Alzheimer's disease is the most common cause of dementia.Current treatment options for Alzheimer's disease are very limited, and non-drug treatment is receiving more and more attention.Cognitive intervention is a relatively new non-drug treatment for Alzheimer's disease.A large number of previous studies have confirmed that cognitive intervention can prevent and mitigate clinical symptoms of Alzheimer's disease.In this review, we systematically introduce cognitive intervention as a prevention tool for Alzheimer's disease and its ability to alleviate clinical symptoms of the disease, and put forward suggestions for the future application of cognitive intervention in Alzheimer's disease.

Objective:To study on performance comparison between clinic digital memory assessment and previously used assessments in dementia risk screening.To compare the performance comparison between Beijing Aging Brain Rejuvenation Initiative(BABRI)Brain Health System's Clinic Digital Memory Detection as study and Alzheimer Disease-8(AD8)and the Brief Community Screening Instrument for Dementia(BCSID)as controls, We calculated and evaluated the accuracy, sensitivity and specificity of screening Mild cognitive impairment(MCI)among these tests.Furthermore, BABRI Brain Health System was used to conduct a large sample brain health examination and early dementia screening to test the validity, adaptability and stability of the evaluation results by BABRI Brain Health System'Clinic Digital Memory Detection.Methods:Dataset 1 contained 669 elderly subjects from five communities in Beijing were recruited according to inclusion and exclusion standard.The diagnosis of MCI was based on the full set of neuropsychological scale and Petersen standard.Dataset 1 was used to compare the discriminant effect of BABRI Brain Health System'Clinic Digital Memory Detection as study versus AD8 and BCSID as controls.The sensitivity, specificity, positive predictive value, negative predictive value and Youden index of each measurement tool were calculated.Then, the receiver operator characteristic(ROC)curve was prepared to compare the discrimination ability of MCI between each measurement tool.While the area under the curve(AUC)of different tools was compared by Wald χ2 test.Dataset 2 contained 284 103 subjects from 16 communities in Beijing, which were used to test the applicability of large sample screening in BABRI Brain Health System. Results:77 patients with MCI were found among 666 people, and incidence rate was 11.56% using the full set of neuropsychological scales in dataset 1.Compared with the results of other tests, the sensitivity of BABRI Brain Health System to correctly distinguish MCI was 0.753, which was close to BCSID, and better than AD8.In addition, BABRI Brain Health System's Youden's index was 0.741 and AUC was 0.905, which suggested that the specificity, positive predictive value, negative predictive value and cognitive domain coverage of MCI screening were generally better in BABRI Brain Health System than in AD8 and BCSID.Finally, the Brain Health Examination results of 284, 000 people in dataset 2 showed that the high-risk detection rate of MCI(8.65%)of the tool for people over 50 years old under a large sample was quite close to the results of dataset 1(8.67%), indicating that the BABRI Brain Health System had high stability.Conclusions:BABRI Brain Health System has not only high sensitivity and specificity, but also wide cognitive field coverage and high stability.BABRI Brain Health System is suitable for large-scale brain health examination and dementia risk screening in grass-roots communities, and is worthy of popularization.

Objective:To investigate the phenotypic heterogeneity and gene penetrance of a dopa-responsive dystonia (DRD) family.Methods:The clinical data of a four-generation DRD family (including 3 patients) admitted to Department of Neurology, China-Japan Friendship Hospital in November 2015 were retrospectively analyzed. The proband underwent whole exon sequence, and the genetic result was verified by Sanger sequencing. Sanger sequencing was performed in the other 14 subjects in the family; the genotypes and clinical manifestations were analyzed.Results:In 15 subjects underwent genetic testing, 7 had heterozygous mutations c.284G>A (p.P95L) in GCH1 gene; the penetrance of GCH1 gene mutation in this family was 0.43 (3/7), the gene penetrance in male was 0.25 (1/4), and the gene penetrance in female was 0.67 (2/3). Three subjects in the DRD family had clinical symptoms; the clinical symptoms of the two female patients were more severe than those of the male patient; the severity of clinical symptoms differed greatly between the 2 female patients. Conclusion:There is a wide intrafamilial phenotypic heterogeneity in DRD family members carrying the same gene mutation, and the phenotype is gender-related; the gene penetrance in male is lower than that in female, and the clinical phenotype is often milder.

Objective:To investigate the clinical phenotypes, imaging features and pathogenic variants of ANO10 gene related autosomal recessive spinocerebellar ataxia-10 (SCAR10).Methods:A cohort of 30 probands of autosomal recessive cerebellar ataxia pedigrees from China-Japan Friendship Hospital from 2018 to 2020 were collected. Friedreich ataxia and other causes of acquired ataxia were excluded, then probands were detected by whole-exome sequencing (WES), and potential pathogenic variants were confirmed by Sanger sequencing and validated in all family members. Clinical phenotypes and auxiliary examinations of the patients were analyzed in detail.Results:A pedigree of SCAR10 caused by ANO10 gene mutations was identified through WES. The 40-year-old male proband of this pedigree carried compound heterozygous mutations: c.1219-2A>C and c.1163-2A>G of the ANO10 gene, both of which were novel mutations, and Sanger sequencing revealed these two mutations were respectively inherited from his healthy parents. Bioinformatic analysis predicted these two mutations were pathogenic. The proband exhibited progressive unsteady walk, dysarthria, mild cognitive impairment. His plasma total coenzyme Q 10 was decreased (0.76 μg/ml). Brain magnetic resonance imaging showed remarkable cerebellar atrophy. Conclusions:Through WES, a SCAR10 patient caused by novel compound heterozygous mutations of ANO10 gene was identified, which is rare in China. The main clinical manifestation was progressive cerebellar ataxia and cognitive decline, and brain image showed remarkable cerebellar atrophy.

Objective:To explore the value of triple fusion positron emission tomography (PET)/MRI in location of epileptogenic focus in patients with focal cortical dysplasia (FCD).Methods:Three patients with refractory partial epilepsy, admitted to our hospital from December 2016 to June 2017, were chosen in our study. The raw MRI and PET images of these patients were processed using Freesurfer and FSL image processing softwares. After extraction and coregistration, precise PET/MRI fusion images were obtained; and the grey-white matter dividing line was highlighted on this fusion image to form triple-fusion images to observe the hypometabolic area and clarify the location.Results:Triple-fusion images of these 3 patients were acquired. In patient 1, a marked decrease in metabolism was noted in the gyrus region delineated by the gray-white matter boundary in the right cingulate gyrus. In patient 2, the area with slightly increased local signal in the right superior frontal gyrus (MRI FLAIR sequence) was the area with reduced metabolism. In patient 3, an area of local decreased metabolism was noted in the right cingulate gyrus. The preoperative evaluation of all 3 patients showed that the above areas were epileptic foci; the patients were followed up for 2 years after surgical resection, no clinical seizures occurred in all patients, and antiepileptic drugs were gradually stopped. All 3 patients were diagnosed as having FCD by postoperative pathology.Conclusion:Triple fusion PET/MRI is a powerful way to assist FCD diagnosis, especially for those FCD cases which are difficult to be diagnosed by other imaging methods, and has a potential clinical application value in epilepsy patients.

Objective:To analyze the characteristics of the apolipoprotein E(Apo E)genotype and cognitive impairment in patients with cerebral microbleeds(CMBs)and positive β-amyloid(Aβ)by using [18F]-AV45 positron emission tomography(PET).Methods:From September 2015 to May 2018, 152 patients with cognitive impairment and CMBs on the susceptibility-weighted imaging(SWI)sequence of head MRI at the neurology department of our hospital, assessed by mini-mental status examination(MMSE)score ≤26 and Montreal cognitive assessment(MoCA)≤25, were consecutively recruited in this retrospective study.After assessment with the inclusion and exclusion criteria, 69 patients aged 68.8±9.3 years were considered eligible for further analysis.Patients were divided into the Aβ-positive group(Aβ + Group, n=37)and the Aβ-negative group(Aβ -Group, n=32)after cognitive assessment, ApoE genotyping and [18F]-AV45 PET examination.Twenty-one healthy elderly controls(HC Group)who took health examination during the same period were enrolled.The results of cognitive assessment and Apo E genotyping were compared between the three groups. Results:The positive rate of the ApoE ε4 allele was 35.6%(32/90), 56.8%(21/37), 18.8%(6/32), and 23.9%(5/21)in the Aβ + , Aβ -and HC groups, respectively, with statistical significant differences between the groups( χ2=12.467, P<0.01). There were significant differences in the positive rate of the ApoE ε4 allele between the Aβ + and HC groups and between the Aβ + and Aβ -groups( χ2=5.880 and 10.407, P<0.05 and P<0.01). The percentage of patients with deep cerebral microbleeds was higher(56.3% or 18/32 vs.8.1% or 3/37, χ2=18.784, P<0.01)and of patients with lobar hemorrhage was lower(12.5% or 4/32 vs.45.9% or 17/37, χ2=9.066, P<0.01)in the Aβ -group than in the Aβ + group, while there was no significant difference in the percentage of patients with mixed cerebral microbleeds between the Aβ -and Aβ + groups( χ2=1.556, P>0.05). There were significant differences in cognitive function between the Aβ + and HC groups, in memory, executive function, visuospatial ability and language between the Aβ + and Aβ -groups, and in executive function, visuospatial ability and attention between the Aβ -and HC groups. Conclusions:Cognitive impairment is more extensive and severe in CMBs patients with Aβ deposition and is associated with positive ApoE ε4.

Objective:To investigate the clinical phenotypes, imaging features and pathogenic variants of POLR3B gene related autosomal recessive cerebellar ataxia with hypogonadism.Methods:A female proband from a Chinese non-consanguineous family was admitted to Department of Neurology, China-Japan Friendship Hospital in March 2016, performed detailed physical and auxiliary examinations and excluded acquired causes of cerebellar ataxia. Genomic DNA was extracted from peripheral blood of the proband and conducted whole exome sequencing (WES) and verified in her asymptomatic parents. Potential pathogenic variants were validated by Sanger sequencing.Results:The proband exhibited progressive unsteady walk, cognitive impairment, dysarthria and dysphagia, dystonia, congenital cataract, hypogonadism as well as delayed puberty, amenorrhea and short stature and was effectively treated by hormone therapy. Magnetic resonance imaging of her brain showed diffused hypomyelination of white matter, relatively sparing the thalamus, globus pallidus, and optic radiations, as well as cerebellar atrophy and thin corpus callosum. X ray of her chest revealed thoraco-lumbar scoliosis. WES identified compound heterozygous mutations c.479A>C (p. E160A) and c.2657G>C (p.R886T) of POLR3B gene in this patient, and they were novel mutations, which were respectively inherited from her father and mother validated by Sanger sequencing. Bioinformatic analysis predicted these two mutations were pathogenic.Conclusion:The clinical and imaging features of POLR3B-associated leukodystrophy with hypogonadism were considerably evident, diagnosis and treatment of which should be conducted as early as possible.

OBJECTIVE: To explore the clinical, neuropathological and genetic characteristics of a patient with Perrault syndrome caused by TWNK mutation. METHODS: Potential variation of the TWNK gene was detected by next-generation sequencing (NGS) and verified by Sanger sequencing. RESULTS: The patient has featured primary amenorrhoea and progressive sensorineural hearing loss since childhood. She also had gait anormaly, distal limb atrophy and weakness, and nystagmus. Further study confirmed sensory neuronopathy accompanied with upper and lower motor neuron involvement as well as cerebellum atrophy. NGS has identified two heterozygous variants of the TWNK gene, namely c.794G>A (p.Arg265His) and c.1181G>A (p.Arg394His). Sanger sequencing confirmed that c.1181G>A (p.Arg394His), a known pathogenic variant, was derived from her farther, while c.794G>A(p.Arg265His), a novel variant, was derived from her mother and likely pathogenic according to the ACMG guidelines. CONCLUSION Perrault syndrome is a group of disorders with a high phenotypic heterogeneity. The compound heterozygous variation of c.794G>A (p.Arg265His) and c.1181G>A(p.Arg394His) of the TWNK gene may underlie Perrault syndrome in the patient.
Child ; Female ; Genetic Testing ; Gonadal Dysgenesis, 46,XX ; Hearing Loss, Sensorineural ; Humans ; Pedigree

Objective To investigate and compare the language features among patients with behavioral variant frontotemporal dementia(bv-FTD),Alzheimer's disease(AD) and healthy controls,and to determine the clinical value of language tests in the diagnosis and differential diagnosis of the two kinds of dementia diseases.Methods A total of 17 bv-FTD patients,18 AD patients and 18 healthy controls were enrolled in Beijing hospital from Nov.2012 to Dec.2013.The language performances in four aspects of listening,speaking,reading and writing by seven items of listening comprehension,repetition,naming,speaking,read aloud,reading comprehension and writing were compared by using the one-way analysis of variance(ANOVA)and least significant difference(LSD)tests.Results There were significant differences among the three groups in speaking general scores (AD 128± 46,bv-FTD 113 ± 19,controls 158 ± 13) (F =23.34,P =0.049) and in writing (AD 8 ± 5,bv-FTD 8 ± 4,controls 11 ± 1) (F =27.07,P =0.000).A t rend of statistical difference was observed in general scores of listening comprehension(F =20.96,P =0.060).No difference was found in general scores of repetition,in naming,in reading aloud and in reading comprehension(all P ＞ 0.05).As compared with controls,bv-FTD patients were comprehensively impaired in sub-items of listening comprehension,in naming and in speaking(all P ＜0.05).As compared with controls,AD patients were significantly impaired in a few sub-items of listening comprehension,in naming and in speaking(P ＜0.05).There were significant differences in naming objects,grammar and word finding between AD patients and bv-FTD patients(51± 19 vs.47±13,6±1 vs.6±1,6±1 vs.6±1,P=0.037,0.010 and 0.021,respectively).Conclusions The detailed language examinations are helpful for screening AD and bv-FTD.However,the values are limited in the differential diagnosis between the two types of dementia diseases.It is necessary to combine the detailed language examinations with other tests.

Subjective memory decline is one of the most common symptoms reported in the elderly,which is considered as a high-risk factor for dementia.This article presented an overview of an update of definition and epidemiology of subjective memory decline,reviewed its risk factors,and summarized neuroimaging changes in brain structure and function.Finally,some suggestions for future research were also proposed.