values in the left middle temporal gyrus (MTG), right superior occipital gyrus (SOG), aright superior parietal lobule (SPL), right angular gyrus (AG), and left precuneus (PE). Additionally, we also found a significant positive correlation between increased ReHo values in the left MTG and the average bone mineral density (BMD AVG), and average T scores (T AVG). The ReHo values of the right SOG and right SPL showed a negative correlation with MOCA scores, as well as a negative correlation between increased ReHo values in the right SPL and osteocalcin (OC) level.ConclusionPatients with DOP showed increased spontaneous activity in multiple brain regions. The results indicated that osteoporosis exacerbated cognitive impairment and brain damage. Also, the OC might be considered as a bone marker to track the progression of cognitive impairment. PubDate: 2022-05-06T00:00:00Z
Authors:Georgina Torrandell-Haro, Gregory L. Branigan, Roberta Diaz Brinton, Kathleen E. Rodgers Abstract: ObjectiveWe sought to determine the impact of Type 2 Diabetes Mellitus (T2D) anti-hyperglycemic medications (A-HgM) on risk of Alzheimer’s disease (AD) and related dementias (ADRD) outcomes including vascular dementia, and non-AD dementia such as frontotemporal, Lewy body, and mixed etiology dementias.Research Design and MethodsThis retrospective cohort study used the US-based Mariner claims dataset. 1,815,032 T2D participants 45 years and older with records 6 months prior and at least 3 years after the diagnosis of T2D were included. Claims were surveyed for a diagnosis of AD and ADRD 12 months post T2D diagnosis. A propensity score approach was used to minimize selection bias. Analyses were conducted between January 1st and February 28th, 2021.ResultsIn this cohort study A-HgM exposure was associated with decreased diagnosis of AD (RR, 0.61; 95% CI, 0.59–0.62; p < 0.001), vascular dementia (RR, 0.72; 95% CI, 0.69–0.74; p < 0.001) and non-AD dementia (RR, 0.67; 95% CI, 0.66–0.68; p < 0.001). Metformin was associated with the greatest risk reduction and insulin with the least reduction in risk compared to patients not receiving A-HgM for ADRD risk. Of interest, patients with a diagnosis of AD, while either on metformin or insulin, were older in age and predominately female, than individuals on these drugs that did not develop AD. Mean (SD) follow-up was 6.2 (1.8) years.ConclusionAfter controlling for age, sex, and comorbidities, A-HgM in patients with T2D was associated with a reduced risk of AD and ADRD. These findings provide evidence in support of T2D as a risk factor for AD and ADRD and the beneficial impact of early and effective control of hyperglycemia to mitigate risk. PubDate: 2022-05-06T00:00:00Z
Authors:Le-Tian Huang, Cheng-Pu Zhang, Yi-Bing Wang, Jia-He Wang Abstract: BackgroundInflammation and immune dysfunction play significant roles in the pathogenesis of Alzheimer's disease (AD)-related dementia. Changes in peripheral blood cell profiles are a common manifestation of inflammation and immune dysfunction and have been reported in patients with AD or mild cognitive impairment (MCI). We systematically evaluated the association of peripheral blood cell counts and indices with AD or MCI through a meta-analysis.MethodsWe electronically searched sources to identify all case–control trials comparing peripheral blood cell counts and/or lymphocyte subsets between patients with AD or MCI and healthy controls (HCs). Meta-analyses were used to estimate the between-group standardized mean difference (SMD) and 95% confidence interval (CI).ResultsA total of 36 studies involving 2,339 AD patients, 608 MCI patients, and 8,352 HCs were included. AD patients had significantly decreased lymphocyte counts (SMD −0.345, 95% CI [−0.545, −0.146], P = 0.001) and significantly increased leukocyte counts (0.140 [0.039, 0.241], P = 0.006), neutrophil counts (0.309 [0.185, 0.434], P = 0.01), and neutrophil–lymphocyte ratio (NLR) (0.644 [0.310, 0.978], P < 0.001) compared to HCs. Similarly, significantly increased leukocyte counts (0.392 [0.206, 0.579], P < 0.001), NLR (0.579 [0.310, 0.847], P < 0.001), and neutrophil counts (0.248 [0.121, 0.376], P < 0.001) were found in MCI patients compared with HCs. A significantly decreased percentage of B lymphocytes (−1.511 [−2.775, −0.248], P = 0.019) and CD8+ T cells (−0.760 [−1.460, −0.061], P = 0.033) and a significantly increased CD4/CD8 ratio (0.615 [0.074, 1.156], P = 0.026) were observed in AD patients compared to HCs. Furthermore, significant changes in hemoglobin level and platelet distribution width were found in patients with AD or MCI compared with HCs. However, no significant difference was found between AD or MCI patients and HCs in terms of platelet counts, mean corpuscular volume, red cell distribution width, mean platelet volume, and CD4+ T, CD3+ T, or natural killer cell counts.ConclusionChanges in peripheral blood cell profiles, particularly involving leukocyte, lymphocyte, neutrophil, and CD8+ T cell counts, as well as the NLR and the CD4/CD8 ratio, are closely associated with AD. The diagnostic relevance of these profiles should be investigated in future. PubDate: 2022-05-06T00:00:00Z
Authors:Shun Yoshida, Takafumi Hasegawa Abstract: Retromer is a highly integrated multimeric protein complex that mediates retrograde cargo sorting from endosomal compartments. In concert with its accessory proteins, the retromer drives packaged cargoes to tubular and vesicular structures, thereby transferring them to the trans-Golgi network or to the plasma membrane. In addition to the endosomal trafficking, the retromer machinery participates in mitochondrial dynamics and autophagic processes and thus contributes to cellular homeostasis. The retromer components and their associated molecules are expressed in different types of cells including neurons and glial cells, and accumulating evidence from genetic and biochemical studies suggests that retromer dysfunction is profoundly involved in the pathogenesis of neurodegenerative diseases including Alzheimer’s Disease and Parkinson’s disease. Moreover, targeting retromer components could alleviate the neurodegenerative process, suggesting that the retromer complex may serve as a promising therapeutic target. In this review, we will provide the latest insight into the regulatory mechanisms of retromer and discuss how its dysfunction influences the pathological process leading to neurodegeneration. PubDate: 2022-05-06T00:00:00Z
Authors:Francesco Asci, Simone Scardapane, Alessandro Zampogna, Valentina D’Onofrio, Lucia Testa, Martina Patera, Marco Falletti, Luca Marsili, Antonio Suppa Abstract: BackgroundHandwriting is an acquired complex cognitive and motor skill resulting from the activation of a widespread brain network. Handwriting therefore may provide biologically relevant information on health status. Also, handwriting can be collected easily in an ecological scenario, through safe, cheap, and largely available tools. Hence, objective handwriting analysis through artificial intelligence would represent an innovative strategy for telemedicine purposes in healthy subjects and people affected by neurological disorders.Materials and MethodsOne-hundred and fifty-six healthy subjects (61 males; 49.6 ± 20.4 years) were enrolled and divided according to age into three subgroups: Younger adults (YA), middle-aged adults (MA), and older adults (OA). Participants performed an ecological handwriting task that was digitalized through smartphones. Data underwent the DBNet algorithm for measuring and comparing the average stroke sizes in the three groups. A convolutional neural network (CNN) was also used to classify handwriting samples. Lastly, receiver operating characteristic (ROC) curves and sensitivity, specificity, positive, negative predictive values (PPV, NPV), accuracy and area under the curve (AUC) were calculated to report the performance of the algorithm.ResultsStroke sizes were significantly smaller in OA than in MA and YA. The CNN classifier objectively discriminated YA vs. OA (sensitivity = 82%, specificity = 80%, PPV = 78%, NPV = 79%, accuracy = 77%, and AUC = 0.84), MA vs. OA (sensitivity = 84%, specificity = 56%, PPV = 78%, NPV = 73%, accuracy = 74%, and AUC = 0.7), and YA vs. MA (sensitivity = 75%, specificity = 82%, PPV = 79%, NPV = 83%, accuracy = 79%, and AUC = 0.83).DiscussionHandwriting progressively declines with human aging. The effect of physiological aging on handwriting abilities can be detected remotely and objectively by using machine learning algorithms. PubDate: 2022-05-06T00:00:00Z
Authors:Dong Cui, Jingna Jin, Weifang Cao, He Wang, Xin Wang, Ying Li, Tianjun Liu, Tao Yin, Zhipeng Liu Abstract: Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (DLPFC) is a non-invasive effective treatment for cognitive disorder, but its underlying mechanism of action remains unknown. The aim of this study was to explore the effect of a 2-week high-frequency (HF) active or sham 10 Hz rTMS on verbal memory in 40 healthy older adults. Resting-state functional magnetic resonance imaging (rs-fMRI) was used to measure functional connectivity (FC) within the default mode network (DMN). Verbal memory performance was evaluated using an auditory verbal learning test (AVLT). Additionally, we evaluated the relationship between memory improvement and FC changes within the DMN. The results revealed that HF-rTMS can enhance immediate recall and delayed recall of verbal memory and increased the FC of the bilateral precuneus (PCUN) within the DMN. The positive correlations between the immediate recall memory and the FC of the left PCUN after a 2-week intervention of HF-rTMS were detected. In conclusion, HF-rTMS may have the potential to improve verbal memory performance in older adults, which relation to FC changes in the DMN. The current findings are useful for increasing the understanding of the mechanisms of HF-rTMS, as well as guiding HF-rTMS treatment of cognitive disorders. PubDate: 2022-05-04T00:00:00Z
Authors:Rui Zhou, Hua-Min Liu, Lian-Wu Zou, Hong-Xia Wei, Yi-Ning Huang, Qi Zhong, Shan-Yuan Gu, Ming-Feng Chen, Shao-Li Wang, Hai-Xia Sun, Xian-Bo Wu Abstract: BackgroundThe evidence of the association between parity and risk of mild cognitive impairment (MCI) or dementia is mixed, and the relationship between parity and longitudinal cognitive changes is less clear. We investigated these issues in a large population of older women who were carefully monitored for development of MCI and probable dementia.MethodsUsing the Women’s Health Initiative Memory Study, 7,100 postmenopausal women (mean age 70.1 ± 3.8 years) with information on baseline parity (defined as the number of term pregnancies), measures of global cognition (Modified Mini-Mental State Examination score) from 1996–2007, and cognitive impairment (centrally adjudicated diagnoses of MCI and dementia) from 1996–2016 were included. Multivariable linear mixed-effects models were used to analyze the rate of changes in global cognition. Cox regression models were used to evaluate the risk of MCI/dementia across parity groups.ResultsOver an average of 10.5 years, 465 new cases of MCI/dementia were identified. Compared with nulliparous women, those with a parity of 1–3 and ≥4 had a lower MCI/dementia risk. The HRs were 0.75 (0.56–0.99) and 0.71 (0.53–0.96), respectively (P < 0.01). Similarly, a parity of 1–3 and ≥4 was related to slower cognitive decline (β = 0.164, 0.292, respectively, P < 0.05).ConclusionHigher parity attenuated the future risk for MCI/dementia and slowed the rates of cognitive decline in elderly women. Future studies are needed to determine how parity affects late-life cognitive function in women. PubDate: 2022-05-04T00:00:00Z
Authors:Kayla B. Corney, Emma C. West, Shae E. Quirk, Julie A. Pasco, Amanda L. Stuart, Behnaz Azimi Manavi, Bianca E. Kavanagh, Lana J. Williams Abstract: BackgroundAlzheimer's disease is a global health concern, and with no present cure, prevention is critical. Exposure to adverse childhood experiences may increase the risk of developing Alzheimer's disease. This systematic review was conducted to synthesize the evidence on the associations between adverse childhood experiences ( PubDate: 2022-05-04T00:00:00Z
Authors:Lise Barbé, Steve Finkbeiner Abstract: Repeat diseases, such as fragile X syndrome, myotonic dystrophy, Friedreich ataxia, Huntington disease, spinocerebellar ataxias, and some forms of amyotrophic lateral sclerosis, are caused by repetitive DNA sequences that are expanded in affected individuals. The age at which an individual begins to experience symptoms, and the severity of disease, are partially determined by the size of the repeat. However, the epigenetic state of the area in and around the repeat also plays an important role in determining the age of disease onset and the rate of disease progression. Many repeat diseases share a common epigenetic pattern of increased methylation at CpG islands near the repeat region. CpG islands are CG-rich sequences that are tightly regulated by methylation and are often found at gene enhancer or insulator elements in the genome. Methylation of CpG islands can inhibit binding of the transcriptional regulator CTCF, resulting in a closed chromatin state and gene down regulation. The downregulation of these genes leads to some disease-specific symptoms. Additionally, a genetic and epigenetic interplay is suggested by an effect of methylation on repeat instability, a hallmark of large repeat expansions that leads to increasing disease severity in successive generations. In this review, we will discuss the common epigenetic patterns shared across repeat diseases, how the genetics and epigenetics interact, and how this could be involved in disease manifestation. We also discuss the currently available stem cell and mouse models, which frequently do not recapitulate epigenetic patterns observed in human disease, and propose alternative strategies to study the role of epigenetics in repeat diseases. PubDate: 2022-05-03T00:00:00Z
Authors:Hui Kong, Xue-Qiang Wang, Xin-An Zhang Abstract: Osteoarthritis (OA) has a very high incidence worldwide and has become a very common joint disease in the elderly. Currently, the treatment methods for OA include surgery, drug therapy, and exercise therapy. In recent years, the treatment of certain diseases by exercise has received increasing research and attention. Proper exercise can improve the physiological function of various organs of the body. At present, the treatment of OA is usually symptomatic. Limited methods are available for the treatment of OA according to its pathogenesis, and effective intervention has not been developed to slow down the progress of OA from the molecular level. Only by clarifying the mechanism of exercise treatment of OA and the influence of different exercise intensities on OA patients can we choose the appropriate exercise prescription to prevent and treat OA. This review mainly expounds the mechanism that exercise alleviates the pathological changes of OA by affecting the degradation of the ECM, apoptosis, inflammatory response, autophagy, and changes of ncRNA, and summarizes the effects of different exercise types on OA patients. Finally, it is found that different exercise types, exercise intensity, exercise time and exercise frequency have different effects on OA patients. At the same time, suitable exercise prescriptions are recommended for OA patients. PubDate: 2022-05-03T00:00:00Z
Authors:Ningxin Dong, Changyong Fu, Renren Li, Wei Zhang, Meng Liu, Weixin Xiao, Hugh M. Taylor, Peter J. Nicholas, Onur Tanglay, Isabella M. Young, Karol Z. Osipowicz, Michael E. Sughrue, Stephane P. Doyen, Yunxia Li Abstract: ObjectiveAlzheimer’s Disease (AD) is a progressive condition characterized by cognitive decline. AD is often preceded by mild cognitive impairment (MCI), though the diagnosis of both conditions remains a challenge. Early diagnosis of AD, and prediction of MCI progression require data-driven approaches to improve patient selection for treatment. We used a machine learning tool to predict performance in neuropsychological tests in AD and MCI based on functional connectivity using a whole-brain connectome, in an attempt to identify network substrates of cognitive deficits in AD.MethodsNeuropsychological tests, baseline anatomical T1 magnetic resonance imaging (MRI), resting-state functional MRI, and diffusion weighted imaging scans were obtained from 149 MCI, and 85 AD patients; and 140 cognitively unimpaired geriatric participants. A novel machine learning tool, Hollow Tree Super (HoTS) was utilized to extract feature importance from each machine learning model to identify brain regions that were associated with deficit and absence of deficit for 11 neuropsychological tests.Results11 models attained an area under the receiver operating curve (AUC-ROC) greater than 0.65, while five models had an AUC-ROC ≥ 0.7. 20 parcels of the Human Connectome Project Multimodal Parcelation Atlas matched to poor performance in at least two neuropsychological tests, while 14 parcels were associated with good performance in at least two tests. At a network level, most parcels predictive of both presence and absence of deficit were affiliated with the Central Executive Network, Default Mode Network, and the Sensorimotor Networks. Segregating predictors by the cognitive domain associated with each test revealed areas of coherent overlap between cognitive domains, with the parcels providing possible markers to screen for cognitive impairment.ConclusionApproaches such as ours which incorporate whole-brain functional connectivity and harness feature importance in machine learning models may aid in identifying diagnostic and therapeutic targets in AD. PubDate: 2022-05-03T00:00:00Z
Authors:Uros Marusic, Manca Peskar, Kevin De Pauw, Nina Omejc, Gorazd Drevensek, Bojan Rojc, Rado Pisot, Voyko Kavcic Abstract: With advanced age, there is a loss of reaction speed that may contribute to an increased risk of tripping and falling. Avoiding falls and injuries requires awareness of the threat, followed by selection and execution of the appropriate motor response. Using event-related potentials (ERPs) and a simple visual reaction task (RT), the goal of our study was to distinguish sensory and motor processing in the upper- and lower-limbs while attempting to uncover the main cause of age-related behavioral slowing. Strength (amplitudes) as well as timing and speed (latencies) of various stages of stimulus- and motor-related processing were analyzed in 48 healthy individuals (young adults, n = 24, mean age = 34 years; older adults, n = 24, mean age = 67 years). The behavioral results showed a significant age-related slowing, where the younger compared to older adults exhibited shorter RTs for the upper- (222 vs. 255 ms; p = 0.006, respectively) and the lower limb (257 vs. 274 ms; p = 0.048, respectively) as well as lower variability in both modalities (p = 0.001). Using ERP indices, age-related slowing of visual stimulus processing was characterized by overall larger amplitudes with delayed latencies of endogenous potentials in older compared with younger adults. While no differences were found in the P1 component, the later components of recorded potentials for visual stimuli processing were most affected by age. This was characterized by increased N1 and P2 amplitudes and delayed P2 latencies in both upper and lower extremities. The analysis of motor-related cortical potentials (MRCPs) revealed stronger MRCP amplitude for upper- and a non-significant trend for lower limbs in older adults. The MRCP amplitude was smaller and peaked closer to the actual motor response for the upper- than for the lower limb in both age groups. There were longer MRCP onset latencies for lower- compared to upper-limb in younger adults, and a non-significant trend was seen in older adults. Multiple regression analyses showed that the onset of the MRCP peak consistently predicted reaction time across both age groups and limbs tested. However, MRCP rise time and P2 latency were also significant predictors of simple reaction time, but only in older adults and only for the upper limbs. Our study suggests that motor cortical processes contribute most strongly to the slowing of simple reaction time in advanced age. However, late-stage cortical processing related to sensory stimuli also appears to play a role in upper limb responses in the elderly. This process most likely reflects less efficient recruitment of neuronal resources required for the upper and lower extremity response task in older adults. PubDate: 2022-05-03T00:00:00Z
Authors:László Ákos Kovács, Nóra Füredi, Balázs Ujvári, Abolfazl Golgol, Balázs Gaszner Abstract: FOS proteins are early-responding gene products that contribute to the formation of activator protein-1. Several acute and chronic stimuli lead to Fos gene expression, accompanied by an increase of nuclear FOS, which appears to decline with aging. FOSB is another marker to detect acute cellular response, while ΔFOSB mirrors long-lasting changes in neuronal activity upon chronic stress. The notion that the occurrence of stress-related mood disorders shows some age dependence suggests that the brain’s stress sensitivity is also a function of age. To study age-dependent stress vulnerability at the immediate-early gene level, we aimed to describe how the course of aging affects the neural responses of FOSB/ΔFOSB in the acute restraint stress (ARS), and chronic variable mild stress (CVMS) in male rats. Fourteen brain areas [central, medial, basolateral (BLA) amygdala; dorsolateral- (BNSTdl), oval- (BNSTov), dorsomedial-, ventral- (BNSTv), and fusiform- (BNSTfu) divisions of the bed nucleus of the stria terminalis; medial and lateral habenula, hypothalamic paraventricular nucleus (PVN), centrally-projecting Edinger-Westphal nucleus, dorsal raphe nucleus, barrel field of somatosensory cortex (S1)] were examined in the course of aging. Eight age groups [1-month-old (M), 1.5 M, 2 M, 3 M, 6 M, 12 M, 18 M, and 24 M] of rats were exposed to a single ARS vs. controls. In addition, rats in six age groups (2, 3, 6, 12, 18, and 24 M) were subjected to CVMS. The FOSB/ΔFOSB immunoreactivity (IR) was a function of age in both controls, ARS- and CVMS-exposed rats. ARS increased the FOSB/ΔFOSB in all nuclei (except in BLA), but only BNSTfu, BNSTv, and PVN reacted throughout the examined lifespan. The CVMS did not increase the FOSB/ΔFOSB in BLA, BNSTov, BNSTdl, and S1. PVN showed a constantly maintained FOSB/ΔFOSB IR during the examined life period. The maximum stress-evoked FOSB/ΔFOSB signal was detected at 2–3 M periods in the ARS- and at 6 M, 18 M in CVMS- model. Corresponding to our previous observations on FOS, the FOSB/ΔFOSB response to stress decreased with age in most of the examined nuclei. Only the PVN exerted a sustained age-independent FOSB/ΔFOSB, which may reflect the long-lasting adaptation response and plasticity of neurons that maintain the hypothalamus-pituitary-adrenal axis response throughout the lifespan. PubDate: 2022-05-03T00:00:00Z
Authors:Dehuan Liang, Cheng Chen, Song Huang, Sujuan Liu, Li Fu, Yanmei Niu Abstract: ObjectiveRegular exercise is a powerful tool that enhances skeletal muscle mass and strength. Lysine acetylation is an important post-translational modification (PTM) involved in a broad array of cellular functions. Skeletal muscle protein contains a considerable number of lysine-acetylated (Kac) sites, so we aimed to investigate the effects of exercise-induced lysine acetylation on skeletal muscle proteins.MethodsWe randomly divided 20 male C57BL/6 mice into exercise and control groups. After 6 weeks of treadmill exercise, a lysine acetylation proteomics analysis of the gastrocnemius muscles of mice was performed.ResultsA total of 2,254 lysine acetylation sites in 693 protein groups were identified, among which 1,916 sites in 528 proteins were quantified. The enrichment analysis suggested that protein acetylation could influence both structural and functional muscle protein properties. Moreover, molecular docking revealed that mimicking protein deacetylation primarily influenced the interaction between substrates and enzymes.ConclusionExercise-induced lysine acetylation appears to be a crucial contributor to the alteration of skeletal muscle protein binding free energy, suggesting that its modulation is a potential approach for improving exercise performance. PubDate: 2022-05-03T00:00:00Z
Open Access journal
