We observed an initial plateau in nuclei response when I

reached 16.4 mW/cm

for RPF 500 Hz and 20.8 mW/cm

for RPF 1 kHz. The number of responding nuclei started decreasing while I

continued increasing. Under 1.5 kHz TUS, no auto-rhythmic patterns have been observed, but slow frequency power was increased during TUS. TUS inhibited most of the frequency band and generated obvious slow waves (theta and delta band) when stimulated at RPF = 1.5 kHz,

= 8.8 mW/cm

.

These results demonstrate that very low intensity Transcranial Ultrasound Stimulation (VLTUS) exerts significant neuromodulator effects under specific parameters in rat models and may be a valid tool to study neuronal physiology.

These results demonstrate that very low intensity Transcranial Ultrasound Stimulation (VLTUS) exerts significant neuromodulator effects under specific parameters in rat models and may be a valid tool to study neuronal physiology.Exercise has multiple beneficial effects on health including decreasing the risk of neurodegenerative diseases. Such effects are thought to be mediated (at least in part) by myokines, a collection of cytokines and other small proteins released from skeletal muscles. As an endocrine organ, skeletal muscle synthesizes and secretes a wide range of myokines which contribute to different functions in different organs, including the brain. One such myokine is the recently discovered protein Irisin, which is secreted into circulation from skeletal muscle during exercise from its membrane bound precursor Fibronectin type III domain-containing protein 5 (FNDC5). Irisin contributes to metabolic processes such as glucose homeostasis and browning of white adipose tissue. Irisin also crosses the blood brain barrier and initiates a neuroprotective genetic program in the hippocampus that culminates with increased expression of brain derived neurotrophic factor (BDNF). Furthermore, exercise and FNDC5/Irisin have been shown to have several neuroprotective effects against injuries in ischemia and neurodegenerative disease models, including Alzheimer’s disease. In addition, Irisin has anxiolytic and antidepressant effects. In this review we present and summarize recent findings on the multiple effects of Irisin on neural function, including signaling pathways and mechanisms involved. We also discuss how exercise can positively influence brain function and mental health via the „skeletal muscle-brain axis.” While there are still many unanswered questions, we put forward the idea that Irisin is a potentially essential mediator of the skeletal muscle-brain crosstalk.Background The impact of exercise on cognition in older adults with hypertension and subjective cognitive decline (SCD) is unclear. Objectives We determined the influence of high-intensity interval training (HIIT) combined with mind-motor training on cognition and systolic blood pressure (BP) in older adults with hypertension and SCD. Methods We randomized 128 community-dwelling older adults [age mean (SD) 71.1 (6.7), 47.7% females] with history of hypertension and SCD to either HIIT or a moderate-intensity continuous training (MCT) group. Both groups received 15 min of mind-motor training followed by 45 min of either HIIT or MCT. Participants exercised in total 60 min/day, 3 days/week for 6 months. We assessed changes in global cognitive functioning (GCF), Trail-Making Test (TMT), systolic and diastolic BP, and cardiorespiratory fitness. Results Participants in both groups improved diastolic BP [F (1, 87.32) = 4.392, p = 0.039], with greatest effect within the HIIT group [estimated mean change (95% CI) -2.64 mmHg, (-4.79 to -0.48), p = 0.017], but no between-group differences were noted (p = 0.17). Both groups also improved cardiorespiratory fitness [F (1, 69) = 34.795, p less then 0.001], and TMT A [F (1, 81.51) = 26.871, p less then 0.001] and B [F (1, 79.49) = 23.107, p less then 0.001]. There were, however, no within- or between-group differences in GCF and systolic BP at follow-up. Conclusion Despite improvements in cardiorespiratory fitness, exercise of high- or moderate-intensity, combined with mind-motor training, did not improve GCF or systolic BP in individuals with hypertension and SCD. Clinical Trial Registration ClinicalTrials.gov (NCT03545958).The ubiquitin proteasome system (UPS) and FOXOs transcription factors play a pivotal role in cellular clearance and minimizing the accumulation of Aβ in neurodegeneration (ND). In African Americans (AAs) with mild cognitive impairment (MCI), the role of components of UPS and FOXOs; and whether they are amenable to exercise effects is unknown. We hypothesized that exercise can enhance cellular clearance systems during aging and ND by increasing expressions of FBXO32 and FOXO1. To test this hypothesis, we used TaqMan gene expression analysis in peripheral blood (PB) to investigate the component of UPS and FOXOs; and provide mechanistic insight at baseline, during exercise, and in both genders. At baseline, levels of FBXO32 were higher in women than in men. In our attempt to discern gender-specific exercise-related changes, we observed that levels of FBXO32 increased in men but not in women. Similarly, levels of FOXO1 increased in men only. These data suggest that a graded dose of FBXO32 and FOXO1 may be beneficial when PB cells carrying FBXO32 and FOXO1 summon into the brain in response to Alzheimer’s disease (AD) perturbation (docking station PB cells). Our observation is consistent with emerging studies that exercise allows the trafficking of blood factors. Given the significance of FBXO32 and FOXO1 to ND and associated muscle integrity, our findings may explain, at least in part, the benefits of exercise on memory, associated gait, and balance perturbation acknowledged to herald the emergence of MCI.Frailty is a dynamic clinical condition characterized by the reduction of interconnections among different psychobiological domains, which leads to a homeostatic vulnerability. The association between physical frailty and cognitive dysfunctions is a possible predictor of poor prognosis in patients with neurodegenerative disorders. However, this construct has not been fully analyzed by a multidimensional neuropsychogeriatric assessment matched with multimodal neuroimaging methods in patients with behavioral variant frontotemporal dementia (bvFTD). We have investigated cognitive dysfunctions and frailty status, assessed by both a neuropsychological evaluation and the Multidimensional Prognostic Index (MPI), in a sample of 18 bvFTD patients and compared to matched healthy controls. Gray matter (GM) volume (as assessed by voxel-based morphometry) and metabolism (on 18fluorodeoxyglucose positron emission tomography) were first separately compared between groups, then voxelwise compared and correlated to each otherorrelated only with the co-occurrence of a decrease of GM density and hypometabolism in the right anterior insular cortex, but not with the separate pathological phenomena. Our results show a correlation between a specific pattern of co-occurring GM atrophy and hypometabolism with early frailty in bvFTD patients. These aspects, combined with executive dysfunction and mood changes, may lead to an increased risk of poor prognosis, highlighting a potentially critical and precocious role of the insula in the pathogenesis of frailty.Postoperative cognitive dysfunction increases mortality and morbidity in perioperative patients and has become a major concern for patients and caregivers. Previous studies demonstrated that synaptic plasticity is closely related to cognitive function, anesthesia and surgery inhibit synaptic function. In central nervous system, autophagy is vital to synaptic plasticity, homeostasis of synapticproteins, synapse elimination, spine pruning, proper axon guidance, and when dysregulated, is associated with behavioral and memory functions disorders. The mammalian target of rapamycin (mTOR) negatively regulates the process of autophagy. This study aimed to explore whether rapamycin can ameliorate anesthesia/surgery-induced cognitive deficits by inhibiting mTOR, activating autophagy and rising synaptic plasticity-related proteins in the hippocampus. Aged C57BL/6J mice were used to establish POCD models with exploratory laparotomy under isoflurane anesthesia. The Morris Water Maze (MWM) was used to measure reference men the hippocampus. An mTOR inhibitor, rapamycin, ameliorated anesthesia/surgery-related cognitive impairments by inhibiting the mTOR activity, inducing activation of autophagy, enhancing SYN and PSD-95 expression.

To develop and validate a prediction nomogram based on motoric cognitive risk syndrome for cognitive impairment in healthy older adults.

Using two longitudinal cohorts of participants (aged ≥ 60 years) with 4-year follow-up, we developed (

= 1,177) and validated (

= 2,076) a prediction nomogram. LASSO (least absolute shrinkage and selection operator) regression model and multivariable Cox regression analysis were used for variable selection and for developing the prediction model, respectively. The performance of the nomogram was assessed with respect to its calibration, discrimination, and clinical usefulness.

The individualized prediction nomogram was assessed based on the following motoric cognitive risk syndrome, education, gender, baseline cognition, and age. The model showed good discrimination [Harrell’s concordance index (C-index) of 0.814; 95% confidence interval, 0.782-0.835] and good calibration. Comparable results were also seen in the validation cohort, which includes good discrimination (C-index, 0.772; 95% confidence interval, 0.776-0.818) and good calibration. Decision curve analysis demonstrated that the prediction nomogram was clinically useful.

This prediction nomogram provides a practical tool with all necessary predictors, which are accessible to practitioners. It can be used to estimate the risk of cognitive impairment in healthy older adults.

This prediction nomogram provides a practical tool with all necessary predictors, which are accessible to practitioners. It can be used to estimate the risk of cognitive impairment in healthy older adults.

The objective of this study was to determine which factors influence brain iron concentrations in deep gray matter in elderly individuals and how these factors influence regional brain iron concentrations.

A total of 105 elderly individuals were enrolled in this study. All participants underwent detailed magnetic resonance imaging (MRI) examinations from October 2018 to August 2019. Among them, 44 individuals had undergone a previous MRI examination from July 2010 to August 2011. Quantitative susceptibility mapping (QSM) was utilized as an indirect quantitative marker of brain iron, and the susceptibility values of deep gray matter structures were obtained. Univariate analysis and multiple linear regression analysis were used to investigate 11 possible determinants for cerebral iron deposition.

Our results showed no sex- or hemisphere-related differences in susceptibility values in any of the regions studied. Aging was significantly correlated with increased insusceptibility values in almost all analyzevealed that aging, T2DM, and smoking could increase iron deposition in some deep gray matter structures. However, hypertension had the opposite effects in the red nuclei and dentate nuclei. Brain iron metabolism could be influenced by many factors in different modes. In future studies, we should strictly control for confounding factors.

Our data revealed that aging, T2DM, and smoking could increase iron deposition in some deep gray matter structures. However, hypertension had the opposite effects in the red nuclei and dentate nuclei. Brain iron metabolism could be influenced by many factors in different modes. In future studies, we should strictly control for confounding factors.