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BACKGROUND AND PURPOSE: Cerebral small vessel disease is characterized by progressive cerebral white matter changes (WMCs). This study aimed to compare the effects of cilostazol and aspirin on changes in WMC volume in patients with cerebral small vessel disease. METHODS: In a multicenter, double-blind, randomized controlled trial, participants with moderate or severe WMCs and at least one lacunar infarction detected on brain magnetic resonance imaging were randomly assigned to the cilostazol and aspirin groups in a 1:1 ratio. Cilostazol slow release (200 mg) or aspirin (100 mg) capsules were administered once daily for 2 years. The primary outcome was the change in WMC volume on magnetic resonance images from baseline to 2 years. Secondary imaging outcomes include changes in the number of lacunes or cerebral microbleeds, fractional anisotropy, and mean diffusivity on diffusion tensor images, and brain atrophy. Secondary clinical outcomes include all ischemic strokes, all ischemic vascular events, and changes in cognition, motor function, mood, urinary symptoms, and disability. RESULTS: Between July 2013 and August 2016, 256 participants were randomly assigned to the cilostazol (n=127) and aspirin (n=129) groups. Over 2 years, the percentage of WMC volume to total WM volume and the percentage of WMC volume to intracranial volume increased in both groups, but neither analysis showed significant differences between the groups. The peak height of the mean diffusivity histogram in normal-appearing WMs was significantly reduced in the aspirin group compared with the cilostazol group. Cilostazol significantly reduced the risk of ischemic vascular event compared with aspirin (0.5 versus 4.5 cases per 100 person-years; hazard ratio, 0.11 [95% CI, 0.02-0.89]). CONCLUSIONS: There was no significant difference between the effects of cilostazol and aspirin on WMC progression in patients with cerebral small vessel disease. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01932203.
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Aspirina/administração & dosagem , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/tratamento farmacológico , Cilostazol/administração & dosagem , Imageamento por Ressonância Magnética , Substância Branca , Idoso , Idoso de 80 Anos ou mais , Aspirina/efeitos adversos , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/etiologia , Doenças de Pequenos Vasos Cerebrais/complicações , Cilostazol/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Substância Branca/irrigação sanguínea , Substância Branca/diagnóstico por imagemRESUMO
BACKGROUND AND AIMS: Little is known about the association between non-alcoholic fatty liver disease (NAFLD) and dementia. Given that hepatic steatosis is linked to abnormal fat metabolism, and fat dysregulation in the brain is related to dementia, we aimed to investigate whether NAFLD is associated with an increased risk of dementia. METHODS: We conducted a nationwide cohort study involving 4 031 948 subjects aged 40-69 years who underwent ≥2 health check-ups provided by the National Health Insurance Service in Korea between January 2004 and December 2007. Based on the hepatic steatosis index (HSI), subjects were categorized into non-NAFLD (HSI <30 at all check-ups) and NAFLD (HSI >36 at one or more check-ups). Dementia defined by ICD-10 codes with prescription data was followed up until December 2017. Cox proportional hazards regression models analysed the dementia risk. RESULTS: At baseline, 31.3% had NAFLD. During the median follow-up of 9.5 years, 138 424 in NAFLD group and 69 982 in non-NAFLD group developed dementia. NAFLD group was associated with a higher risk of dementia than non-NAFLD group on multivariable-adjusted analysis (hazard ratio [HR], 1.05; p < .001), competing risk analysis (HR, 1.08; p < .001) and propensity-score matched analysis (HR, 1.09; p < .001). The association between NAFLD and dementia risk was more prominent among females (HR, 1.16; p < .001). The association was stronger among non-obese NAFLD subjects (BMI <25 kg/m2 , HR, 1.09; p < .001) than obese NAFLD subjects. CONCLUSIONS: This nationwide study found that NAFLD is associated with an increased risk of dementia. The association was prominent among females and non-obese NAFLD subjects.
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Demência , Hepatopatia Gordurosa não Alcoólica , Estudos de Coortes , Demência/epidemiologia , Demência/etiologia , Feminino , Humanos , Masculino , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , República da Coreia/epidemiologia , Medição de Risco , Fatores de RiscoRESUMO
Parosmia, defined as the distorted perception of an odor stimulus, has been reported to be associated with head trauma, upper respiratory tract infections, sinonasal diseases, and toxin/drug consumption. To date, little is known about parosmia in right-lateralized semantic variant primary progressive aphasia. A 60-year-old right-handed man presented with a 2-year history of parosmia and prosopagnosia. Brain magnetic resonance imaging demonstrated severe atrophy of the right anterior and mesial temporal lobe, particularly in the fusiform cortex and the regions known as the primary olfactory cortex. 18F-fluorodeoxyglucose position emission tomography showed asymmetric hypometabolism of the bilateral temporal lobes (right > left). We clinically diagnosed him with right-lateralized semantic variant primary progressive aphasia. As the right hemisphere is known to be more involved in the processing of pleasant odors than the left hemisphere, we speculate that the unique manifestation of parosmia observed in this patient might be associated with the lateralization of the olfactory system.
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Afasia Primária Progressiva/diagnóstico por imagem , Lateralidade Funcional , Transtornos do Olfato , Afasia Primária Progressiva/patologia , Atrofia/patologia , Fluordesoxiglucose F18 , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos/estatística & dados numéricos , Transtornos do Olfato/etiologia , Tomografia por Emissão de Pósitrons , Prosopagnosia/etiologia , Lobo Temporal/patologiaRESUMO
BACKGROUND: The K variant of butyrylcholinesterase (BCHE-K) exhibits a reduced acetylcholine-hydrolyzing capacity; so the clinical response to rivastigmine may differ in Alzheimer's disease (AD) patients with the BCHE-K gene. OBJECTIVE: To investigate the clinical response to rivastigmine transdermal patch monotherapy or memantine plus rivastigmine transdermal patch therapy in AD patients based on the BCHE-K gene. METHODS: A total of 146 probable AD patients consented to genetic testing for butyrylcholinesterase and underwent the final efficacy evaluations. Responders were defined as patients with an equal or better score on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) at 16 weeks compared to their baseline score. RESULTS: BCHE-K carriers showed a lower responder rate on the ADAS-cog than non-carriers (38.2 vs. 61.7%, p = 0.02), and this trend was evident in AD patients with apolipoprotein E ε 4 (35 vs. 60.7%, p = 0.001). The presence of the BCHE-K allele predicted a worse response on the ADAS-cog (odds ratio 0.35, 95% confidence interval 0.14-0.87), after adjusting for demographic and baseline cognitive and functional variables. CONCLUSION: The BCHE-K genotype may be related to a poor cognitive response to rivastigmine patch or memantine add-on therapy, especially in the presence of apolipoprotein E ε 4.
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Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Butirilcolinesterase/genética , Memantina/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Rivastigmina/administração & dosagem , Idoso , Alelos , Apolipoproteína E4/genética , Feminino , Testes Genéticos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Adesivo TransdérmicoRESUMO
Apelin, which is an endogenous ligand for the orphan G-protein-coupled receptor APJ, was reported to be up-regulated by hypoxia-inducible factor 1-α (HIF1-α) in hypoxia- and insulin-treated cell systems. However, a negative transcriptional regulator of apelin has not yet been identified. In this study, we showed that apelin is down-regulated by ATF4 via the pro-apoptotic p38 MAPK pathway under endoplasmic reticulum (ER) stress. First, we analyzed the human apelin promoter to characterize the effects of ER stress on apelin expression in hepatocytes. Treatment with thapsigargin, an inducer of ER stress, and over-expression of ATF4 decreased apelin expression in hepatocytes. This work identified an ATF4-responsive region within the apelin promoter. Interestingly, ATF4-mediated repression of apelin was dependent upon the N-terminal domain of ATF4. C/EBP-ß knockdown experiments suggest that C/EBP-ß, which acts as an ATF4 binding partner, is critical for the ER stress-induced down-regulation of apelin. We also demonstrated that ATF4 regulates apelin gene expression via p38 pathways. Ectopic expression of constitutively active MKK6, an upstream kinase of p38, suggested that activation of the p38 pathway is sufficient to induce ATF4-mediated repression of apelin. Moreover, apelin enhanced cell migration in a wound healing assay in a p38 MAPK-dependent manner. Furthermore, analysis of caspase-3 activation indicated that ATF4 knockdown up-regulated apelin expression, leading to the inability of MKK6 (CA) to exert pro-apoptotic effects. Taken together, our results suggest that ATF4-mediated repression of apelin contributes substantially to the pro-apoptotic effects of p38.
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Fator 4 Ativador da Transcrição/genética , Estresse do Retículo Endoplasmático , Peptídeos e Proteínas de Sinalização Intercelular/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Fator 4 Ativador da Transcrição/metabolismo , Apelina , Apoptose , Proteína beta Intensificadora de Ligação a CCAAT/genética , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Caspase 3/metabolismo , Movimento Celular , Regulação para Baixo , Inibidores Enzimáticos/farmacologia , Células Hep G2 , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , MAP Quinase Quinase 6/metabolismo , Sistema de Sinalização das MAP Quinases , Regiões Promotoras Genéticas , Tapsigargina/farmacologiaRESUMO
Accumulating evidence suggests that endoplasmic reticulum (ER) stress plays a major role in the development of many diseases. A previous study indicated that the apoptotic regulator p53 is significantly increased in response to ER stress and participates in ER stress-induced apoptosis. However, the regulators of p53 expression during ER stress are still not fully understood. Here, we investigated whether p53 contributes to the impairment of Pin1 signaling under ER stress. We found that treatment with thapsigargin, a stimulator of p53 expression and an inducer of ER stress, decreased Pin1 expression in HCT116 cells. Also, we identified functional p53 response elements (p53REs) in the Pin1 promoter. Overexpression of p53 significantly decreased Pin1 expression in HCT116 cells while abolition of p53 gene expression induced Pin1 expression. Pin1 expression was significantly increased by treatment with the p53 inhibitor pifithrin-α or down-regulation of p53 expression. Taken together, ER stress decreased Pin1 expression through p53 activation, and this mechanism may be associated with ER stress-induced cell death. These data reported here support the importance of Pin1 as a potential target molecule mediating tumor development.
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Estresse do Retículo Endoplasmático , Regulação Enzimológica da Expressão Gênica , Peptidilprolil Isomerase de Interação com NIMA/biossíntese , Peptidilprolil Isomerase de Interação com NIMA/genética , Proteína Supressora de Tumor p53/metabolismo , Apoptose , Sobrevivência Celular , Células Cultivadas , Células HCT116 , Humanos , Peptidilprolil Isomerase de Interação com NIMA/metabolismoAssuntos
Peptídeos beta-Amiloides/metabolismo , Afasia Primária Progressiva/complicações , Transtornos Cognitivos/etiologia , Semântica , Idoso , Compostos de Anilina/metabolismo , Compostos de Anilina/farmacocinética , Afasia Primária Progressiva/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Tomografia por Emissão de Pósitrons , Ligação Proteica/efeitos dos fármacos , Estilbenos/metabolismo , Estilbenos/farmacocinética , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/patologiaAssuntos
Infarto Cerebral/complicações , Infarto Cerebral/diagnóstico , Neurossífilis/complicações , Neurossífilis/diagnóstico , Doenças Talâmicas/complicações , Doenças Talâmicas/diagnóstico , Idoso , Encéfalo/diagnóstico por imagem , Infarto Cerebral/tratamento farmacológico , Diagnóstico Diferencial , Humanos , Masculino , Neurossífilis/tratamento farmacológico , Doenças Talâmicas/tratamento farmacológicoRESUMO
BACKGROUND AND OBJECTIVE: To investigate the clinical relevance of CSF myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG) testing in a large multicenter cohort. METHODS: In this multicenter cohort study, paired serum-CSF samples from 474 patients with suspected inflammatory demyelinating disease (IDD) from 11 referral hospitals were included. After serum screening, patients were grouped into seropositive myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD, 31), aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4-IgG + NMOSD, 60), other IDDs (217), multiple sclerosis (MS, 45), and non-IDDs (121). We then screened CSF for MOG-IgG and compared the clinical and serologic characteristics of patients uniquely positive for MOG-IgG in the CSF to seropositive patients with MOGAD. RESULTS: Nineteen patients with seropositive MOGAD (61.3%), 9 with other IDDs (CSF MOG + IDD, 4.1%), 4 with MS (8.9%), but none with AQP4-IgG + NMOSD nor with non-IDDs tested positive in the CSF for MOG-IgG. The clinical, pathologic, and prognostic features of patients uniquely positive for CSF MOG-IgG, with a non-MS phenotype, were comparable with those of seropositive MOGAD. Intrathecal MOG-IgG synthesis, observed from the onset of disease, was shown in 12 patients: 4 of 28 who were seropositive and 8 who were uniquely CSF positive, all of whom had involvement of either brain or spinal cord. Both CSF MOG-IgG titer and corrected CSF/serum MOG-IgG index, but not serum MOG-IgG titer, were associated with disability, CSF pleocytosis, and level of CSF proteins. DISCUSSION: CSF MOG-IgG is found in IDD other than MS and also in MS. In IDD other than MS, the CSF MOG-IgG positivity can support the diagnosis of MOGAD. The synthesis of MOG-IgG in the CNS of patients with MOGAD can be detected from the onset of the disease and is associated with the severity of the disease. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that the presence of CSF MOG-IgG can improve the diagnosis of MOGAD in the absence of an MS phenotype, and intrathecal synthesis of MOG-IgG was associated with increased disability.
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Autoanticorpos/líquido cefalorraquidiano , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/líquido cefalorraquidiano , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/diagnóstico , Glicoproteína Mielina-Oligodendrócito/imunologia , Adolescente , Adulto , Autoanticorpos/sangue , Biomarcadores/líquido cefalorraquidiano , Estudos de Coortes , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/sangue , Pessoas com Deficiência , Feminino , Humanos , Imunoglobulina G , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
RATIONALES: Cholinergic modification by anticholinergic medication can produce adverse effects in central nervous system (CNS) and cyclopentolate is an antimuscarinic agent widely used for ophthalmologic management. We demonstrate a rare case of hyperactive delirium caused by topical administration of cyclopentolate in a patient with amnestic mild cognitive impairment (MCI) due to Alzheimer's disease (AD). PATIENT CONCERNS: A 74-year-old man showed acute confusion after preparation for cataract operation in day surgery clinic. The patient became confused and agitated after instillation of topical cyclopentolate drop into the eye and the symptoms persisted over several hours. DIAGNOSIS: Previously the patient had been diagnosed with amnestic MCI with the finding of bilateral medial temporal atrophy on brain magnetic resonance imaging. 18F-flutemetamol positron emission tomography scan demonstrated multifocal amyloid deposition in the brain. INTERVENTIONS: The patient was closely observed with the supportive management. OUTCOMES: The patient began to recover 5âh after the onset of symptoms and the cognitive function was reverted to previous state within 24âh. LESSONS: It is well known that several drugs with anticholinergic effects used in perioperative periods make the patients susceptible to delirium, but even the topical administration of cyclopentolate for cataract surgery also produce adverse CNS effects in a vulnerable patient who is diagnosed with MCI due to AD in this case.
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Doença de Alzheimer/complicações , Disfunção Cognitiva/complicações , Ciclopentolato/efeitos adversos , Delírio/induzido quimicamente , Delírio/complicações , Administração Tópica , Idoso , Extração de Catarata/métodos , Ciclopentolato/administração & dosagem , Humanos , MasculinoRESUMO
We aimed to analyze plasma amyloid-ß (Aß)1-40 and Aß1-42 using a highly sensitive dielectrophoretic-driven biosensor platform to demonstrate the possibility of precise cerebral amyloid angiopathy (CAA) diagnosis in participants classified according to Aß-positron emission tomography (PET) positivity and the neuroimaging criteria for CAA. We prospectively recruited 25 people with non-Alzheimer's disease (non-AD) and 19 patients with Alzheimer's disease (AD), which were further classified into the CAA- and CAA+ (possible and probable CAA) groups according to the modified Boston criteria. Patients underwent plasma Aß analysis using a highly sensitive nano-biosensor platform, Aß-PET scanning, and detailed neuropsychological testing. As a result, the average signal levels of Aß1-42/1-40 differed significantly between the non-AD and AD groups, and the CAA+ group exhibited significantly higher Aß1-40 signal levels than the CAA- group in both non-AD and AD groups. The concordance between the Aß1-40 signal level and the neuroimaging criteria for CAA was nearly perfect, with areas under the curve of 0.954 (95% confidence interval (CI) 0.856-1.000), 0.969 (0.894-1.000), 0.867 (0.648-1.000), and 1.000 (1.000-1.000) in the non-AD/CAA- vs. non-AD/possible CAA, non-AD/CAA- vs. non-AD/probable CAA, AD/CAA- vs. AD/possible CAA, and AD/CAA- vs. AD/probable CAA groups, respectively. Higher Aß1-40 signal levels were significantly associated with the presence of CAA according to regression analyses, and the neuroimaging pattern analysis partly supported this result. Our findings suggest that measuring plasma Aß1-40 signal levels using a highly sensitive biosensor platform could be a useful non-invasive CAA diagnostic method.
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Doença de Alzheimer , Técnicas Biossensoriais , Angiopatia Amiloide Cerebral , Doença de Alzheimer/diagnóstico por imagem , Peptídeos beta-Amiloides , Biomarcadores , Angiopatia Amiloide Cerebral/diagnóstico por imagem , HumanosRESUMO
OBJECTIVE: Chemical exchange-dependent saturation transfer (CEST) MRI is sensitive for detecting solid-like proteins and may detect changes in the levels of mobile proteins and peptides in tissues. The objective of this study was to evaluate the characteristics of chemical exchange proton pools using the CEST MRI technique in patients with dementia. MATERIALS AND METHODS: Our institutional review board approved this cross-sectional prospective study and informed consent was obtained from all participants. This study included 41 subjects (19 with dementia and 22 without dementia). Complete CEST data of the brain were obtained using a three-dimensional gradient and spin-echo sequence to map CEST indices, such as amide, amine, hydroxyl, and magnetization transfer ratio asymmetry (MTRasym) values, using six-pool Lorentzian fitting. Statistical analyses of CEST indices were performed to evaluate group comparisons, their correlations with gray matter volume (GMV) and Mini-Mental State Examination (MMSE) scores, and receiver operating characteristic (ROC) curves. RESULTS: Amine signals (0.029 for non-dementia, 0.046 for dementia, p = 0.011 at hippocampus) and MTRasym values at 3 ppm (0.748 for non-dementia, 1.138 for dementia, p = 0.022 at hippocampus), and 3.5 ppm (0.463 for non-dementia, 0.875 for dementia, p = 0.029 at hippocampus) were significantly higher in the dementia group than in the non-dementia group. Most CEST indices were not significantly correlated with GMV; however, except amide, most indices were significantly correlated with the MMSE scores. The classification power of most CEST indices was lower than that of GMV but adding one of the CEST indices in GMV improved the classification between the subject groups. The largest improvement was seen in the MTRasym values at 2 ppm in the anterior cingulate (area under the ROC curve = 0.981), with a sensitivity of 100 and a specificity of 90.91. CONCLUSION: CEST MRI potentially allows noninvasive image alterations in the Alzheimer's disease brain without injecting isotopes for monitoring different disease states and may provide a new imaging biomarker in the future.
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Encéfalo/diagnóstico por imagem , Demência/diagnóstico , Imageamento por Ressonância Magnética/métodos , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Mapeamento Encefálico , Estudos Transversais , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROCRESUMO
BACKGROUND: Patients with Alzheimer disease (AD) and mild cognitive impairment (MCI) have high variability in brain tissue loss, making it difficult to use a disease-specific standard brain template. The objective of this study was to develop an AD-specific three-dimensional (3D) T1 brain tissue template and to evaluate the characteristics of the populations used to form the template. METHODS: We obtained 3D T1-weighted images from 294 individuals, including 101 AD, 96 amnestic MCI, and 97 cognitively normal (CN) elderly individuals, and segmented them into different brain tissues to generate AD-specific brain tissue templates. Demographic data and clinical outcome scores were compared between the three groups. Voxel-based analyses and regions-of-interest-based analyses were performed to compare gray matter volume (GMV) and white matter volume (WMV) between the three participant groups and to evaluate the relationship of GMV and WMV loss with age, years of education, and Mini-Mental State Examination (MMSE) scores. RESULTS: We created high-resolution AD-specific tissue probability maps (TPMs). In the AD and MCI groups, losses of both GMV and WMV were found with respect to the CN group in the hippocampus (F >44.60, P<0.001). GMV was lower with increasing age in all individuals in the left (r=-0.621, P<0.001) and right (r=-0.632, P<0.001) hippocampi. In the left hippocampus, GMV was positively correlated with years of education in the CN groups (r=0.345, P<0.001) but not in the MCI (r=0.223, P=0.0293) or AD (r=-0.021, P=0.835) groups. WMV of the corpus callosum was not significantly correlated with years of education in any of the three subject groups (r=0.035 and P=0.549 for left, r=0.013 and P=0.821 for right). In all individuals, GMV of the hippocampus was significantly correlated with MMSE scores (left, r=0.710 and P<0.001; right, r=0.680 and P<0.001), while WMV of the corpus callosum showed a weak correlation (left, r=0.142 and P=0.015; right, r=0.123 and P=0.035). CONCLUSIONS: A 3D, T1 brain tissue template was created using imaging data from CN, MCI, and AD participants considering the participants' age, sex, and years of education. Our disease-specific template can help evaluate brains to promote early diagnosis of MCI individuals and aid treatment of MCI and AD individuals.
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Objective: To investigate the association between plasma amyloid-ß (Aß) levels and neuropsychological performance in patients with cognitive decline using a highly sensitive nano-biosensing platform. Methods: We prospectively recruited 44 patients with cognitive decline who underwent plasma Aß analysis, amyloid positron emission tomography (PET) scanning, and detailed neuropsychological tests. Patients were classified into a normal control (NC, n = 25) or Alzheimer's disease (AD, n = 19) group based on amyloid PET positivity. Multiple linear regression was performed to determine whether plasma Aß (Aß40, Aß42, and Aß42/40) levels were associated with neuropsychological test results. Results: The plasma levels of Aß42/40 were significantly different between the NC and AD groups and were the best predictor of amyloid PET positivity by receiver operating characteristic curve analysis [area under the curve of 0.952 (95% confidence interval, 0.892-1.000)]. Although there were significant differences in the neuropsychological performance of cognitive domains (language, visuospatial, verbal/visual memory, and frontal/executive functions) between the NC and AD groups, higher levels of plasma Aß42/40 were negatively correlated only with verbal and visual memory performance. Conclusion: Our results demonstrated that plasma Aß analysis using a nano-biosensing platform could be a useful tool for diagnosing AD and assessing memory performance in patients with cognitive decline.
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Background: The aim of the present study was to investigate the associations between thyroid hormones, cognitive performance, and apolipoprotein E (APOE) genotype in euthyroid patients with subjective cognitive decline (SCD). Methods: We recruited 197 euthyroid patients that fulfilled the criteria for SCD. All participants were classified into APOE ε4 carriers and non-carriers based on the presence of the APOE ε4 allele. Patients with SCD who had the APOE ε2/ε4 genotype were excluded from the study. We then performed correlation and regression analyses to evaluate the associations between cognitive performance and thyroid hormones in APOE ε4 carriers and non-carriers. Results: We found no significant differences in cognitive function between APOE ε4 carriers and non-carriers. However, higher levels of triiodothyronine (T3) were associated with better verbal memory performance (immediate and delayed recall tasks) in APOE ε4 carriers, whereas a negative association was found in APOE ε4 non-carriers. Furthermore, there was a significant interactive effect of APOE ε4 status and T3 levels on verbal memory performance (immediate and delayed recall tasks). Conclusions: These findings suggest that in patients with SCD, T3 might have a protective effect on memory in those who are APOE ε4 carriers. The differential susceptibility hypothesis would thus support a gene-by-hormone crossover interaction between APOE ε4 allele and T3 in this study. Early identification and intervention of high-risk individuals for cognitive decline is important to establish new strategies for preventing dementia.
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This study investigated distinct neuroimaging features measured by cortical thickness and subcortical structural shape abnormality in early-onset (EO, onset age <65 years) and late-onset (LO, onset age ≥65 years) nonfluent/agrammatic variant of primary progressive aphasia (nfvPPA) patients. Cortical thickness and subcortical structural shape analyses were performed using a surface-based method from 38 patients with nfvPPA and 76 cognitively normal individuals. To minimize the effects of physiological aging, we used W-scores in comparisons between the groups. The EO-nfvPPA group exhibited more extensive cortical thickness reductions predominantly in the left perisylvian, lateral and medial prefrontal, temporal, posterior cingulate, and precuneus regions than the LO-nfvPPA group. The EO-nfvPPA group also exhibited significantly greater subcortical structural shape abnormality than the LO-nfvPPA group, mainly in the left striatum, hippocampus, and amygdala. Our findings suggested that there were differences in neuroimaging features between these groups by the age of symptom onset, which might be explained by underlying heterogeneous neuropathological differences or the age-related brain reserve hypothesis.
Assuntos
Afasia de Broca/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética , Neuroimagem , Idoso , Afasia de Broca/patologia , Encéfalo/patologia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To investigate the association between APOE genotype and ß-amyloid (Aß) burden, as measured by PET in patients with subcortical vascular cognitive impairment (SVCI) and those with Alzheimer disease-related cognitive impairment (ADCI). METHODS: This was a cross-sectional study of 310 patients with SVCI and 999 with ADCI. To evaluate the effects of APOE genotype or diagnostic group on Aß positivity, we performed multivariate logistic regression analyses. Further distinctive underlying features of latent subgroups were examined by employing a latent class cluster analysis approach. RESULTS: In comparison with ε3 homozygotes, in the ADCI group, ε2 carriers showed a lower frequency of Aß positivity (odds ratio [OR] 0.43, 95% confidence interval [CI] 0.23-0.79), while in the SVCI group, ε2 carriers showed a higher frequency of Aß positivity (OR 2.26, 95% CI 1.02-5.01). In particular, we observed an interaction effect of ε2 carrier status and diagnostic group on Aß positivity (OR 5.12, 95% CI 1.93-13.56), in that relative to ε3 homozygotes, there were more Aß-positive ε2 carriers in the SVCI group than in the ADCI group. We also identified latent subgroups of Aß-positive APOE ε2 carriers with SVCI and Aß-positive APOE ε4 carriers with ADCI. CONCLUSIONS: Our findings suggest that APOE ε2 is distinctly associated with Aß deposition in patients with SVCI and those with ADCI. Our findings further suggest that there is a distinctive subgroup of Aß-positive APOE ε2 carriers with SVCI among patients with cognitive impairment.
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Doença de Alzheimer/genética , Peptídeos beta-Amiloides/genética , Apolipoproteína E2/genética , Demência Vascular/genética , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/epidemiologia , Carga Corporal (Radioterapia) , Disfunção Cognitiva/genética , Estudos Transversais , Demência Vascular/diagnóstico por imagem , Demência Vascular/epidemiologia , Feminino , Predisposição Genética para Doença , Genótipo , Heterozigoto , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , PrevalênciaRESUMO
BACKGROUND: Patients with neglect often repeatedly cancel the same targets, a form of motor perseveration (MP). There seems to be 2 types of MP, making uninterrupted multiple strokes for each target, consecutive MP (CMP) or return MP (RMP) where patients return to previously canceled targets and remark them. OBJECTIVE: The purpose of this study is to learn whether these 2 forms of MP are dissociable. METHODS: We studied 3 patients, 1 with primarily CMP, another with primarily RMP and a third with mixed CMP and RMP by having them perform the cancellation task with and without background movement. RESULTS: In the patient with primarily RMPs (patient 1), leftward background movement decreased the severity of the neglect and the perseveration. Rightward background movement increased both. In contrast to patient 1, who showed the correspondence between the severity of neglect and perseveration, the patient with both CMP and RMP (patient 2) and the patient with primarily CMPs (patient 3) did not show such correspondence. CONCLUSIONS: The different responses of CMP and RMP to the treatment of neglect suggest that different mechanisms account for these 2 forms of MP. Although RMP might be related to neglect induced aberrant approach behaviors, CMP seems to be related to a disengagement disorder.
Assuntos
Movimento/fisiologia , Transtornos da Percepção/psicologia , Desempenho Psicomotor/fisiologia , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Feminino , Lateralidade Funcional , Humanos , Masculino , Transtornos da Percepção/classificação , Transtornos da Percepção/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Percepção Visual/fisiologiaRESUMO
Although cognitive impairment after a posterior cerebral artery (PCA) infarct is frequently observed, the important functional areas associated with cognitive decline, other than the thalamus, have not been determined. We investigated the locus or loci that might induce cognitive decline after a PCA infarct. Forty-one patients with unilateral PCA infarctions involving only the occipital lobe or the occipital lobe plus other PCA areas were included. All subjects received a mini-mental status examination (MMSE) within 2 months of onset; 43.9% had cognitive impairment. The severity of cognitive impairment was not associated with left hemisphere lesion location, sex, age, education level, or the time between stroke and the MMSE assessment. Only the lesion volume was negatively correlated with MMSE score. Lesion location analysis revealed that an occipital plus splenial or parahippocampal lesion contributed to a decline in MMSE, which suggests that parahippocampal or splenial involvement with an occipital lesion is associated with the cognitive decline seen after PCA infarction.
Assuntos
Transtornos Cognitivos/etiologia , Corpo Caloso/patologia , Infarto da Artéria Cerebral Posterior/complicações , Infarto da Artéria Cerebral Posterior/patologia , Giro Para-Hipocampal/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos Cognitivos/diagnóstico por imagem , Transtornos Cognitivos/patologia , Corpo Caloso/diagnóstico por imagem , Feminino , Humanos , Infarto da Artéria Cerebral Posterior/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Masculino , Entrevista Psiquiátrica Padronizada , Pessoa de Meia-Idade , Testes Neuropsicológicos , Giro Para-Hipocampal/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodosRESUMO
This study aimed to investigate the cognition-enhancing effect of Panax ginseng. A randomized, double-blind, placebo-controlled clinical trial was conducted to address the cognition-enhancing effects of Panax ginseng. A total of 90 Korean volunteers with mild cognitive impairment participated in this study. All subjects were allocated randomly into 'Ginseng' group or 'Placebo' group. All subjects were administered 3g of Panax ginseng powder or starch (placebo) for 6 months. The Korean version of the Mini-Mental Status Examination (K-MMSE), Korean version of Instrumental Activities of Daily Living (K-IADL), and Seoul Neuropsychological Screening Battery (SNSB) were used to assess the changes in cognitive function at the end of the 6 month study period. The subjects of the 'Ginseng' group improved significantly on the Rey Complex Figure Test (RCFT) immediate recall (P = 0.0405 and P = 0.0342 in per-protocol (PP) and intention-to-treat (ITT) analysis, respectively) and on the RCFT 20-min delayed recall (P = 0.0396 and P = 0.0355 in PP and ITT analysis, respectively) compared with 'placebo' group throughout the 6 months of Panax ginseng administration. There were no serious adverse events. These results suggest that Panax ginseng has a cognition-enhancing effect.