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Objective To analyze the efficacy and adverse reactions of donepezil in the treatment of patients with a continuous disease spectrum of Alzheimer's disease(AD)with pharmacogenomics.Methods Seventy-two patients who took donepezil therapy at the time of initial molecular pa-thology diagnosis of AD continuous disease spectrum in Chinese PLA General Hospital from Jan-uary 2022 to January 2023 were recruited.Cells from the oral buccal mucosa were collected,and MassARRAY nucleic acid mass spectrometry was applied to detect the genotypes of CYP2D6,the gene encoding cytochrome P450 2D6 enzyme,and CHAT,the gene encoding acetylcholine trans-ferase.After 9 months of follow-up,drug efficacy was indirectly determined by neurological func-tion scales,caregiver evaluations,and drug prescribing behaviors,and thus,the 50 patients on donepezil alone were divide into effective group(n=28)and ineffective group(n=22).Seventy-two patients were divided into adverse reaction group(n=12)and no adverse reaction group(n=60).Multivariate logistic regression analysis was used to analyze the correlation between donepezil efficacy and pharmacogenomics.Results The frequencies of CHAT rs3793790 locus carrying G allele and rs2177370 locus carrying A allele were significantly higher in the effective group than the ineffective group(35.71％vs 9.09％,P=0.029;42.86％vs 9.09％,P=0.008).Multivariate lo-gistic regression analysis showed that donepezil was more effective in those who carrying rs3793790 G allele and/or rs2177370 A allele in the CHAT gene than those who carrying neither of the alleles(95％CI:1.20-34.47,P=0.030).There were no statistical differences in the CYP2D6 gene-adjusted activity score and whether or not carrying*10 between the patients with and without adverse reactions(P＞0.0 5).Conclusion In patients with a continuous spectrum of AD,donepezil efficacy is associated with CHAT gene polymorphisms,but there is no correlation between donepezil adverse reactions and CYP2D6 genotype.
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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.
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Anti-Sry-like high mobility group box (SOX) 1 antibodies (abs) are partly characterized onconeural autoantibodies (autoabs) due to their correlation with neoplastic diseases. AntiSOX1 abs are associated with various clinical manifestations, including Lambert-Eaton myasthenic syndrome (LEMS) and paraneoplastic cerebellar degeneration (PCD). However, the clinical characteristics of patients with anti-SOX1 abs have not been described in detail. This review systematically explores the reported patients with anti-SOX1 abs and analyzes these cases for demographic characteristics, clinical features, coexisting neuronal autoabs, neuroimaging findings, treatment, and clinical outcomes. In addition, considering that PCD is the most common paraneoplastic neurological syndrome and that the association between PCD and anti-SOX1 abs remains unclear, we focus on the presence of autoabs in relation to PCD and associated tumors. PCD-associated autoabs include various intracellular autoabs (e.g., anti-Hu, anti-Yo, anti-Ri, and anti-SOX1) and cell-surface autoabs (anti-P/Q-type voltage-gated calcium channel). Commonly involved tumors in PCD are small-cell lung cancer (SCLC), gynecological, and breast tumors. LEMS is the most common clinical symptom in patients with antiSOX1 abs, followed by PCD, and multiple neuronal autoabs coexist in 47.1% of these patients.SCLC is still the predominant tumor in patients with anti-SOX1 abs, while non-SCLC is uncommon. No consistent imaging feature is found in patients with anti-SOX1 abs, and there is no consensus on either the therapy choice or therapeutic efficacy. In conclusion, the presence of anti-SOX1 abs alone is a potential predictor of an uncommon paraneoplastic neurological disorder, usually occurring in the setting of LEMS, PCD, and SCLC. The detection of anti-SOX1 abs contributes to an early diagnosis of underlying tumors, given the diversity of clinical symptoms and the absence of characteristic neuroimaging features.
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Objective To study the association between white matter hyperintensities(WMH)and cognitive function in silent lacunar cerebral infarction patients and its risk factors.Methods One hundred and seventy-four silent lacunar cerebral infarction patients were included in this study. They underwent MRI to show the site and severity of their WMH,including degrees 0-3of periventricular WMH in 21,102,39,12patients respectively,and deep WMH in 19,53,86,16patients respectively.Then,their cognitive function scores were compared.Results The degree of WMH was significantly higher and the age was significantly older in silent lacunar cerebral infarction patients(P＜0.05).The situation memory,working memory and Simplified Intelligent State Scale score were significantly different in patients with different degrees of WMH in peripheral brain(P＜0.05,P＜0.01).The working memory was significantly different in patients with different degrees of WMH in deep brain(P＜0.05).Degrees 1and 2of periventricular WMH were the independent risk factors for the impaired working memory(β=-0.264,P=0.038;β=-0.325,P=0.011)while degree 3of periventricular WMH was the independent risk factor for the impaired cognitive function(β=-0.273,P=0.014).Conclusion The memory is easy to be impaired in silent lacunar cerebral infarction patients with WMH of aging brain.Periventricular WMH is the major risk factor for cognitive impairment.
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Objective To investigate the prevalence of cognitive and motor disorders as well as emotional and sleep abnormality in the veterans from military communities in Beijing. Methods The participants underwent a comprehensive in-person evaluation including detailed neuropsychological testing,Hospital Anxiety and Depression Scale and special questionnaires for movement and sleep disorders. Results The overall prevalence of cognitive impairment, extrapyramidal diseases was 32.7%, 8.8% . The prevalence of mild cognitive impairment, dementia, Parkinson disease, essential tremor, anxiety and depression was 26.2% , 6.5% , 2.0% , 6.1 % , 1.4% and 4.1% respectively. Prevalence of all kinds of sleep disorders ranged from 10. 3% to 53. 9%. The prevalence of cognitive impairment had no significant difference of sex, but were correlated to age and education, the correlation coefficient was 0. 326 and -0.221 ( P<0.01) . Conclusion Veterans from military communities had higher prevalence of cognitive impairment, extrapyramidal diseases and sleep disorders and lower that of anxiety and depression relatively.
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@#ObjectiveTo investigate the effects of swallowing training combined with real-time electrical stimulation on dysphagia after stroke. Methods17 patients, older than 80 years old, with dysphagia after stroke, were treated with Vocastim-Master Physiomed Elektromedizin. They were assessed with the Watian drinking water test, swallowing disorder evaluation, swallowing ability evaluation, and α. ResultsAll the assessment significantly improved in the 17 patients (P<0.001). ConclusionSwallowing training combined with real-time electrical stimulation can significantly improve the swallowing capacity of the patients older than 80 after stroke.
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@#ObjectiveTo determine the responsiveness of 3 assessment for swallowing disorder on elderly people. Methods40 elderly cases with were assessed with drinking test, classification of swallowing disorder, and swallowing ability evaluation before and 3 weeks after treatment. ResultsThe effect size was 1.04 for drinking test, 1.74 for classification of swallowing disorder and 2.06 for swallowing ability evaluation. The standardized response mean was 2.49 for drinking test, 2.35 for classification of swallowing disorder and 2.78 for swallowing ability evaluation. There was very significant difference before and after treatment in the score of all the scales (P<0.001). ConclusionDrinking test, classification of swallowing disorder, and swallowing ability evaluation are responsive for swallowing disorder in elderly people receiving rehabilitation.
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Objective To evaluate the roles of positron emission tomography (PET) with N-methyl [11C]2-(4' -methylaminophenyi-6-hydroxybenzathiazole) (11C-PIB) in the early diagnosis of Alzheimer's disease (AD).Methods Six AD patients,7 mild cognitive impairment (MCI) patients and 6 normal controls (NC) were diagnosed and assessed with brain PET with 11C-PIB.The emission images obtained at 5,25 and 45 min after 11C-PIB administration were analysed.Results Using visual analysis to summarize the characteristics of the imagings of each group: comparing to NC,the AD patients show high 11C -PIB up take,and low clearance rate of 11C-PIB at 45 min.The imagings of MCI group show heterogeneous,overlapping with AD and NC group.The statistical analysis shows: in AD group,the standard uptake value (SUV) ratio of parietal lobe,frontal lobe,temporal lobe,occipital lobe and hippocampal at 45 min was 1.91±0.21,2.09±0.41,1.92±0.35,1.66±0.41,1.55±0.28 respectively,and were higher than that of NC group (value being 1.48±0.53,1.57±0.64,1.36±0.53,1.27±0.40,1.17±0.33) with statistical significance,t=8.114,5.620,5.705,3.650 and 2.866,P=0.0001,0.0002,0.0002,0.0045 and 0.0170 respectively.In MCI group,the SUV ratio of parietal lobe,frontal lobe,temporal lobe,occipital lobe and hippocampal at 45 min was 1.48 ± 0.53,1.57 ± 0.64,1.36±0.53,1.27 ± 0.40,1.17±0.33 respectively,and were higher than that of NC group,but there was no statistical significance.Conclusion 11C-PIB PET imaging can differentiate AD patients from normal and anticipate the transformation of MCI patients.
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BACKGROUND:At present, some neurological imaging methods, including MRI, fMRI, 2-(1-(6-[(2-[18F]fluoroethyl)(methyl)amino]-2-naphthyi) ethylidene) malononitrile (18F-FDDNP) positron emission tomography (PET), are helpful but not specific for the diagnosis of Alzheimer disease (AD). 18F-FDG is a special marker of beta-amyloid (Aβ), thus AD can be diagnosed by 18F-FDDNP PET at early period.OBJECTIVE: To evaluate the role of 18F-FDDNP PET in the diagnosis of AD, and establish reliable clinical biological indexes for the diagnosis of AD patients.DESIGN: A controlled analysis.SETTINGS : Department of Geriatric Neurology and Department of Nuclear Medicine, the General Hospital of Chinese PLA. PARTICIPANTS: Patients visiting the General Hospital of Chinese PLA from May 2004 to March 2005 were selected. Informed consents were obtained from all the participants. ① AD group (n =7): (74.88±12.03) years old; Accorded with the criteria related to diagnosis of AD in NINCDS/ADRDA (National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer Disease and Related Disease Association) and revision of Diagnostic and statistical Manual (DSM-Ⅳ, 4th ed.); brain CT or magnetic resonance imaging (MRI) examination displayed that inter-uncus distance of temporal lobes was ≥ 30 mm. ② Vascular dementia group (n =6): (73.83±4.75) years old; Accorded with the diagnostic criteria of NINDS-AIREN (National Institute of Neurological Diseases and Stroke, USA) and DSM-Ⅳ for vascular dementia; Inter-uncus distance of temporal lobes ＜ 30 mm. ③ Control group (n =6): (71.17±3.71) years old; Without rarefaction of white matter; Intelligence examination was normal.METHODS: PET was performed in all the subjects. PET scanner type was SEIMENS ECAT EXACT HR. The tracer selected was 18F-FDDNP which had radiochemical purity higher than 95% and error of radioactivity measurement lower than 10%. The images were collected at 5, 25 and 45 minutes after injection of 18F-FDDNP. Horizontal and coronary tomograms of brain were obtained after reconstruction.MAIN OUTCOME MEASURES: Characteristics of 18F-FDDNP brain PET images.RESULTS: ① In the control group, signs of obvious atrophy of brain were not seen. At about 45 minutes, the radioactivity in cortex and subcortical nucleus groups was essentially cleared and the structures of brain could not be differentiated clearly. ② In the vascular dementia group, brain atrophy and enlargement of ventricular system to various degrees could be seen. The clearance of radioactivity at three time points was similar to that in the control images. ③ In the AD group, the brain was obviously atrophied and the ventricular system was enlarged. The clearance of radioactivity at the three time points was significantly different from the images of other two groups. The radioactivity in cortex and hippocampus was cleared slower. At 45 minutes, the gray matter could still be clearly differentiated from the white matter, but the radioactivity in corpus striatum and thalamus was not higher than that in cortex and much radioactivity retention could be seen in cortex and hippocampus.CONCLUSION: 18F-FDDNP PET brain images can differentiate AD and vascular dementia, and it is an effective imaging index for the diagnosis of AD.
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<p><b>OBJECTIVE</b>To study cognitive function and cerebral metabolic changes in patients with transient global amnesia (TGA).</p><p><b>METHODS</b>Three patients with TGA were given mini-mental state examination (MMSE), revised Wechsler memory scale (WMS-R) examination and magnetic resonance imaging (MRI) scans after they had been diagnosed as TGA. Using (18)F labelled deoxyglucose as tracer, patients were given a positron emission tomography (PET) examination at different periods during recovery.</p><p><b>RESULTS</b>No obvious abnormality was found in MMSE and MRI scans in the three patients. However, WMS-R examination and cerebral PET imaging displayed cognitive dysfunction of varying degrees and low metabolism in local areas related to memory in 2 of 3 patients.</p><p><b>CONCLUSIONS</b>In TGA patients, cognitive function and cerebral metabolic levels are closely correlated with duration of symptoms. It is necessary to stop the TGA attack as quickly as possible early time.</p>
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Amnesia, Transient Global , Diagnostic Imaging , Psychology , Cognition , Magnetic Resonance Imaging , Tomography, Emission-ComputedABSTRACT
Objective To investigate the effects of mifepristone on the ultrastructure of Hofbauer cells in human early pregnant placenta. Methods Twenty 6-9 week pregnant women with indications of pregnancy termination were recruited and randomlied to mifepristone (n=10) and D & C group (n=10).Villi were collected and studied with transmission electron microscope. Results In comparison with the control group,the ultrastructure of Hofbauer cells of mifepristone group showed the following changes: the cells were markedly edematous. The number of cytoplasmic processes of Hofbauer cells deceased obviously. In the cytoplasm of Hofbauer cells,the size of vacuoles enlarged and of mitochondrias minimized.Rough endoplasmic reticulum and Golgi complex were under-developed.Lysosomes were rare.The nuclei enlarged and showed irregular shape. Conclusions Mifepristone may change the phagocytosis'water and electrolyte transportation and immunological function of Hofbauer cells by influencing the ultrastructure of the Hofbauer cells.Therefore it can influence the development of pregnancy.
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Objective To investigate the clinical effects of Shenlong decoction(main ingredients consisted of ginsent root,radix polygonimultiflori,Pheretima,Ligusticum wallichii,Fructas Alpiniae oryphyllee etc.)on the treatment of cerebral vascular dementia (VD)in the elderly patients.Methods VD in all the patients(age:72.1?5.3 years old)was diagnosed according to the APA criteria, and the cerebrovascular diseases were confirmed by CT or MRI.68 patients were divided into 2 groups randomly.The experimental group consisting of 36 patients was given Chinese traditional medicine,Shenlong decoction,orally 500ml q.i.d.for 3 months,and the other 32 patients were given acetamide pyrrolidone(piracetam)orally 1.6g,tid for 3 months as a control group.The MMSE(Mini Mental State Examination)and BBS(Bless Behaviour Schedule)were used to evaluate the cognitive function and the daily activity in those patients be- fore and after treatment.Results After treatment,the scores of cognition and daily activity were improved in all the patients with VD. The effective rate in the Shenlong group was 52.8%,and 53.13% in the piracetam group.There was no significant difference in the im- provement of the short time memory and orientation ability between the two groups.However,compared with the control group,the score of daily activity was significantly improved in the Shenlong decoction group only(P