RESUMEN
This study examined the single-nucleotide polymorphism heritability and genetic correlations of cognitive abilities and brain structural measures (regional subcortical volume and cortical thickness) in middle-aged and elderly East Asians (Korean) from the Gwangju Alzheimer's and Related Dementias cohort study. Significant heritability was found in memory function, caudate volume, thickness of the entorhinal cortices, pars opercularis, superior frontal gyri, and transverse temporal gyri. There were 3 significant genetic correlations between (i) the caudate volume and the thickness of the entorhinal cortices, (ii) the thickness of the superior frontal gyri and pars opercularis, and (iii) the thickness of the superior frontal and transverse temporal gyri. This is the first study to describe the heritability and genetic correlations of cognitive and neuroanatomical traits in middle-aged to elderly East Asians. Our results support the previous findings showing that genetic factors play a substantial role in the cognitive and neuroanatomical traits in middle to advanced age. Moreover, by demonstrating shared genetic effects on different brain regions, it gives us a genetic insight into understanding cognitive and brain changes with age, such as aging-related cognitive decline, cortical atrophy, and neural compensation.
Asunto(s)
Encéfalo , Pueblos del Este de Asia , Anciano , Persona de Mediana Edad , Humanos , Estudios de Cohortes , Encéfalo/diagnóstico por imagen , Corteza Cerebral , Cognición , Imagen por Resonancia Magnética/métodosRESUMEN
INTRODUCTION: Our previously developed blood-based transcriptional risk scores (TRS) showed associations with diagnosis and neuroimaging biomarkers for Alzheimer's disease (AD). Here, we developed brain-based TRS. METHODS: We integrated AD genome-wide association study summary and expression quantitative trait locus data to prioritize target genes using Mendelian randomization. We calculated TRS using brain transcriptome data of two independent cohorts (N = 878) and performed association analysis of TRS with diagnosis, amyloidopathy, tauopathy, and cognition. We compared AD classification performance of TRS with polygenic risk scores (PRS). RESULTS: Higher TRS values were significantly associated with AD, amyloidopathy, tauopathy, worse cognition, and faster cognitive decline, which were replicated in an independent cohort. The AD classification performance of PRS was increased with the inclusion of TRS up to 16% with the area under the curve value of 0.850. DISCUSSION: Our results suggest brain-based TRS improves the AD classification of PRS and may be a potential AD biomarker. HIGHLIGHTS: Transcriptional risk score (TRS) is developed using brain RNA-Seq data. Higher TRS values are shown in Alzheimer's disease (AD). TRS improves the AD classification power of PRS up to 16%. TRS is associated with AD pathology presence. TRS is associated with worse cognitive performance and faster cognitive decline.
Asunto(s)
Enfermedad de Alzheimer , Tauopatías , Humanos , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/genética , Estudio de Asociación del Genoma Completo , Cognición , Factores de Riesgo , Biomarcadores , Puntuación de Riesgo GenéticoRESUMEN
INTRODUCTION: Alzheimer's disease (AD) involves the complement cascade, with complement component 3 (C3) playing a key role. However, the relationship between C3 and amyloid beta (Aß) in blood is limited. METHODS: Plasma C3 and Aß oligomerization tendency (AßOt) were measured in 35 AD patients and 62 healthy controls. Correlations with cerebrospinal fluid (CSF) biomarkers, cognitive impairment, and amyloid positron emission tomography (PET) were analyzed. Differences between biomarkers were compared in groups classified by concordances of biomarkers. RESULTS: Plasma C3 and AßOt were elevated in AD patients and in CSF or amyloid PET-positive groups. Weak positive correlation was found between C3 and AßOt, while both had strong negative correlations with CSF Aß42 and cognitive performance. Abnormalities were observed for AßOt and CSF Aß42 followed by C3 changes. DISCUSSION: Increased plasma C3 in AD are associated with amyloid pathology, possibly reflecting a defense response for Aß clearance. Further studies on Aß-binding proteins will enhance understanding of Aß mechanisms in blood.
Asunto(s)
Enfermedad de Alzheimer , Humanos , Enfermedad de Alzheimer/líquido cefalorraquídeo , Amiloide , Péptidos beta-Amiloides/líquido cefalorraquídeo , Biomarcadores/líquido cefalorraquídeo , Complemento C3 , Fragmentos de Péptidos/líquido cefalorraquídeo , Tomografía de Emisión de Positrones/métodos , Proteínas tau/líquido cefalorraquídeoRESUMEN
Autosomal recessive spastic ataxia in Charlevoix-Saguenay (ARSACS) is a neurodegenerative disorder caused by mutations in the sacsin molecular chaperone protein (SACS) gene. Since the first report from Quebec in 1978, many pathogenic ARSACS variants with significantly reduced chaperone activities have been reported worldwide in adolescents, with presumably altered protein folding. In this study, a novel SACS mutation (p.Val1335IIe, Heterozygous) was identified in a Korean patient in their 50s with late-onset ARSACS characterized by cerebellar ataxia and spasticity without peripheral neuropathy. The mutation was confirmed via whole exome sequencing and Sanger sequencing and was predicted to likely cause disease using prediction software. RT-PCR and ELISA showed decreased SACS mRNA expression and sacsin protein concentrations in the proband, supporting its implications in diseases with pathogenicity and reduced chaperone function from haploinsufficiency. Our results revealed the pathogenicity of the SACS Val1335IIe mutation in the proband patient's disease manifestation, even though the symptoms had a limited correlation with the typical ARSACS clinical triad, which could be due to the reduced chaperon function from haploinsufficiency. Furthermore, our study suggests that variants of SACS heterozygosity may have diverse symptoms, with a wide range of disease onsets for late-onset sacsinopathy.
RESUMEN
We report the dual-catalytic enantioselective allylic alkylation of 2-(pyridylmethyl)amine-derived ketimines with allylic carbonates. The reaction proceeds under mild reaction conditions to generate α-amino heteroaryl benzylamine stereocenters in good yield and enantioselectivity. Enantioselectivity is achieved through the use of a copper catalyst modified with chiral bisphosphine ligand (2S,4S)-bis(diphenylphosphino)pentane.
Asunto(s)
Aminas , Cobre , Estereoisomerismo , Catálisis , IminasRESUMEN
INTRODUCTION: Semantic dementia (SD) is a progressive neurodegenerative disease associated with impaired vocabulary that progresses to memory impairment. Post-mortem immunohistochemical analysis is the current reliable method of differentiating TDP-43 deposits in cortical tissue; no means of antemortem diagnosis exists in biofluids, let alone in plasma. METHODS: Here the multimer detection system (MDS) was used to quantify the oligomeric TDP-43 (o-TDP-43) concentrations in plasma of Korean SD patients (n = 16, 6 male, 10 female, ages 59-87). The o-TDP-43 concentrations were compared with the total TDP-43 (t-TDP-43) concentrations quantified through conventional enzyme-linked immunosorbent assay (ELISA). RESULTS AND DISCUSSION: Only MDS showed a significant increase in o-TDP-43 concentrations in the plasma of patients with SD compared to other neurodegenerative disorders and normal controls (p < 0.05). Based on these results, o-TDP-43 concentrations through the application of MDS may be a useful plasma biomarker in SD-FTD (frontotemporal dementia) diagnosis.
Asunto(s)
Demencia Frontotemporal , Enfermedades Neurodegenerativas , Humanos , Masculino , Femenino , Enfermedades Neurodegenerativas/complicaciones , Proteínas de Unión al ADN , República de CoreaRESUMEN
A pathogenic mutation in presenilin-1 (PSEN1), His214Asn, was found in a male patient with memory decline at the age of 41 in Korea for the first time. The proband patient was associated with a positive family history from his father, paternal aunt, and paternal grandmother without genetic testing. He was diagnosed with early onset Alzheimer's disease (EOAD). PSEN1 His214Asn was initially reported in an Italian family, where the patient developed phenotypes similar to the current proband patient. Magnetic resonance imaging (MRI) scans revealed a mild hippocampal atrophy. The amyloid positron emission tomography (amyloid-PET) was positive, along with the positive test results of the increased amyloid ß (Aß) oligomerization tendency with blood. The PSEN1 His214 amino acid position plays a significant role in the gamma-secretase function, especially from three additional reported mutations in this residue: His214Asp, His214Tyr, and His214Arg. The structure prediction model revealed that PSEN1 protein His214 may interact with Trp215 of His-Trp cation-π interaction, and the mutations of His214 would destroy this interaction. The His-Trp cation-π interaction between His214 and Trp215 would play a crucial structural role in stabilizing the 4th transmembrane domain of PSEN1 protein, especially when aromatic residues were often reported in the membrane interface of the lipid-extracellular region of alpha helices or beta sheets. The His214Asn would alter the cleavage dynamics of gamma-secretase from the disappeared interactions between His214 and Trp215 inside of the helix, resulting in elevated amyloid production. Hence, the increased Aß was reflected in the increased Aß oligomerization tendency and the accumulations of Aß in the brain from amyloid-PET, leading to EOAD.
Asunto(s)
Enfermedad de Alzheimer , Histidina , Humanos , Masculino , Histidina/genética , Triptófano , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/genética , Presenilina-1/genética , Secretasas de la Proteína Precursora del Amiloide , Mutación , Proteínas Amiloidogénicas , Cationes , República de CoreaRESUMEN
INTRODUCTION: Subjective memory complaints (SMCs) are common among patients with stroke, significantly affect long-term disability, and contribute to poor functional outcomes. We explored changes in the subjective memory complaints questionnaire (SMCQ) score of stroke patients, correlations among SMCs, objective cognitive performance (OCP), and functional status. We also explored whether participants could be divided into groups based on the presence or absence of SMCs and OCP impairment, which could be related to rehabilitation outcomes. METHODS: A total of 102 stroke patients were recruited from a single rehabilitation center. Their OCP was determined on admission. The Mini-Mental State Evaluation (MMSE), SMCQ, and modified Barthel Index (MBI) scores were obtained at admission and at discharge. These variables were compared and time and group interactions were explored. RESULTS: The SMCQ score did not show consistent patterns of change among individuals. The objective cognitive function and activities of daily living consistently improved after rehabilitation. The proposed cognitive impairment classification after stroke based on SMCs and objective cognitive decline was able to predict improvement attributable to rehabilitation. CONCLUSION: Changes in SMCQ scores of stroke patients were inconsistent and varied when compared to changes in MMSE and MBI scores, indicating that it is not a reliable metric on its own. SMCs have a clinical relationship with OCP and significant emotional and motivational effects. In clinical practice, it is important to understand and consider SMCs after stroke.
Asunto(s)
Disfunción Cognitiva , Accidente Cerebrovascular , Humanos , Actividades Cotidianas , Pruebas Neuropsicológicas , Trastornos de la Memoria/psicología , Disfunción Cognitiva/psicología , CogniciónRESUMEN
INTRODUCTION: Subjective cognitive decline (SCD) is a self-reported cognitive decline without objective cognitive impairment. The relationship between audiometric hearing loss (HL) and cognitive function has not been reported in SCD. The purpose of this study was to investigate whether HL affects cognition-related indexes in SCD individuals. METHODS: This is a cross-sectional study that used the baseline data of a multicenter cohort study that monitors clinical progression from SCD to dementia. Individuals aged ≥60 years who reported cognitive decline but had no objective cognitive impairment on comprehensive neuropsychological tests were recruited. Participants were grouped into the normal-hearing (NH) and bilateral HL groups. The demographics, clinical characteristics, dementia biomarkers, global cognition, questionnaire scores, neuropsychological test scores, and segmental brain volumes from MRI were compared between the groups. RESULTS: Of a total of 120 participants, one hundred and two had NH (n = 57) or bilateral HL (n = 45). There were no group differences in the demographic and clinical data except the age. The biomarkers, global cognition, and questionnaire scores were not different between the groups. The HL group performed worse (the z-score of -0.06) in the Stroop Color Word Test than the NH group (0.27) (p = 0.025). Brain volumetric analysis revealed that the HL group had reduced gray matter volumes in four brain subregions: left temporal pole, left caudal middle frontal gyrus, left hippocampus, and right isthmus of the cingulate gyrus. CONCLUSION: In SCD, HL exerted an adverse effect on cognitive function, primarily frontal executive function tested in the Stroop task. HL was also related to gray matter volume reductions in brain subregions, although causality needs further investigation. This study may provide evidence for a potential link between hearing and cognition in SCD, an emerging clinical entity.
Asunto(s)
Disfunción Cognitiva , Demencia , Pérdida Auditiva , Humanos , Estudios de Cohortes , Estudios Transversales , Disfunción Cognitiva/psicología , Cognición , Pruebas Neuropsicológicas , BiomarcadoresRESUMEN
INTRODUCTION: Subjective cognitive decline (SCD) can be considered as the preclinical manifestation of Alzheimer's disease (AD). The National Institute on Aging and the Alzheimer's Association criteria for preclinical AD proposed that subtle cognitive changes appear along with AD biomarkers in the late stage of preclinical AD. The objective of this study was to explore whether subtle cognitive impairment (SCI) in individuals with SCD is associated with brain amyloid-ß (Aß) status and SCD severity. METHODS: One hundred twenty individuals with SCD (mean age: 70.87 ± 6.10 years) were included in this study. SCI was defined as performance ≤ -1.0 SD on at least two neuropsychological tests. Participants underwent an amyloid positron emission tomography, which was assessed visually and quantitatively using standardized uptake value ratio (SUVR). The severity of SCD was assessed using two self-reported questionnaires: the SCD questionnaire based on the SCD-plus features and the Korean-Everyday Cognition (K-ECog) scale. RESULTS: SCD individuals with SCI (n = 25) had more Aß positivity than the SCD only group (n = 95) (44% vs. 15.79%; p = 0.002). In addition, the SCI group had a higher global SUVR than the SCD only group (p = 0.048). For self-reported questionnaires, there were no differences in SCD questionnaire total scores and K-ECog global and cognitive domain-specific scores between two groups. CONCLUSIONS: In SCD individuals, SCI was associated with higher Aß positivity, but not with the severity of self-reported cognitive decline, compared to the SCD only group. These results suggest that the recognition of objectively defined subtle cognitive deficits may contribute to the early identification of AD in SCD.
Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Anciano , Péptidos beta-Amiloides , Cognición , Disfunción Cognitiva/diagnóstico , Humanos , Pruebas Neuropsicológicas , Tomografía de Emisión de Positrones , AutoinformeRESUMEN
Bisphenol F (BPF, 4,4'-methylenediphenol) has recently been selected as an alternative to bisphenol A (BPA), which is used in the manufacturing of polycarbonates and epoxy resins. This study aimed to investigate the general, and reproductive/developmental effects of BPF. Therefore, BPF at dose levels of 0, 1, 5, 20, and 100 mg/kg/day was administered daily by oral gavage to Sprague-Dawley rats during the pre-mating, mating, gestation, and early lactation periods, and reproductive and developmental toxicities including general systemic toxicities were investigated. A decrease in body weight and food consumption was observed in the female rats treated with BPF at 20 and 100 mg/kg/day during the pre-mating and gestation periods. Additionally, gamma glutamyl transpeptidase levels were increased in the female rats administered 100 mg/kg/day. At 100 mg/kg/day, ovarian weight decreased and vaginal mucification increased according to a necropsy and histopathological examination, respectively. Moreover, the number of implantation sites and litter size decreased at 100 mg/kg/day. However, no significant BPF-related changes were observed in the male rats. Based on the results of this study, the no-observed-adverse-effect levels (NOAELs) of BPF for general systemic and reproductive effects were 5 and 20 mg/kg/day, respectively.
Asunto(s)
Reproducción , Ratas , Masculino , Femenino , Animales , Ratas Sprague-Dawley , Relación Dosis-Respuesta a Droga , Nivel sin Efectos Adversos ObservadosRESUMEN
Alzheimer's disease (AD) is the most common form of age-associated dementia. Several studies have predicted that AD is caused by the production and deposition of the ß-amyloid peptide (Aß) in the brain, which is one of pathologic hallmarks of AD. In particular, Aß oligomers are reportedly the most toxic and pathogenic of other peptide forms. We previously developed Multimer Detection System-Oligomeric Amyloid-ß (MDS-OAß), a technique for measuring Aß oligomerization in plasma to diagnose AD. Here, we clarified the molecular sizes of oligomers that can be detected by the MDS and investigated differences in plasma spiking with a synthetic Aß peptide in the plasma of AD patients and individuals with non-AD neurological conditions. To determine Aß oligomer sizes detectable by MDS, size exclusion chromatography (SEC) was first performed on incubated samples of synthetic Aß42 peptides. As a result, no MDS signals were observed for the Aß42 monomer fractions, but strong signals were found for oligomers of 7-35-mers long. Also, an amplified luminescent proximity homogeneous assay-linked immunoassay (AlphaLISA) was used to confirm that synthetic Aß peptides not only recruited endogenous Aß in plasma but also induced significantly stronger seeding in AD plasma than in healthy control plasma. In addition, the absence of the MDS signals in Aß-depleted plasma confirmed that the increased oligomerization tendency in AD plasma is dependent on the presence of endogenous Aß in plasma. Therefore, the MDS-OAß measurement of oligomerization differences in plasma after incubation with spiked synthetic Aß peptides has significant potential in AD diagnosis.
Asunto(s)
Enfermedad de Alzheimer/sangre , Péptidos beta-Amiloides/sangre , Multimerización de Proteína , Anciano , Péptidos beta-Amiloides/química , Biomarcadores/sangre , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: The tendency of amyloid-ß to form oligomers in the blood as measured with Multimer Detection System-Oligomeric Amyloid-ß (MDS-OAß) is a valuable biomarker for Alzheimer's disease and has been verified with heparin-based plasma. The objective of this study was to evaluate the performance of ethylenediaminetetraacetic acid (EDTA)-based MDS-OAß and to develop machine learning algorithms to predict amyloid positron emission tomography (PET) positivity. METHODS: The performance of EDTA-based MDS-OAß in predicting PET positivity was evaluated in 312 individuals with various machine learning models. The models with various combinations of features (i.e., MDS-OAß level, age, apolipoprotein E4 alleles, and Mini-Mental Status Examination [MMSE] score) were tested 50 times on each dataset. RESULTS: The random forest model best-predicted amyloid PET positivity based on MDS-OAß combined with other features with an accuracy of 77.14 ± 4.21% and an F1 of 85.44 ± 3.10%. The order of significance of predictive features was MDS-OAß, MMSE, Age, and APOE. The Support Vector Machine using the MDS-OAß value only showed an accuracy of 71.09 ± 3.27% and F-1 value of 80.18 ± 2.70%. CONCLUSIONS: The Random Forest model using EDTA-based MDS-OAß combined with the MMSE and apolipoprotein E status can be used to prescreen for amyloid PET positivity.
Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Ácido Edético , Péptidos beta-Amiloides , Enfermedad de Alzheimer/diagnóstico por imagen , Tomografía de Emisión de Positrones , Biomarcadores , Aprendizaje Automático , Algoritmos , Disfunción Cognitiva/diagnósticoRESUMEN
Presenilin-2 (PSEN2) mutation Thr421Met was identified from a 57-years old patient with early onset Alzheimer's disease (EOAD) for the first time in Korea. Previously, this mutation was discovered in an EOAD patient in Japan without a change on amyloid production from the cellular study. Both Korean and Japanese patients developed the disease in their 50s. Memory loss was prominent in both cases, but no additional clinical information was available on the Japanese patient. Magnetic resonance imaging (MRI) images of the Korean patient revealed asymmetric atrophies in both temporo-parietal lobes. In addition, amyloid positron emission tomography (PET) also revealed amyloid deposits in the gray matter of the temporo-parietal lobes asymmetrically. PSEN2 Thr421 was conserved among a majority of vertebrates (such as zebras, elephants, and giant pandas); hence, Thr421 could play an important role in its functions and any mutations could cause detrimental ramifications in its interactions. Interestingly, PSEN2 Thr421 could have homology with PSEN1 Thr440, as PSEN1 T440del mutations were reported from patients with AD or dementia with Lewy bodies. Hence, the changed amino acid from threonine to methionine of PSEN2 Thr421 could cause significant structural alterations in causing local protein dynamics, leading to its pathogenicity in EOAD. Lastly, PSEN2 Thr421Met may interact with other mutations in neurodegenerative disease related genes, which were found in the proband patient, such as ATP binding cassette subfamily A member 7 (ABCA7), Notch Receptor 3 (NOTCH3), or Leucine-rich repeat kinase 2 (LRRK2). These interactions of pathway networks among PSEN2 and other disease risk factors could be responsible for the disease phenotype through other pathways. For example, PSEN2 and ABCA7 may impact amyloid processing and reduce amyloid clearance. Interaction between PSEN2 and NOTCH3 variants may be associated with abnormal NOTCH signaling and a lower degree of neuroprotection. Along with LRRK2 variants, PSEN2 Thr421Met may impact neurodegeneration through Wnt related pathways. In the future, cellular studies of more than one mutation by CRISPR-Cas9 method along with biomarker profiles could be helpful to understand the complicated pathways.
Asunto(s)
Enfermedad de Alzheimer , Enfermedades Neurodegenerativas , Humanos , Presenilina-2/genética , Enfermedad de Alzheimer/genética , Mutación , Pueblo Asiatico , Presenilina-1/genética , Precursor de Proteína beta-Amiloide/genéticaRESUMEN
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).
Asunto(s)
Enfermedad de Alzheimer , Enfermedad de Alzheimer/tratamiento farmacológico , Peso Corporal , Inhibidores de la Colinesterasa/efectos adversos , Donepezilo/efectos adversos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Humanos , Indanos/efectos adversos , Piperidinas/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: This study investigated the differences in caregiver activity, caregiver burden, and awareness of both caregivers and patients with Alzheimer's disease (AD) across different Asian locations. METHODS: This was a secondary analysis of a multi-national cohort study that aimed to assess caregiver activity and caregiver burden using the Caregiver Activity Scale (CAS) and Zarit Burden Interview (ZBI), respectively. Patients' awareness of their dementia diagnosis was assessed by asking the following yes/no question: "Do you have dementia?" Caregivers' awareness of the patient's dementia diagnosis was assessed by asking the following yes/no question: "Does your patient have dementia?" RESULTS: In total, 524 caregivers of patients with AD from China, Hong Kong, South Korea, the Philippines, Singapore, Thailand, and Taiwan participated. The CAS and ZBI score were significantly different across most locations (p < 0.001 and p = 0.033, respectively). Overall, 56.6% of caregivers and 37.5% of patients had awareness of the dementia diagnosis, and the proportion of patients and caregivers with awareness were also different between each location (all, p < 0.001). CONCLUSIONS: Caregiving, caregiver burden, and the awareness of caregivers and patients were different across many Asian locations. With understanding of cultural differences, further public education on dementia could help increase the awareness of patients and caregivers and reduce caregiver burden. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02262975 . Registered 13 October 2014.
Asunto(s)
Cuidadores , Demencia , China , Estudios de Cohortes , Costo de Enfermedad , Demencia/diagnóstico , Demencia/terapia , Hong Kong/epidemiología , Humanos , República de Corea , Singapur/epidemiología , Taiwán , TailandiaRESUMEN
ABSTRACT: The authors analyzed the three-dimensional postoperative condylar position change across the plating systems. This retrospective study was conducted with the patients who underwent bilateral sagittal split ramus osteotomy with setback surgery. The condylar change was analyzed from preoperative cone-beam computed tomography to postoperative 1âmonth (T1) and postoperative 6âmonths (T2) using superimposition software, automatically merging based on the anterior cranial base. The condylar changes during T1 and T2 were analyzed across the four types of plates (4-hole sliding, heart-shaped, 3-hole sliding, and 4-hole conventional) Mean intraclass correlation coefficient values were consistently high for each measurement (>0.850). During T1, the conventional plate had a decreased condylar anterior distance when compared with the 3-hole sliding plate (Pâ=â0.032). During T2, the conventional plate had an increased condylar posterior distance when compared with the 3-hole sliding plate (Pâ=â0.031). Superimposition software based on the anterior cranial base could be available for measurement of condylar position with highly reproducible results. After bilateral sagittal split ramus osteotomy, the 3-hole sliding plate could effectively compensate for the anterior displacement of the condyle compared to other plates.
Asunto(s)
Implantes Dentales , Procedimientos Quirúrgicos Ortognáticos , Humanos , Mandíbula/diagnóstico por imagen , Mandíbula/cirugía , Cóndilo Mandibular/diagnóstico por imagen , Cóndilo Mandibular/cirugía , Osteotomía Sagital de Rama Mandibular , Estudios RetrospectivosRESUMEN
BACKGROUND: Fibrinogen is considered a marker of vascular pathology, indicating a weakened blood-brain barrier, and has a causative role in neuroinflammation and neurodegeneration. Little is known about the relationship between fibrinogen levels and cognitive function in patients with mild cognitive impairment (MCI). We aimed to investigate differences in cognitive profiles according to plasma fibrinogen levels in patients with MCI and the influence of plasma fibrinogen levels on cognitive decline. METHODS: This retrospective cohort study included 643 patients with MCI: 323 patients in the high fibrinogen (high fib) group and 320 patients in the low fibrinogen (low fib) group. A multiple linear regression model was performed to compare cognitive test performance between groups. The Cox proportional hazard model was used to analyze the hazard ratio of fibrinogen level for disease progression. RESULTS: The high fib group demonstrated poorer performance in attention, executive function, and confrontation naming than the low fib group. After adjustment for APOE genotype, the high fib group was associated with poor attention and executive function. After adjustment for vascular risk factors including body mass index, hypertension, diabetes mellitus, dyslipidemia, and smoking history, the high fib group showed declined attention and confrontation naming ability. High fibrinogen levels did not predict disease progression to CDR 1. CONCLUSION: High plasma fibrinogen levels were associated with poor performance in attention in patients with MCI, regardless of APOE genotype or vascular risk factors.
Asunto(s)
Cognición/fisiología , Disfunción Cognitiva , Fibrinógeno/análisis , Pruebas Neuropsicológicas , Anciano , Atención/fisiología , Biomarcadores/análisis , Disfunción Cognitiva/sangre , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/psicología , Correlación de Datos , Femenino , Humanos , Masculino , Estudios Retrospectivos , Factores de RiesgoRESUMEN
INTRODUCTION: Subjective memory complaints (SMCs) among stroke patients are common. To date, reports on SMCs using the Subjective Memory Complaint Questionnaire (SMCQ) are limited. We provided descriptive information on SMCs using the SMCQ alongside objective neuropsychological function assessment in stroke patients and established the sensitivity of SMCQ for post-stroke dementia. METHODS: In total, 419 consecutive stroke patients who were admitted to a stroke unit for younger populations (age <65 years) at a rehabilitation hospital from June 1, 2014, to January 1, 2020, were reviewed. SMCs were measured using the SMCQ. Objective neuropsychological function was assessed using protocols of the Vascular Cognitive Impairment Harmonization Standards. RESULTS: SMCs were significantly correlated with objective neuropsychological functions including memory, executive function, language, and depression. SMCs were not significantly correlated with visuospatial function. The SMCQ exhibited comparable sensitivity to that of Mini-Mental Status Examination for evaluating post-stroke dementia. CONCLUSIONS: The SMCQ may be a valid measure of cognitive function among patients with stroke, is sensitive for post-stroke dementia, and may assume a complementary role for assessing patients with stroke.
Asunto(s)
Demencia , Autoevaluación Diagnóstica , Trastornos de la Memoria , Pruebas Neuropsicológicas , Accidente Cerebrovascular , Encuestas y Cuestionarios/normas , Anciano , Cognición , Trastornos del Conocimiento/psicología , Demencia/diagnóstico , Demencia/etiología , Función Ejecutiva , Femenino , Humanos , Masculino , Trastornos de la Memoria/diagnóstico , Trastornos de la Memoria/etiología , Trastornos de la Memoria/psicología , Reproducibilidad de los Resultados , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/psicologíaRESUMEN
BACKGROUND: Compared to Western populations, familial frontotemporal lobar degeneration (FTLD) is rare among Asians. Progranulin (GRN) gene mutation, which is a major cause of FTLD, is likewise rare. We present a family with FTLD from the Philippines with an autosomal dominant pattern of inheritance and GRN mutation and briefly review reports of GRN mutations in Asia. CASE PRESENTATION: The proband is 66 years old with progressive nonfluent aphasia (PNFA)-corticobasal syndrome . We assessed 3 generations of her pedigree and found 11 affected relatives with heterogenous phenotypes, usually behavioral variant frontotemporal dementia (FTD) and PNFA. Neuroimaging showed atrophy and hypometabolism consistent with FTD syndromes. White matter hyperintensities were seen in affected members even in the absence of vascular risk factors. A GRN mutation R110X was found in 6 members, 3 with symptoms and 3 were asymptomatic. Plasma GRN was low (<112 ng/mL) in all mutation carriers. No mutations were found in microtubule-associated protein tau, APP, PSEN1, and PSEN2 genes, and all were APOE3. CONCLUSION: This is the first Filipino family with autosomal dominant FTD documented with GRN mutation. Identifying families and cohorts would contribute to therapeutic developments in an area with FTD-GRN.