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1.
Biomed Environ Sci ; 34(1): 19-28, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33531104

RESUMO

Objective: In the present study, the ABCA1 was used as a label to capture specific exosomes, the level of ABCA1-labeled exosomal microRNA-135a (miR-135a) was evaluated for the diagnosis of Alzheimer's disease (AD), especially in patients with early stages of AD. Methods: This is a preliminary research focused on the levels of ABCA1 in WBCs, RBCs, HT-22 cells, and neuron cells. The diagnostic value of ABCA1-labeled exosomal miR-135a was examined using the CSF and serum of APP/PS1 double transgenic mice, and 152 patients with SCD, 131 patients with MCI, 198 patients with DAT, and 30 control subjects. Results: The level of ABCA1 exosomes harvested from HT-22 cells and neuron culture medium was significantly higher compared to that of RBCs and WBCs ( P < 0.05). The levels of ABCA1-labeled exosomal miR-135a increased in the CSF of MCI and DAT group compared to those of control group ( P < 0.05), slightly increased ( P > 0.05) in the serum of SCD patient group, and significantly increased in MCI and DAT patient groups compared to those of the control group ( P < 0.05). Conclusion: This study outlines a method to capture specific exosomes and detect them using immunological methods, which is more efficient for early diagnosis of AD.


Assuntos
Transportador 1 de Cassete de Ligação de ATP , Disfunção Cognitiva/sangue , Exossomos , MicroRNAs/sangue , Transportador 1 de Cassete de Ligação de ATP/sangue , Transportador 1 de Cassete de Ligação de ATP/líquido cefalorraquidiano , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/sangue , Doença de Alzheimer/líquido cefalorraquidiano , Animais , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Linhagem Celular , Disfunção Cognitiva/líquido cefalorraquidiano , Eritrócitos/metabolismo , Feminino , Humanos , Leucócitos/metabolismo , Masculino , Camundongos Transgênicos , Neurônios/metabolismo
2.
JAMA Netw Open ; 3(12): e2028634, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33331917

RESUMO

Importance: Plasma measurement of amyloid-ß (Aß) peptides has been associated with cognitive function, but evidence of its ability to identify cognitive decline is still scarce. Objective: To investigate the associations between plasma Aß42/40 and cognitive decline over time among community-dwelling older adults with subjective memory concerns. Design, Setting, and Participants: This multicenter cohort study used data from volunteers in the 5-year study Multidomain Alzheimer Preventive Trial (MAPT). Participants were aged 70 years or older and observed for a median (interquartile range) of 3.9 (2.0-4.0) years. Recruitment of participants started in May 2008 and ended in February 2011. Follow-up ended in April 2016. Data analysis was conducted from April to October 2020. Exposure: Plasma Aß42 and Aß40 were measured at 12 months for 448 participants (92.8%) and at 24 months for the rest. The moment of Aß assessment was defined as the baseline for this study. Main Outcomes and Measures: Cognitive function was assessed at 12, 24, 36, 48, and 60 months by a composite cognitive score based on 4 tests; Mini Mental State Examination (MMSE); Clinical Dementia Rating, sum of boxes; and Alzheimer Disease Cooperative Study-Activities of Daily Living. Mixed-effect linear regressions were performed. Results: A total of 483 participants (median [IQR] age, 76.0 [73.0-80.0]; 286 [59.2%] women) were analyzed. Of them, 161 (33.3%) were classified as low plasma Aß42/40 (≤0.107). After adjusting for age, sex, education, body mass index, Geriatric Depression Scale score, apolipoprotein E ε4 genotype, and MAPT intervention groups, low plasma Aß42/40 was associated with more pronounced decline in composite cognitive score (adjusted between-group mean difference: -0.20, 95% CI, -0.34 to -0.07; P = .004) and decline in MMSE score (adjusted between-group mean difference: -0.59; 95% CI, -1.07 to -0.11; P = .02) during the follow-up period compared with the group with an Aß42/40 ratio greater than 0.107. Conclusions and Relevance: In this study, low plasma Aß42/40 was associated with more pronounced decline in cognitive function (measured by multiple outcomes) over time. Findings suggest that plasma Aß42/40 may be used to identify people at risk of cognitive decline, being an alternative to more complex and expensive measures, such as positron emission tomography imaging or cerebrospinal fluid measurement.


Assuntos
Peptídeos beta-Amiloides/sangue , Disfunção Cognitiva , Vida Independente , Fragmentos de Peptídeos/sangue , Idoso , Apolipoproteína E4/genética , Cognição/fisiologia , Disfunção Cognitiva/sangue , Disfunção Cognitiva/diagnóstico , Correlação de Dados , Autoavaliação Diagnóstica , Feminino , Avaliação Geriátrica/métodos , Humanos , Masculino , Transtornos da Memória/sangue , Transtornos da Memória/diagnóstico , Transtornos da Memória/psicologia
3.
Medicine (Baltimore) ; 99(31): e21390, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756130

RESUMO

Prior evidence suggested that inflammation and inflammatory cytokines polymorphisms might be essential in the development of coronary heart disease (CHD) and cognitive decline. The following study investigated the associations between interleukin-35 (IL-35) polymorphisms and cognitive decline in CHD patients over a 2-year period.CHD patients were enrolled between January 2015 and January 2016. Cognitive function, including memory, orientation, verbal and attention were assessed using Telephone Interview for Cognitive Status-Modified (TICS-m) during a 2-year follow-up. Genotypes of the single nucleotide polymorphisms (SNPs), including rs2243115, rs568408, rs582054, rs583911, rs428253, rs4740 and rs393581 of IL-35 were examined by MassArray (Sequenom). The differences of TICS-m score between 2-year interval were used to estimate the cognitive decline; linear regression model was used to analyze the association between IL-35 polymorphisms and cognitive decline in CHD patients after a 2-year follow-up.The mean age of study individuals was 60.58 (±7.86) years old. There were 255 (68.5%) males and 117 (31.5%) female patients. The TICS-m scores, including overall cognition score, verbal attention and memory scores gradually decreased over a 2 year follow up period (P < .001, respectively), whereas there was no difference in orientation function score between the 1-year and 2-year follow-up (P = .448). Furthermore, after adjusting for age, sex, history of hypertension(HT) and Diabetes mellitus(DM), smoking, education, Therapy regimen (PCI, CABG, medication) left ventricular ejection fraction (LVEF), and the severity of coronary artery stenosis (Gensini score), no association was found between IL-35 rs2243115, rs568408, rs582054, rs583911, rs428253, rs4740 genotypes and cognitive decline in CHD patients over a 2-year period.Our data reveled that IL-35 polymorphisms was not associated with cognitive decline in CHD patients over a 2-year period. Yet, further studies are needed to confirm the role of cytokine gene polymorphisms in cognitive decline among CHD patients.


Assuntos
Disfunção Cognitiva/sangue , Doença das Coronárias/sangue , Interleucinas/sangue , Idoso , Disfunção Cognitiva/complicações , Doença das Coronárias/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Estudos Retrospectivos
4.
Medicine (Baltimore) ; 99(30): e21371, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32791746

RESUMO

Vitamin B12 (B12), also known as cobalamin, is a water-soluble vitamin. It is a cofactor in DNA synthesis and is involved in the metabolism of every cell of the human body, including the central nervous system. Those with a deficiency of B12 can present with peripheral neuropathy, pernicious anemia, or a cognitive disorder. Previous studies have revealed that a deficiency of B12 is associated with cognitive decline or Alzheimer disease.The data of 2991 people were evaluated from 2 years of the Korean Frailty and Aging Cohort Study, a nationwide multicenter survey. To assess cognitive function, a short form of the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD-K) was used. Of the CERAD-K tests, we included the Mini-Mental State Examination in the Korean version of the CERAD assessment packet (MMSE-KC), the word list: memory/recall/recognition, digit span (forward, backward), trail making test-A, and the frontal assessment battery. B12 concentrations were classified into clinically relevant categories, insufficient (<350 pg/mL) and sufficient (≥350 pg/mL). A linear regression analysis was used to evaluate the relationship between cognitive function and B12 levels.The mean age of the 2991 participants was 76.4 ±â€Š3.9 years old. Overall, 414 (13.8%) were classified as B12 insufficient, and 2577 (86.2%) as B12 sufficient. The sufficient B12 group performed better in the MMSE-KC, Wordlist: memory, Wordlist: recognition, TMT-A test, digit span, and FAB tests. This was statistically significant (P < .05). However, in the multivariable linear regression analysis, after adjusting for age, sex, education period, marriage, smoking and drinking habits, and comorbidities, the association between the B12 group and cognitive function was not statistically significant.Although our study does not show that B12 insufficiency is a direct risk factor to cognitive decline, B12 levels could be a contributing factor to cognitive function. Our results suggest that cognition was affected by the B12 levels, along with demographic and sociological variables.


Assuntos
Cognição , Disfunção Cognitiva/etiologia , Deficiência de Vitamina B 12/complicações , Idoso , Idoso de 80 Anos ou mais , Disfunção Cognitiva/sangue , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , República da Coreia/epidemiologia , Vitamina B 12/sangue , Deficiência de Vitamina B 12/epidemiologia
5.
PLoS One ; 15(7): e0236453, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32726329

RESUMO

OBJECTIVES: To assess the potential value of some miRNAs as diagnostic biomarkers for mild cognitive impairment (MCI) among patients with type2 diabetes mellitus (T2DM) and to identify other risk factors for MCI among them. METHODS: This study enrolled 163 adults with T2DM using face to face interview. Cognitive function with its domains was assessed using Adenbrooke's Cognitive Examination III (ACE III). Lipid profile, glycated hemoglobin, and miR-128, miR-132, miR- 874, miR-134, miR-323, and miR-382 expressions, using quantitative real-time PCR, were assessed. RESULTS: MCI was detected among 59/163 (36.2%) patients with T2DM. Plasma expression of miR-132 was significantly higher in T2DM patients with MCI compared to those without MCI and to normal cognitive healthy individuals (median = 2, 1.1 and 1.2 respectively, P < 0.05. Logistic regression analysis showed that higher miR-132 expression with adjusted odds ratio (AOR): 1.2 (95% CI 1.0-1.3), female gender (AOR:2.1; 95%CI 1.0-4.3), education below postgraduate (secondary and university education with AOR: 9.5 & 19.4 respectively) were the significant predicting factors for MCI among T2DM patients. Using ROC curve, miR-132 was the only assayed miRNA that significantly differentiates T2DM patients with MCI from those with normal cognition with 72.3% sensitivity, 56.2% specificity, and 63.8% accuracy (P < 0.05). Other studied miRNAs showed lower sensitivity and specificity for detecting MCI among studied T2DM participants. CONCLUSION: MCI affects nearly one-third of adult patients with T2DM. A significantly over expression of miR-132 was detected among T2DM with MCI compared to those with normal cognition.


Assuntos
Biomarcadores/sangue , Disfunção Cognitiva/sangue , Diabetes Mellitus Tipo 2/sangue , MicroRNAs/sangue , Adulto , Cognição/fisiologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/genética , Disfunção Cognitiva/patologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Feminino , Hemoglobina A Glicada/genética , Humanos , Lipídeos/sangue , Masculino , MicroRNAs/classificação , MicroRNAs/genética , Pessoa de Meia-Idade , Testes Neuropsicológicos , Fatores de Risco
6.
Science ; 369(6500): 167-173, 2020 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-32646997

RESUMO

Reversing brain aging may be possible through systemic interventions such as exercise. We found that administration of circulating blood factors in plasma from exercised aged mice transferred the effects of exercise on adult neurogenesis and cognition to sedentary aged mice. Plasma concentrations of glycosylphosphatidylinositol (GPI)-specific phospholipase D1 (Gpld1), a GPI-degrading enzyme derived from liver, were found to increase after exercise and to correlate with improved cognitive function in aged mice, and concentrations of Gpld1 in blood were increased in active, healthy elderly humans. Increasing systemic concentrations of Gpld1 in aged mice ameliorated age-related regenerative and cognitive impairments by altering signaling cascades downstream of GPI-anchored substrate cleavage. We thus identify a liver-to-brain axis by which blood factors can transfer the benefits of exercise in old age.


Assuntos
Envelhecimento/sangue , Encéfalo/fisiologia , Cognição/fisiologia , Fígado/enzimologia , Neurogênese , Fosfolipase D/sangue , Condicionamento Físico Animal , Animais , Circulação Sanguínea , Encéfalo/irrigação sanguínea , Disfunção Cognitiva/sangue , Disfunção Cognitiva/fisiopatologia , Glicosilfosfatidilinositóis/metabolismo , Camundongos , Fosfolipase D/metabolismo , Regeneração , Transdução de Sinais
7.
Life Sci ; 258: 118107, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32682919

RESUMO

Cognitive impairment has been widely recognized as a common symptom of chronic stress. Ginsenoside Rd (GRd), the major active compound in Panax ginseng, was previously reported in various neurological researches. However, little research is available regarding on the effect of GRd on cognitive improvement in mice subjected to chronic stress. In the present study, we investigated the neuroprotective effects of GRd in chronic restraint stress (CRS)-induced cognitive deficits and explored the potential mechanism in male C57BL/6J mice. Our results demonstrated that oral administration of GRd for 28 days markedly increased the spontaneous alternation in Y-maze and the relative discrimination index in novel object or location recognition tests following CRS. Additionally, GRd treatment considerably increased the antioxidant enzymes activities in the hippocampus. The expression levels of hippocampus and serum inflammation factors in the CRS groups were also counter-regulated by GRd treatment. Meanwhile, GRd treatment could reverse CRS-induced the decrease in phosphorylated phosphoinositide 3-kinase (PI3K), camp-reflecting element binding protein (CREB), brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) expression in the hippocampus. These findings provided evidences that GRd improves cognitive impairment in CRS mice by mitigating oxidative stress and inflammation, while upregulating the hippocampal BDNF-mediated CREB signaling pathway.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Ginsenosídeos/uso terapêutico , Restrição Física , Transdução de Sinais , Estresse Psicológico/tratamento farmacológico , Animais , Doença Crônica , Disfunção Cognitiva/sangue , Disfunção Cognitiva/fisiopatologia , Modelos Animais de Doenças , Ginsenosídeos/química , Ginsenosídeos/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/enzimologia , Hipocampo/patologia , Hipocampo/fisiopatologia , Inflamação/sangue , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória de Curto Prazo/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Modelos Biológicos , Atividade Motora/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Receptor trkB/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estresse Psicológico/sangue , Estresse Psicológico/fisiopatologia
8.
BMC Psychiatry ; 20(1): 315, 2020 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-32552785

RESUMO

BACKGROUND: Vitamin C deficiency may be more common than is generally assumed, and the association between vitamin C deficiency and adverse psychiatric effects has been known for centuries. This paper aims to systematically review the evidence base for the neuropsychiatric effects of vitamin C deficiency. METHODS: Relevant studies were identified via systematic literature review. RESULTS: Nine studies of vitamin C deficiency, including subjects both with and without the associated physical manifestations of scurvy, were included in this review. Vitamin C deficiency, including scurvy, has been linked to depression and cognitive impairment. No effect on affective or non-affective psychosis was identified. CONCLUSIONS: Disparate measurement techniques for vitamin C, and differing definitions of vitamin C deficiency were apparent, complicating comparisons between studies. However, there is evidence suggesting that vitamin C deficiency is related to adverse mood and cognitive effects. The vitamin C blood levels associated with depression and cognitive impairment are higher than those implicated in clinical manifestations of scurvy. While laboratory testing for ascorbic acid can be practically difficult, these findings nonetheless suggest that mental health clinicians should be alerted to the possibility of vitamin C deficiency in patients with depression or cognitive impairment. Vitamin C replacement is inexpensive and easy to deliver, although as of yet there are no outcome studies investigating the neuropsychiatric impact of vitamin C replacement in those who are deficient.


Assuntos
Deficiência de Ácido Ascórbico/complicações , Deficiência de Ácido Ascórbico/psicologia , Disfunção Cognitiva/etiologia , Ácido Ascórbico/sangue , Deficiência de Ácido Ascórbico/sangue , Deficiência de Ácido Ascórbico/fisiopatologia , Disfunção Cognitiva/sangue , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/psicologia , Depressão/sangue , Depressão/complicações , Depressão/fisiopatologia , Depressão/psicologia , Humanos , Escorbuto/sangue , Escorbuto/complicações , Vitaminas/sangue
9.
Neurology ; 95(9): e1126-e1133, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32571850

RESUMO

OBJECTIVE: To determine whether blood-based biomarkers can differentiate older veterans with and without traumatic brain injury (TBI) and cognitive impairment (CogI). METHODS: We enrolled 155 veterans from 2 veterans' retirement homes: 90 without TBI and 65 with TBI history. Participants were further separated into CogI groups: controls (no TBI, no CogI), n = 60; no TBI with CogI, n = 30; TBI without CogI, n = 30; and TBI with CogI, n = 35. TBI was determined by the Ohio State University TBI Identification Method. CogI was defined as impaired cognitive testing, dementia diagnosis, or use of dementia medication. Blood specimens were enriched for CNS-derived exosomes. Proteins (neurofilament light [NfL], total tau, glial fibrillary acidic protein [GFAP], α-synuclein, ß-amyloid 42 [Aß42], and phosphorylated tau [p-tau]) and cytokines (tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6], and interleukin-10) were measured using ultrasensitive immunoassays. RESULTS: Veterans were, on average, 79 years old. In participants with TBI history, 65% had mild TBI; average time from most recent TBI was 37 years. In adjusted analyses, the TBI and CogI groups differed on CNS-enriched exosome concentration of p-tau, NfL, IL-6, TNF-α (all p < 0.05), and GFAP (p = 0.06), but not on Aß42 or other markers. Adjusted area under the curve (AUC) analyses found that all significantly associated biomarkers combined separated TBI with/without CogI (AUC, 0.85; 95% confidence interval [CI], 0.74-0.95) and CogI with/without TBI (AUC, 0.88; 95% CI, 0.77-0.99). CONCLUSIONS: Increased levels of blood-based, CNS-enriched exosomal biomarkers associated with TBI and CogI can be detected even decades after TBI. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in veterans with a history of TBI, CNS-enriched exosome concentration of p-tau, NfL, IL-6, and TNF-α are associated with CogI.


Assuntos
Lesões Encefálicas Traumáticas/sangue , Disfunção Cognitiva/sangue , Interleucina-6/sangue , Proteínas de Neurofilamentos/sangue , Fator de Necrose Tumoral alfa/sangue , Veteranos , Proteínas tau/sangue , Idoso , Idoso de 80 Anos ou mais , Peptídeos beta-Amiloides/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Exossomos/metabolismo , Feminino , Proteína Glial Fibrilar Ácida/sangue , Humanos , Interleucina-10/sangue , Masculino , Testes de Estado Mental e Demência , Molécula L1 de Adesão de Célula Nervosa/metabolismo , Testes Neuropsicológicos , Fragmentos de Peptídeos/sangue , Fosforilação , alfa-Sinucleína/sangue
10.
PLoS One ; 15(6): e0234519, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32530970

RESUMO

Axonal damage leads to the release of neurofilament light chain (NFL), which enters the CSF or blood. In this work, an assay kit for plasma NFL utilizing immunomagnetic reduction (IMR) was developed. Antibodies against NFL were immobilized on magnetic nanoparticles to develop an IMR NFL kit. The preclinical properties, such as the standard curve, limit of detection (LoD), and dynamic range, were characterized. Thirty-one normal controls (NC), fifty-two patients with Parkinson's disease (PD) or PD dementia (PDD) and thirty-one patients with Alzheimer's disease (AD) were enrolled in the study evaluating the plasma NFL assay using an IMR kit. T-tests and receiver operating characteristic (ROC) curve analysis were performed to investigate the capability for discrimination among the clinical groups according to plasma NFL levels. The LoD of the NFL assay using the IMR kit was found to be 0.18 fg/ml. The dynamic range of the NFL assay reached 1000 pg/ml. The NC group showed a plasma NFL level of 7.70 ± 4.00 pg/ml, which is significantly lower than that of the PD/PDD (15.85 ± 7.82 pg/ml, p < 0.001) and AD (19.24 ± 8.99 pg/ml, p < 0.001) groups. A significant difference in plasma NFL levels was determined between the PD and AD groups (p < 0.01). Through ROC curve analysis, the cut-off value of the plasma NFL concentration for differentiating NCs from dementia patients (AD and PD/PDD) was found to be 12.71 pg/ml, with a clinical sensitivity and specificity of 73.5% and 90.3%, respectively. The AUC was 0.868. Furthermore, the cut-off value of the plasma NFL concentration for discriminating AD from PD/PDD was found to be 18.02 pg/ml, with a clinical sensitivity and specificity of 61.3% and 65.4%, respectively. The AUC was 0.630. An ultrasensitive assay for measuring plasma NFL utilizing IMR technology was developed. Clear differences in plasma NFL concentrations were observed among NCs and PD and AD patients. These results imply that the determination of plasma NFL is promising not only for screening dementia but also for differential diagnosis.


Assuntos
Peptídeos beta-Amiloides/sangue , Biomarcadores/sangue , Proteínas de Neurofilamentos/sangue , Proteínas tau/sangue , Doença de Alzheimer/sangue , Doença de Alzheimer/patologia , Axônios/metabolismo , Axônios/patologia , Disfunção Cognitiva/sangue , Disfunção Cognitiva/genética , Disfunção Cognitiva/patologia , Feminino , Humanos , Separação Imunomagnética , Filamentos Intermediários/genética , Filamentos Intermediários/patologia , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/sangue , Doença de Parkinson/genética , Doença de Parkinson/patologia
11.
Neurology ; 94(20): e2088-e2098, 2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32358220

RESUMO

OBJECTIVE: To investigate the association of triglyceride (TG) principal component scores with Alzheimer disease (AD) and the amyloid, tau, neurodegeneration, and cerebrovascular disease (A/T/N/V) biomarkers for AD. METHODS: Serum levels of 84 TG species were measured with untargeted lipid profiling of 689 participants from the Alzheimer's Disease Neuroimaging Initiative cohort, including 190 cognitively normal older adults (CN), 339 with mild cognitive impairment (MCI), and 160 with AD. Principal component analysis with factor rotation was used for dimension reduction of TG species. Differences in principal components between diagnostic groups and associations between principal components and AD biomarkers (including CSF, MRI and [18F]fluorodeoxyglucose-PET) were assessed with a generalized linear model approach. In both cases, the Bonferroni method of adjustment was used to correct for multiple comparisons. RESULTS: The 84 TGs yielded 9 principal components, 2 of which, consisting of long-chain, polyunsaturated fatty acid-containing TGs (PUTGs), were significantly associated with MCI and AD. Lower levels of PUTGs were observed in MCI and AD compared to CN. PUTG principal component scores were also significantly associated with hippocampal volume and entorhinal cortical thickness. In participants carrying the APOE ε4 allele, these principal components were significantly associated with CSF ß-amyloid1-42 values and entorhinal cortical thickness. CONCLUSION: This study shows that PUTG component scores were significantly associated with diagnostic group and AD biomarkers, a finding that was more pronounced in APOE ε4 carriers. Replication in independent larger studies and longitudinal follow-up are warranted.


Assuntos
Biomarcadores/líquido cefalorraquidiano , Disfunção Cognitiva/diagnóstico , Neuroimagem , Triglicerídeos/sangue , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/metabolismo , Biomarcadores/sangue , Cognição/fisiologia , Disfunção Cognitiva/sangue , Disfunção Cognitiva/líquido cefalorraquidiano , Progressão da Doença , Feminino , Hipocampo/metabolismo , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Testes Neuropsicológicos , Triglicerídeos/líquido cefalorraquidiano
12.
Medicine (Baltimore) ; 99(20): e20178, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443336

RESUMO

BACKGROUND: The objective of this study is to examine the association between serum lipoprotein levels (SLL) and cognitive impairment (CI) in patients with acute cerebral infarction (ACI). METHODS: All published studies will be searched from the following electronic databases: PubMed, EMBASE, Cochrane Library, PsycINFO, Web of Science, WANGFANG, and China National Knowledge Infrastructure from inauguration of each electronic database up to March 1, 2020. In addition, we will also search other sources, such as dissertations, Google scholar, conference proceedings, and reference lists of relevant reviews. We will not apply any language restrictions to the electronic databases. Two researchers will independently carry out literature selection, data collection, and methodological quality. A third researcher will help to solve any divergences by discussion. The RevMan 5.3 software will be employed to pool the collected data and to analyze the outcome data. RESULTS: This study will scrutinize the association between SLL and CI in patients with ACI. CONCLUSIONS: The results of this study will present helpful evidence of the association between SLL and CI in patients with ACI.Registration number: INPLASY202040018.


Assuntos
Isquemia Encefálica/patologia , Infarto Cerebral/complicações , Disfunção Cognitiva/etiologia , Lipoproteínas/sangue , Doença Aguda , Infarto Cerebral/epidemiologia , China/epidemiologia , Disfunção Cognitiva/sangue , Feminino , Humanos , Masculino , Sensibilidade e Especificidade
13.
Lancet Neurol ; 19(5): 422-433, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32333900

RESUMO

BACKGROUND: CSF and PET biomarkers of amyloid ß and tau accurately detect Alzheimer's disease pathology, but the invasiveness, high cost, and poor availability of these detection methods restrict their widespread use as clinical diagnostic tools. CSF tau phosphorylated at threonine 181 (p-tau181) is a highly specific biomarker for Alzheimer's disease pathology. We aimed to assess whether blood p-tau181 could be used as a biomarker for Alzheimer's disease and for prediction of cognitive decline and hippocampal atrophy. METHODS: We developed and validated an ultrasensitive blood immunoassay for p-tau181. Assay performance was evaluated in four clinic-based prospective cohorts. The discovery cohort comprised patients with Alzheimer's disease and age-matched controls. Two validation cohorts (TRIAD and BioFINDER-2) included cognitively unimpaired older adults (mean age 63-69 years), participants with mild cognitive impairment (MCI), Alzheimer's disease, and frontotemporal dementia. In addition, TRIAD included healthy young adults (mean age 23 years) and BioFINDER-2 included patients with other neurodegenerative disorders. The primary care cohort, which recruited participants in Montreal, Canada, comprised control participants from the community without a diagnosis of a neurological condition and patients referred from primary care physicians of the Canadian National Health Service for specialist care. Concentrations of plasma p-tau181 were compared with established CSF and PET biomarkers and longitudinal measurements using Spearman correlation, area under the curve (AUC), and linear regression analyses. FINDINGS: We studied 37 individuals in the discovery cohort, 226 in the first validation cohort (TRIAD), 763 in the second validation cohort (BioFINDER-2), and 105 in the primary care cohort (n=1131 individuals). In all cohorts, plasma p-tau181 showed gradual increases along the Alzheimer's disease continuum, from the lowest concentrations in amyloid ß-negative young adults and cognitively unimpaired older adults, through higher concentrations in the amyloid ß-positive cognitively unimpaired older adults and MCI groups, to the highest concentrations in the amyloid ß-positive MCI and Alzheimer's disease groups (p<0·001, Alzheimer's disease vs all other groups). Plasma p-tau181 distinguished Alzheimer's disease dementia from amyloid ß-negative young adults (AUC=99·40%) and cognitively unimpaired older adults (AUC=90·21-98·24% across cohorts), as well as other neurodegenerative disorders, including frontotemporal dementia (AUC=82·76-100% across cohorts), vascular dementia (AUC=92·13%), progressive supranuclear palsy or corticobasal syndrome (AUC=88·47%), and Parkinson's disease or multiple systems atrophy (AUC=81·90%). Plasma p-tau181 was associated with PET-measured cerebral tau (AUC=83·08-93·11% across cohorts) and amyloid ß (AUC=76·14-88·09% across cohorts) pathologies, and 1-year cognitive decline (p=0·0015) and hippocampal atrophy (p=0·015). In the primary care cohort, plasma p-tau181 discriminated Alzheimer's disease from young adults (AUC=100%) and cognitively unimpaired older adults (AUC=84·44%), but not from MCI (AUC=55·00%). INTERPRETATION: Blood p-tau181 can predict tau and amyloid ß pathologies, differentiate Alzheimer's disease from other neurodegenerative disorders, and identify Alzheimer's disease across the clinical continuum. Blood p-tau181 could be used as a simple, accessible, and scalable test for screening and diagnosis of Alzheimer's disease. FUNDING: Alzheimer Drug Discovery Foundation, European Research Council, Swedish Research Council, Swedish Alzheimer Foundation, Swedish Dementia Foundation, Alzheimer Society Research Program.


Assuntos
Doença de Alzheimer/diagnóstico , Disfunção Cognitiva/sangue , Proteínas tau/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/sangue , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Fosforilação , Estudos Prospectivos , Adulto Jovem
14.
J Clin Neurosci ; 75: 188-194, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32223973

RESUMO

BACKGROUND: Alzheimer's Disease (AD) is the most common form of dementia seen in advanced age. It is characterized by progressive deterioration in cognitive functions. The prevalence of Alzheimer's disease increasing day by day due to the increase in the share of the elderly population in the general population due to developing health and living conditions, is limited and early diagnosis and effective treatment possibilities are very limited. From this point of view, a specific biomarker for AD is very important. As a new oxidative stress biomarker, the levels of thiol-disulfide balance, ischemia-modified albumin and seroloplazminin were evaluated. The aim of this study was to determine the serum levels of oxidative stress biomarkers in the early stages of the disease and to compare these oxidative stress markers with patients with mild cognitive impairment as a precursor form of Alzheimer's disease and to determine whether these markers develop at an earlier stage. METHODS: 30 volunteers with early stage AD according to NINCDS-ARDRA criteria, 19 volunteers with Midl Cognitive Impairment according to PCA criteria and 30 volunteers with defined criteria were selected from the subjects aged between 55 and 88 who applied to Gazi University Health Research. Statistical analysis of the data showed that there was a significant difference between the endgroups and biomarkers for the early diagnosis of Alzheimer's disease, but this complicated matter has to be investigated in more comprehensive and detailed studie. RESULTS: In the present study, we investigated oxidative stress parameters, thiol-disulphide balance, ischemia modified abumin and seruloplasmin in parallel with the impairment in cognitive dysfunction from control group to Mild Cognitive Impairment (MCD) and AD group by using a newly-developed method. CONCLUSIONS: This is the first study in literature comparing Early Stages Alzheimer Disease (ESAD), MCD and healthy volunteer groups. Our study has revealed that these newly developed tests may be candidates as oxidative stress biomarkers in pathgenesis of AD. However it was concluded that more comprehensive and detailed studies are required to enlighten this issue.


Assuntos
Doença de Alzheimer/sangue , Disfunção Cognitiva/sangue , Estresse Oxidativo/fisiologia , Compostos de Sulfidrila/sangue , Sulfitos/sangue , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Biomarcadores/sangue , Calorimetria/métodos , Cognição/fisiologia , Disfunção Cognitiva/diagnóstico , Diagnóstico Precoce , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Albumina Sérica Humana
15.
Stroke ; 51(5): 1604-1607, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32279621

RESUMO

Background and Purpose- Our study aim was to assess whether high-sensitivity cardiac troponin T (hs-cTnT), a specific biomarker for myocardial injury, is associated with cognitive function in patients after mild-to-moderate first-ever ischemic stroke. Methods- We used data from PROSCIS-B (Prospective Cohort With Incident Stroke Berlin). Cognitive function was assessed by Mini-Mental-State-Examination at baseline, and Telephone Interview for Cognitive Status-modified after 1 to 3 years of follow-up. Patients were categorized according to hs-cTnT quartiles. We performed generalized linear regression to calculate risk ratios of cognitive impairment (Mini-Mental-State-Examination <27; Telephone Interview for Cognitive Status-modified <32). Association of hs-cTnT with cognitive function over time was estimated using a linear mixed model. Results- We included 555 patients (mean age, 67 years, 62% male, median National Institutes of Health Stroke Scale 2 [interquartile range, 1-5], hs-cTnT above upper reference limit 40%, baseline cognitive impairment 28%). Baseline Mini-Mental-State-Examination score and rate of cognitive impairment were lower in patients in the highest versus lowest hs-cTnT quartile (median Mini-Mental-State-Examination 27 versus 29, and 15.3% versus 43.0%, adjusted risk ratio, 1.76 [95% CI, 1.07-2.90], respectively). If anything, cognition seemed to improve in all groups, yet Telephone Interview for Cognitive Status-modified scores were consistently lower in patients within the highest versus lowest hs-cTnT quartile (adjusted ß, -1.33 [95% CI, -2.65 to -0.02]), without difference in the rate of change over time. Conclusions- In patients with mild-to-moderate first-ever ischemic stroke without dementia, higher hs-cTnT was associated with higher prevalence of cognitive impairment at baseline and lower Telephone Interview for Cognitive Status-modified during 3-year follow-up. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT01363856.


Assuntos
Disfunção Cognitiva/sangue , Acidente Vascular Cerebral/sangue , Troponina T/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Cognição , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/psicologia , Feminino , Seguimentos , Humanos , Modelos Lineares , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Prognóstico , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/psicologia , Adulto Jovem
16.
Neurology ; 94(15): e1580-e1591, 2020 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-32179698

RESUMO

OBJECTIVE: To explore whether the plasma total ß-amyloid (Aß) Aß42/Aß40 ratio is a reliable predictor of the amyloid-PET status by exploring the association between these 2 variables in a subset of the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging cohort. METHODS: Taking plasma samples at 3 separate time points, month 18 (n = 176), month 36 (n = 169), and month 54 (n = 135), we assessed the total Aß42/Aß40 ratio in plasma (TP42/40) with regard to neocortical Aß burden via PET standardized uptake value ratio (SUVR) and investigated both association with Aß-PET status and correlation (and agreement) with SUVR. RESULTS: The TP42/40 plasma ratio was significantly reduced in amyloid-PET-positive participants at all time points (p < 0.0001). Adjusting for covariates age, gender, APOE ε4 allele status, and clinical classification clearly affects the significance, with p values reduced and only comparisons at 54 months retaining significance (p = 0.006). Correlations with SUVR were similar across each time point, with Spearman ρ reaching -0.64 (p < 0.0001). Area under the curve values were highly reproducible over time points, with values ranging from 0.880 at 36 months to 0.913 at 54 months. In assessments of the healthy control group only, the same relationships were found. CONCLUSIONS: The current study demonstrates reproducibility of the plasma assay to discriminate between amyloid-PET positive and negative over 3 time points, which can help to substantially reducing the screening rate of failure for clinical trials targeting preclinical or prodromal disease. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that plasma total Aß42/Aß40 ratio is associated with neocortical amyloid burden as measured by PET SUVR.


Assuntos
Doença de Alzheimer/diagnóstico , Amiloide/sangue , Biomarcadores/sangue , Encéfalo/metabolismo , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Doença de Alzheimer/sangue , Peptídeos beta-Amiloides/metabolismo , Proteínas Amiloidogênicas/sangue , Disfunção Cognitiva/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Reprodutibilidade dos Testes
17.
PLoS One ; 15(3): e0226688, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32191705

RESUMO

BACKGROUND: Schizophrenia is linked with abnormal brain neurodevelopment, on which IGF-2 (insulin-like growth factor-2) has a great impact. The purpose of this study was to assess the levels of serum IGF-2 and its binding proteins IGFBP-3 and IGFBP-7 in schizophrenia patients and the associations of these proteins with schizophrenia psychopathology and cognitive deficits. METHODS: Thirty-two schizophrenia patients and 30 healthy controls were recruited. The PANSS and a neurocognitive test battery were used to assess schizophrenic symptomatology and cognition, respectively. Serum IGF-2, IGFBP-3 and IGFBP-7 levels were determined using ELISA. RESULTS: The schizophrenia patients had a much lower content of serum IGF-2, IGFBP-3 and IGFBP-7 than controls. For the patients, IGF-2 levels were negatively correlated with the PANSS negative scores and positively associated with working memory, attention, and executive function. The correlations between IGF-2 and the PANSS negative scores, working memory or executive function were still significant after controlling for age, sex, education level, BMI, illness history and age of onset. No significant associations of IGFBP-3 or IGFBP-7 with the PANSS scores and cognitive function were observed in the patients. CONCLUSIONS: Our study demonstrates that serum IGF-2 was significantly correlated with negative and cognitive symptoms in patients with schizophrenia, suggesting that altered IGF-2 signaling may be implicated in the psychopathology and cognitive deficits in schizophrenia.


Assuntos
Encéfalo/fisiopatologia , Disfunção Cognitiva/metabolismo , Fator de Crescimento Insulin-Like II/metabolismo , Esquizofrenia/metabolismo , Adulto , Encéfalo/crescimento & desenvolvimento , Estudos de Casos e Controles , Disfunção Cognitiva/sangue , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/fisiopatologia , Função Executiva/fisiologia , Feminino , Humanos , Fator de Crescimento Insulin-Like II/análise , Masculino , Memória de Curto Prazo/fisiologia , Testes Neuropsicológicos , Esquizofrenia/sangue , Esquizofrenia/diagnóstico , Esquizofrenia/fisiopatologia , Transdução de Sinais/fisiologia , Adulto Jovem
18.
Ageing Res Rev ; 60: 101043, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32194194

RESUMO

Plasma fatty acids have been reported to be dysregulated in mild cognitive impairment (MCI) and Alzheimer's disease (AD), though outcomes are not always consistent, and subject numbers often small. Our aim was to use a meta-analysis and systematic review approach to identify if plasma fatty acid dysregulation would be observed in case control studies of AD and MCI. Six databases were searched for studies reporting quantified levels of fatty acids in MCI and/or AD individuals, relative to cognitively normal controls. Docosahexaenoic (DHA) and vaccenic acids were significantly lower and higher respectively in MCI relative to controls. Total fatty acids were 27.2% lower in AD relative to controls, and this was reflected almost uniformly in all specific fatty acids in AD. Changes to plasma/serum fatty acids were identified in both MCI and AD relative to age and gender matched controls. Differences were greatest in AD, in both total number of fatty acids significantly altered, and the degree of change. Docosahexaenoic acid was lower in both MCI and AD, suggesting that it may be a driver of pathology.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Ácidos Graxos , Doença de Alzheimer/sangue , Estudos de Casos e Controles , Disfunção Cognitiva/sangue , Ácidos Docosa-Hexaenoicos , Ácidos Graxos/sangue , Humanos
19.
ACS Appl Mater Interfaces ; 12(8): 9693-9700, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32013375

RESUMO

Alzheimer's disease (AD) is the most common neurodegenerative disorder with a continuous pathophysiological process starting from the preclinical and mild cognitive impairment (MCI) phases to the dementia phase. Early diagnosis is prerequisite for the early intervention of AD but meanwhile challenging. Amyloid-beta 1-42 (Aß42) plays a crucial part in AD pathology. Positron-emission tomography (PET) imaging of Aß42 in the brain and the measurement of Aß42 in the cerebrospinal fluid (CSF) have been adopted for the auxiliary diagnosis of AD, but their widespread clinical application has been limited due to the radiation and the high-cost of PET and the invasive lumbar puncture for collecting CSF. Noninvasive and cost-effective blood-based assay is desirable for the early diagnosis of AD. Here, a label-free assay for the quantification of blood Aß42 was developed using the high-throughput surface plasmon resonance imaging method with the aid of an antibody-mimetic peptoid nanosheet equipping Aß42-recognizing loops. We demonstrated that this nanosheet-based sensor system could distinguish the plasma and sera from normal individuals and patients suffering AD and amnestic MCI with high sensitivity and specificity, preceding the diagnostic performance of the Aß42-recognizing molecule and the antibody specific to Aß42. This work provides a label-free, cost-effective, highly sensitive, and high-throughput blood-based assay for early detection of AD.


Assuntos
Doença de Alzheimer/sangue , Peptídeos beta-Amiloides/sangue , Disfunção Cognitiva/sangue , Membranas Artificiais , Fragmentos de Peptídeos/sangue , Peptoides/química , Ressonância de Plasmônio de Superfície , Idoso , Feminino , Humanos , Masculino
20.
Biochem Biophys Res Commun ; 524(3): 525-532, 2020 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-32014256

RESUMO

Diabetes mellitus (DM) is currently a major global health problem, which is associated with the development of cognitive dysfunction. However, although numerous clinical drugs for hyperglycemia have been used at present, safer and more effective therapeutic intervention strategies for diabetic cognitive impairments are still a huge challenge. Recently, several studies have indicated that a novel class of branched palmitic acid esters of hydroxyl stearic acids (PAHSAs) may have anti-diabetes and anti-inflammatory effects in insulin-resistant mice. Herein, whether the 9-PAHSA that one of the PAHSAs can attenuates DM-associated cognitive impairment in a mouse model of type 2 diabetes has been investigated. Our results showed that 9-PAHSA mildly prevented deficits of spatial working memory in Y-maze test while reversed the preference bias toward novel mice in Social choice test. Furthermore, the effect of REST on cognitive impairment of diabetes was explored for the first time. It was found that the expression of REST in diabetic mice increased, and the expression of target protein BDNF (Brain-derived neurotrophic factor) was decreased. After administration of 9-PAHSA, the situation was reversed. In summary, we conclude that exogenous supplement of 9-PAHSA can improve DM-related cognitive impairment to some extent, and the protective effect may be associated with decreased REST/NRSF (repressor element-1 silencing transcription factor/neuron-restrictive silence factor) and upregulated BDNF expression in frontal cortex.


Assuntos
Disfunção Cognitiva/tratamento farmacológico , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/fisiopatologia , Ácido Palmítico/uso terapêutico , Ácidos Esteáricos/uso terapêutico , Envelhecimento/sangue , Envelhecimento/patologia , Animais , Comportamento Animal , Glicemia/metabolismo , Peso Corporal , Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Disfunção Cognitiva/sangue , Diabetes Mellitus Experimental/sangue , Comportamento Exploratório , Masculino , Transtornos da Memória/sangue , Transtornos da Memória/complicações , Transtornos da Memória/fisiopatologia , Camundongos , Proteínas Repressoras/metabolismo , Comportamento Social , Memória Espacial
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