Chunbo Li

The effects of multi-domain versus single-domain cognitive training in non-demented older people: a randomized controlled trial

BackgroundWhether healthy older people can benefit from cognitive training (CogTr) remains controversial. This study explored the benefits of CogTr in community dwelling, healthy, older adults and compared the effects of single-domain with multi-domain CogTr interventions.MethodsA randomized, controlled, 3-month trial of CogTr with double-blind assessments at baseline and immediate, 6-month and 12-month follow-up after training completion was conducted. A total of 270 healthy Chinese older people, 65 to 75 years old, were recruited from the Ganquan-area community in Shanghai. Participants were randomly assigned to three groups: multi-domain CogTr, single-domain CogTr, and a wait-list control group. Twenty-four sessions of CogTr were administrated to the intervention groups over a three-month period. Six months later, three booster training sessions were offered to 60% of the initial training participants. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS, Form A), the Color Word Stroop test (CWST), the Visual Reasoning test and the Trail Making test (TMT) were used to assess cognitive function.ResultsMulti-domain CogTr produced statistically significant training effects on RBANS, visual reasoning, and immediate and delayed memory, while single-domain CogTr showed training effects on RBANS, visual reasoning, word interference, and visuospatial/constructional score (all P < 0.05). At the 12-month posttest, the multi-domain CogTr showed training effects on RBANS, delayed memory and visual reasoning, while single-domain CogTr only showed effects on word interference. Booster training resulted in effects on RBANS, visual reasoning, time of trail making test, and visuospatial/constructional index score.ConclusionsCognitive training can improve memory, visual reasoning, visuospatial construction, attention and neuropsychological status in community-living older people and can help maintain their functioning over time. Multi-domain CogTr enhanced memory proficiency, while single-domain CogTr augmented visuospatial/constructional and attention abilities. Multi-domain CogTr had more advantages in training effect maintenance.Clinical Trial RegistrationChinese Clinical Trial Registry. Registration number: ChiCTR-TRC-09000732.

Localized connectivity in depression: A meta-analysis of resting state functional imaging studies

Resting-state fMRI studies investigating the pathophysiology of depression have identified prominent abnormalities in large-scale brain networks. However, it is unclear if localized dysfunction of specialized brain regions contribute to network-level abnormalities. We employed a meta-analytical procedure and reviewed studies conducted in China investigating changes in regional homogeneity (ReHo), a measure of localized intraregional connectivity, from resting-state fMRI in depression. Exploiting the statistical power gained from pooled analysis, we also investigated the effects of age, gender, illness duration and treatment on ReHo. The medial prefrontal cortex (MPFC) showed the most robust and reliable increase in ReHo in depression, with greater abnormality in medication-free patients with multiple episodes. Brain networks that relate to this region have been identified previously to show aberrant connectivity in depression, and we propose that the localized neuronal inefficiency of MPFC exists alongside wider network level disruptions involving this region.

Repetitive transcranial magnetic stimulation versus electroconvulsive therapy for major depression: a systematic review and meta-analysis

Electroconvulsive therapy (ECT) is the most effective treatment of depression. During the last decades repetitive transcranial magnetic stimulation (rTMS), an alternative method using electric stimulation of the brain, has revealed possible alternative to ECT in the treatment of depression. There are some clinical trials comparing their efficacies and safeties but without clear conclusions, mainly due to their small sample sizes. In the present study, a meta-analysis had been carried out to gain statistical power. Outcomes were response, remission, acceptability and cognitive effects in depression. Following a comprehensive literature search that included both English and Chinese language databases, we identified all randomized controlled trials that directly compared rTMS and ECT for major depression. 10 articles (9 trials) with a total of 425 patients were identified. Methodological quality, heterogeneity, sensitivity and publication bias were systematically evaluated. ECT was superior to high frequency rTMS in terms of response (64.4% vs. 48.7%, RR = 1.41, p = 0.03), remission (52.9% vs. 33.6%, RR = 1.38, p = 0.006) while discontinuation was not significantly different between the two treatments (8.3% vs. 9.4%, RR = 1.11, p = 0.80). According to the subgroup analysis, the superiority of ECT was more apparent in those with psychotic depression, while high frequency rTMS was as effective as ECT in those with non-psychotic depression. The same results were obtained in the comparison of ECT with low frequency rTMS. ECT had a non-significant advantage over high frequency rTMS on the overall improvement in HAMD scores (p = 0.11). There was insufficient data on medium or long term efficacy. Both rTMS and ECT were well tolerated with only minor side effects reported. Results based on 3 studies suggested that specific cognitive domains such as visual memory and verbal fluency were more impaired in patients receiving ECT. In conclusion, ECT seemed more effective than and at least as acceptable as rTMS in the short term, especially in the presence of psychotic depression. This review identified the lack of good quality trials comparing the long-term outcome and cognitive effects of rTMS and ECT, especially using approaches to optimize stimulus delivery and reduce clinical heterogeneity.

Reliability and validity of the Repeatable Battery for the Assessment of Neuropsychological Status in community- dwelling elderly

Introduction The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is a widely used screening instrument in neuropsychological assessment and is a brief, individually administered measure. The present study aims to assess the reliability and validity of the Chinese version of the RBANS in community-dwelling elderly. Material and methods All subjects come from the community-dwelling elderly in Shanghai, China. They completed a questionnaire concerning demographic information, the mini-mental state examination (MMSE) and the Chinese version of the RBANS. To test for internal consistency, Cronbachs α was calculated for all six RBANS indices. Correlations between each of the RBANS and MMSE subtests were conducted to measure the concurrent validity. A confirmatory factor analysis (CFA) was conducted to test the construct validity. Results The final sample of participants included 236 community-dwelling elderly. The mean total score on the RBANS was 86.02 (±14.19). The RBANS total score showed strong internal consistency (r = 0.806), and the coefficient α value for each of the RBANS scales ranged from 0.142 to 0.727. The total RBANS score was highly correlated with that of the MMSE (r = 0.594, p<0.001), and the RBANS subtests also demonstrated strong correlations with most of the MMSE subtests. The results of the CFA indicated an acceptable fit between the Chinese version of the RBANS and the original. Conclusions The Chinese version of the RBANS had relatively good reliability and validity in a community-dwelling elderly sample. It may be a useful screening instrument for conducting cognitive assessments in community-dwelling elderly.

Greater attenuation of retinal nerve fiber layer thickness in Alzheimer's disease patients.

Thinning of retinal nerve fiber layer (RNFL) may reflect neurodegeneration of the central nervous system, which has been reported as part of the neuropathogenesis of Alzheimers disease (AD). Specifically, AD patients have thinner RNFL as compared to age-matched normal controls. However, whether reduction of RNFL over time can predict those at higher risk to develop cognitive deterioration remains unknown. We therefore set out a prospective clinical investigation to determine both the reduction of RNFL thickness and the deterioration of cognitive function over a period of 25 months in 78 participants (mean age 72.31 ± 3.98 years, 52% men). The participants were categorized as stable participants whose cognitive status remained unchanged (n = 60) and converted participants whose cognitive status deteriorated, which was diagnosed by DSM-VI (for AD) and Petersens definition (for mild cognitive impairment) (n = 18). Here we show for the first time that the converted participants had greater reduction of RNFL thickness than the stable participants. Specifically, the reduction in the thickness of the inferior quadrant RNFL in the converted participants was greater than that in stable participants [-11.0 ± 12.8 (mean ± standard deviation) μm versus 0.4 ± 15.7 μm, p = 0.009]. These data showed that greater reduction in the inferior quadrant of RNFL thickness might indicate a higher risk for the old adults to develop cognitive deterioration. These findings have established a system to embark on a larger scale study to further test whether changes in RNFL thickness can serve as a biomarker of AD.

Brain-Wide Analysis of Functional Connectivity in First-Episode and Chronic Stages of Schizophrenia

Published reports of functional abnormalities in schizophrenia remain divergent due to lack of staging point-of-view and whole-brain analysis. To identify key functional-connectivity differences of first-episode (FE) and chronic patients from controls using resting-state functional MRI, and determine changes that are specifically associated with disease onset, a clinical staging model is adopted. We analyze functional-connectivity differences in prodromal, FE (mostly drug naïve), and chronic patients from their matched controls from 6 independent datasets involving a total of 789 participants (343 patients). Brain-wide functional-connectivity analysis was performed in different datasets and the results from the datasets of the same stage were then integrated by meta-analysis, with Bonferroni correction for multiple comparisons. Prodromal patients differed from controls in their pattern of functional-connectivity involving the inferior frontal gyri (Brocas area). In FE patients, 90% of the functional-connectivity changes involved the frontal lobes, mostly the inferior frontal gyrus including Brocas area, and these changes were correlated with delusions/blunted affect. For chronic patients, functional-connectivity differences extended to wider areas of the brain, including reduced thalamo-frontal connectivity, and increased thalamo-temporal and thalamo-sensorimoter connectivity that were correlated with the positive, negative, and general symptoms, respectively. Thalamic changes became prominent at the chronic stage. These results provide evidence for distinct patterns of functional-dysconnectivity across FE and chronic stages of schizophrenia. Importantly, abnormalities in the frontal language networks appear early, at the time of disease onset. The identification of stage-specific pathological processes may help to understand the disease course of schizophrenia and identify neurobiological markers crucial for early diagnosis.

Abnormal white matter microstructure in drug-naive first episode schizophrenia patients before and after eight weeks of antipsychotic treatment

BACKGROUND Abnormal white matter integrity has been reported among first episode schizophrenia patients. However, findings on whether it can be reversed by short-term antipsychotic medications are inconsistent. METHOD Diffusion tensor imaging (DTI) was obtained from 55 drug-naive first episode schizophrenia patients and 61 healthy controls, and was repeated among 25 patients and 31 controls after 8 weeks during which patients were medicated with antipsychotics. White matter integrity is measured using fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). These measures showing a group difference by Tract-based spatial statistics (TBSS) at baseline were extracted for longitudinal comparisons. RESULTS At baseline, patients exhibited lower FA, higher MD and higher RD versus controls in forceps, left superior longitudinal fasciculus, inferior fronto-occipital fasciculus, left corticospinal tract, left uncinate fasciculus, left anterior thalamic radiation, and bilateral inferior longitudinal fasciculi. FA values of schizophrenia patients correlated with their negative symptoms (r=-0.412, P=0.002), working memory (r=0.377, P=0.005) and visual learning (r=0.281, P=0.038). The longitudinal changes in DTI indices in these tracts did not differ between patients and controls. However, among the patients the longitudinal changes in FA values in left superior longitudinal fasciculus correlated with the change of positive symptoms (r=-0.560, p=0.004), and the change of processing speed (r=0.469, p=0.018). CONCLUSIONS White matter deficits were validated in the present study by a relatively large sample of medication naïve and first episode schizophrenia patients. They could be associated with negative symptoms and cognitive impairment, whereas improvement in white matter integrity of left superior longitudinal fasciculus correlated with improvement in psychosis and processing speed. Further examination of treatment-related changes in white matter integrity may provide clues to the mechanism of antipsychotic response and provide a biomarker for clinical studies.

Differential alterations of resting-state functional connectivity in generalized anxiety disorder and panic disorder

Generalized anxiety disorder (GAD) and panic disorder (PD) are most common anxiety disorders with high lifetime prevalence while the pathophysiology and disease‐specific alterations still remain largely unclear. Few studies have taken a whole‐brain perspective in the functional connectivity (FC) analysis of these two disorders in resting state. It limits the ability to identify regionally and psychopathologically specific network abnormalities with their subsequent use as diagnostic marker and novel treatment strategy. The whole brain FC using a novel FC metric was compared, that is, scaled correlation, which they demonstrated to be a reliable FC statistics, but have higher statistical power in two‐sample t‐test of whole brain FC analysis. About 21 GAD and 18 PD patients were compared with 22 matched control subjects during resting‐state, respectively. It was found that GAD patients demonstrated increased FC between hippocampus/parahippocampus and fusiform gyrus among the most significantly changed FC, while PD was mainly associated with greater FC between somatosensory cortex and thalamus. Besides such regional specificity, it was observed that psychopathological specificity in that the disrupted FC pattern in PD and GAD correlated with their respective symptom severity. The findings suggested that the increased FC between hippocampus/parahippocampus and fusiform gyrus in GAD were mainly associated with a fear generalization related neural circuit, while the greater FC between somatosensory cortex and thalamus in PD were more likely linked to interoceptive processing. Due to the observed regional and psychopathological specificity, their findings bear important clinical implications for the potential treatment strategy. Hum Brain Mapp 37:1459‐1473, 2016.

A randomized double-blind clinical trial on analgesic efficacy of fluoxetine for persistent somatoform pain disorder

OBJECTIVES To verify the efficacy and safety of fluoxetine in treating patients with persistent somatoform pain disorder (PSPD). METHODS In this 8-week, randomized double-blind placebo-controlled study, 80 patients with an ICD-10 diagnosis of PSPD were randomly assigned to receive 20mg fluoxetine or a placebo. Several psychological scales including Medical Outcomes Study Pain Measures (MOSPM), Hamilton Depression Scale-17 items (HAMD(17)) and Treatment Emergent Symptom Scale (TESS) were used to assess analgesic efficacy and safety of fluoxetine, and the possible analgesic mechanism of fluoxetine was preliminarily analyzed. All data were analyzed by SPSS11.5 with t-test, one-way ANOVA and a mixed-effects model repeated measures analysis. Intent-to-treat (ITT) analysis was performed and the last observation carry forward (LOCF) was used for missing values. RESULTS There was a significant difference of MOSPM total score between the fluoxetine and placebo group after 2 weeks of treatment. The analgesic effect of fluoxetine was related with treatment time, and depressive patients showed a better analgesic effect than non-depressive patients. An adverse effect of fluoxetine was scarcely found. CONCLUSIONS Fluoxetine has a better analgesic effect than a placebo in treating persistent somatoform pain disorder, and is considered a safe treatment; its analgesic effect may be related to an antidepressant effect.

Retinal nerve fiber layer thickness is associated with episodic memory deficit in mild cognitive impairment patients.

Changes in retinal nerve fiber layer (RNFL) thickness have been reported in patients with mild cognitive impairment (MCI), the pre-dementia stage of Alzheimers disease (AD). However, whether RNFL thickness is associated with specific cognitive impairment of MCI patients remains unknown. Therefore, we set out to investigate the potential association between RNFL thickness and episodic memory in MCI patients. Seventy five older adults (mean age 74 ± 3 years, 55% men) were included in the study. Fifty-two participants had normal cognition (NC), and 23 participants were diagnosed with MCI. RNFL thickness was obtained by optical coherence tomography measurement. Cognitive function was evaluated by the Repeatable Battery for the Assessment of Neuropsychological Status on the same day of the optical examination. We found that nasal quadrant RNFL thickness was positively associated with episodic memory scores in the participants with normal cognition: word list learning (r=0.392, p=0.004) and story recall (r=0.307, p=0.027). In the participants with MCI, however, the inferior quadrant RNFL thickness was inversely associated with the episodic memory score: word list learning (r=-0.652, p=0.001), story memory (r=-0.429, p=0.041), and story recall (r=-0.502, p=0.015,). The findings from this pilot study suggest that the inferior quadrant RNFL thickness was associated with specific episodic memory in MCI patients and could serve as a biomarker of MCI and AD. These findings would promote more studies to determine the potential application of RNFL as an AD biomarker.