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| 1 | MicroRNAs as diagnostic and therapeutic tools for Alzheimer's disease: advances and limitations显示文摘Alzheimer's disease(AD) is the most common age-related, progressive neurodegenerative disease. It is characterized by memory loss and cognitive decline and responsible for most cases of dementia in the elderly. Late-onset or sporadic AD accounts for > 95% of cases, with age at onset > 65 years. Currently there are no drugs or other therapeutic agents available to prevent or delay the progression of AD. The cellular and molecular changes occurring in the brains of individuals with AD include accumulation of β-amyloid peptide and hyperphosphorylated tau protein, decrease of acetylcholine neurotransmitter, inflammation, and oxidative stress. Aggregation of β-amyloid peptide in extracellular plaques and the hyperphosphorylated tau protein in intracellular neurofibrillary tangles are characteristic of AD. A major challenge is identifying molecular biomarkers of the early-stage AD in patients as most studies have been performed with blood or brain tissue samples(postmortem) at late-stage AD. Subjects with mild cognitive impairment almost always have the neuropathologic features of AD with about 50% of mild cognitive impairment patients progressing to AD. They could provide important information about AD pathomechanism and potentially also highlight minimally or noninvasive, easy-to-access biomarkers. MicroRNAs are dysregulated in AD, and may facilitate the early detection of the disease and potentially the continual monitoring of disease progression and allow therapeutic interventions to be evaluated. Four recent reviews have been published of microRNAs in AD, each of which identified areas of weakness or limitations in the reported studies. Importantly, studies in the last three years have shown considerable progress in overcoming some of these limitations and identifying specific microRNAs as biomarkers for AD and mild cognitive impairment. Further large-scale human studies are warranted with less disparity in the study populations, and using an appropriate method to validate the findings. | Bridget Martinez Philip V.Peplow | 2019 | Neural Regeneration Research2019，14，2： | 18 |
| 2 | Differentiating between Alzheimer’s disease, amnestic mild cognitive impairment, and normal aging via diffusion kurtosis imaging显示文摘Diffusion kurtosis imaging can be used to assess pathophysiological changes in tissue structure and to diagnose central nervous system diseases. However, its sensitivity in assessing hippocampal differences between patients with Alzheimer’s disease and those with amnestic mild cognitive impairment has not been characterized. Here, we examined 20 individuals with Alzheimer’s disease (11 men and 9 women, mean 73.2 ± 4.49 years), 20 with amnestic mild cognitive impairment (10 men and 10 women, mean 71.55 ± 4.77 years), and 20 normal controls (11 men and 9 women, mean 70.45 ± 5.04 years). We conducted diffusion kurtosis imaging, using a 3.0 T magnetic resonance scanner, to compare hippocampal differences among the three groups. The results demonstrated that the right hippocampal volume and bilateral mean kurtosis were remarkably smaller in individuals with Alzheimer’s disease compared with those with amnestic mild cognitive impairment and normal controls. Further, the mean kurtosis was lower in the amnestic mild cognitive impairment group compared with the normal control group. The mean diffusion in the left hippocampus was lower in the Alzheimer’s disease group than in the amnestic mild cognitive impairment and normal control groups, while the mean diffusion in the right hippocampus was lower in the Alzheimer’s disease group than in the normal control group. Fractional anisotropy was similar among the three groups. These results verify that bilateral mean kurtosis and mean diffusion are sensitive to the diagnosis of Alzheimer’s disease and amnestic mild cognitive impairment. This study was approved by the Ethics Review Board of Affiliated Sixth People’s Hospital of Shanghai Jiao Tong University, China on May 4, 2010 (approval No. 2010(C)-6). | Guo-Ping Song Ting-Ting Yao Dan Wang Yue-Hua Li | 2019 | Neural Regeneration Research2019，14，12： | 11 |
| 3 | The Glutamatergic Postrhinal Cortex–Ventrolateral Orbitofrontal Cortex Pathway Regulates Spatial Memory Retrieval显示文摘A deficit in spatial memory has been taken as an early predictor of Alzheimer’s disease(AD) or mild cognitive impairment(MCI). The uncinate fasciculus(UF) is a long-range white-matter tract that connects the anterior temporal lobe with the orbitofrontal cortex(OFC)in primates. Previous studies have shown that the UF impairment associated with spatial memory deficits may be an important pathological change in aging and AD, but its exact role in spatial memory is not well understood. The pathway arising from the postrhinal cortex(POR) and projecting to the ventrolateral orbitofrontal cortex(vlOFC)performs most of the functions of the UF in rodents.Although the literature suggests an association between spatial memory and the regions connected by the POR–vlOFC pathway, the function of the pathway in spatialmemory is relatively unknown. To further illuminate the function of the UF in spatial memory, we dissected the POR–vlOFC pathway in mice. We determined that the POR–vlOFC pathway is a glutamatergic structure, and that glutamatergic neurons in the POR regulate spatial memory retrieval. We also demonstrated that the POR–vlOFC pathway specifically transmits spatial information to participate in memory retrieval. These findings provide a deeper understanding of UF function and dysfunction related to disorders of memory, as in MCI and AD. | Xinyang Qi Zhanhong Jeff Du Lin Zhu Xuemei Liu Hua Xu Zheng Zhou Cheng Zhong Shijiang Li Liping Wang Zhijun Zhang | 2019 | Neuroscience Bulletin2019，35，3： | 7 |
| 4 | The efficacy and safety of nimodipine in acute ischemic stroke patients with mild cognitive impairment: a double-blind, randomized,placebo-controlled trial显示文摘Nimodipine might be effective in subcortical vascular dementia(VaD). Its benefit in preventing further cognitive decline in patients with acute ischemic stroke(AIS) and vascular mild cognitive impairment(VaMCI) remains to be established. In this multicenter, double-blind trial, we randomly assigned 654 eligible patients to nimodipine 30 mg three times a day or placebo. The primary outcome was any cognitive decline defined by the changes on the Mini-Mental State Examination(DMMSE à3) or vascular AD assessment scale cognitive subscale(DADAS-cog ! 4) at 6 months. Secondary outcomes included any distribution shift of DADAS-cog, DMMSE or cognitive improvement defined by DADAS-cog à2, or DMMSE ! 0. The primary outcome in the nimodipine group and placebo group were similar for DMMSE à3(4.18% and 7.22%, respectively, P = 0.15) and DADAS-cog ! 4(8.36% and 8.93% respectively,P = 0.88). The distribution shift of DADAS-cog and DMMSE differed significantly between the two groups(P = 0.03 and P = 0.05 respectively). Cognitive improvement occurred in 55.4% in the nimodipine group and 43.6% in the placebo group measured by DADAS-cog à2(Odds Ratio, 1.54; 95% confidence interval[CI] 1.10–2.14, P < 0.01) or 84.0% and 74.6% respectively by DMMSE ! 0(Odds Ratio, 1.79; 95% CI 1.18–2.70, P < 0.01). Nimodipine was associated with better cognitive function in the memory domain. The adverse events rate was similar in two groups. This study is registered with ClinicalTrials.gov,NCT01220622. Nimodipine did not show benefit to prevent cognitive decline in AIS patients with VaMCI, but improved cognition moderately, especially measured in the memory domain. | Huaguang Zheng Yilong Wang Anxin Wang Hao Li David Wang Xingquan Zhao Penglian Wang Haipeng Shen Lijun Zuo Yuesong Pan Zixiao Li Xia Meng Xianwei Wang Weixiong Shi Yi Ju Liping Liu Kehui Dong Chunxue Wang Rubo Sui Rong Xue Xiaoping Pan Xiaoyua Niu Benyan Luo Yi Sui Huali Wang Tao Feng Yongjun Wang | 2019 | Science Bulletin2019，64，2： | 5 |
| 5 | The role of the DLPFC in inductive reasoning of MCI patients and normal agings:An fMRI study显示文摘Previous studies of young people have revealed that the left dorsolateral prefrontal cortex(DLPFC) plays an important role in inductive reasoning.An fMRI experiment was performed in this study to examine whether the left DLPFC was involved in inductive reasoning of MCI patients and normal agings,and whether the activation pattern of this region was different between MCI patients and normal agings.The fMRI results indicated that MCI patients had no difference from normal agings in behavior performance(reaction time and accuracy) and the activation pattern of DLPFC.However,the BOLD response of the DLPFC region for MCI patients was weaker than that for normal agings,and the functional connectivity between the bilateral DLPFC regions for MCI patients was significantly higher than for normal agings.Taken together,these results indicated that DLPFC plays an important role in inductive reasoning of agings,and the functional abnormity of DLPFC may be an earlier marker of MCI before structural alterations. | YANG YanHui1,3,LIANG PeiPeng2,3,LU ShengFu2,3,LI KunCheng1,3 & ZHONG Ning2,3,4 1 Xuanwu Hospital,Capital Medical University,Beijing 100053,China 2 The International WIC Institute,Beijing University of Technology,Beijing 100124,China 3 Beijing Municipal Lab of Brain Informatics,Beijing 100124,China 4 Department of Life Science and Informatics,Maebashi Institute of Technology,Maebashi 371-0816,Japan | 2009 | Science China(Life Sciences)2009，52，8： | 5 |
| 6 | Traumatic axonal injury of the cingulum in patients with mild traumatic brain injury: a diffusion tensor tractography study显示文摘The cingulum,connecting the orbitofrontal cortex to the medial temporal lobe,involves in diverse cognition functions including attention,memory,and motivation.To investigate the relationship between the cingulum injury and cognitive impairment in patients with chronic mild traumatic brain injury,we evaluated the integrity between the anterior cingulum and the basal forebrain using diffusion tensor tractography in 73 patients with chronic mild traumatic brain injury(39 males,34 females,age 43.29±11.42 years)and 40 healthy controls(22 males,18 females,age 40.11±16.81 years).The patients were divided into three subgroups based on the integrity between the anterior cingulum and the basal forebrain on diffusion tensor tractography:subgroup A(n=19 patients)– both sides of the anterior cingulum were intact;subgroup B(n=36 patients)– either side of the anterior cingulum was intact;and subgroup C(18 patients)– both sides of the anterior cingulum were discontinued.There were significant differences in total Memory Assessment Scale score between subgroups A and B and between subgroups A and C.There were no significant differences in diffusion tensor tractography parameters(fractional anisotropy,apparent diffusion coefficient,and fiber volume)between patients and controls.These findings suggest that the integrity between the anterior cingulum and the basal forebrain,but not diffusion tensor tractography parameter,can be used to predict the cognitive function of patients with chronic mild traumatic brain injury.This study was approved by Yeungnam University Hospital Institutional Review Board(approval No.YUMC-2014-01-425-010)on August 16,2017. | Sung Ho Jang Seong Ho Kim Han Do Lee | 2019 | Neural Regeneration Research2019，14，9： | 4 |
| 7 | Study of brain morphology change in Alzheimer’s disease and amnestic mild cognitive impairment compared with normal controls显示文摘Background With an aggravated social ageing level, the number of patients with Alzheimer's disease (AD) is gradually increasing, and mild cognitive impairment (MCI) is considered to be an early form of Alzheimer's disease. How to distinguish diseases in the early stage for the purposes of early diagnosis and treatment is an important topic. Aims The purpose of our study was to investigate the differences in brain cortical thickness and surface area among elderly patients with AD, elderly patients with amnestic MCI (aMCI) and normal controls (NC). Methods 20 AD patients, 21 aMCIs and 25 NC were recruited in the study. FreeSurfer software was used to calculate cortical thickness and surface area among groups. Results The patients with AD had less cortical thickness both in the left and right hemisphere in 17 of the 36 brain regions examined than the patients with aMCI or NC. The patients with AD also had smaller cerebral surface area both in the left and right hemisphere in 3 of the 36 brain regions examined than the patients with aMCI or NC. Compared with the NC, the patients with aMCI only had slight atrophy in the inferior parietal lobe of the left hemisphere, and no significant difference was found. Conclusion AD, as well as aMCI (to a lesser extent), is associated with reduced cortical thickness and surface area in a few brain regions associated with cognitive impairment. These results suggest that cortical thickness and surface area could be used for early detection of AD. | Huanqing Yang Hua Xu Qingfeng Li Yan Jin Weixiong Jiang Jinghua Wang Yina Wu Wei Li Cece Yang Xia Li Shifu Xiao Feng Shi Tao Wang | 2019 | General Psychiatry2019，32，2： | 3 |
| 8 | Amyloid positron emission tomography and cognitive reserve显示文摘Alzheimer's disease(AD) is characterized by a nonlinear progressive course and several aspects influence the relationship between cerebral amount of AD pathology and the clinical expression of the disease. Brain cognitive reserve(CR) refers to the hypothesized capacity of an adult brain to cope with brain damage in order to minimize symptomatology. CR phenomenon contributed to explain the disjunction between the degree of neurodegeneration and the clinical phenotype of AD. The possibility to track brain amyloidosis(Aβ) in vivo has huge relevance for AD diagnosis and new therapeutic approaches. The clinical repercussions of positron emission tomography(PET)-assessed Aβ load are certainly mediated by CR thus potentially hampering the prognostic meaning of amyloid PET in selected groups of patients. Similarly, amyloid PET and cerebrospinal fluid amyloidosis biomarkers have recently provided new evidence for CR. The present review discusses the concept of CR in the framework of available neuroimaging studies and specifically deals with the reciprocal influences between amyloid PET and CR in AD patients and with the potential consequent interventional strategies for AD. | Matteo Bauckneht Agnese Picco Flavio Nobili Silvia Morbelli | 2015 | World Journal of Radiology2015，7，12： | 3 |
| 9 | Selective impairment of musical emotion recognition in patients with amnesic mild cognitive impairment and mild to moderate Alzheimer disease显示文摘Background:Patients with Alzheimer disease(AD)and amnesic mild cognitive impairment(aMCI)have deficits in emotion recognition.However,it has not yet been determined whether patients with AD and aMCI also experience difficulty in recognizing the emotions conveyed by music.This study was conducted to investigate whether musical emotion recognition is impaired or retained in patients with AD and aMCI.Methods:All patients were recruited from the First Affiliated Hospital of Anhui Medical University between March 1,2015 and January 31,2017.Using the musical emotion recognition test,patients with AD(n=16),patients with aMCI(n=19),and healthy controls(HCs,n=16)were required to choose one of four emotional labels(happy,sad,peaceful,and fearful)that matched each musical excerpt.Emotion recognition scores in three groups were compared using one-way analysis of variance(ANOVA)test.We also investigated the relationship between the emotion recognition scores and Mini-Mental State Examination(MMSE)using Pearson’s correlation analysis test in patients with AD and aMCI.Results:Compared to the HC group,both of the patient groups showed deficits in the recognition of fearful musical emotions(HC:7.88±1.36;aMCI:5.05±2.34;AD:3.69±2.02),with results of a one-way ANOVA confirming a significant main effect of group(F(2,50)=18.70,P<0.001).No significant differences were present among the three groups for the happy(F(2,50)=2.57,P=0.09),peaceful(F(2,50)=0.38,P=0.09),or sad(F(2,50)=2.50,P=0.09)musical emotions.The recognition of fearful musical emotion was positively associated with general cognition,which was evaluated by MMSE in patients with AD and aMCI(r=0.578,P<0.001).The correlations between the MMSE scores and recognition of the remaining emotions were not significant(happy,r=0.228,P=0.11;peaceful,r=0.047,P=0.74;sad,r=0.207,P=0.15).Conclusion:This study showed that both patients with AD and aMCI had decreased ability to distinguish fearful emotions,which might be correlated with diminished cognitive function. | Shan-Shan Zhou Xin Gao Ya-Juan Hu Yi-Ming Zhu Yang-Hua Tian Kai Wang | 2019 | Chinese Medical Journal2019，，19： | 1 |
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