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1.
Sci Rep ; 12(1): 507, 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35017546

RESUMO

Few studies have demonstrated treatment strategies about the duration and cessation of medications in patients with Crohn's disease (CD). We investigated factors affecting clinical relapse after infliximab (IFX) or azathioprine (AZA) withdrawal in pediatric patients with CD on combination therapy. Pediatric patients with moderate-to-severe CD receiving combination therapy were analyzed retrospectively and factors associated with clinical relapse were investigated. Discontinuation of IFX or AZA was performed in patients who sustained clinical remission (CR) for at least two years and achieved deep remission. A total of 75 patients were included. Forty-four patients (58.7%) continued with combination therapy and 31 patients (41.3%) discontinued AZA or IFX (AZA withdrawal 10, IFX withdrawal 15, both withdrawal 6). Cox proportional-hazards regression and statistical internal validation identified three factors associated with clinical relapse: IFX cessation (hazard ratio; HR 2.982, P = 0.0081), IFX TLs during maintenance therapy (HR 0.581, P = 0.003), 6-thioguanine nucleotide (6-TGN) level (HR 0.978, P < 0.001). However, AZA cessation was not associated with clinical relapse (P = 0.9021). Even when applied in pediatric patients who met stringent criteria, IFX cessation increased the relapse risk. However, withdrawal of AZA could be contemplated in pediatric patients with CD who have sustained CR for at least 2 years and achieved deep remission.

2.
Front Neurol ; 12: 762251, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34950100

RESUMO

Objective: We investigated the mediation effects of subcortical volume change in the relationship of amyloid beta (Aß) and lacune with cognitive function in patients with mild cognitive impairment (MCI). Methods: We prospectively recruited 101 patients with MCI who were followed up with neuropsychological tests, MRI, or Pittsburgh compound B (PiB) PET for 3 years. The mediation effect of subcortical structure on the association of PiB or lacunes with cognitive function was analyzed using mixed effects models. Results: Volume changes in the amygdala and hippocampus partially mediated the effect of PiB changes on memory function (direct effect = -0.168/-0.175, indirect effect = -0.081/-0.077 for amygdala/hippocampus) and completely mediated the effect of PiB changes on clinical dementia rating scale sum of the box (CDR-SOB) (indirect effect = 0.082/0.116 for amygdala/hippocampus). Volume changes in the thalamus completely mediated the effect of lacune on memory, frontal executive functions, and CDR-SOB (indirect effect = -0.037, -0.056, and 0.047, respectively). Conclusions: Our findings provide a better understanding of the distinct role of subcortical structures in the mediation of the relationships of amyloid or vascular changes with a decline in specific cognitive domains.

3.
J Alzheimers Dis ; 2021 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-34958024

RESUMO

BACKGROUND: Alzheimer's disease (AD) and normal pressure hydrocephalus (NPH) commonly coexist. OBJECTIVE: We aimed to characterize an overlapping syndrome of AD and NPH that presents with gait disturbance, ventriculomegaly on magnetic resonance imaging, and significant amyloid deposition on positron emission tomography (PET). METHODS: Of 114 patients who underwent cerebrospinal fluid (CSF) drainage for a possible diagnosis of NPH between 2015 and 2020 in Samsung Medical Center, we identified 24 patients (21.1%) with the NPH patients with amyloid deposition on PET, which we referred to as hydrocephalic AD in this study. We compared their clinical and imaging findings with those of 123 typical AD without hydrocephalic signs/symptoms. We also investigated the frequency and potential predictors of the tap test response in hydrocephalic AD. RESULTS: Evans' index was 0.36±0.03, and a disproportionately enlarged subarachnoid space was present in 54.2% of the hydrocephalic AD patients. The mean age (75.2±7.3 years) and the APOE4 frequency (68.2%) did not differ from those of AD controls. However, the hydrocephalic AD patients showed better memory and language performance, and a thinner cingulate cortex. About 42% of the hydrocephalic AD patients responded to the tap test, of whom seven underwent shunt surgery. Cognition did not improve, whereas gait improved after shunt surgery in all. CONCLUSION: Hydrocephalic AD has different neuropsychological and imaging characteristics from typical AD. Future studies are warranted to further investigate the effect of CSF removal on their clinical course and to elucidate the pathophysiological interaction between amyloid and NPH.

4.
Eur J Neurol ; 2021 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-34972256

RESUMO

BACKGROUND: Previous studies have developed several cognitive composites in preclinical AD. However, more sensitive measures to track cognitive changes and therapeutic efficacy in preclinical Alzheimer's disease (AD) are needed considering diverse sociocultural and linguistic backgrounds. This study developed a composite score that can sensitively detect the Aß-related cognitive trajectory of preclinical AD using Korean data. METHODS: A total of 196 cognitively normal (CN) participants who underwent amyloid positron emission tomography were followed-up with neuropsychological assessments. We developed the Longitudinal Amyloid cognitive Composite in Preclinical AD (LACPA) using the linear mixed-effects model (LMM) and z-scores. The LMM was also used to investigate the longitudinal sensitivity of LACPA and the association between time-varying brain atrophy and LACPA. RESULTS: Considering the group-time interaction effects of each subtest, the Seoul Verbal Learning Test-Elderly's version (SVLT-E) immediate recall/delayed recall/recognition, the Korean Trail Making Test B time, and the Korean Mini-Mental State Examination were selected as components of LACPA. LACPA exhibited a significant group-time interaction effect between the Aß+ and Aß- groups (t = -3.288, p = 0.001). Associations between time-varying LACPA and brain atrophy were found in the bilateral medial temporal, right lateral parietal, and right lateral frontal regions, and hippocampal volume. CONCLUSION: LACPA may contribute to reduction in time and financial burden when monitoring Aß-related cognitive decline and therapeutic efficacy of the disease-modifying agents specifically targeting Aß in secondary prevention trials.

5.
Epidemiol Health ; : e2021067, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34607405

RESUMO

General populations are exposed to numerous environmental pollutants, and it is still unclear what pollutants affect the brain, accelerating brain aging and increasing the risk of dementia. The Environmental-Pollution-Induced Neurological Effects study is a multi-city prospective cohort study that aimed to comprehensively investigate the effect of different environmental pollutants on brain structures, neuropsychological function, and development of dementia in adults. The baseline data of 3,775 healthy elderly people were collected from August 2014 to March 2018. The eligibility criteria were ≥ 50 years of age and no self-reported history of dementia, movement disorders, or stroke. The assessment includes demographics and anthropometrics, laboratory test, and individual levels of exposure to air pollution. Additionally, a neuroimaging sub-cohort was recruited with 1,022 participants, during the same period, and brain magnetic resonance imaging and neuropsychological tests were conducted. The first follow-up environmental pollutant measurements will start in 2022 and the follow-up for the sub-cohort is conducted every 3-4 years. We found that subtle structural changes in the brain may be induced by exposure to airborne pollutants such as PM10, PM2.5, and NO2 in healthy adults. This study provides a research base for large-scale, long-term neuroimaging assessment in community-based populations.

6.
Alzheimers Res Ther ; 13(1): 164, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34610832

RESUMO

BACKGROUND: Accumulating evidence suggests that BMI1 confers protective effects against Alzheimer's disease (AD). However, the mechanism remains elusive. Based on recent pathophysiological evidence, we sought for the first time to identify genetic variants in BMI1 as associated with AD biomarkers, including amyloid-ß. METHODS: We used genetic, longitudinal cognition, and cerebrospinal fluid (CSF) biomarker data from participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort (N = 1565). First, we performed a gene-based association analysis of common single nucleotide polymorphisms (SNPs) (minor allele frequency (MAF) > 5%) located within ± 20 kb of the gene boundary of BMI1, an optimal width for including potential regulatory SNPs in the 5' and 3' untranslated regions (UTR) of BMI1, with CSF Aß1-42 levels. Second, we performed cross-sectional and longitudinal association analyses of SNPs in BMI1 with cognitive performance using linear and mixed-effects models. We replicated association of SNPs in BMI1 with cognitive performance in an independent cohort (N=1084), Religious Orders Study and the Rush Memory and Aging Project (ROS/MAP). RESULTS: Gene-based genetic association analysis showed that BMI1 was significantly associated with CSF Aß1-42 levels after adjusting for multiple testing using permutation (permutation-corrected p value=0.005). rs17415557 in BMI1 showed the most significant association with CSF Aß1-42 levels. Participants with minor alleles of rs17415557 have increased CSF Aß1-42 levels compared to those with no minor alleles. Further analysis identified and replicated the minor allele of rs17415557 as being significantly associated with slower cognitive decline rates in AD. CONCLUSIONS: Our findings provide fundamental evidence that BMI1 rs17415557 may serve as a protective mechanism related to AD pathogenesis, which supports the results of previous studies linking BMI1 to protection against AD.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doença de Alzheimer/complicações , Doença de Alzheimer/genética , Peptídeos beta-Amiloides , Disfunção Cognitiva/genética , Estudos Transversais , Humanos , Complexo Repressor Polycomb 1 , Proteínas tau
7.
Sci Rep ; 11(1): 19529, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34593890

RESUMO

Accumulating evidence indicates that amyloid-beta (Aß) deposition and biogenic aldehyde accumulation contribute to the pathogenesis of neurodegenerative diseases. Human aldehyde dehydrogenase 2 (ALDH2) metabolizes biogenic aldehydes produced in the brain to prevent damage. However, r671G>A, a single nucleotide polymorphism of ALDH2, causes aldehyde accumulation and decreased ALDH2 activity. We aimed to investigate whether Aß deposition and rs671 polymorphism have an interaction effect on cortical thickness (CTh). We grouped 179 participants in the Biobank Innovations for chronic Cerebrovascular disease With ALZheimer's disease Study as follows: amyloid (-) [A(-)] and amyloid (+) [A(+)] groups based on the Aß deposition degree; A-carrier (AC) and GG (GG) groups based on the presence/absence of the rs671 A allele; and their combinations, i.e., A(-)AC, A(-)GG, A(+)AC, and A(+)GG groups. A multiple regression analysis identified nine regions of interest. Compared with the A(-)GG group, the A(-)AC group showed thinner CTh in all regions. There were no significant differences between the A(+)AC and A(+)GG groups. We observed an interaction effect of amyloid deposition and rs671 polymorphism on CTh. The CTh in the A(-) group appeared to be strongly influenced by rs671 polymorphism, which could have contributed to cortical thinning and biogenic aldehyde accumulation in the AC group. Additionally, CTh in the A(+) group appeared to be strongly influenced by amyloid deposition.

8.
Yonsei Med J ; 62(11): 1062-1068, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34672140

RESUMO

This study was conducted as a pilot project to evaluate the feasibility of building an integrate dementia platform converging preexisting dementia cohorts from several variable levels. The following four cohorts were used to develop this pilot platform: 1) Clinical Research Center for Dementia of South Korea (CREDOS), 2) Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's disease (K-BASE), 3) Environmental Pollution-induced Neurological Effects (EPINEF) study, and 4) a prospective registry in Dementia Platform Korea project (DPKR). A total of 29916 patients were included in the platform with 348 integrated variables. Among participants, 13.9%, 31.5%, and 44.2% of patients had normal cognition, mild cognitive impairment, and dementia, respectively. The mean age was 72.4 years. Females accounted for 65.7% of all patients. Those with college or higher education and those without problems in reading or writing accounted for 12.3% and 46.8%, respectively. Marital status, cohabitation, family history of Parkinson's disease, smoking and drinking status, physical activity, sleep status, and nutrition status had rates of missing information of 50% or more. Although individual cohorts were of the same domain and of high quality, we found there were several barriers to integrating individual cohorts, including variability in study variables and measurements. Although many researchers are trying to combine pre-existing cohorts, the process of integrating past data has not been easy. Therefore, it is necessary to establish a protocol with considerations for data integration at the cohort establishment stage.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Demência , Idoso , Encéfalo , Demência/diagnóstico , Demência/epidemiologia , Feminino , Humanos , Projetos Piloto
9.
Eur J Neurol ; 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34716964

RESUMO

BACKGROUND AND PURPOSE: Subcortical vascular cognitive impairment (SVCI) is characterized by the presence of cerebral small vessel disease (CSVD) markers. Some SVCI patients also show Alzheimer's disease and cerebral amyloid angiopathy markers. However, the effects of these imaging markers on long-term clinical outcomes have not yet been established. The present study, therefore, aimed to determine how these imaging markers influence functional disability and/or mortality. METHODS: We recruited 194 participants with SVCI from the memory clinic and followed them up. All participants underwent brain magnetic resonance imaging at baseline, and 177 (91.2%) participants underwent beta-amyloid (Aß) positron emission tomography. We examined the occurrence of ischemic or hemorrhagic strokes. We also evaluated functional disability and mortality using the modified Rankin scale. To determine the effects of imaging markers on functional disability or mortality, we used Fine and Gray competing regression or Cox regression analysis. RESULTS: During a 8.6-year follow-up period, 46 of 194 patients (23.7%) experienced a stroke, 110 patients (56.7%) developed functional disabilities and 75 (38.6%) died. Aß positivity (subdistribution hazard ratio [SHR] = 2.73), greater white matter hyperintensity (WMH) volume (SHR = 3.11) and ≥3 microbleeds (SHR = 2.29) at baseline were independent predictors of functional disability regardless of the occurrence of stroke. Greater WMH volume (hazard ratio = 2.07) was an independent predictor of mortality. CONCLUSIONS: Our findings suggest that diverse imaging markers may predict long-term functional disability and mortality in patients with SVCI, which in turn may provide clinicians with a more insightful understanding of the long-term outcomes of SVCI.

10.
Alzheimers Res Ther ; 13(1): 179, 2021 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-34686209

RESUMO

BACKGROUND: We assessed the feasibility of plasma Aß42/Aß40 determined using a novel liquid chromatography-mass spectrometry method (LC-MS) as a useful biomarker of PET status in a Korean cohort from the DPUK Study. METHODS: A total of 580 participants belonging to six groups, Alzheimer's disease dementia (ADD, n = 134), amnestic mild cognitive impairment (aMCI, n = 212), old controls (OC, n = 149), young controls (YC, n = 15), subcortical vascular cognitive impairment (SVCI, n = 58), and cerebral amyloid angiopathy (CAA, n = 12), were included in this study. Plasma Aß40 and Aß42 were quantitated using a new antibody-free, LC-MS, which drastically reduced the sample preparation time and cost. We performed receiver operating characteristic (ROC) analysis to develop the cutoff of Aß42/Aß40 and investigated its performance predicting centiloid-based PET positivity (PET+). RESULTS: Plasma Aß42/Aß40 were lower for PET+ individuals in ADD, aMCI, OC, and SVCI (p < 0.001), but not in CAA (p = 0.133). In the group of YC, OC, aMCI, and ADD groups, plasma Aß42/Aß40 predicted PET+ with an area under the ROC curve (AUC) of 0.814 at a cutoff of 0.2576. When adding age, APOE4, and diagnosis, the AUC significantly improved to 0.912. CONCLUSION: Plasma Aß42/Aß40, as measured by this novel LC-MS method, showed good discriminating performance based on PET positivity.


Assuntos
Doença de Alzheimer , Espectrometria de Massas em Tandem , Doença de Alzheimer/diagnóstico por imagem , Peptídeos beta-Amiloides , Biomarcadores , Cromatografia Líquida de Alta Pressão , Humanos , Fragmentos de Peptídeos , República da Coreia
11.
J Alzheimers Dis ; 84(2): 633-645, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34569949

RESUMO

BACKGROUND: Primary progressive aphasia (PPA) is associated with amyloid-ß (Aß) pathology. However, clinical feature of PPA based on Aß positivity remains unclear. OBJECTIVE: We aimed to assess the prevalence of Aß positivity in patients with PPA and compare the clinical characteristics of patients with Aß-positive (A+) and Aß-negative (A-) PPA. Further, we applied Aß and tau classification system (AT system) in patients with PPA for whom additional information of in vivo tau biomarker was available. METHODS: We recruited 110 patients with PPA (41 semantic [svPPA], 27 non-fluent [nfvPPA], 32 logopenic [lvPPA], and 10 unclassified [ucPPA]) who underwent Aß-PET imaging at multi centers. The extent of language impairment and cortical atrophy were compared between the A+ and A-PPA subgroups using general linear models. RESULTS: The prevalence of Aß positivity was highest in patients with lvPPA (81.3%), followed by ucPPA (60.0%), nfvPPA (18.5%), and svPPA (9.8%). The A+ PPA subgroup manifested cortical atrophy mainly in the left superior temporal/inferior parietal regions and had lower repetition scores compared to the A-PPA subgroup. Further, we observed that more than 90% (13/14) of the patients with A+ PPA had tau deposition. CONCLUSION: Our findings will help clinicians understand the patterns of language impairment and cortical atrophy in patients with PPA based on Aß deposition. Considering that most of the A+ PPA patents are tau positive, understanding the influence of Alzheimer's disease biomarkers on PPA might provide an opportunity for these patients to participate in clinical trials aimed for treating atypical Alzheimer's disease.

12.
Alzheimers Res Ther ; 13(1): 154, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34521461

RESUMO

BACKGROUNDS: Alzheimer's disease is the most common cause of dementia, and currently, there is no disease-modifying treatment. Favorable functional outcomes and reduction of amyloid levels were observed following transplantation of mesenchymal stem cells (MSCs) in animal studies. OBJECTIVES: We conducted a phase I clinical trial in nine patients with mild-to-moderate Alzheimer's disease dementia to evaluate the safety and dose-limiting toxicity of three repeated intracerebroventricular injections of human umbilical cord blood-derived MSCs (hUCB-MSCs). METHODS: We recruited nine mild-to-moderate Alzheimer's disease dementia patients from Samsung Medical Center, Seoul, Republic of Korea. Four weeks prior to MSC administration, the Ommaya reservoir was implanted into the right lateral ventricle of the patients. Three patients received a low dose (1.0 × 107 cells/2 mL), and six patients received a high dose (3.0 × 107 cells/2 mL) of hUCB-MSCs. Three repeated injections of MSCs were performed (4-week intervals) in all nine patients. These patients were followed up to 12 weeks after the first hUCB-MSC injection and an additional 36 months in the extended observation study. RESULTS: After hUCB-MSC injection, the most common adverse event was fever (n = 9) followed by headache (n = 7), nausea (n = 5), and vomiting (n = 4), which all subsided within 36 h. There were three serious adverse events in two participants that were considered to have arisen from the investigational product. Fever in a low dose participant and nausea with vomiting in another low dose participant each required extended hospitalization by a day. There were no dose-limiting toxicities. Five participants completed the 36-month extended observation study, and no further serious adverse events were observed. CONCLUSIONS: Three repeated administrations of hUCB-MSCs into the lateral ventricle via an Ommaya reservoir were feasible, relatively and sufficiently safe, and well-tolerated. Currently, we are undergoing an extended follow-up study for those who participated in a phase IIa trial where upon completion, we hope to gain a deeper understanding of the clinical efficacy of MSC AD therapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT02054208. Registered on 4 February 2014. ClinicalTrials.gov NCT03172117. Registered on 1 June 2017.


Assuntos
Doença de Alzheimer , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Doença de Alzheimer/terapia , Animais , Sangue Fetal , Seguimentos , Humanos
13.
J Alzheimers Dis ; 83(3): 1025-1031, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34366354

RESUMO

Atypical psychological symptoms frequently occur in early-onset Alzheimer's disease (EOAD), which makes it difficult to differentiate it from other psychiatric disorders. We report the case of a 28-year-old woman with EOAD, carrying a presenilin-1 mutation (S170P), who was initially misdiagnosed with schizophrenia because of prominent psychiatric symptoms in the first 1-2 years of the disease. Amyloid-ß positron emission tomography (PET) showed remarkably high tracer uptake in the striatum and thalamus. Tau PET showed widespread cortical uptake and relatively low uptake in the subcortical and medial temporal regions. Our case advocates for considering EOAD diagnosis for young patients with psychiatric and atypical cognitive symptoms.

14.
Sci Rep ; 11(1): 17255, 2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-34446742

RESUMO

We investigated the effect of education on the edge efficiency in resting state functional networks (RSFNs) in amnestic mild cognitive impairment (aMCI) and Alzheimer's disease dementia (ADD). We collected the data of 57 early aMCI, 141 late aMCI, 173 mild ADD, and 39 moderate-to-severe ADD patients. We used years of education as a proxy for cognitive reserve. We measured edge efficiency for each edge in RSFNs, and performed simple slope analyses to discover their associations with education level among the four groups. In the late aMCI, a sub-network that had hub nodes in the right middle frontal gyrus and the right posterior cingulate gyrus, showed a positive association between RSFN edge efficiency and education (threshold = 2.5, p = 0.0478). There was no negative effect of education on the RSFN edge efficiency. In the early aMCI, mild ADD, and moderate-to-severe ADD, there were no sub-networks showing positive or negative correlation between education and RSFN edge efficiency. There was a positive effect of higher education on RSFN edge efficiency in the late aMCI, but not in the early aMCI or ADD. This indicates that in late aMCI, those who have higher education level have greater ability to resist collapsed functional network.


Assuntos
Doença de Alzheimer/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Demência/fisiopatologia , Escolaridade , Rede Nervosa/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Cognição/fisiologia , Feminino , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/fisiopatologia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Memória/fisiologia , Pessoa de Meia-Idade , Modelos Neurológicos , Testes Neuropsicológicos/estatística & dados numéricos
15.
Artigo em Inglês | MEDLINE | ID: mdl-34328533

RESUMO

PURPOSE: In this study, we used machine learning to develop a new method derived from a ligand-independent amyloid (Aß) positron emission tomography (PET) classifier to harmonise different Aß ligands. METHODS: We obtained 107 paired 18F-florbetaben (FBB) and 18F-flutemetamol (FMM) PET images at the Samsung Medical Centre. To apply the method to FMM ligand, we transferred the previously developed FBB PET classifier to test similar features from the FMM PET images for application to FMM, which in turn developed a ligand-independent Aß PET classifier. We explored the concordance rates of our classifier in detecting cortical and striatal Aß positivity. We investigated the correlation of machine learning-based cortical tracer uptake (ML-CTU) values quantified by the classifier between FBB and FMM. RESULTS: This classifier achieved high classification accuracy (area under the curve = 0.958) even with different Aß PET ligands. In addition, the concordance rate of FBB and FMM using the classifier (87.5%) was good to excellent, which seemed to be higher than that in visual assessment (82.7%) and lower than that in standardised uptake value ratio cut-off categorisation (93.3%). FBB and FMM ML-CTU values were highly correlated with each other (R = 0.903). CONCLUSION: Our findings suggested that our novel classifier may harmonise FBB and FMM ligands in the clinical setting which in turn facilitate the biomarker-guided diagnosis and trials of anti-Aß treatment in the research field.

16.
Yonsei Med J ; 62(8): 717-725, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34296549

RESUMO

PURPOSE: Muscle relaxation following electrical automatic massage (EAM) has been found to reduce fatigue, depression, stress, anxiety, and pain in individuals with various conditions. However, the effects of EAM have not been extensively explored in patients with Alzheimer's disease (AD). MATERIALS AND METHODS: Here, we conducted a randomized controlled study to evaluate the effects of EAM on the cognitive and non-cognitive functions of patients with AD spectrum disorders. RESULTS: We found that EAM attenuated changes in attention-associated cognitive scores and subjective sleep quality relative to those in controls. CONCLUSION: While further studies in a clinical setting are needed to support our findings, these encouraging results suggest that EAM may be an alternative therapy for the management of associated symptoms in AD (ClinicalTrials.gov ID: NCT03507192, 24/04/2018).


Assuntos
Doença de Alzheimer , Doença de Alzheimer/terapia , Ansiedade/terapia , Cognição , Humanos , Massagem , Sono
17.
J Neurol Sci ; 428: 117565, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34311139

RESUMO

BACKGROUND: Telomeres are repetitive DNA sequences of TTAGGG at the ends of chromosomes. Many studies have shown that telomere shortening is associated with aging-related diseases, such as cardiovascular diseases, hypertension, diabetes, cancer, and various neurodegenerative diseases, including Alzheimer's disease, vascular dementia, Parkinson's disease, and dementia with Lewy bodies. However, changes in telomere length (TL) in patients with frontotemporal dementia (FTD) syndrome are unclear. Accordingly, in this study, we assessed TL in blood samples from patients with FTD syndrome. METHODS: Absolute TL was measured in peripheral blood leukocytes from 53 patients with FTD syndromes (25 with behavioral variant FTD, 19 with semantic variant primary progressive aphasia [PPA], six with nonfluent/agrammatic variant PPA, and three with amyotrophic lateral sclerosis [ALS] plus) and 28 cognitively unimpaired (CU) controls using terminal restriction fragment analysis. RESULTS: TL was significantly longer in the FTD group than in the CU group. All FTD subtypes had significantly longer TL than controls. There were no significant differences in TL among FTD syndromes. No significant correlations were found between TL and demographic factors in the FTD group. CONCLUSIONS: Longer telomeres were associated with FTD syndrome, consistent with a recent report demonstrating that longer telomeres are related to ALS. Therefore, our results may support a shared biology between FTD and ALS. More studies with larger sample sizes are needed.


Assuntos
Doença de Alzheimer , Esclerose Amiotrófica Lateral , Demência Frontotemporal , Demência Frontotemporal/genética , Humanos , Síndrome , Telômero/genética
18.
Neuroimage Clin ; 30: 102685, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34215155

RESUMO

OBJECTIVE: Neuropsychological test-specific neural substrates in subcortical vascular cognitive impairment (SVCI) are expected to differ from those in Alzheimer's disease-related cognitive impairment (ADCI) but the details are unclear. To determine neural substrates related to cerebral small vessel disease, we investigated the correlations between cognitive dysfunctions measured by standardized neuropsychological tests and cortical thickness in a large sample of participants with amyloid negative (Aß (-)) SVCI. METHODS: One hundred ninety-eight participants with Aß (-) SVCI were recruited from the memory clinic between November 2007 to August 2018. To acquire neural substrates, we performed linear regression using the scores of each neuropsychological test as a predictor, cortical thickness as an outcome, and age, sex, education years, intracranial volume and white matter hyperintensity (WMH) as confounders. RESULTS: Poor performances in each neuropsychological test were associated with cortical atrophy in certain brain regions regardless of WMH. Especially, not the medial temporal but the frontal and posterior cingulate regions with cortical atrophy were mainly associated with memory impairment. Poor performance in animal fluency was more likely to be associated with cortical atrophy in the left hemisphere, while poor performance in the visuospatial memory test was more likely to be associated with cortical atrophy in the right hemisphere. CONCLUSIONS: Our findings suggested that cortical atrophy was an important factor of cognitive impairment in Aß (-) SVCI regardless of WMH. Furthermore, our findings might give clinicians a better understanding of specific neural substrates of neuropsychological deficits in patients with SVCI.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Encéfalo , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Humanos , Imageamento por Ressonância Magnética , Testes Neuropsicológicos
19.
J Alzheimers Dis ; 82(4): 1591-1599, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34180413

RESUMO

BACKGROUND: An association between Helicobacter pylori (H. pylori) infection and dementia was reported in previous studies; however, the evidence is inconsistent. OBJECTIVE: In the present study, the association between H. pylori infection and brain cortical thickness as a biomarker of neurodegeneration was investigated. METHODS: A cross-sectional study of 822 men who underwent a medical health check-up, including an esophagogastroduodenoscopy and 3.0 T magnetic resonance imaging, was performed. H. pylori infection status was assessed based on histology. Multiple linear regression analyses were conducted to evaluate the relationship between H. pylori infection and brain cortical thickness. RESULTS: Men with H. pylori infection exhibited overall brain cortical thinning (p = 0.022), especially in the parietal (p = 0.008) and occipital lobes (p = 0.050) compared with non-infected men after adjusting for age, educational level, alcohol intake, smoking status, and intracranial volume. 3-dimentional topographical analysis showed that H. pylori infected men had cortical thinning in the bilateral lateral temporal, lateral frontal, and right occipital areas compared with non-infected men with the same adjustments (false discovery rate corrected, Q < 0.050). The association remained significant after further adjusting for inflammatory marker (C-reactive protein) and metabolic factors (obesity, dyslipidemia, fasting glucose, and blood pressure). CONCLUSION: Our results indicate H. pylori infection is associated with neurodegenerative changes in cognitive normal men. H. pylori infection may play a pathophysiologic role in the neurodegeneration and further studies are needed to validate this association.


Assuntos
Espessura Cortical do Cérebro , Encéfalo/patologia , Demência/fisiopatologia , Infecções por Helicobacter/complicações , Estudos Transversais , Demência/etiologia , Endoscopia do Sistema Digestório , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Lobo Occipital/patologia , Lobo Parietal/patologia , República da Coreia
20.
J Psychiatr Res ; 140: 488-495, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34153903

RESUMO

Brain atrophy is related to vascular risk factors and can increase cognitive dysfunction risk. This community-based, cross-sectional study investigated whether glucose metabolic disorders due to body fatness are linked to regional changes in brain structure and a decline in neuropsychological function in cognitively healthy older adults. From 2016 to 2019, 429 participants underwent measurements for cortical thickness and subcortical volume using 3 T magnetic resonance imaging and for cognitive function using the neuropsychological screening battery. The effects of body fatness mediated by impaired glucose metabolism on neuroimaging markers and cognitive function was investigated using partial least square structural equation modeling. Total grey matter volume (ß = -0.020; bias-corrected (BC) 95% confidence interval (CI) = -0.047 to -0.006), frontal (ß = -0.029; BC 95% CI = -0.063 to -0.005) and temporal (ß = -0.022; BC 95% CI = -0.051 to -0.004) lobe cortical thickness, and hippocampal volume (ß = -0.029; BC 95% CI = -0.058 to -0.008) were indirectly related to body fatness. Further, frontal/temporal lobe thinning was associated with recognition memory (ß = -0.005; BC 95% CI = -0.012 to -0.001/ß = -0.005; BC 95% CI = -0.013 to -0.001) and delayed recall for visual information (ß = -0.005; BC 95% CI = -0.013 to -0.001/ß = -0.005; BC 95% CI = -0.013 to -0.001). Additionally, the smaller the hippocampal volume, the lower the score in recognition memory (ß = -0.005; BC 95% CI = -0.012 to -0.001), delayed recall for visual information (ß = -0.005; BC 95% CI = -0.012 to -0.001), and verbal learning (ß = -0.008; BC 95% CI = -0.017 to -0.002). Our findings indicate that impaired glucose metabolism caused by excess body fatness affects memory decline as well as regional grey matter atrophy in elderly individuals with no neurological disease.


Assuntos
Encéfalo , Disfunção Cognitiva , Idoso , Atrofia/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Cognição , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/patologia , Estudos Transversais , Glucose , Humanos , Imageamento por Ressonância Magnética , Neuroimagem , Testes Neuropsicológicos
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