Altered dynamic amplitude of low-frequency fluctuation in individuals at high risk for Alzheimer's disease.

The brain's dynamic spontaneous neural activity is significant in supporting cognition; however, how brain dynamics go awry in subjective cognitive decline (SCD) and mild cognitive impairment (MCI) remains unclear. Thus, the current study aimed to investigate the dynamic amplitude of low-frequency fluctuation (dALFF) alterations in patients at high risk for Alzheimer's disease and to explore its correlation with clinical cognitive assessment scales, to identify an early imaging sign for these special populations. A total of 152 participants, including 72 SCD patients, 44 MCI patients and 36 healthy controls (HCs), underwent a resting-state functional magnetic resonance imaging and were assessed with various neuropsychological tests. The dALFF was measured using sliding-window analysis. We employed canonical correlation analysis (CCA) to examine the bi-multivariate correlations between neuropsychological scales and altered dALFF among multiple regions in SCD and MCI patients. Compared to those in the HC group, both the MCI and SCD groups showed higher dALFF values in the right opercular inferior frontal gyrus (voxel P < .001, cluster P < .05, correction). Moreover, the CCA models revealed that behavioural tests relevant to inattention correlated with the dALFF of the right middle frontal gyrus and right opercular inferior frontal gyrus, which are involved in frontoparietal networks (R = .43, P = .024). In conclusion, the brain dynamics of neural activity in frontal areas provide insights into the shared neural basis underlying SCD and MCI.

Effects of repetitive transcranial magnetic stimulation over the contralesional dorsal premotor cortex on upper limb function in severe ischaemic stroke: study protocol for a randomised controlled trial.

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) is an evidence-based treatment widely recommended to promote hand motor recovery after ischaemic stroke. However, the therapeutic efficacy of rTMS over the motor cortex in stroke patients is currently restricted and heterogeneous. This study aimed to determine whether excitatory rTMS over the contralesional dorsal premotor cortex (cPMd) facilitates the functional recovery of the upper limbs during the postacute stage of severe ischaemic stroke. METHODS AND ANALYSIS: This study will be conducted as a single-blind, controlled, randomised study, in which 44 patients with poststroke hemiplegia with a course of disease ranging from 1 week to 3 months and Fugl-Meyer upper limb score ≤22 will be enrolled. The study participants will be randomly assigned to groups A (n=22) and B (n=22). The two groups are based on routine rehabilitation training and drug treatment; group A will be treated with low-frequency (1 Hz) rTMS over the contralesional primary motor cortex (cM1), and group B will be treated with high-frequency (10 Hz) rTMS over cPMd. For 2 weeks, rTMS will be administered once a day, 5 days a week. The primary outcome is the Fugl-Meyer assessment of the upper limb. The secondary outcomes include the Arm Subscore of the Motricity Index, Hong Kong edition of Functional Test for the Hemiplegic Upper Extremity, Modified Barthel Index and Modified Ashworth Scale score of the paralysed pectoralis major and biceps brachii. Furthermore, data of diffusion tensor imaging and functional MRI will be collected. These outcomes will be assessed before and after the completion of the intervention. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee of the First Affiliated Hospital of Nanjing Medical University (2020 SR-266). The findings of this study will be spread through networks of scientists, professionals and the general public as well as peer-reviewed scientific papers and presentations at pertinent conferences. TRIAL REGISTRATION NUMBER: ChiCTR2000038049.

Investigating the spontaneous brain activities of patients with subjective cognitive decline and mild cognitive impairment: an amplitude of low-frequency fluctuation functional magnetic resonance imaging study.

Background: Subjective cognitive decline (SCD) and mild cognitive impairment (MCI) are neurodegenerative processing stages of Alzheimer's disease (AD). Cognitive decline is thought to manifest in intrinsic brain activity changes, but research results yielded conflicting and few studies have explored the roles of brain regions in cognitive decline, and sensitivity of the cognitive field to changes in the altered intrinsic brain activity. Methods: In this cross-sectional study, 158 elderly participants were recruited from the memory clinic of the First Affiliated Hospital of Nanjing Medical University from July 2019 to May 2021, and grouped into SCD (n=73), MCI (n=46), and normal controls (NC) (n=39). The amplitude of low-frequency fluctuation (ALFF) was calculated and evaluated among the groups. Then canonical correlation analysis (CCA) was conducted to investigate the associations between imaging outcomes and cognitive behaviors. Results: Neuropsychological tests in different cognitive dimensions and ALFF values of the prefrontal, parietal, and temporal gyrus, were significantly different (P<0.05) among the three groups, with no appreciable decline in daily activity. The changes in intrinsic activities were closely related to the decline in cognitive function (R=0.73, P=0.002). ALFF values in the left middle occipital gyrus, right middle frontal gyrus, left superior frontal gyrus, left angular gyrus, and superior temporal gyrus played significant roles in the analysis, while the Montreal Cognitive Assessment (MoCA) and Auditory-Verbal Learning Test scores were found to be more sensitive to changes in ALFF values. Conclusions: Spontaneous brain activity is a stable imaging biomarker of cognitive impairment. ALFF changes of the prefrontal, occipital, left angular, and temporal gyrus were sensitive to identifying cognitive decline, and the scores of the Auditory-Verbal Learning Test and MoCA could predict the abnormal intrinsic activities.

Topological properties of individual gray matter morphological networks in identifying the preclinical stages of Alzheimer's disease: a preliminary study.

Background: Subjective cognitive decline (SCD) and mild cognitive impairment (MCI) are preclinical stages of Alzheimer's disease (AD). Individual biomarkers are essential for evaluating altered neurological outcomes at both SCD and MCI stages for early diagnosis and intervention of AD. In this study, we aimed to investigate the relationships between topological properties of the individual brain morphological network and clinical cognitive performances among healthy controls (HCs) and patients with SCD or MCI. Methods: The topological measurements of individual morphological networks were analyzed using graph theory, and inter-group differences of standard graph topology were correlated and regressed to scores of clinical cognitive functions. Results: Compared with HCs, the topology of the individual morphological networks in SCD and MCI patients was significantly altered. At the global level, altered topology was characterized by lower global efficiency, shorter characteristics path length, and normalized characteristics path length [all P<0.05, false discovery rate (FDR) corrected]. In addition, at the regional level, SCD and MCI patients exhibited abnormal degree centrality in the caudate nucleus and nodal efficiency in the caudate nucleus, right insula, lenticular nucleus, and putamen (all P<0.05, FDR corrected). Conclusions: The topological features of individual gray matter morphological networks may serve as biomarkers to improve disease prognosis and intervention in the early stages of AD, namely SCD and MCI. Moreover, these findings may further elucidate the relationships between brain morphological alterations and cognitive dysfunctions in SCD and MCI.

Effect of 3-Month Aerobic Dance on Hippocampal Volume and Cognition in Elderly People With Amnestic Mild Cognitive Impairment: A Randomized Controlled Trial.

As an intermediate state between normal aging and dementia, mild cognitive impairment (MCI), especially amnestic MCI (aMCI), is a key stage in the prevention and intervention of Alzheimer's disease (AD). Whether dancing could increase the hippocampal volume of seniors with aMCI remains debatable. The aim of this study was to investigate the influence of aerobic dance on hippocampal volume and cognition after 3 months of aerobic dance in older adults with aMCI. In this randomized controlled trial, 68 elderly people with aMCI were randomized to either the aerobic dance group or the control group using a 1:1 allocation ratio. Ultimately, 62 of 68 participants completed this study, and the MRI data of 54 participants were included. A specially designed aerobic dance routine was performed by the dance group three times per week for 3 months, and all participants received monthly healthcare education after inclusion. MRI with a 3.0T MRI scanner and cognitive assessments were performed before and after intervention. High-resolution three-dimensional (3D) T1-weighted anatomical images were acquired for the analysis of hippocampal volume. A total of 35 participants (mean age: 71.51 ± 6.62 years) were randomized into the aerobic dance group and 33 participants (mean age: 69.82 ± 7.74 years) into the control group. A multiple linear regression model was used to detect the association between intervention and the difference of hippocampal volumes as well as the change of cognitive scores at baseline and after 3 months. The intervention group showed greater right hippocampal volume (ß [95% CI]: 0.379 [0.117, 0.488], p = 0.002) and total hippocampal volume (ß [95% CI]: 0.344 [0.082, 0.446], p = 0.005) compared to the control group. No significant association of age or gender was found with unilateral or global hippocampal volume. There was a correlation between episodic memory and intervention, as the intervention group showed a higher Wechsler Memory Scale-Revised Logical Memory (WMS-RLM) score (ß [95% CI]: 0.326 [1.005, 6.773], p = 0.009). Furthermore, an increase in age may cause a decrease in the Mini-Mental State Examination (MMSE) score (ß [95% CI]: -0.366 [-0.151, -0.034], p = 0.002). In conclusion, 3 months of aerobic dance could increase the right and total hippocampal volumes and improve episodic memory in elderly persons with aMCI. Clinical Trial Registration: This study was registered on the Chinese Clinical Trial Registry [www.chictr.org.cn], identifier [ChiCTR-INR-15007420].

Quantitative Evaluation of Intraspinal Lumbar Disc Herniation-related Lumbosacral Radiculopathy Before and After Percutaneous Transforaminal Endoscopic Discectomy Using Diffusion Tensor Imaging.

STUDY DESIGN: A prospective study. OBJECTIVE: The aim of this study was to investigate the relationship between diffusion tensor imaging (DTI) derived parameters of compressed nerve roots at subregions and the corresponding clinical symptoms to evaluate the patients with intraspinal lumbar disc herniation (LDH)-related lumbosacral radiculopathy pre- and postoperatively. SUMMARY OF BACKGROUND DATA: It is crucial to explore whether magnetic resonanve imaging (MRI) can quantitatively evaluate intraspinal LDH-related lumbosacral radiculopathy before and after surgery. METHODS: In all, 66 patients underwent MRI scans and Clinical assessment before and after percutaneous transforaminal endoscopic discectomy (PTED). Pre- and postoperative findings of the related lumbar disk and nerve tractography were compared with two-way contingency table analysis. The embedded paired t test toolbox was applied to respectively compare the fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values of nerves at the symptomatic and asymptomatic sides in three subregions pre- and postoperatively. The correlation of clinical Japanese Orthopedic Association (JOA) scores and FA/ADC values of nerves at three sub-regions was analyzed by stepwise multiple linear regression analysis. RESULTS: The postoperative FA values were significantly higher than the corresponding preoperative values (P < 0.001), while comparable ADC values were found. Using tractography, a notable improvement of compressed nerve was revealed after surgery (61 cases, 92.4%). Additionally, multiple linear regression analysis identified significant associations between JOA scores and FA values of the compressed nerves with the greatest effect at the proximal region. CONCLUSION: The FA values at subarticular zone can reflect the microstructural changes of the corresponding compressed nerves and well associate with clinical symptoms. Therefore, the DTI parameter FA can be considered an effective tool in clinic to quantitatively evaluate intraspinal LDH-related lumbosacral radiculopathy before and after PTED surgery.Level of Evidence: 3.

A quantitative and clinical evaluation of nerve roots in lumbosacral radiculopathy using diffusion tensor imaging.

PURPOSE: This study aimed to investigate the relationship between the fractional anisotropy (FA) values of compressed nerves derived in diffusion tensor imaging (DTI) and the corresponding clinical symptoms for quantitative and clinical evaluation in patients with lumbosacral radiculopathy. METHODS: Thirty-six patients and ten volunteers participated in the study and measured with DTI. The resultant FA values for L5-S1 lumbar nerve roots were calculated at three sub-regions. Additionally, the DTI relevant tractography was also performed on L4-S1 nerve roots. Clinical symptoms were performed by Japanese Orthopedic Association (JOA) scoring for each patient and volunteer. RESULTS: The FA values of the nerves at the symptomatic side were significantly lower than those at the asymptomatic side (p < 0.001). Diffusion tensor tractography distinctly showed abnormalities in the symptomatic nerve tracts. There was a significant correlation between JOA scores and the FA values of the compressed nerves at middle and distal sub-regions (p < 0.005). CONCLUSION: The clinical symptoms associated robustly with the DTI derived FA values of the compressed nerves in patients with lumbosacral radiculopathy. Therefore, the FA values can be a potential clinical tool to evaluate the nerve roots in lumbosacral radiculopathy quantitatively.

Chemical exchange saturation transfer magnetic resonance imaging and its main and potential applications in pre-clinical and clinical studies.

Chemical exchange saturation transfer (CEST) imaging is a novel contrast mechanism, relying on the exchange between mobile protons in amide (-NH), amine (-NH2) and hydroxyl (-OH) groups and bulk water. Due to the targeted protons present in endogenous molecules or exogenous compounds applied externally, CEST imaging can respectively, generate endogenous or exogenous contrast. Nowadays, CEST imaging for endogenous contrast has been explored in pre-clinical and clinical studies. Amide CEST, also called amide proton transfer weighted (APT) imaging, generates CEST effect at 3.5 ppm away from the water signal and has been widely investigated. Given the sensitivity to amide proton concentration and pH level, APT imaging has shown robust performance in the assessment of ischemia, brain tumors, breast and prostate cancer as well as neurodegenerative diseases. With advanced methods proposed, pure APT and Nuclear Overhauser Effect (NOE) mediated CEST effects were separately fitted from original APT signal. Using both effects, early but promising results were obtained for glioma patients in the evaluation of tumor response to therapy and patient survival. Compared to amide CEST, amine CEST is also mobile proton concentration and pH dependent, but has a faster exchange rate between amine protons and water. The resultant CEST effect is usually introduced at 1.8-3 ppm. Glutamate and creatine, as two main metabolites with amine groups for CEST imaging, have been applied to quantitatively assess diseases in the central nervous system and muscle system, respectively. Glycosaminoglycan (Gag) as a representative metabolite with hydroxyl groups has also been measured to evaluate the cartilage of knee or intervertebral discs in CEST MRI. Due to limited frequency difference between hydroxyl protons and water, 7T for better spectral separation is preferred over 3T for GagCEST measurement. The applications of CEST MRI with exogenous contrast agents are still quite limited in clinic. While certain diamagnetic CEST agents, such as dynamic-glucose, have been tried in human for brain tumor or neck cancer assessment, most exogenous agents, i.e., paramagnetic CEST agents, are still tested in the pre-clinical stage, mainly due to potential toxicity. Engineered tissues for tissue regeneration and drug delivery have also shown a great potential in CEST imaging, as many of them, such as hydrogel and polyamide materials, contain mobile protons or can be incorporated with CEST specific chemical compounds. These engineered tissues can thus generate CEST effect in vivo, allowing a possibility to understand the fate of them in vivo longitudinally. Although the CEST MRI with engineered tissues has only been established in early stage, the obtained first evidence is crucial for further optimizing these biomaterials and finally accomplishing the translation into clinical use.

Effect of laterality, gender, age and body mass index on the fat fraction of salivary glands in healthy volunteers: assessed using iterative decomposition of water and fat with echo asymmetry and least-squares estimation method.

OBJECTIVES:: To evaluate the effect of laterality, gender, age and body mass index (BMI) on fat fraction (FF) measurements of both parotid glands (PGs) and submandibular glands (SMGs) by using: Iterative decomposition of water and fat with echo asymmetry and least-squares estimation method (IDEAL-IQ). METHODS:: A total of 87 healthy participants were enrolled in our study. IDEAL-IQ image was scanned using a 3.0 T scanner. Paired t test was performed to compare the difference on FF of both PGs and SMGs between left and right side. The FF of two glands between male and female healthy participants were compared using an unpaired t-test. The correlation between the FF of two glands and participant age or BMI were analyzed by Pearson's correlation. RESULTS:: Excellent inter- and intrareader agreements were obtained during the measurements of FF by IDEAL-IQ method (ICC, 0.952-0.981). FF values correlated positively with the age and BMI in both left and right PGs and SMGs (p < 0.05). No significant difference was found on FF between left and right PGs and SMGs (p > 0.05). There was also no difference on FF between male and female healthy participants (p > 0.05). CONCLUSIONS:: FFs of PGs and SMGs were age- and BMI- dependent, but not laterality- and gender-dependent. The effect of age and BMI need to be considered in further studies using Ideal-IQ technology to evaluate FFs of salivary gland diseases.