RESUMO
INTRODUCTION: Prediction of the dementia progression is important for patient management. We aimed to investigate the cognitive trajectories of Alzheimer's disease dementia (ADD) and dementia with Lewy bodies (DLB) according to the initial structural change measured by comprehensive visual rating scales (CVRS). METHODS: We retrospectively included the patients who initially visited the Dementia Clinic of Chonnam National University Hospital between 2010 and 2012. All patients underwent dementia workup including neuropsychological battery (Seoul Neuropsychological Screening Battery, SNSB). We recruited the participant who underwent SNSB annually for 3 years successively. A total of 136 patients of ADD and 63 patients of DLB were included for analysis. We analyzed the decline pattern of the cognitive profile according to the initial brain structural changes. RESULTS: The general cognitive trajectories between ADD and DLB patients were not different. However, DLB patients showed more rapid decline of cognitive function in language and related function, visual memory function, and frontal executive function. The scores were lower in participants with DLB with the lesser atrophy group in attention, visuospatial function, and frontal executive function. In analysis of the cognitive trajectories, the visual memory domain declined rapidly in the DLB with lesser atrophy group compared with the ADD with lesser atrophy group. CONCLUSION: We founded that the differences in the visual cognitive profile in ADD and DLB patients in serial follow-up of neuropsychological tests. It is prominent in the mild structural change group of ADD and DLB.
RESUMO
INTRODUCTION: This study aimed to explore the potential of whole brain white matter patterns as novel neuroimaging biomarkers for assessing cognitive impairment and disability in older adults. METHODS: We conducted an in-depth analysis of magnetic resonance imaging (MRI) and amyloid positron emission tomography (PET) scans in 454 participants, focusing on white matter patterns and white matter inter-subject variability (WM-ISV). RESULTS: The white matter pattern ensemble model, combining MRI and amyloid PET, demonstrated a significantly higher classification performance for cognitive impairment and disability. Participants with Alzheimer's disease (AD) exhibited higher WM-ISV than participants with subjective cognitive decline, mild cognitive impairment, and vascular dementia. Furthermore, WM-ISV correlated significantly with blood-based biomarkers (such as glial fibrillary acidic protein and phosphorylated tau-217 [p-tau217]), and cognitive function and disability scores. DISCUSSION: Our results suggest that white matter pattern analysis has significant potential as an adjunct neuroimaging biomarker for clinical decision-making and determining cognitive impairment and disability. HIGHLIGHTS: The ensemble model combined both magnetic resonance imaging (MRI) and amyloid positron emission tomography (PET) and demonstrated a significantly higher classification performance for cognitive impairment and disability. Alzheimer's disease (AD) revealed a notably higher heterogeneity compared to that in subjective cognitive decline, mild cognitive impairment, or vascular dementia. White matter inter-subject variability (WM-ISV) was significantly correlated with blood-based biomarkers (glial fibrillary acidic protein and phosphorylated tau-217 [p-tau217]) and with the polygenic risk score for AD. White matter pattern analysis has significant potential as an adjunct neuroimaging biomarker for clinical decision-making processes and determining cognitive impairment and disability.
RESUMO
We previously developed a novel machine-learning-based brain age model that was sensitive to amyloid. We aimed to independently validate it and to demonstrate its utility using independent clinical data. We recruited 650 participants from South Korean memory clinics to undergo magnetic resonance imaging and clinical assessments. We employed a pretrained brain age model that used data from an independent set of largely Caucasian individuals (n = 757) who had no or relatively low levels of amyloid as confirmed by positron emission tomography (PET). We investigated the association between brain age residual and cognitive decline. We found that our pretrained brain age model was able to reliably estimate brain age (mean absolute error = 5.68 years, r(650) = 0.47, age range = 49-89 year) in the sample with 71 participants with subjective cognitive decline (SCD), 375 with mild cognitive impairment (MCI), and 204 with dementia. Greater brain age was associated with greater amyloid and worse cognitive function [Odds Ratio, (95% Confidence Interval {CI}): 1.28 (1.06-1.55), p = 0.030 for amyloid PET positivity; 2.52 (1.76-3.61), p < 0.001 for dementia]. Baseline brain age residual was predictive of future cognitive worsening even after adjusting for apolipoprotein E e4 and amyloid status [Hazard Ratio, (95% CI): 1.94 (1.33-2.81), p = 0.001 for total 336 follow-up sample; 2.31 (1.44-3.71), p = 0.001 for 284 subsample with baseline Clinical Dementia Rating ≤ 0.5; 2.40 (1.43-4.03), p = 0.001 for 240 subsample with baseline SCD or MCI]. In independent data set, these results replicate our previous findings using this model, which was able to delineate significant differences in brain age according to the diagnostic stages of dementia as well as amyloid deposition status. Brain age models may offer benefits in discriminating and tracking cognitive impairment in older adults.
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Idoso , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Pré-Escolar , Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Cognição , Tomografia por Emissão de Pósitrons/métodos , Imageamento por Ressonância Magnética , Apolipoproteína E4RESUMO
Histone deacetylase (HDAC) inhibitors promote differentiation through post-translational modifications of histones. BML-281, an HDAC6 inhibitor, has been known to prevent tumors, acute dextran sodium sulfate-associated colitis, and lung injury. However, the neurogenic differentiation effect of BML-281 is poorly understood. In this study, we investigated the effect of BML-281 on neuroblastoma SH-SY5Y cell differentiation into mature neurons by immunocytochemistry (ICC), reverse transcriptase PCR (RT-PCR), quantitative PCR (qPCR), and western blotting analysis. We found that the cells treated with BML-281 showed neurite outgrowth and morphological changes into mature neurons under a microscope. It was confirmed that the gene expression of neuronal markers (NEFL, MAP2, Tuj1, NEFH, and NEFM) was increased with certain concentrations of BML-281. Similarly, the protein expression of neuronal markers (NeuN, Synaptophysin, Tuj1, and NFH) was upregulated with BML-281 compared to untreated cells. Following treatment with BML-281, the expression of Wnt5α increased, and downstream pathways were activated. Interestingly, both Wnt/Ca2+ and Wnt/PCP pathways activated and regulated PKC, Cdc42, RhoA, Rac1/2/3, and p-JNK. Therefore, BML-281 induces the differentiation of SH-SY5Y cells into mature neurons by activating the non-canonical Wnt signaling pathway. From these results, we concluded that BML-281 might be a novel drug to differentiation into neuronal cells through the regulation of Wnt signaling pathway to reduce the neuronal cell death.
RESUMO
A spinal cord injury (SCI) is the devastating trauma associated with functional deterioration due to apoptosis. Most laboratory SCI models are generated by a direct impact on an animal's spinal cord; however, our model does not involve the direct impact on the spinal cord. Instead, we use a clamp compression to create an ischemia in the descending aortas of mice. Following the success of inducing an ischemic SCI (ISCI), we hypothesized that this model may show apoptosis via an endoplasmic reticulum (ER) stress pathway. This apoptosis by the ER stress pathway is enhanced by the inducible nitric oxide synthase (iNOS). The ER is used for the protein folding in the cell. When the protein folding capacity is overloaded, the condition is termed the ER stress and is characterized by the accumulation of misfolded proteins inside the ER lumen. The unfolded protein response (UPR) signaling pathways that deal with the ER stress response then become activated. This UPR activates the three signal pathways that are regulated by the inositol-requiring enzyme 1α (IRE1α), the activating transcription factor 6 (ATF6), and the protein kinase RNA-like ER kinase (PERK). IRE1α and PERK are associated with the expression of the apoptotic proteins. Apoptosis caused by an ISCI is assessed using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) test. An ISCI also reduces synaptophysin and the neuronal nuclear protein (NeuN) in the spinal cord. In conclusion, an ISCI increases the ER stress proteins, resulting in apoptosis in neuronal cells in the spinal cord.
Assuntos
Proteínas Serina-Treonina Quinases , Traumatismos da Medula Espinal , Camundongos , Animais , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Endorribonucleases/metabolismo , Chaperona BiP do Retículo Endoplasmático , Apoptose , Estresse do Retículo Endoplasmático/fisiologia , Resposta a Proteínas não Dobradas , Modelos Animais de Doenças , Isquemia , Traumatismos da Medula Espinal/metabolismoRESUMO
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.
Assuntos
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
Excessive stimulation of the quinolinic acid induces neuronal cell death and is implicated in developing several neurodegenerative diseases. This study investigated whether a Wnt5a antagonist plays a neuroprotective role by regulating the Wnt pathway, activating cellular signaling mechanisms, including MAP kinase and ERK, and acting on the antiapoptotic and the proapoptotic genes in N18D3 neural cells. The cells were pretreated with a Wnt5a antagonist Box5, for one hour and then exposed to quinolinic acid (QUIN), an NMDA receptor agonist for 24 hours. An MTT assay and DAPI staining were used to evaluate cell viability and apoptosis, respectively, demonstrating that Box5 protected the cells from apoptotic death. In addition, a gene expression analysis revealed that Box5 prevented the QUIN-induced expression of the pro-apoptotic genes, BAD and BAX, and increased that of the anti-apoptotic genes, Bcl-xL, BCL2, and BCLW. Further examination of potential cell signaling candidates involved in this neuroprotective effect showed that the immunoreactivity of ERK was significantly increased in the cells treated with Box5. These results suggest that the neuroprotective mechanism of Box5 against QUIN-induced excitotoxic cell death involves the regulation of ERK and modulation of cell survival and death genes through decreasing the Wnt pathway, specifically Wnt5a.
Assuntos
Fármacos Neuroprotetores , Via de Sinalização Wnt , Apoptose , Morte Celular , Fármacos Neuroprotetores/farmacologia , Ácido Quinolínico/toxicidade , Animais , Camundongos , Linhagem Celular , Via de Sinalização Wnt/efeitos dos fármacosRESUMO
Rotenone (ROT) inhibits mitochondrial complex I, leading to reactive oxygen species formation, which causes neurodegeneration and alpha-synuclein (α-syn) aggregation and, consequently, Parkinson's disease. We previously found that a neurogenic differentiated human adipose tissue-derived stem cell-conditioned medium (NI-hADSC-CM) was protective against ROT-induced toxicity in SH-SY5Y cells. In the present study, ROT significantly decreased the phospho (p)-mTORC1/total (t)-mTOR, p-mTORC2/t-mTOR, and p-/t-ULK1 ratios and the ATG13 level by increasing the DEPTOR level and p-/t-AMPK ratio. Moreover, ROT increased the p-/t-Akt ratio and glycogen synthase kinase-3ß (GSK3ß) activity by decreasing the p-/t-ERK1/2 ratios and beclin-1 level. ROT also promoted the lipidation of LC3B-I to LC3B-II by inducing autophagosome formation in Triton X-100-soluble and -insoluble cell lysate fractions. Additionally, the levels of ATG3, 5, 7, and 12 were decreased, along with those of lysosomal LAMP1, LAMP2, and TFEB, leading to lysosomal dysfunction. However, NI-hADSC-CM treatment increased the p-mTORC1, p-mTORC2, p-ULK1, p-Akt, p-ERK1/2, ATG13, and beclin-1 levels and decreased the p-AMPK level and GSK3ß activity in response to ROT-induced toxicity. Additionally, NI-hADSC-CM restored the LC3B-I level, increased the p62 level, and normalized the ATG and lysosomal protein amounts to control levels. Autophagy array revealed that the secreted proteins in NI-hADSC-CM could be crucial in the neuroprotection. Taken together, our results showed that the neuroprotective effects of NI-hADSC-CM on the autophagy signaling pathways could alleviate the aggregation of α-syn in Parkinson's disease and other neurodegenerative disorders.
Assuntos
Células-Tronco Neurais , Doença de Parkinson , Proteínas Quinases Ativadas por AMP , Tecido Adiposo/metabolismo , Autofagia , Proteína Beclina-1/metabolismo , Meios de Cultivo Condicionados/farmacologia , Glicogênio Sintase Quinase 3 beta , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/farmacologia , Alvo Mecanístico do Complexo 1 de Rapamicina , Alvo Mecanístico do Complexo 2 de Rapamicina , Células-Tronco Neurais/metabolismo , Proteínas Proto-Oncogênicas c-akt , Rotenona/toxicidade , Serina-Treonina Quinases TORRESUMO
Alzheimer's disease (AD), a common form of dementia, is caused in part by the aggregation and accumulation in the brain of amyloid ß (Aß), a product of the proteolytic cleavage of amyloid precursor protein (APP) in endosomes. Trafficking of APP, such as surface-intracellular recycling, is an early critical step required for Aß generation. Less is known, however, about the molecular mechanism regulating APP trafficking. This study investigated the mechanism by which SPIN90, along with Rab11, modulates APP trafficking, Aß motility and accumulation, and synaptic functionality. Brain Aß deposition was lower in the progeny of 5xFAD-SPIN90KO mice than in 5xFAD-SPIN90WT mice. Analysis of APP distribution and trafficking showed that the surface fraction of APP was locally distinct in axons and dendrites, with these distributions differing significantly in 5xFAD-SPIN90WT and 5xFAD-SPIN90KO mice, and that neural activity-driven APP trafficking to the surface and intracellular recycling were more actively mobilized in 5xFAD-SPIN90KO neurons. In addition, SPIN90 was found to be cotrafficked with APP via axons, with ablation of SPIN90 reducing the intracellular accumulation of APP in axons. Finally, synaptic transmission was restored over time in 5xFAD-SPIN90KO but not in 5xFAD-SPIN90WT neurons, suggesting SPIN90 is implicated in Aß production through the regulation of APP trafficking.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Doença de Alzheimer , Precursor de Proteína beta-Amiloide , Proteínas do Tecido Nervoso , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Axônios/metabolismo , Modelos Animais de Doenças , Camundongos , Camundongos Transgênicos , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismoRESUMO
Parkinson's disease (PD) patients are at risk for developing bone health problems, and freezing of gait (FOG) in PD is associated with a high risk of falling and fracture. This study aimed to determine the association between FOG and bone mineral density (BMD) in patients with PD. We included 148 PD patients. FOG was assessed using the FOG Questionnaire (FOG-Q), and BMD was measured by dual-energy X-ray absorptiometry. Of 148 PD patients, 102 (68.9%) had FOG. PD patients with FOG were older and had longer disease duration, higher levodopa equivalent dose, higher modified Hoehn and Yahr stage, higher Unified PD Rating Scale motor score, higher FOG-Q score, higher total Non-Motor Symptom Scale score, and lower BMD scores in the femoral neck area than those without FOG. Pearson correlation analysis revealed that age, sex, body mass index, and age at onset were significantly correlated with areal BMDs in all areas. FOG-Q scores correlated negatively with areal BMDs in the total hip area and femoral neck, but not with areal BMD in the lumbar spine. Multivariate regression analysis showed that FOG-Q score was significantly correlated with areal BMD in the femoral neck, but not with areal BMDs in the lumbar spine or total hip. FOG in PD patients correlates significantly with BMD in the femoral neck area. Therefore, PD patients with FOG should be screened for osteoporosis.
Assuntos
Transtornos Neurológicos da Marcha , Doença de Parkinson , Densidade Óssea , Marcha , Transtornos Neurológicos da Marcha/diagnóstico por imagem , Transtornos Neurológicos da Marcha/etiologia , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/epidemiologia , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Isolated central positional vertigo (CPV) due to cerebellar infarction is often difficult to differentiate from benign paroxysmal positional vertigo (BPPV). Here, we aimed to evaluate whether vascular risk factors and serum vitamin D level can differentiate between positional vertigo types. METHODS: A total of 78 consecutive patients were consecutively enrolled from January 2017. All CPV patients had a National Institutes of Health Stroke Scale score of 0 and cerebellar infarctions confirmed by brain MR imaging. Vascular risk factors and serum 25-hydroxyvitamin D levels were compared between the two groups of patients. RESULTS: The proportion of men was higher in the CPV than in the BPPV group (p = 0.004). Atrial fibrillation was common in the CPV group on univariate analysis (p = 0.046). However, there were no independent differentiating factors between the two groups. The proportion of patients according to the number of risk factors was significantly different between the two groups (linear by linear association test, p = 0.02). The mean serum 25-hydroxyvitamin D level did not differ. Also, the proportions of vitamin D insufficiency and deficiency did not differ significantly between the two groups. CONCLUSIONS: Increased number of vascular risk factors including male sex suggested more CPV than BPPV. However, the serum vitamin D level was below the normal range in both groups. Our results demonstrate that serum vitamin D level has little value in the differential diagnosis of positional vertigo. Efforts to identify differentiating factors are warranted, and accumulating evidences including our research may lead to a diagnostic algorithm for isolated positional vertigo.
Assuntos
Vertigem Posicional Paroxística Benigna , Deficiência de Vitamina D , Vertigem Posicional Paroxística Benigna/complicações , Vertigem Posicional Paroxística Benigna/diagnóstico , Calcifediol , Humanos , Infarto , Masculino , Fatores de RiscoRESUMO
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a rapid accumulation of amyloid ß (Aß) protein in the hippocampus, which impairs synaptic structures and neuronal signal transmission, induces neuronal loss, and diminishes memory and cognitive functions. The present study investigated the impact of neuregulin 1 (NRG1)-ErbB4 signaling on the impairment of neural networks underlying hippocampal long-term potentiation (LTP) in 5xFAD mice, a model of AD with greater symptom severity than that of TG2576 mice. Specifically, we observed parvalbumin (PV)-containing hippocampal interneurons, the effect of NRG1 on hippocampal LTP, and the functioning of learning and memory. We found a significant decrease in the number of PV interneurons in 11-month-old 5xFAD mice. Moreover, synaptic transmission in the 5xFAD mice decreased at 6 months of age. The 11-month-old transgenic AD mice showed fewer inhibitory PV neurons and impaired NRG1-ErbB4 signaling than did wild-type mice, indicating that the former exhibit the impairment of neuronal networks underlying LTP in the hippocampal Schaffer-collateral pathway. In conclusion, this study confirmed the impaired LTP in 5xFAD mice and its association with aberrant NRG1-ErbB signaling in the neuronal network.
Assuntos
Envelhecimento/patologia , Doença de Alzheimer/patologia , Região CA1 Hipocampal/patologia , Potenciação de Longa Duração/fisiologia , Rede Nervosa/patologia , Neurônios/patologia , Envelhecimento/metabolismo , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Região CA1 Hipocampal/metabolismo , Cognição/fisiologia , Modelos Animais de Doenças , Feminino , Interneurônios/metabolismo , Interneurônios/patologia , Aprendizagem/fisiologia , Masculino , Memória/fisiologia , Camundongos , Camundongos Transgênicos , Rede Nervosa/metabolismo , Neuregulina-1/metabolismo , Neurônios/metabolismo , Parvalbuminas/metabolismo , Receptor ErbB-4/metabolismo , Transdução de Sinais/fisiologia , Transmissão Sináptica/fisiologiaRESUMO
PURPOSE: We developed a new method to directly calculate Centiloid (CL) units of 18F-florbetaben (FBB) and 18F-flutemetamol (FMM) without conversion to the PiB standardized uptake value ratio (SUVR). METHODS: Paired FBB and FMM PET scans were obtained from 20 Alzheimer's disease-related cognitive impairment patients, 16 old controls, and 20 young controls. We investigated the correlations between the FBB and FMM CL units using the direct comparison of FBB-FMM CL (dcCL) method and the standard CL method and compare differences in FBB and FMM CL units between dcCL method and the standard method. RESULTS: Following the conversion of FBB or FMM SUVRs into CL units, a direct relationship was formed between the FBB or FMM SUVRs and the CL units using dcCL method (FBB dcCL = 151.42 × FBB dcSUVR - 142.24 and FMM dcCL = 148.52 × FMM dcSUVR - 137.09). The FBB and FMM CL units were highly correlated in both our method (R2 = 0.97, FMM dcCL = 0.97 × FBB dcCL + 1.64) and the standard method (R2 = 0.97, FMM CLstandard = 0.79 × FBB CLstandard + 1.36). However, the CL variations between FBB and FMM were smaller when calculated by dcCL method (6.15) than when calculated by the previous method (10.22; P = 0.01). CONCLUSIONS: Our findings suggest that our direct comparison of FBB-FMM method, rather than the standard method, is a reasonable way to convert FBB or FMM SUVRs into CL units, at least in environments where FBB or FMM ligands are used frequently.
Assuntos
Doença de Alzheimer , Estilbenos , Compostos de Anilina , Benzotiazóis , Encéfalo , Humanos , Tomografia por Emissão de PósitronsRESUMO
Funding information from the original version of this article was incomplete. Complete information is presented here.
RESUMO
Background and Purpose- The purpose of this study was to investigate the association between adiposity using adipose tissue imaging and stroke outcomes in acute ischemic stroke patients treated with intravenous thrombolysis. Methods- A total of 127 patients with acute ischemic stroke treated with intravenous thrombolysis who underwent abdominal computed tomography on admission were enrolled in this prospective cohort study. Patients were grouped according to their visceral adipose tissue (VAT) proportion tertile. The primary outcome was measured using the modified Rankin Scale 3 months after symptom onset. Favorable and excellent outcomes were defined as modified Rankin Scale scores of 0 to 2 and 0 to 1, respectively. Results- As VAT proportion tertile increased, the number of patients exhibiting a favorable or excellent outcome decreased. In the final multivariable analysis after adjustments for confounders, patients in the highest VAT proportion tertile showed a decreased probability of a favorable and excellent outcome compared with those in the lowest tertile (odds ratio=0.18; 95% CI, 0.05-0.60; P=0.005 and odds ratio=0.13; 95% CI, 0.02-0.64; P=0.012, respectively). Obese patients (body mass index ≥25) also showed an excellent outcome compared with nonobese patients (odds ratio=4.88; 95% CI, 1.47-7.85; P=0.011). Among obese patients, those with an excellent outcome presented a significantly lower VAT proportion than those without (38.2% versus 46.1%, P=0.006). Conclusions- Results of this study indicate that low visceral abdominal fat proportion is associated with a favorable and excellent outcome in acute ischemic stroke patients treated with intravenous thrombolysis. Better clinical outcomes in obese patients were also associated with a lower proportion of VAT.
Assuntos
Adiposidade , Isquemia Encefálica , Gordura Intra-Abdominal/diagnóstico por imagem , Obesidade , Sistema de Registros , Acidente Vascular Cerebral , Terapia Trombolítica , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/mortalidade , Isquemia Encefálica/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico por imagem , Obesidade/mortalidade , Obesidade/terapia , Estudos Prospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/terapiaRESUMO
BACKGROUND: Coffee consumption represents a negative risk factor for Parkinson's disease (PD) and seems to affect PD motor symptoms. We aimed to investigate the association between coffee consumption and motor symptoms in de novo PD patients. METHODS: In total, 284 patients with de novo PD were included in the current study. Motor and non-motor symptoms were evaluated using various scales. History of coffee consumption was obtained via a semi-structured interview. RESULTS: In total, 204 patients were categorized as coffee drinkers and 80 as non-coffee drinkers. Coffee drinkers were predominantly male and had early symptom onset; in addition, they were younger, reported more years in formal education, and had better motor and non-motor scores than did non-coffee drinkers. After adjustments, coffee drinkers had lower tremor scores than did non-coffee drinkers, and coffee consumption was related to tremors in a dose-dependent manner. These relationships were statistically significant in case of rest tremor but not in case of action tremor. The dose-dependent relationship between coffee consumption and tremor severity was significant only in men. Non-motor symptom scores were not significantly different between coffee drinkers and non-coffee drinkers. CONCLUSIONS: Coffee consumption and tremor severity are inversely related in male patients with de novo PD.
Assuntos
Café , Doença de Parkinson , Tremor , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Tremor/etiologiaRESUMO
Patients with Parkinson's disease (PD) are liable to experience impairment in their activities of daily living (ADL), which include ambulating, eating, dressing, bathing, and personal hygiene. The aim of this study is to assess which clinical characteristics contribute significantly to instrumental ADL (IADL) in PD patients without dementia. We included 106 PD patients in our study, and each patient's motor and non-motor status and basic and instrumental ADL were assessed using the appropriate scales. Of the 106 PD patients, 31 (29.2%) had abnormal Korean IADL (K-IADL) scores. These patients were older and had higher scores in terms of the modified Hoehn and Yahr (mHY) staging scale, Unified Parkinson's Disease Rating Scale (UPDRS) parts II and III, UPDRS part IV motor fluctuation, Beck Depression Inventory (BDI), and total Non-Motor Symptoms assessment scale for PD (NMSS), as well as lower scores in the Mini-Mental State Examination (MMSE). Pearson's correlation analysis showed significant associations between the scores of K-IADL and each of the following characteristics of the patients: age, mHY stage, UPDRS parts II and III, UPDRS part IV motor fluctuation, BDI, total NMSS, and MMSE. Multivariate linear regression analysis showed that the significant clinical characteristics associated with the K-IADL scores were determined to be the UPDRS part II, MMSE, and BDI scores. The results of our study revealed that the cognitive, depression, and motor symptoms were the significant predictors of IADL in PD patients without dementia.
Assuntos
Atividades Cotidianas , Demência/epidemiologia , Doença de Parkinson/epidemiologia , Fatores Etários , Idoso , Estudos Transversais , Demência/complicações , Feminino , Humanos , Masculino , Testes de Estado Mental e Demência , Doença de Parkinson/complicações , Doença de Parkinson/fisiopatologia , Doença de Parkinson/psicologia , Escalas de Graduação Psiquiátrica , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Freezing of gait (FOG) is a common and debilitating problem in patients with Parkinson's disease (PD). The aim of this study was to estimate the prevalence of FOG, and to identify factors that independently contribute to FOG in patients with PD. METHOD: We included 157 PD patients. FOG was assessed using the FOG Questionnaire (FOG-Q). Patients with or without FOG were defined as item 3 in the FOG-Q. RESULTS: One hundred eleven (70.7%) out of 157 PD patients presented with FOG. Patients with FOG were older, had long disease duration, were taking higher doses of dopaminergic agents, and had higher motor and non-motor scores than those without FOG. Multivariate linear regression analysis showed that high modified Hoehn and Yahr (mHY) stage, Unified PD Rating Scale (UPDRS) part II score, and non-motor symptom assessment scale for PD (NMSS) total score were significant predictors of a high FOG-Q score. Patients with FOG had significantly higher scores for cardiovascular, gastrointestinal tract, urinary, and miscellaneous NMSS domains than those without FOG. CONCLUSIONS: FOG in PD was associated with higher mHY stage, UPDRS part II score, and total NMSS score. Therefore, clinicians should consider non-motor, motor features and activities of daily living states for the proper management of FOG.
Assuntos
Transtornos Neurológicos da Marcha/epidemiologia , Transtornos Neurológicos da Marcha/etiologia , Doença de Parkinson/complicações , Doença de Parkinson/epidemiologia , Atividades Cotidianas , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Neuropsychological tests (NPTs) are important tools for informing diagnoses of cognitive impairment (CI). However, interpreting NPTs requires specialists and is thus time-consuming. To streamline the application of NPTs in clinical settings, we developed and evaluated the accuracy of a machine learning algorithm using multi-center NPT data. METHODS: Multi-center data were obtained from 14,926 formal neuropsychological assessments (Seoul Neuropsychological Screening Battery), which were classified into normal cognition (NC), mild cognitive impairment (MCI) and Alzheimer's disease dementia (ADD). We trained a machine learning model with artificial neural network algorithm using TensorFlow (https://www.tensorflow.org) to distinguish cognitive state with the 46-variable data and measured prediction accuracies from 10 randomly selected datasets. The features of the NPT were listed in order of their contribution to the outcome using Recursive Feature Elimination. RESULTS: The ten times mean accuracies of identifying CI (MCI and ADD) achieved by 96.66 ± 0.52% of the balanced dataset and 97.23 ± 0.32% of the clinic-based dataset, and the accuracies for predicting cognitive states (NC, MCI or ADD) were 95.49 ± 0.53 and 96.34 ± 1.03%. The sensitivity to the detection CI and MCI in the balanced dataset were 96.0 and 96.0%, and the specificity were 96.8 and 97.4%, respectively. The 'time orientation' and '3-word recall' score of MMSE were highly ranked features in predicting CI and cognitive state. The twelve features reduced from 46 variable of NPTs with age and education had contributed to more than 90% accuracy in predicting cognitive impairment. CONCLUSIONS: The machine learning algorithm for NPTs has suggested potential use as a reference in differentiating cognitive impairment in the clinical setting.
Assuntos
Doença de Alzheimer/diagnóstico , Disfunção Cognitiva/diagnóstico , Aprendizado de Máquina , Testes Neuropsicológicos , Fatores Etários , Algoritmos , Conjuntos de Dados como Assunto , Aprendizado Profundo , Humanos , Redes Neurais de Computação , Sensibilidade e EspecificidadeRESUMO
This study aimed to detect different patterns of cerebral hypoperfusion in DLB according to clinical staging. Thirty-three patients with DLB were recruited by clinical dementia rating (CDR) stage. Compared with control, cerebral hypoperfusion was mainly observed in the lingual gyrus, the cuneus, the occipital gyrus in CDR 0.5 group; the fusiform gyrus, the middle temporal gyrus, and the posterior cingulate in CDR 1; and the lingual gyrus, the cuneus, the hippocampus, the fusiform gyrus, and the inferior frontal gyrus in CDR 2. Our findings suggest that cerebral hypoperfusion spreads to the frontal cortex and temporal lobes as disease progresses.