Transcranial alternating current stimulation for treating depression: a randomized controlled trial.

Treatment of depression with antidepressants is partly effective. Transcranial alternating current stimulation can provide a non-pharmacological alternative for adult patients with major depressive disorder. However, no study has used the stimulation to treat first-episode and drug-naïve patients with major depressive disorder. We used a randomized, double-blind, sham-controlled design to examine the clinical efficacy and safety of the stimulation in treating first-episode drug-naïve patients in a Chinese Han population. From 4 June 2018 to 30 December 2019, 100 patients were recruited and randomly assigned to receive 20 daily 40-min, 77.5 Hz, 15 mA, one forehead and two mastoid sessions of active or sham stimulation (n = 50 for each group) in four consecutive weeks (Week 4), and were followed for additional 4-week efficacy/safety assessment without stimulation (Week 8). The primary outcome was a remission rate defined as the 17-item Hamilton Depression Rating Scale (HDRS-17) score ≤ 7 at Week 8. Secondary analyses were response rates (defined as a reduction of ≥ 50% in the HDRS-17), changes in depressive symptoms and severity from baseline to Week 4 and Week 8, and rates of adverse events. Data were analysed in an intention-to-treat sample. Forty-nine in the active and 46 in the sham completed the study. Twenty-seven of 50 (54%) in the active treatment group and 9 of 50 (18%) in the sham group achieved remission at the end of Week 8. The remission rate was significantly higher in the active group compared to that in the sham group with a risk ratio of 1.78 (95% confidence interval, 1.29, 2.47). Compared with the sham, the active group had a significantly higher remission rate at Week 4, response rates at Weeks 4 and 8, and a larger reduction in depressive symptoms from baseline to Weeks 4 and 8. Adverse events were similar between the groups. In conclusion, the stimulation on the frontal cortex and two mastoids significantly improved symptoms in first-episode drug-naïve patients with major depressive disorder and may be considered as a non-pharmacological intervention for them in an outpatient setting.

Neuroimaging basis in the conversion of aMCI patients with APOE-ε4 to AD: study protocol of a prospective diagnostic trial.

BACKGROUND: The ε4 allele of the Apolipoprotein E gene (APOE-ε4) is a potent genetic risk factor for sporadic Alzheimer's disease (AD). Amnestic mild cognitive impairment (aMCI) is an intermediate state between normal cognitive aging and dementia, which is easy to convert to AD dementia. It is an urgent problem in the field of cognitive neuroscience to reveal the conversion of aMCI-ε4 to AD. Based on our preliminary work, we will study the neuroimaging features in the special group of aMCI-ε4 with multi-modality magnetic resonance imaging (structural MRI, resting state-fMRI and diffusion tensor imaging) longitudinally. METHODS/DESIGN: In this study, 200 right-handed subjects who are diagnosed as aMCI with APOE-ε4 will be recruited at the memory clinic of the Neurology Department, XuanWu Hospital, Capital Medical University, Beijing, China. All subjects will undergo the neuroimaging and neuropsychological evaluation at a 1 year-interval for 3 years. The primary outcome measures are 1) Microstructural alterations revealed with multimodal MRI scans including structure MRI (sMRI), resting state functional MRI (rs-fMRI), diffusion tensor imaging (DTI); 2) neuropsychological evaluation, including the World Health Organization-University of California-LosAngeles Auditory Verbal Learning Test (WHO-UCLA AVLT), Addenbrook's cognitive examination-revised (ACE-R), mini-mental state examination (MMSE), Montreal Cognitive Assessment (MoCA), Clinical Dementia Rating scale (CDR). DISCUSSION: This study is to find out the neuroimaging biomarker and the changing laws of the marker during the progress of aMCI-ε4 to AD, and the final purpose is to provide scientific evidence for new prevention, diagnosis and treatment of AD. TRIAL REGISTRATION: This study has been registered to ClinicalTrials.gov (NCT02225964, https://www.clinicaltrials.gov/ ) in August 24, 2014.

The impact of carbon emission trading policy on energy efficiency-evidence from China.

Energy efficiency (EE) plays an important role in achieving the dual-carbon goal, and improving EE is thus indispensable. This paper evaluates the impact of carbon emission trading policy (CETP) on EE based on a difference-in-difference (DID) method, using 16-year data of 30 provinces and cities from 2005 to 2020. Conclusions are as follows: (1) CETP significantly promotes EE, and this conclusion still appears valid after robustness tests. (2) The positive impact of CETP on EE is more effective in regions of high foreign direct investment (FDI) and high government intervention (GOVI). (3) The positive impact of CETP on EE is through impact mechanisms of energy structure adjustment (ESA), green innovation (GI), and industrial structure upgrading (ISU). The findings in this paper may enrich current research in CETP and offer more pragmatic suggestions for policy advancement as well.

Mussel-inspired anchoring for patterning cells using polydopamine.

This Article introduces a simple method of cell patterning, inspired by the mussel anchoring protein. Polydopamine (PDA), artificial polymers made from self-polymerization of dopamine (a molecule that resembles mussel-adhesive proteins), has recently been studied for its ability to make modifications on surfaces in aqueous solutions. We explored the interfacial interaction between PDA and poly(ethylene glycol) (PEG) using microcontact printing (µCP). We patterned PDA on several substrates such as glass, polystyrene, and poly(dimethylsiloxane) and realized spatially defined anchoring of mammalian cells as well as bacteria. We applied our system in investigating the relationship between areas of mammalian nuclei and that of the cells. The combination of PDA and PEG enables us to make cell patterns on common laboratorial materials in a mild and convenient fashion.

Abnormal Dynamic Functional Networks in Subjective Cognitive Decline and Alzheimer's Disease.

Subjective cognitive decline (SCD) is considered to be the preclinical stage of Alzheimer's disease (AD) and has the potential for the early diagnosis and intervention of AD. It was implicated that CSF-tau, which increases very early in the disease process in AD, has a high sensitivity and specificity to differentiate AD from normal aging, and the highly connected brain regions behaved more tau burden in patients with AD. Thus, a highly connected state measured by dynamic functional connectivity may serve as the early changes of AD. In this study, forty-five normal controls (NC), thirty-six individuals with SCD, and thirty-five patients with AD were enrolled to obtain the resting-state functional magnetic resonance imaging scanning. Sliding windows, Pearson correlation, and clustering analysis were combined to investigate the different levels of information transformation states. Three states, namely, the low state, the middle state, and the high state, were characterized based on the strength of functional connectivity between each pair of brain regions. For the global dynamic functional connectivity analysis, statistically significant differences were found among groups in the three states, and the functional connectivity in the middle state was positively correlated with cognitive scales. Furthermore, the whole brain was parcellated into four networks, namely, default mode network (DMN), cognitive control network (CCN), sensorimotor network (SMN), and occipital-cerebellum network (OCN). For the local network analysis, statistically significant differences in CCN for low state and SMN for middle state and high state were found in normal controls and patients with AD. Meanwhile, the differences were also found in normal controls and individuals with SCD. In addition, the functional connectivity in SMN for high state was positively correlated with cognitive scales. Converging results showed the changes in dynamic functional states in individuals with SCD and patients with AD. In addition, the changes were mainly in the high strength of the functional connectivity state.

Exploring brain glucose metabolic patterns in cognitively normal adults at risk of Alzheimer's disease: A cross-validation study with Chinese and ADNI cohorts.

OBJECTIVE: Disease-related metabolic brain patterns have been verified for a variety of neurodegenerative diseases including Alzheimer's disease (AD). This study aimed to explore and validate the pattern derived from cognitively normal controls (NCs) in the Alzheimer's continuum. METHODS: This study was based on two cohorts; one from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the other from the Sino Longitudinal Study on Cognitive Decline (SILCODE). Each subject underwent [18F]fluoro-2-deoxyglucose positron emission tomography (PET) and [18F]florbetapir-PET imaging. Participants were binary-grouped based on ß-amyloid (Aß) status, and the positivity was defined as Aß+. Voxel-based scaled subprofile model/principal component analysis (SSM/PCA) was used to generate the "at-risk AD-related metabolic pattern (ARADRP)" for NCs. The pattern expression score was obtained and compared between the groups, and receiver operating characteristic curves were drawn. Notably, we conducted cross-validation to verify the robustness and correlation analyses to explore the relationships between the score and AD-related pathological biomarkers. RESULTS: Forty-eight Aß+ NCs and 48 Aß- NCs were included in the ADNI cohort, and 25 Aß+ NCs and 30 Aß- NCs were included in the SILCODE cohort. The ARADRPs were identified from the combined cohorts and the two separate cohorts, characterized by relatively lower regional loadings in the posterior parts of the precuneus, posterior cingulate, and regions of the temporal gyrus, as well as relatively higher values in the superior/middle frontal gyrus and other areas. Patterns identified from the two separate cohorts showed some regional differences, including the temporal gyrus, basal ganglia regions, anterior parts of the precuneus, and middle cingulate. Cross-validation suggested that the pattern expression score was significantly higher in the Aß+ group of both cohorts (p < 0.01), and contributed to the diagnosis of Aß+ NCs (with area under the curve values of 0.696-0.815). The correlation analysis revealed that the score was related to tau pathology measured in cerebrospinal fluid (p-tau: p < 0.02; t-tau: p < 0.03), but not Aß pathology assessed with [18F]florbetapir-PET (p > 0.23). CONCLUSIONS: ARADRP exists for NCs, and the acquired pattern expression score shows a certain ability to discriminate Aß+ NCs from Aß- NCs. The SSM/PCA method is expected to be helpful in the ultra-early diagnosis of AD in clinical practice.

Using self-polymerized dopamine to modify the antifouling property of oligo(ethylene glycol) self-assembled monolayers and its application in cell patterning.

We report a one-step, mild method to modify antifouling oligo(ethylene glycol)-terminated self-assembled monolayers. We demonstrate for the first time that self-polymerized dopamine, previously reported as an underwater adhesive, can be patterned on typical antifouling surfaces by microfluidic patterning or microcontact printing. The patterns can be applied in spatiotemporal cell patterning.

Associations between low-density lipoprotein cholesterol and haemorrhagic stroke.

OBJECTIVE: To investigate the associations between the blood concentrations of low-density lipoprotein cholesterol (LDL-C) and the clinical features of haemorrhagic stroke. METHODS: This study analysed the data from patients with acute haemorrhagic stroke at a comprehensive stroke centre from 2013 to 2018. Patients were stratified into three groups according to their baseline LDL-C levels: < 70, 70 to < 100 and ≥ 100 mg/dL. We used multivariate logistic regression models to analyse the associations between LDL-C and the risks of having severe neurological deficits (National Institute Health Stroke Scale [NIHSS] scores ≥ 15) and unfavourable outcomes (modified Rankin Scale [mRS] scores>2) at discharge. RESULTS: Six-hundred and six patients were analysed. Their median age was 58 years. Among the patients, 75 (12%) patients had LDL-C levels < 70 mg/dL, 194 (32%) patients had LDL-C levels between 70 to < 100 mg/dL and the other 337 (56%) patients had LDL-C levels ≥ 100 mg/dL. Patients with higher LDL-C levels were less likely to suffer severe neurological deficits (LDL-C: 70 to < 100 vs. < 70 mg/dL, adjusted odds ratio [OR]: 0.29, 95% CI: 0.15-0.57; LDL-C: ≥ 100 vs. < 70 mg/dL, adjusted OR = 0.27, 95% CI: 0.15-0.51) and to have unfavourable outcomes at discharge (LDL-C: 70 to < 100 vs. < 70 mg/dL, adjusted OR = 0.50, 95% CI: 0.29-0.87 and LDL-C: ≥ 100 vs. < 70 mg/dL, adjusted OR = 0.46, 95% CI: 0.28-0.78). CONCLUSIONS: An LDL-C level < 70 mg/dL was independently associated with severe neurological deficits of haemorrhagic stroke and may increase the risks of unfavourable outcomes at discharge.

Efficacy and safety of normobaric hyperoxia combined with intravenous thrombolysis on acute ischemic stroke patients.

Intravenous thrombolysis elevates the prognostic level of acute ischemic stroke (AIS) patients. Normobaric hyperoxia (NBO) delays the progression of the infarct core and promotes neurological recovery. However, it is uncertain whether NBO can further raise the prognostic level of AIS patients based on intravenous thrombolysis. To explore the efficacy and safety of NBO combined with intravenous thrombolysis on AIS patients. This observational study included anterior circulation stroke patients who received intravenous thrombolysis within 4.5 h after stroke onset. These patients were divided into two groups based on whether or not they received NBO therapy. The baseline data and the prognosis of the two groups were compared. The primary outcome was the proportion of functional independence (modified Rankin Scale 0-2) at 90 days post discharge. A total of 227 patients were included in this study. 125 patients received NBO therapy combined with intravenous thrombolysis, while 102 patients received intravenous thrombolysis only. Overall, the rate of recanalization was 83.3%. Consequently, 101 patients (80.8%) who received NBO combined with intravenous thrombolysis and 63 patients (61.8%) in the control group achieved functional independence (P = 0.002). Multivariable logistic regression analysis showed that NBO combined with intravenous thrombolysis over intravenous thrombolysis alone was associated with 90-day functional independence (OR: 2.318; 95% CI: 1.226-4.381; P = 0.01). This study verified the efficacy and safety of NBO combined with intravenous thrombolysis in AIS patients. Prospective study is needed to further substantiate these findings.

APOE ε4 and cognitive reserve effects on the functional network in the Alzheimer's disease spectrum.

The apolipoprotein E (APOE) ε4 allele is a genetic risk factor for Alzheimer's disease, whereas educational attainments have protective effects against cognitive decline in aging and patients with Alzheimer's disease. We examined the possible effects of years of education and APOE genotype on the topological properties of the functional network in normal aging, mild cognitive impairment and Alzheimer's disease. The years of education showed a significant, negative association with the local efficiency, clustering coefficient and small-worldness of functional networks in APOE ε4 noncarriers but not in ε4 carriers. These associations were mainly observed in normal aging and were reduced in mild cognitive impairment and Alzheimer's disease. Moreover, regions of the inferior frontal gyrus, temporal pole, and cuneus also showed correlations between education and nodal degree. Our findings demonstrated that the protective effects of education persist in APOE ε4 noncarriers but diminish in ε4 carriers. In addition, the protective effects of education were attenuated or reduced in the progression of Alzheimer's disease.

Cognitive rehabilitation interventions after stroke: protocol for a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Stroke is the second leading cause of death worldwide, and 53.4% of stroke survivors suffer from post-stroke cognitive impairment. Post-stroke cognitive impairment can increase hospitalization rate and cost of care and decrease the quality of life of stroke patients. To date, multiple cognitive rehabilitation interventions have been tested in stroke populations with post-stroke cognitive impairment. However, the most efficacious intervention has not been established. This systematic review aims to compare the efficacy of cognitive rehabilitation interventions for patients with post-stroke cognitive impairment. METHODS: We will search MEDLINE, EMBASE, CENTRAL, PsycINFO, CINAHL, PubMed, and clinical trial registries to identify eligible randomized clinical trials with no restrictions in the date of publication and language. Studies conducted with patients aged 18 or over, with the presence of cognitive impairment after being diagnosed with stroke will be included. Studies will be restricted to randomized controlled trials comparing a cognitive rehabilitation intervention with another intervention. The primary outcome is any clinical changes in the general or specific cognitive domain (e.g., executive function, attention, memory, or perception). The secondary outcomes that will be collected include adverse effects (e.g., stroke, disability, or mortality) and quality of life. Two independent reviewers will assess articles to identify trials eligible for inclusion. Data extraction and risk of bias assessment of the included studies will also be done independently. Any discrepancies will be solved by discussion, or a third reviewer will be consulted if necessary. A meta-analysis will be carried out if appropriate. DISCUSSION: This systematic review for patients with post-stroke cognitive impairment will assess the efficacy of cognitive rehabilitation interventions. And our results will help clinical decision-making and support the development of clinical practice guidelines. TRIAL REGISTRATION: Systematic review registration: PROSPERO CRD42020173988.

Exploring the Pattern Associated With Longitudinal Changes of ß-Amyloid Deposition During Cognitively Normal Healthy Aging.

The aim of this study was to determine a pattern associated with longitudinal changes of ß-amyloid (Aß) deposition during cognitively normal(CN) healthy aging. We used 18F-florbetapir (AV-45) PET images of the brains of 207 cognitively normal subjects (CN1), obtained through the Alzheimer's Disease Neuroimaging Initiative (ADNI), to identify the healthy aging pattern and 76 cognitively normal healthy subjects (CN2), obtained through the Xuanwu Hospital of Capital Medical University, Beijing, China, to verify it. A voxel-based correlation analysis of standardized uptake value ratio (SUVR) map image and age was conducted using the DPABI (Data Processing & Analysis of Brain Imaging) software to identify the pattern. The sum of squares due to errors (SSE), R-square (R2) and the root-mean-square error (RMSE) were calculated to assess the quality of curve fitting. Among them, R2 was proposed as the coherence coefficient, which was as an index to assess the correlation between SUVR value of the pattern and subjects' age. The pattern characterized by age-associated longitudinal changes of Aß deposition was mainly distributed in the right middle and inferior temporal gyrus, the right temporal pole: middle temporal gyrus, the right inferior occipital gyrus, the right inferior frontal gyrus (triangular portion), and the right precentral gyrus. There were a significant positive correlation between the SUVR value of the pattern and age for each CN group (CN1: R2 = 0.120, p < 0.001 for quadratic model; CN2: R2 = 0.152, p = 0.002 for quadratic model). These findings suggest a pattern of changes in Aß deposition that can be used to distinguish physiological changes from pathophysiological changes, constituting a new method for elucidating the neuropathological mechanism of Alzheimer's disease.

Abnormal Anatomical Rich-Club Organization and Structural-Functional Coupling in Mild Cognitive Impairment and Alzheimer's Disease.

Emerging research indicates interruptions in the wiring organization of the brain network in Mild cognitive impairment (MCI) and Alzheimer's disease (AD). Due to the important role of rich-club organization in distinguishing abnormalities of AD patients and the close relationship between structural connectivity (SC) and functional connectivity (FC), our study examined whether changes in SC-FC coupling and the relationship with abnormal rich-club organizations during the development of diseases may contribute to the pathophysiology of AD. Structural diffusion-tensor imaging (DTI) and resting-state functional magnetic resonance imaging (fMRI) were performed in 38 normal controls (NCs), 40 MCI patients and 19 AD patients. Measures of the rich-club structure and its role in global structural-functional coupling were administered. Our study found decreased levels of feeder and local connectivity in MCI and AD patients, which were the main contributing factors to the lower efficiency of the brain structural network. Another important finding was that we have more accurately characterized the changing pattern of functional brain dynamics. The enhanced coupling between SC and FC in MCI and AD patients might be due to disruptions in optimal structural organization. More interestingly, we also found increases in the SC-FC coupling for feeder and local connections in MCI and AD patients. SC-FC coupling also showed significant differences between MCI and AD patients, mainly between the abnormal feeder connections. The connection density and coupling strength were significantly correlated with clinical metrics in patients. The present findings enhanced our understanding of the neurophysiologic mechanisms associated with MCI and AD.

Beneficial Effects of Brain Reserve on Cognition in Individuals with Subjective Cognitive Decline from the SILCODE Study.

BACKGROUND: Clinical research has demonstrated that brain reserve (BR) could exert positive effects on cognition for patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). However, the effects of BR on cognition in individuals with subjective cognitive decline (SCD) are not clear. OBJECTIVE: To examine cross-sectional effects of BR on cognition in SCD populations. METHODS: One hundred forty-nine subjects were studied from the Sino Longitudinal Study on Cognitive Decline (SILCODE) study. Head circumference was used as a proxy of BR. Cognition was assessed across four domains (memory, executive, language, and general cognitive functions). Multiple linear regression models were conducted to examine effects of BR on cognitive scores. Furthermore, we addressed the question that whether the degree of self-perception of cognitive decline modified the effect of BR on cognitive performance in SCD subjects. RESULTS: We found a positive effect of BR on language cognition in subjects with SCD. Furthermore, the positive effect of BR on language cognition survived in SCD participants with a low degree of self-perception of cognitive decline while disappeared in SCD participants with a high degree of self-perception of cognitive decline. CONCLUSION: This study suggests that BR has the potential to delay or slow down cognitive decline in SCD individuals, especially for mild SCD.

Cognitive Reserve, Brain Reserve, APOEɛ4, and Cognition in Individuals with Subjective Cognitive Decline in the SILCODE Study.

BACKGROUND: Cognitive reserve (CR) and brain reserve (BR) could offer protective effects on cognition in the early stage of Alzheimer's disease (AD). However, the effects of CR or BR on cognition in individuals with subjective cognitive decline (SCD) are not clear. OBJECTIVE: To explore the effects of CR and BR on cognition in subjects with SCD. METHODS: We included 149 subjects from the Sino Longitudinal Study on Cognitive Decline (SILCODE) study. Education was used as a proxy for CR, and head circumference was used as a proxy for BR. Multiple linear regression models were conducted to examine the effects of CR and BR on cognitive scores. Furthermore, we assessed differences in effects between APOEɛ4 carriers with SCD (n = 35) and APOEɛ4 non-carriers with SCD (n = 114) and linear trends among 4 reserve levels (low BR/CR, high BR/low CR, low BR/high CR, and high BR/high CR). RESULTS: Both CR and BR had independent positive effects on multiple cognitive measures in SCD participants, and the effects of CR were greater than those of BR. CR has positive effects on cognitive measures in both APOEɛ4 carriers and non-carriers with SCD. However, the positive effects of BR on cognitive measures were observed in APOEɛ4 non-carriers with SCD but not in APOEɛ4 carriers with SCD. Furthermore, there was a linear trend toward better cognitive performance on all cognitive measures in the BR+/CR+ group, followed by the BR-/CR+, BR+/CR-, and BR-/CR-groups. CONCLUSION: This study suggests that both CR and BR have the potential to delay or slow cognitive decline in individuals with SCD.

The efficacy of transcranial alternating current stimulation for treating post-stroke depression: Study Protocol Clinical Trial (SPIRIT Compliant).

BACKGROUND: The treatment of post-stroke depression (PSD) with anti-depressant drugs is partly practical. Transcranial alternating current stimulation (tACS) offers the potential for a novel treatment modality for adult patients with PSD. In this study, we will assess the efficacy and safety of tACS for treating PSD and explore its effect on gamma and beta-oscillations involving in emotional regulation. METHODS: The prospective study is an 8-week, double-blind, randomized, placebo-controlled trial. Seventy eligible participants with mild to moderate PSD aged between 18 years and 70 years will be recruited and randomly assigned to either active tACS intervention group or sham group. Daily 40-minute, 77.5-Hz, 15-mA sessions of active or sham tACS targeting the forehead and both mastoid areas on weekdays for 4 consecutive weeks (week 4), and an additional 4-week observational period (week 8) will be followed up. The primary outcome is the proportion of participants having an improvement at week 8 according to the Hamilton Depression Rating Scale 17-Item (HAMD-17) score, including the proportion of participants having a decrease of ≥ 50% in HAMD-17 score or clinical recovery (HAMD-17 score ≤ 7). Secondary outcomes include neurological function, independence level, activities of daily living, disease severity, anxiety, and cognitive function. The exploratory outcomes are gamma and beta-oscillations assessed at baseline, week 4, and week 8. Data will be analyzed by logistical regression analyses and mixed-effects models. DISCUSSION: The study will be the first randomized controlled trial to evaluate the efficacy and safety of tACS at a 77.5-Hz frequency and 15-mA current in reducing depressive severity in patients with PSD. The results of the study will present a base for future studies on the tACS in PSD and its possible mechanism. TRIAL REGISTRATION NUMBER: NCT03903068, pre-results.

Using azobenzene-embedded self-assembled monolayers to photochemically control cell adhesion reversibly.

A celling point: A mixed self-assembled monolayer comprising two types of alkanethiols--one containing an azobenzene unit terminated with a peptide, the other containing a hexa(ethylene glycol) group that resists nonspecific cell adhesion--enables cell adhesion to be modulated photochemically. The reversible conversion of the azobenzene moiety between E and Z configurations allows the surface to either support or resist cell adhesion.

Changes in Centrality Frequency of the Default Mode Network in Individuals With Subjective Cognitive Decline.

Despite subjective cognitive decline (SCD), a preclinical stage of Alzheimer's disease (AD), being widely studied in recent years, studies on centrality frequency in individuals with SCD are lacking. This study aimed to investigate the differences in centrality frequency between individuals with SCD and normal controls (NCs). Forty individuals with SCD and 53 well-matched NCs underwent a resting-state functional magnetic resonance imaging scan. We assessed individual dynamic functional connectivity using sliding window correlations. In each time window, brain regions with a high degree centrality were defined as hubs. Across the entire time window, the proportion of time that the hub appeared was characterized as centrality frequency. The centrality frequency correlated with cognitive performance differently in individuals with SCD and NCs. Our results revealed that in individuals with SCD, compared with NCs, correlations between centrality frequency of the anterior cortical regions and cognitive performance decreased (79.2% for NCs and 43.5% for individuals with SCD). In contrast, correlations between centrality frequency of the posterior cortical regions and cognitive performance increased in SCD individuals compared with NCs (20.8% for NCs and 56.5% for individuals with SCD). Moreover, the changes mainly focused on the anterior (93.3% for NCs and 45.5% for individuals with SCD) and posterior (6.7% for NCs and 54.5% for individuals with SCD) regions associated with the default mode network (DMN). In addition, we used absolute thresholds (correlation efficient r = 0.2, 0.25) and proportional thresholds (sparsity = 0.2, 0.25) to verify the results. Dynamic results are relative stable at absolute thresholds while static results are relative stable at proportional thresholds. Converging findings provide a new framework for the detection of the changes occurring in individuals with SCD via centrality frequency of the DMN.

Decreased resting-state brain signal complexity in patients with mild cognitive impairment and Alzheimer's disease: a multiscale entropy analysis.

Multiscale entropy (MSE) analysis is a novel entropy-based analysis method for quantifying the complexity of dynamic neural signals and physiological systems across multiple temporal scales. This approach may assist in elucidating the pathophysiologic mechanisms of amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD). Using resting-state fNIRS imaging, we recorded spontaneous brain activity from 31 healthy controls (HC), 27 patients with aMCI, and 24 patients with AD. The quantitative analysis of MSE revealed that reduced brain signal complexity in AD patients in several networks, namely, the default, frontoparietal, ventral and dorsal attention networks. For the default and ventral attention networks, the MSE values also showed significant positive correlations with cognitive performances. These findings demonstrated that the MSE-based analysis method could serve as a novel tool for fNIRS study in characterizing and understanding the complexity of abnormal cortical signals in AD cohorts.

Clinical characterization of an APP mutation (V717I) in five Han Chinese families with early-onset Alzheimer's disease.

The missense mutation V717I in amyloid precursor protein (APP) gene has been reported in many early-onset familial Alzheimer's disease (EOFAD) families. However, no detailed clinical picture regarding this mutation has ever been described for Chinese EOFAD. We investigate the age at onset (AAO), initial clinical features and non-cognitive neurological symptoms in 34 affected subjects from five Han Chinese EOFAD families with the APPV717I mutation to characterize the clinical phenotype. The AAO was 54.7±4.9years (n=34), with the APOE ɛ4 allele correlating with a decreased AAO. Prominent early affective symptoms, executive dysfunction and disorientation at onset were exhibited in 26 (76.5%), 18 (52.9%) and 16 (47%) cases, respectively. Spastic paraparesis and cerebellar ataxia occurred frequently in 13 (38.2%) and 12 (35.3%) cases, respectively, during the late stages of disease. The specific clinical phenotype of the APPV717I mutation for Chinese families is characterized by prominent early affective symptoms, executive dysfunction and disorientation as well as frequent late spastic paraparesis and cerebellar ataxia as compared to Western reports. We conclude that ethnic differences, environment or additional unknown factors may challenge the homogeneity of EOFAD with identical APP mutations.