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PURPOSE: To evaluate the effects of toothpaste tablets on the gloss and surface roughness of resin-based composite materials and determine the relationship between gloss and roughness. METHODS: Rectangular jigs were designed and printed. Wells (2 mm deep x 7 mm diameter) were filled with Filtek Supreme Ultra A2B, light-cured and polished. A small-area glossmeter was used for gloss (GU) measurements and a profilometer for roughness measurements (Ra) at baseline and after challenge with each toothpaste. An automated tooth-brushing machine was set at 120 strokes/minute for a total of 10,000 strokes to evaluate four test groups with 16 specimens in each group. NC: Brushing with distilled water; TABS: Colgate Anywhere Travel Tooth Tabs; CP: Colgate Cavity Protection Toothpaste and AW: Colgate Whitening Advanced Toothpaste. Kruskal-Wallis test was used to test the difference in gloss and surface roughness among the groups and Pearson correlation was used to compare the relationship between gloss and roughness. RESULTS: There was no statistically significant difference in gloss and roughness among the four groups at baseline. At post-brushing, there was a statistically significant difference among the groups (P< 0.001) with increased roughness and decreased gloss for CP and AW when compared to TABS. There was a statistically significant correlation between post-brushing roughness and post-brushing gloss (P< 0.001, rho: -0.815). Thus, the higher the surface roughness the lower the gloss. CLINICAL SIGNIFICANCE: Toothpaste tablets retain better gloss and roughness of resin-based composite materials when compared to conventional toothpastes.
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Polimento Dentário , Cremes Dentais , Materiais Dentários , Resinas Compostas , Escovação Dentária , Propriedades de Superfície , Teste de MateriaisRESUMO
BACKGROUND: Amyloid-negative amnestic mild cognitive impairment (MCI) patients have a conversion rate to dementia of approximately 10% within 2 years. This study aimed to investigate whether brain age, calculated using quantitative data obtained from brain magnetic resonance imaging (MRI) artificial intelligence (AI) software can be an important factor in predicting the conversion of dementia in amyloid-negative amnestic MCI patients. METHODS: We conducted a retrospective cohort study of patients with amyloid-negative amnestic MCI who visited the memory clinic of Asan Medical Center. All participants underwent detailed neuropsychological testing, brain MRI, and [18F]-florbetaben (FBB) positron emission tomography (PET) scan. Conversion to dementia was determined by a neurologist based on a clinical interview with a detailed neuropsychological test or a decline in the Korean version of the Mini-Mental State Examination score of more than 4 points per year combined with impaired activities of daily living. Brain age was determined through volumetric assessment of 12 distinct brain regions using commercially available segmentation software, Neurophet AQUA. RESULTS: During the follow-up period, 38% (35/91) of patients converted to dementia from amnestic MCI. 73% (66/91) of patients had a higher brain age than their actual chronological age. In the conversion group, all participants except three (91%, 32/35) had a brain age older than their chronological age. Conversely, the conversion rate to dementia was significantly lower in the group with a younger brain age than their actual age. The subjects were divided into eight groups based on sex, education level, and brain age. When defining the 'survival' as the non-conversion of MCI to dementia, these groups significantly differed in survival probability with a p-value of 0.036. The low-educated female group with a higher brain age than their actual age had the lowest survival rate of all groups. CONCLUSION: Our findings suggest that MRI-based brain age used in this study can contribute to predicting conversion to dementia in patients with amyloid-negative amnestic MCI.
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Encéfalo , Disfunção Cognitiva , Imageamento por Ressonância Magnética , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons , Humanos , Masculino , Feminino , Idoso , Estudos Retrospectivos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Testes Neuropsicológicos/estatística & dados numéricos , Demência , Progressão da Doença , Inteligência Artificial , Pessoa de Meia-Idade , Compostos de AnilinaRESUMO
Amyloid (Aß) and tau proteins are pathologic hallmarks of Alzheimer disease (AD). It is well known that there is spatial disparity between Aß and tau protein deposition but, crossed hemispheric accumulation of these 2 proteins has not been reported. Here we report the case of a 76-year-old woman with typical AD who underwent amyloid positron emission tomography (PET) ([ 18 F]-florbetaben) and tau PET scans ([ 18 F]PI-2620), revealing crossed accumulation of Aß and tau in the cerebral hemisphere. A neuropsychological assessment showed impairment in memory with spared activities of daily living. In the PET analysis, amyloid deposition was observed only in the left side of the cerebral hemisphere and tau only in the right side. Neuroimaging follow-up indicated that the spatial pattern of these protein accumulations had not changed. This case suggests the possibility of independent Aß and tau pathogenic pathways in AD.
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Doença de Alzheimer , Proteínas tau , Atividades Cotidianas , Idoso , Doença de Alzheimer/patologia , Amiloide , Peptídeos beta-Amiloides/metabolismo , Feminino , Humanos , Tomografia por Emissão de Pósitrons/métodos , Proteínas tau/metabolismoRESUMO
BACKGROUND AND PURPOSE: As part of network-specific neurodegeneration, changes in cerebellar gray matter (GM) volume and impaired cerebello-cerebral functional networks have been reported in Alzheimer disease (AD). Compared with healthy controls, a volume loss in the cerebellum has been observed in patients with continuum of AD. However, little is known about the anatomical or functional changes in patients with clinical AD but no brain amyloidosis. We aimed to identify the relationship between cerebellar volume and dementia conversion of amyloid-negative mild cognitive impairment (MCI). METHODS: This study was a retrospective cohort study of patients over the age 50 years with amyloid-negative amnestic MCI who visited the memory clinic of Asan Medical Center with no less than a 36-month follow-up period. All subjects underwent detailed neuropsychological tests, 3 T brain magnetic resonance imaging scans including three-dimensional T1 imaging, and fluorine-18[F18 ]-florbetaben amyloid positron emission tomography scans. A spatially unbiased atlas template of the cerebellum and brainstem was used for analyzing cerebellar GM volume. RESULTS: During the 36 months of follow-up, 39 of 107 (36.4%) patients converted to dementia from amnestic MCI. The converter group had more severe impairments in all visual memory tasks. In terms of volumetric analysis, reduced crus I/II volume adjusted with total intracranial volume, and age was observed in the converter group. CONCLUSIONS: Significant cerebellar GM atrophy involving the bilateral crus I/II may be a novel imaging biomarker for predicting dementia progression in amyloid-negative amnestic MCI patients.
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Doença de Alzheimer , Amiloidose , Disfunção Cognitiva , Biomarcadores , Cerebelo , Disfunção Cognitiva/diagnóstico por imagem , Progressão da Doença , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons , Estudos RetrospectivosRESUMO
INTRODUCTION: Action verbal fluency (AVF) task, a word fluency test, involves language and executive function and is known to be sensitive to fronto-striatal degeneration. However, the ability may also decrease qualitatively as well as quantitatively in normal aging. The objective of this study is to investigate the age-related quantitative and qualitative differences in AVF of Korean adults. METHODS: We analyzed data from 78 participants of 40 young (mean age = 28.9) and 38 older adults (mean age = 67.7). The correct responses in the AVF task were measured for quantitative analysis. Qualitatively, the mean number of arguments required by each verb was calculated for syntactic analysis. For semantic analysis, we subclassified verbs according to their characteristics (e.g., moment vs. non-moment verbs/active vs. non-active verbs) and calculated the ratio for comparison. The results of AVF were also compared to those of semantic/phonemic fluency and the Korean version of the Montreal Cognitive Assessment (MoCA-K). RESULTS: The older group showed quantitatively lower performance in AVF than the young group (p < 0.01). The result of the AVF task significantly correlated (p < 0.01) with both semantic/phonemic fluency and the MoCA-K. Also, the older group produced syntactically more simple verbs than the counterpart (p < 0.01). In the semantic analysis, the older group produced fewer moment verbs (p < 0.05) but more non-moment verbs (p < 0.05) than the young group. There was no difference in active or non-active verbs between two groups. CONCLUSION: These results indicated that the ability of AVF declines with age not only quantitatively but also qualitatively in relation to their cognitive changes.
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Idioma , Semântica , Idoso , Envelhecimento , Povo Asiático , Função Executiva , HumanosRESUMO
BACKGROUND: Donepezil 23 mg is considered for Alzheimer's disease (AD) to optimize cognitive benefits; however, increased adverse events (AEs) can negatively influence drug adherence. We investigated whether body weight (BW) differs based on the presence of AEs, and which baseline factors were relevant to the safety of high-dose donepezil. METHODS: This study was a post hoc analysis of a multicenter randomized trial between 2014 and 2016. We included patients with moderate to severe AD treated with 10 mg/day of donepezil, and the daily dose was escalated to 23 mg with/without dose titration. Dose titration indicates 15 mg/day of donepezil before escalation or 10 mg and 23 mg/day on alternate days before escalation during the first 4 weeks. The patients were divided into 2 groups based on occurrence of AEs of special interest (AESIs) to compare baseline characteristics. We also assessed relationships between BW and AESIs. RESULTS: Among the 160 participants in the safety population, the baseline BWs differed between the AESI (+) (n = 67) and AESI (-) (n = 93) groups. Baseline BW was inversely correlated with the occurrence of AESIs (p = 0.020), and this relationship was prominent in the no-dose titration group (p = 0.009) but absent in the dose-titration groups (p > 0.05). CONCLUSIONS: BW is the most important factor that correlated with cholinergic AEs. Hence, stepwise dose titration should be considered, particularly in patients with low BW, to minimize the inverse relationship between BW and the occurrence of AEs ("Clinicaltrials.gov" No. NCT02550665 registered on September 15, 2015).
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Doença de Alzheimer , Doença de Alzheimer/tratamento farmacológico , Peso Corporal , Inibidores da Colinesterase/efeitos adversos , Donepezila/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Humanos , Indanos/efeitos adversos , Piperidinas/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Around 15% to 20% of patients with clinically probable Alzheimer disease have been found to have no significant Alzheimer pathology on amyloid positron emission tomography. A previous study showed that conversion to dementia from amyloid-negative mild cognitive impairment (MCI) was observed in up to 11% of patients, drawing attention to this condition. OBJECT: We gathered the detailed neuropsychological and neuroimaging data of this population to elucidate factors for conversion to dementia from amyloid-negative amnestic MCI. METHODS: This study was a single-institutional, retrospective cohort study of amyloid-negative MCI patients over age 50 with at least 36 months of follow-up. All subjects underwent detailed neuropsychological testing, 3 tesla brain magnetic resonance imaging), and fluorine-18(18F)-florbetaben amyloid positron emission tomography scans. RESULTS: During the follow-up period, 39 of 107 (36.4%) patients converted to dementia from amnestic MCI. The converter group had more severe impairment in all visual memory tasks. The volumetric analysis revealed that the converter group had significantly reduced total hippocampal volume on the right side, gray matter volume in the right lateral temporal, lingual gyri, and occipital pole. CONCLUSION: Our study showed that reduced gray matter volume related to visual memory processing may predict clinical progression in this amyloid-negative MCI population.
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Doença de Alzheimer , Disfunção Cognitiva , Disfunção Cognitiva/diagnóstico , Progressão da Doença , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons , Estudos Retrospectivos , Vias VisuaisRESUMO
[This corrects the article on p. 117 in vol. 22, PMID: 37545866.].
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Objective: To explore the concurrent validity of the dual-task walking speed assessments in older adults using the Consortium to Establish a Registry for Alzheimer's Disease Neuro-Psychological (CERAD-NP) Assessment Battery. Design: Cross-sectional design. Setting: Welfare care centers, Senior complex centers, and Dementia prevention care centers. Participants: A total of 163 community-dwelling older adults (N=163) were recruited using consecutive sampling. Participants were composed of 65 older adults with cognitive decline and 98 without cognitive decline. Interventions: Not applicable. Main Outcome Measures: This study assessed the concurrent validity between dual-task walking speed assessments and the Total II score of CERAD-NP using Spearman's rank order correlations. The effect of the dual-task walking speed assessments on the Total II score was further investigated through multiple linear regression analysis. Results: There was a moderate and statically significant association between the Total II score and all 8 dual-task walking speed assessments (P<.05). The Total II score was strongly associated with the dual tasks of walking on a straight path while counting backward and crossing over an obstacle (r=0.698, r=0.697, respectively; P<.05). According to multiple linear regression, only the dual task of walking while counting backward was significantly associated with the Total II score (P<.05). Conclusion: The dual-task walking speed assessments, which involved walking and performing a secondary task such as counting backward or crossing an obstacle on a straight path, were highly indicative of cognitive decline. The combination of results from both tasks may provide a more comprehensive evaluation of cognitive decline compared with relying solely on a single-task assessment.
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Patients with amyloid-negative amnestic mild cognitive impairment (MCI) have a conversion rate of approximately 10% to dementia within 2 years. We aimed to investigate whether brain age is an important factor in predicting conversion to dementia in patients with amyloid-negative amnestic MCI. We conducted a retrospective cohort study of patients with amyloid-negative amnestic MCI. All participants underwent detailed neuropsychological evaluation, brain magnetic resonance imaging (MRI), and [18F]-florbetaben positron emission tomography. Brain age was determined by the volumetric assessment of 12 distinct brain regions using an automatic segmentation software. During the follow-up period, 38% of the patients converted from amnestic MCI to dementia. Further, 73% of patients had a brain age greater than their actual chronological age. When defining 'survival' as the non-conversion of MCI to dementia, these groups differed significantly in survival probability (p = 0.036). The low-educated female group with a brain age greater than their actual age had the lowest survival rate among all groups. Our findings suggest that the MRI-based brain age used in this study can contribute to predicting conversion to dementia in patients with amyloid-negative amnestic MCI.
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Doença de Alzheimer , Disfunção Cognitiva , Demência , Humanos , Feminino , Estudos Retrospectivos , Progressão da Doença , Tomografia Computadorizada por Raios X , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Disfunção Cognitiva/patologia , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Amiloide , Testes Neuropsicológicos , Demência/diagnóstico por imagem , Demência/patologia , Doença de Alzheimer/patologiaRESUMO
The aim of the present study was to predict amyloid-beta positivity using a conventional T1-weighted image, radiomics, and a diffusion-tensor image obtained by magnetic resonance imaging (MRI). We included 186 patients with mild cognitive impairment (MCI) who underwent Florbetaben positron emission tomography (PET), MRI (three-dimensional T1-weighted and diffusion-tensor images), and neuropsychological tests at the Asan Medical Center. We developed a stepwise machine learning algorithm using demographics, T1 MRI features (volume, cortical thickness and radiomics), and diffusion-tensor image to distinguish amyloid-beta positivity on Florbetaben PET. We compared the performance of each algorithm based on the MRI features used. The study population included 72 patients with MCI in the amyloid-beta-negative group and 114 patients with MCI in the amyloid-beta-positive group. The machine learning algorithm using T1 volume performed better than that using only clinical information (mean area under the curve [AUC]: 0.73 vs. 0.69, p < 0.001). The machine learning algorithm using T1 volume showed better performance than that using cortical thickness (mean AUC: 0.73 vs. 0.68, p < 0.001) or texture (mean AUC: 0.73 vs. 0.71, p = 0.002). The performance of the machine learning algorithm using fractional anisotropy in addition to T1 volume was not better than that using T1 volume alone (mean AUC: 0.73 vs. 0.73, p = 0.60). Among MRI features, T1 volume was the best predictor of amyloid PET positivity. Radiomics or diffusion-tensor images did not provide additional benefits.
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Estilbenos , Tomografia Computadorizada por Raios X , Humanos , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Compostos de Anilina , Imageamento por Ressonância Magnética , Peptídeos beta-Amiloides/metabolismo , Estudos RetrospectivosRESUMO
Normal pressure hydrocephalus (NPH) patients had altered white matter tract integrities on diffusion tensor imaging (DTI). Previous studies suggested disproportionately enlarged subarachnoid space hydrocephalus (DESH) as a prognostic sign of NPH. We examined DTI indices in NPH subgroups by DESH severity and clinical symptoms. This retrospective case-control study included 33 NPH patients and 33 age-, sex-, and education-matched controls. The NPH grading scales (0-12) were used to rate neurological symptoms. Patients with NPH were categorized into two subgroups, high-DESH and low-DESH groups, by the average value of the DESH scale. DTI indices, including fractional anisotropy, were compared across 14 regions of interest (ROIs). The high-DESH group had increased axial diffusivity in the lateral side of corona radiata (1.43 ± 0.25 vs. 1.72 ± 0.25, p = 0.04), and showed decreased fractional anisotropy and increased mean, and radial diffusivity in the anterior and lateral sides of corona radiata and the periventricular white matter surrounding the anterior horn of lateral ventricle. In patients with a high NPH grading scale, fractional anisotropy in the white matter surrounding the anterior horn of the lateral ventricle was significantly reduced (0.36 ± 0.08 vs. 0.26 ± 0.06, p = 0.03). These data show that DESH may be a biomarker for DTI-detected microstructural alterations and clinical symptom severity.
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Hidrocefalia de Pressão Normal , Hidrocefalia , Substância Branca , Humanos , Hidrocefalia de Pressão Normal/diagnóstico por imagem , Imagem de Tensor de Difusão/métodos , Substância Branca/diagnóstico por imagem , Estudos de Casos e Controles , Estudos Retrospectivos , Anisotropia , Hidrocefalia/diagnóstico por imagemRESUMO
Introduction: This study aimed to determine the efficacy of combining plasma phosphorylated tau (p-tau)181, amyloid beta (Aß)42/Aß40, neurofilament light (NfL), and apolipoprotein E (APOE) genotypes for detecting positive amyloid positron emission tomography (PET), which is little known in the Asian population, in two independent cohorts. Methods: Biomarkers were measured using a single-molecule array (Simoa) in a cohort study (Asan). All participants underwent amyloid PET. Significant changes in the area under the curve (AUC) and Akaike Information Criterion values were considered to determine the best model. The generalizability of this model was tested using another cohort (KBASE-V). Results: In the Asan cohort, after adjusting for age and sex, p-tau181 (AUC = 0.854) or APOE ε4 status (AUC = 0.769) distinguished Aß status with high accuracy. Combining them or adding NfL and Aß42/40 improved model fitness. The best-fit model included the plasma p-tau181, APOE ε4, NfL and Aß42/40. The models established from the Asan cohort were tested in the KBASE-V cohort. Additionally, in the KBASE-V cohort, these three biomarker models had similar AUC in cognitively unimpaired (AUC = 0.768) and mild cognitive impairment (MCI) (AUC = 0.997) participants. Conclusions: Plasma p-tau181 showed a high performance in determining Aß-PET positivity. Adding plasma NfL and APOE ε4 status improved the model fit without significant improvement in AUC.
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Accumulation of aggregated amyloid-ß (Aß) in the brain is considered the first pathological event within the pathogenesis of Alzheimer's disease (AD). It is difficult to accurately identify the initial brain regions of Aß accumulation due to the time-lag between the start of the pathophysiology and symptom onset. However, focal regional amyloid uptake on amyloid PET scans may provide insights into this. Hence, we aimed to evaluate the topographic distribution of amyloid deposition in patients with cognitive impairment and to identify the starting order of amyloid accumulation in the brain using conditional probability. We enrolled 58 patients composed of 9 normal cognition (NC), 32 mild cognitive impairment (MCI), and 17 dementia showing focal regional amyloid deposition corresponding to a brain amyloid plaque load (BAPL) score of 2 among those who visited the Memory Clinic of Asan Medical Center and underwent an 18F-florbetaben PET scan (March 2013 to April 2019). Regions of interest (ROI) included the frontal, parietal, lateral temporal, and occipital cortices, the posterior cingulate/precuneus, and the striatum. The most frequent occurrence of Aß deposition was in the posterior cingulate/precuneus (n = 41, 68.3%). The second most frequent site was the lateral temporal cortex (n = 24, 40.0%), followed by the lateral parietal cortex (n = 21, 35.6%) and other lesions, such as the frontal and occipital cortices. The striatum was the least frequently affected. Our study found that the posterior cingulate/precuneus and the lateral temporal and parietal cortices may be the earliest areas to be affected by Aß accumulation. Longitudinal follow-up of focal brain amyloid deposition may help elucidate the evolutionary pattern of Aß accumulation in the brain of people with AD continuum.
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BACKGROUND: About 40-50% of patients with amnestic mild cognitive impairment (MCI) are found to have no significant Alzheimer's pathology based on amyloid PET positivity. Notably, conversion to dementia in this population is known to occur much less often than in amyloid-positive MCI. However, the relationship between MCI and brain amyloid deposition remains largely unknown. Therefore, we investigated the influence of subthreshold levels of amyloid deposition on conversion to dementia in amnestic MCI patients with negative amyloid PET scans. METHODS: This study was a retrospective cohort study of patients with amyloid-negative amnestic MCI who visited the memory clinic of Asan Medical Center. All participants underwent detailed neuropsychological testing, brain magnetic resonance imaging, and [18F]-florbetaben (FBB) positron emission tomography scan (PET). Conversion to dementia was determined by a neurologist based on a clinical interview with a detailed neuropsychological test or a decline in the Korean version of the Mini-Mental State Examination score of more than 4 points per year combined with impaired activities of daily living. Regional cortical amyloid levels were calculated, and a receiver operating characteristic (ROC) curve for conversion to dementia was obtained. To increase the reliability of the results of the study, we analyzed the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset together. RESULTS: During the follow-up period, 36% (39/107) of patients converted to dementia from amnestic MCI. The dementia converter group displayed increased standardized uptake value ratio (SUVR) values of FBB on PET in the bilateral temporal, parietal, posterior cingulate, occipital, and left precuneus cortices as well as increased global SUVR. Among volume of interests, the left parietal SUVR predicted conversion to dementia with the highest accuracy in the ROC analysis (area under the curve [AUC] = 0.762, P < 0.001). The combination of precuneus, parietal cortex, and FBB composite SUVRs also showed a higher accuracy in predicting conversion to dementia than other models (AUC = 0.763). Of the results of ADNI data, the SUVR of the left precuneus SUVR showed the highest AUC (AUC = 0.596, P = 0.006). CONCLUSION: Our findings suggest that subthreshold amyloid levels may contribute to conversion to dementia in patients with amyloid-negative amnestic MCI.
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Doença de Alzheimer , Amiloidose , Disfunção Cognitiva , Atividades Cotidianas , Doença de Alzheimer/patologia , Amiloide , Proteínas Amiloidogênicas , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/patologia , Progressão da Doença , Humanos , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
BACKGROUND: Cerebral amyloid angiopathy (CAA) often presents as cognitive impairment, but the mechanism of cognitive decline is unclear. Recent studies showed that number of microbleeds were associated with cognitive decline. OBJECTIVE: We aimed to investigate how microbleeds contribute to cognitive impairment in association with white matter tract abnormalities or cortical thickness in CAA. METHODS: This retrospective comparative study involved patients with probable CAA according to the Boston criteria (Aß+ CAA) and patients with Alzheimer's disease (Aß+ AD), all of whom showed severe amyloid deposition on amyloid PET. Using mediation analysis, we investigated how FA or cortical thickness mediates the correlation between the number of lobar microbleeds and cognition. RESULTS: We analyzed 30 patients with Aß+ CAA (age 72.2±7.6, female 53.3%) and 30 patients with Aß+ AD (age 71.5±7.6, female 53.3%). The two groups showed similar degrees of cortical amyloid deposition in AD-related regions. The Aß+ CAA group had significantly lower FA values in the clusters of the posterior area than did the Aß+ AD group(family-wise error-corrected pâ<â0.05). The correlation between the number of lobar microbleeds and visuospatial function was indirectly mediated by white matter tract abnormality of right posterior thalamic radiation (PTR) and tapetum, while lobar microbleeds and language function was indirectly mediated by the abnormality of left PTR and sagittal stratum. Cortical thickness did not mediate the association between lobar microbleeds and cognition. CONCLUSION: This result supports the hypothesis that microbleeds burden leads to white matter tract damage and subsequent cognitive decline in CAA.
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Angiopatia Amiloide Cerebral , Disfunção Cognitiva , Leucoaraiose , Substância Branca , Idoso , Angiopatia Amiloide Cerebral/complicações , Angiopatia Amiloide Cerebral/diagnóstico por imagem , Angiopatia Amiloide Cerebral/psicologia , Hemorragia Cerebral/complicações , Hemorragia Cerebral/diagnóstico por imagem , Disfunção Cognitiva/complicações , Disfunção Cognitiva/etiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Estudos Retrospectivos , Substância Branca/diagnóstico por imagemRESUMO
Obesity is associated with autoimmunity, a phenomenon considered as harmful. Here we show that obese mice and humans produce IgG-type autoantibodies that specifically recognize apolipoprotein B-100 (ApoB100), its native epitope p210, and the synthetic p210 mimotope pB1. By contrast, antibodies against epitopes p45 and p240, which have been associated with atherosclerosis, were not detected in either the humans or mice. In a longitudinal analysis of high fat diet-fed mice, autoantibody production rose with increasing body weight, then decreased and plateaued at morbid obesity. Likewise, in a cross-sectional analysis of sera from 148 human volunteers spanning a wide BMI range and free of comorbidities, the immunoreactivity increased and then decreased with increasing BMI. Thus, the obesity-related ApoB100-specific natural autoantibodies characteristically showed the same epitope recognition, IgG-type, and biphasic serum levels in humans and mice. We previously reported that a pB1-based vaccine induces similar antibodies and can prevent obesity in mice. Therefore, our present results suggest that autoantibodies directed against native ApoB100 may mitigate obesity, and that the vaccination approach may be effective in humans.
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Microglial activation is a central player in the pathophysiology of Alzheimer's disease (AD). The soluble fragment of triggering receptor expressed on myeloid cells 2 (sTREM2) can serve as a marker for microglial activation and has been shown to be overexpressed in AD. However, the relationship of sTREM2 with other AD biomarkers has not been extensively studied. We investigated the relationship between cerebrospinal fluid (CSF) sTREM2 and other AD biomarkers and examined the correlation of plasma sTREM2 with CSF sTREM2 in a cohort of individuals with AD and without AD. Participants were consecutively recruited from Asan Medical Center from 2018 to 2020. Subjects were stratified by their amyloid positivity and clinical status. Along with other AD biomarkers, sTREM2 level was measured in the plasma as well as CSF. In 101 patients with either amyloid-positive or negative status, CSF sTREM2 was closely associated with CSF T-tau and P-tau and not with Abeta42. CSF sTREM2 levels were found to be strongly correlated with CSF neurofilament light chain. The comparison of CSF and plasma sTREM2 levels tended to have an inverse correlation. Plasma sTREM2 and P-tau levels were oppositely influenced by age. Our results suggest that neuroinflammation may be closely associated with tau-induced neurodegeneration.
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Doença de Alzheimer/sangue , Doença de Alzheimer/líquido cefalorraquidiano , Glicoproteínas de Membrana/sangue , Glicoproteínas de Membrana/líquido cefalorraquidiano , Receptores Imunológicos/sangue , Fatores Etários , Idoso , Amiloide/metabolismo , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Estudos de Coortes , Bases de Dados como Assunto , Feminino , Humanos , Masculino , Degeneração Neural/sangue , Fosforilação , Solubilidade , Proteínas tau/líquido cefalorraquidianoRESUMO
INTRODUCTION: Apraxia is a core clinical feature of corticobasal syndrome (CBS). Among the subtypes of apraxia, ideomotor and imitation apraxia are frequently found in CBS. However, little is known about the brain networks that are characteristic of each apraxia subtype or their clinical implication. In this study, we used 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) to explore the specific patterns of glucose hypometabolism that are characteristic of apraxia subtypes by focusing on ideomotor and imitation apraxia. METHODS: We compared the areas of glucose hypometabolism in the brains of 52 patients with CBS and 13 healthy controls, both as a whole and according to apraxia subtypes. In addition, we investigated the relationship between the apraxia subtypes and the clinical phenotype of CBS. RESULTS: In patients with CBS, common hypometabolism was observed in the frontal gyrus, precentral gyrus and caudate regardless of apraxia subtypes. In particular, ideomotor apraxia was associated with hypometabolism in the angular gyrus, while imitation apraxia was associated with hypometabolism in the posterior part including the postcentral gyrus, precuneus, and posterior cingulate gyrus. Patients who showed both ideomotor and imitation apraxia were more likely to show the typical features of CBS and progressive supranuclear palsy compared with patients showing only one type of apraxia. CONCLUSION: Group comparison analysis using FDG-PET revealed distinct pathways of ideomotor and imitation apraxia in CBS. These findings add to our understanding of the brain networks underlying apraxia in association with the clinical features of CBS.
Assuntos
Apraxias/fisiopatologia , Núcleo Caudado/fisiopatologia , Córtex Cerebral/fisiopatologia , Degeneração Corticobasal/fisiopatologia , Comportamento Imitativo , Rede Nervosa/fisiopatologia , Idoso , Apraxia Ideomotora/diagnóstico por imagem , Apraxia Ideomotora/etiologia , Apraxia Ideomotora/metabolismo , Apraxia Ideomotora/fisiopatologia , Apraxias/diagnóstico por imagem , Apraxias/etiologia , Apraxias/metabolismo , Núcleo Caudado/diagnóstico por imagem , Núcleo Caudado/metabolismo , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/metabolismo , Degeneração Corticobasal/complicações , Degeneração Corticobasal/diagnóstico por imagem , Degeneração Corticobasal/metabolismo , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/metabolismo , Tomografia por Emissão de PósitronsRESUMO
INTRODUCTION: False memory, observed as intrusion errors or false positives (FPs), is prevalent in patients with Alzheimer's disease, but has yet to be thoroughly investigated in patients with amnestic mild cognitive impairment (a-MCI) with Alzheimer's disease pathology (ADP). We analyzed false versus veridical memory in individuals with a-MCI and measured the utility of false memory for ADP discrimination. METHODS: Patients with a-MCI who received neuropsychological testing and amyloid PET were included. Patients were categorized into "with" and "without ADP" groups according to PET results. Memory tests assessed veridical and false memory, and the verity of patient responses was analyzed. A logistic regression model was used to evaluate false memory efficiency in discriminating ADP, and the sensitivity and specificity at the optimal level were estimated using the receiver-operating characteristic curve. RESULTS: Thirty-seven ADP and 46 non-ADP patients were enrolled. The ADP group made more FPs in the recognition tests, and their response verity was significantly lower in every delayed memory test. No group difference, however, was observed in the veridical memory. The logistic regression analysis demonstrated that as the FPs increased, the risk of ADP increased 1.31 and 1.36 times in the verbal and visual recognition tests, respectively. The discriminatory accuracy of the FPs was estimated "low" to "moderate" in the visual and verbal recognition, respectively, with an optimal cutoff above 2.5. CONCLUSION: Increased false memory was the only feature to discriminate ADP from non-ADP in individuals with a-MCI. Further studies regarding false memory and its mechanism are warranted.