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1.
Ter Arkh ; 96(5): 447-452, 2024 Jun 03.
Artigo em Russo | MEDLINE | ID: mdl-38829804

RESUMO

This article examines the role of uric acid (UA) in cognitive changes and neurodegeneration, focusing on its functions as an antioxidant and prooxidant. Research suggests that changes in serum UA levels may be associated with the development or delay of cognitive impairment, especially in the context of neurodegenerative diseases such as Alzheimer's disease. It was revealed that there is a relationship between the level of UA and the dynamics of cognitive functions, indicating the potential neuroprotective properties of UA. Particular attention is paid to the balance between the antioxidant and prooxidant properties of UA, which may play a key role in protecting neurons from damage. However, research results are not clear-cut, highlighting the need for further research to more fully understand the role of UA in cognitive processes. Determining the optimal serum UA level may be an important step in developing strategies for the prevention and treatment of cognitive impairment associated with neurodegeneration. Overall, these studies advance the understanding of the mechanisms underlying the interaction between uric acid metabolism and brain health.


Assuntos
Doenças Neurodegenerativas , Ácido Úrico , Humanos , Ácido Úrico/sangue , Ácido Úrico/metabolismo , Doenças Neurodegenerativas/fisiopatologia , Doenças Neurodegenerativas/metabolismo , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/prevenção & controle , Transtornos Cognitivos/fisiopatologia , Antioxidantes , Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Estresse Oxidativo/fisiologia
2.
Nihon Ronen Igakkai Zasshi ; 61(2): 163-168, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38839315

RESUMO

OBJECTIVE: To examine the relationship between decreased appetite and the cognitive function in elderly diabetic patients. METHODS: The study subjects were outpatients with diabetes who were 60 years of age or older, and who were managed at Ise Red Cross Hospital. The cognitive function was assessed using a self-administered Dementia Checklist. The Japanese version of the Simplified Nutritional Appetite Questionnaire (SNAQ) was used to measure decreased appetite. A logistic regression analysis, in which the dependent variable was cognitive decline and the explanatory variables were appetite loss and adjustment variables, was used to calculate the odds ratio for cognitive decline according to the presence of appetite loss. RESULTS: Four hundred eighty patients were included in the analysis. Seventeen percent of the patients had decreased appetite and 21% had a decreased cognitive function. The unadjusted and adjusted odds ratios of cognitive decline for those with decreased appetite were 2.78 (95% confidence interval (CI), 1.66-4.65; P<0.001) and 2.26 (95% CI, 1.16-4.37; P=0.015), respectively, based on the absence of decreased appetite. CONCLUSION: Decreased appetite in elderly patients with diabetes was associated with a decreased cognitive function.


Assuntos
Apetite , Humanos , Idoso , Masculino , Feminino , Cognição , Diabetes Mellitus , Transtornos Cognitivos/etiologia , Idoso de 80 Anos ou mais
3.
Thromb Res ; 238: 132-140, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38704897

RESUMO

BACKGROUND: This systematic review assesses the likelihood of developing dementia and cognitive impairment in patients with atrial fibrillation (AF) receiving non-vitamin K antagonist oral anticoagulants (NOACs) as opposed to vitamin K antagonists (VKAs). METHODS: We performed a systematic review with meta-analysis and trial sequential analysis (TSA), which encompassed both randomized controlled trials (RCTs) and observational studies. The objective was to assess the impact of NOACs and VKAs on the incidence of dementia in individuals diagnosed with AF. RESULTS: Out of 1914 studies that were screened, 31 studies were included in the final analysis, which consisted of nine RCTs or their subsequent post-hoc analyses, in addition to 22 observational studies. The meta-analysis shows that NOACs were associated with a decreased probability of developing dementia of any cause [Rate Ratio (RR): 0.88; 95 % confidence interval (95 % CI): 0.82-0.94], especially in patients below the age of 75 (RR: 0.78; 95 % CI: 0.73-0.84). Consistent patterns were observed across all forms of dementia and cognitive function decline. The overall evidence indicates notable variability in the outcome with a moderate-to-low degree of certainty. The TSA suggests that the total sample size of the included trials (155,647 patients) was significantly smaller than the required information size of 784,692 patients to discern the true effect of NOAC versus VKA in terms of reducing dementia risk. CONCLUSION: NOACs may reduce the likelihood of developing dementia in patients with AF, particularly in those under the age of 75. This review highlights the urgent necessity for thorough research to determine the efficacy of NOACs in safeguarding cognitive health.


Assuntos
Anticoagulantes , Fibrilação Atrial , Humanos , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/complicações , Anticoagulantes/uso terapêutico , Administração Oral , Demência , Disfunção Cognitiva , Ensaios Clínicos Controlados Aleatórios como Assunto , Transtornos Cognitivos , Idoso
4.
J Diabetes Complications ; 38(6): 108764, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38701667

RESUMO

OBJECTIVE: Dysglycemia is a significant risk factor for cognitive impairment. However, which pathophysiologic determinant(s) of dysglycemia, impaired insulin sensitivity (ISens) or the islet ß-cell's response (IResp), contribute to poorer cognitive function, independent of dysglycemia is not established. Among 1052 adults with pre-diabetes from the Diabetes Prevention Program Outcomes Study (DPPOS), we investigated the relationship between IResp, ISens and cognitive function. RESEARCH DESIGN AND METHODS: IResp was estimated by the insulinogenic index (IGI; pmol/mmol) and ISens as 1/fasting insulin from repeated annual oral glucose tolerance tests. The mean IResp and mean ISens were calculated over approximately 12 years of follow-up. Verbal learning (Spanish-English Verbal Learning Test [SEVLT]) and executive function (Digital Symbol Substitution Test [DSST]) were assessed at the end of the follow-up period. Linear regression models were run for each cognitive outcome and were adjusted for dysglycemia and other factors. RESULTS: Higher IResp was associated with poorer performance on the DSST (-0.69 points per 100 unit increase in IGI, 95 % CI: -1.37, -0.01). ISens was not associated with DSST, nor were IResp or ISens associated with performance on the SEVLT. CONCLUSIONS: These results suggest that a greater ß-cell response in people at high risk for type 2 diabetes is associated with poorer executive function, independent of dysglycemia and ISens.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Insulina , Estado Pré-Diabético , Humanos , Estado Pré-Diabético/psicologia , Estado Pré-Diabético/complicações , Estado Pré-Diabético/sangue , Estado Pré-Diabético/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Insulina/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/psicologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/prevenção & controle , Cognição/fisiologia , Teste de Tolerância a Glucose , Células Secretoras de Insulina/fisiologia , Células Secretoras de Insulina/metabolismo , Seguimentos , Transtornos Cognitivos/prevenção & controle , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/sangue , Idoso , Função Executiva/fisiologia
5.
J Neuroinflammation ; 21(1): 141, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38807149

RESUMO

The lectin pathway (LP) of complement mediates inflammatory processes linked to tissue damage and loss of function following traumatic brain injury (TBI). LP activation triggers a cascade of proteolytic events initiated by LP specific enzymes called MASPs (for Mannan-binding lectin Associated Serine Proteases). Elevated serum and brain levels of MASP-2, the effector enzyme of the LP, were previously reported to be associated with the severity of tissue injury and poor outcomes in patients with TBI. To evaluate the therapeutic potential of LP inhibition in TBI, we first conducted a pilot study testing the effect of an inhibitory MASP-2 antibody (α-MASP-2), administered systemically at 4 and 24 h post-TBI in a mouse model of controlled cortical impact (CCI). Treatment with α-MASP-2 reduced sensorimotor and cognitive deficits for up to 5 weeks post-TBI. As previous studies by others postulated a critical role of MASP-1 in LP activation, we conducted an additional study that also assessed treatment with an inhibitory MASP-1 antibody (α-MASP-1). A total of 78 mice were treated intraperitoneally with either α-MASP-2, or α-MASP-1, or an isotype control antibody 4 h and 24 h after TBI or sham injury. An amelioration of the cognitive deficits assessed by Barnes Maze, prespecified as the primary study endpoint, was exclusively observed in the α-MASP-2-treated group. The behavioral data were paralleled by a reduction of the lesion size when evaluated histologically and by reduced systemic LP activity. Our data suggest that inhibition of the LP effector enzyme MASP-2 is a promising treatment strategy to limit neurological deficits and tissue loss following TBI. Our work has translational value because a MASP-2 antibody has already completed multiple late-stage clinical trials in other indications and we used a clinically relevant treatment protocol testing the therapeutic mechanism of MASP-2 inhibition in TBI.


Assuntos
Lesões Encefálicas Traumáticas , Modelos Animais de Doenças , Serina Proteases Associadas a Proteína de Ligação a Manose , Camundongos Endogâmicos C57BL , Animais , Serina Proteases Associadas a Proteína de Ligação a Manose/antagonistas & inibidores , Serina Proteases Associadas a Proteína de Ligação a Manose/metabolismo , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/patologia , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/psicologia , Camundongos , Masculino , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/tratamento farmacológico , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia
6.
Rev Med Suisse ; 20(873): 941-943, 2024 05 08.
Artigo em Francês | MEDLINE | ID: mdl-38717001

RESUMO

Improving the state and future of patients severely impaired following brain injury is at the heart of early rehabilitation, established from the first days of hospitalization. For cognitive deficits, this management involves several challenges, related to hospital conditions and to the patients' capacities during the acute phase. A relevant intervention can be provided, as long as it involves an assessment adapted to these particularities and a rehabilitation targeting the most limiting deficits at this stage. These findings, discussed in the light of our clinical experience and current knowledge in the field, have yet to be scientifically tested since randomized clinical trials are still lacking. The integration of new technologies to facilitate the bedside work presents another prospect for the future.


Améliorer sans délai l'état et le devenir des patients sévèrement touchés par une lésion cérébrale constitue l'essence de la rééducation précoce, instaurée dès les premiers jours de l'hospitalisation. Pour les aspects cognitifs, cette prise en charge comporte plusieurs défis, liés aux conditions hospitalières et aux capacités des patients. Une intervention pertinente peut être pratiquée, sous réserve d'une évaluation adaptée à ces particularités et d'une rééducation ciblant les déficits les plus limitants à ce stade. Ces constats, discutés à la lumière de notre expérience clinique et des connaissances actuelles, doivent encore être prouvés scientifiquement car les essais cliniques randomisés manquent cruellement. L'intégration des nouvelles technologies pour faciliter le travail au chevet des patients constitue une autre perspective d'avenir.


Assuntos
Lesões Encefálicas , Humanos , Lesões Encefálicas/reabilitação , Lesões Encefálicas/complicações , Disfunção Cognitiva/reabilitação , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/terapia , Transtornos Cognitivos/reabilitação , Transtornos Cognitivos/etiologia , Índice de Gravidade de Doença , Fatores de Tempo , Doenças do Sistema Nervoso/reabilitação , Hospitalização , Treino Cognitivo
7.
Zh Nevrol Psikhiatr Im S S Korsakova ; 124(4. Vyp. 2): 64-71, 2024.
Artigo em Russo | MEDLINE | ID: mdl-38696153

RESUMO

OBJECTIVE: To establish the characteristics of clinical manifestations and cognitive tests in patients with schizophrenia, with a predominance of cognitive and negative disorders. MATERIAL AND METHODS: We examined 76 patients, 66 in the main group, 10 in the comparison group, who were treated in Psychiatric Hospital No. 1 and Psychiatric Hospital No. 4 (Moscow). Clinical-psychopathological, psychometric and statistical methods were used. Features of cognitive functioning were studied using the Frontal Assessment Battery (FAB) and the Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis (ALS) Screen (ECAS). Emotional intelligence scores were assessed using the Ekman Face Emotion Recognition (EFER) test. RESULTS: Patients with schizophrenia showed dominance of one of 3 types of deficit symptoms: cognitive, emotional, and volitional. Cognitive functions were significantly reduced in patients with schizophrenia when compared with the comparison group (mean FAB score (M±SD) 13.44±2.97 in patients with schizophrenia vs. 16.10±1.70 in the comparison group; t=4.10; p<0.001). Cognitive functions were particularly reduced in patients with volitional deficit (mean EFER total score 42.40±9.0 in patients with volitional deficit vs. 47.21±633 in patients with cognitive deficit; t=2.12; p=0.039; mean FAB score 12.83±3.29 in patients with volitional deficit vs. 16.10±1.70 in the comparison group; t=4.24; p<0.001; mean ECAS score specific to ALS 78.80±9.07 in patients with volitional deficit vs. 84.50±6.71 in the comparison group; t=2.18; p=0.034). CONCLUSION: The greatest contribution to the development of cognitive disorders in schizophrenia is made by dysfunction of frontal (especially) and temporal cortex. Executive functions, speech skills and verbal fluency are most severely damaged.


Assuntos
Psicometria , Esquizofrenia , Psicologia do Esquizofrênico , Humanos , Masculino , Feminino , Adulto , Esquizofrenia/diagnóstico , Esquizofrenia/complicações , Pessoa de Meia-Idade , Cognição , Testes Neuropsicológicos , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia
8.
J Neuroimmunol ; 392: 578372, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38788317

RESUMO

BACKGROUND AND PURPOSE: Immune dysfunction is one of the risk factors which plays an important role in the development of non-Hodgkin lymphoma (NHL), and inflammation may be involved in its etiology. Minimal data is available on the effect of cytokine levels on neurobehavioral function in lymphoma before the initiation of chemotherapy. Therefore, we aimed to explore the risk of NHL by assessment of cytokine and adipokine levels and their correlation with neurobehavioral changes. METHODS: This case-control study enrolled 62 subjects (age-sex matched: 31 cases and 31 controls). Neurobehavioral assessment was done using Montreal Cognitive Assessment questionnaire (MoCA) and Patient Health Questionnaire (PHQ-9). EORTC Core Quality of Life questionnaire (EORTC QLQ-C30) was used to assess quality of life. Questionnaire assessment and sample collection were done after the patient enrolment and before first cycle of chemotherapy. RESULTS: Mean age of NHL patients and healthy controls was 51.9 ± 11.8 and 50 ± 10.9 years, respectively. NHL patients showed significantly higher levels of IL-6 (0.77 ± 0.11) and TNF- α (1.47 ± 1.31) than controls (0.55 ± 0.4 and 0.66 ± 0.89, respectively) with p-value<0.005. Also, NHL patients showed significantly lower levels of adiponectin (0.31 ± 0.24) and omentin (0.46 ± 0.1) than controls (0.42 ± 0.13 and 0.53 ± 0.11, respectively) with p-value<0.005. Lower MoCA and EORTC QLQ C-30 scores and higher PHQ-9 scores were observed in NHL patients in comparison to healthy control. CONCLUSION: Our results showed that adiponectin, omentin IL-6 and TNF-α may be used as pre-diagnostic markers of NHL risk. Neurobehavioral changes observed in NHL patients may alter the quality of life.


Assuntos
Adiponectina , Citocinas , Proteínas Ligadas por GPI , Interleucina-6 , Lectinas , Linfoma não Hodgkin , Fator de Necrose Tumoral alfa , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Linfoma não Hodgkin/sangue , Linfoma não Hodgkin/psicologia , Linfoma não Hodgkin/complicações , Estudos de Casos e Controles , Adiponectina/sangue , Citocinas/sangue , Fator de Necrose Tumoral alfa/sangue , Adulto , Interleucina-6/sangue , Lectinas/sangue , Proteínas Ligadas por GPI/sangue , Depressão/sangue , Depressão/etiologia , Idoso , Qualidade de Vida , Transtornos Cognitivos/sangue , Transtornos Cognitivos/etiologia
9.
Int J Biol Macromol ; 269(Pt 1): 131995, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38692529

RESUMO

In the present work, a neutral polysaccharide (DHP-2W) with attenuating cognitive disorder was identified from Dendrobium huoshanense and its structure was clarified. The polysaccharide was successfully purified from D. huoshanense by column chromatography and its activity was evaluated. With a molecular weight of 508.934kDa, this polysaccharide is composed of mannose and glucose at a molar ratio of 75.81: 24.19. Structural characterization revealed that DHP-2W has a backbone consisting of 4)-ß-D-Manp-(1 and 4)-ß-D-Glcp-(1. In vivo experiments revealed that DHP-2W improved cognitive disorder in D-galactose treated mice and relieved oxidative stress and inflammation. DHP-2W attenuates D-galactose-induced cognitive disorder by inhibiting the BCL2/BAX/CASP3 pathway and activating the AMPK/SIRT pathway, thereby inhibiting apoptosis. Furthermore, DHP-2W had a significant effect on regulating the serum levels of Flavin adenine dinucleotide, Shikimic acid, and Kynurenic acid in aged mice. These, in turn, had a positive impact on AMPK/SIRT1 and BCL2/BAX/CASP3, resulting in protective effects against cognitive disorder.


Assuntos
Envelhecimento , Dendrobium , Mananas , Animais , Dendrobium/química , Camundongos , Mananas/farmacologia , Mananas/química , Envelhecimento/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Transtornos Cognitivos/tratamento farmacológico , Masculino , Apoptose/efeitos dos fármacos , Galactose
10.
J Alzheimers Dis ; 99(2): 485-488, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38701148

RESUMO

Midlife cerebrovascular risk factors increase risk of late life cognitive impairment and dementia, while their presence in patients with dementia may lead to cognitive improvement or stabilization in late life. Defining the best measure of blood pressure (BP) to be associated with cognitive decline remains debatable, also due to possible bidirectionality. BP variability, pulse pressure, systolic and diastolic BP have been associated with cognitive status, dementia risk and Alzheimer's disease biomarkers. Proper BP control notwithstanding, BP variability increases risk for pathophysiological change in the Alzheimer's disease continuum, implying the need for selection of anti-hypertensive drugs with neurobiological evidence of benefits.


Assuntos
Pressão Sanguínea , Demência , Humanos , Pressão Sanguínea/fisiologia , Demência/epidemiologia , Fatores de Risco , Transtornos Cognitivos/etiologia , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/etiologia , Hipertensão/complicações , Hipertensão/fisiopatologia
11.
Nutrients ; 16(9)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38732599

RESUMO

In this study, a systematic review of randomized clinical trials conducted from January 2000 to December 2023 was performed to examine the efficacy of psychobiotics-probiotics beneficial to mental health via the gut-brain axis-in adults with psychiatric and cognitive disorders. Out of the 51 studies involving 3353 patients where half received psychobiotics, there was a notably high measurement of effectiveness specifically in the treatment of depression symptoms. Most participants were older and female, with treatments commonly utilizing strains of Lactobacillus and Bifidobacteria over periods ranging from 4 to 24 weeks. Although there was a general agreement on the effectiveness of psychobiotics, the variability in treatment approaches and clinical presentations limits the comparability and generalization of the findings. This underscores the need for more personalized treatment optimization and a deeper investigation into the mechanisms through which psychobiotics act. The research corroborates the therapeutic potential of psychobiotics and represents progress in the management of psychiatric and cognitive disorders.


Assuntos
Transtornos Mentais , Probióticos , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Probióticos/uso terapêutico , Feminino , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/terapia , Transtornos Cognitivos/tratamento farmacológico , Masculino , Resultado do Tratamento , Adulto , Eixo Encéfalo-Intestino/efeitos dos fármacos , Pessoa de Meia-Idade , Microbioma Gastrointestinal/efeitos dos fármacos , Lactobacillus , Idoso , Bifidobacterium
13.
BMC Geriatr ; 24(1): 405, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714934

RESUMO

BACKGROUND: Cognitive dysfunction is one of the leading causes of disability and dependence in older adults and is a major economic burden on the public health system. The aim of this study was to investigate the risk factors for cognitive dysfunction and their predictive value in older adults in Northwest China. METHODS: A cross-sectional study was conducted using a multistage sampling method. The questionnaires were distributed through the Elderly Disability Monitoring Platform to older adults aged 60 years and above in Northwest China, who were divided into cognitive dysfunction and normal cognitive function groups. In addition to univariate analyses, logistic regression and decision tree modelling were used to construct a model to identify factors that can predict the occurrence of cognitive dysfunction in older adults. RESULTS: A total of 12,494 valid questionnaires were collected, including 2617 from participants in the cognitive dysfunction group and 9877 from participants in the normal cognitive function group. Univariate analysis revealed that ethnicity, BMI, age, educational attainment, marital status, type of residence, residency status, current work status, main economic source, type of chronic disease, long-term use of medication, alcohol consumption, participation in social activities, exercise status, social support, total scores on the Balanced Test Assessment, total scores on the Gait Speed Assessment total score, and activities of daily living (ADL) were significantly different between the two groups (all P < 0.05). According to logistic regression analyses, ethnicity, BMI, educational attainment, marital status, residency, main source of income, chronic diseases, annual medical examination, alcohol consumption, exercise status, total scores on the Balanced Test Assessment, and activities of daily living (ADLs) were found to influence cognitive dysfunction in older adults (all P < 0.05). In the decision tree model, the ability to perform activities of daily living was the root node, followed by total scores on the Balanced Test Assessment, marital status, educational attainment, age, annual medical examination, and ethnicity. CONCLUSIONS: Traditional risk factors (including BMI, literacy, and alcohol consumption) and potentially modifiable risk factors (including balance function, ability to care for oneself in daily life, and widowhood) have a significant impact on the increased risk of cognitive dysfunction in older adults in Northwest China. The use of decision tree models can help health care workers better assess cognitive function in older adults and develop personalized interventions. Further research could help to gain insight into the mechanisms of cognitive dysfunction and provide new avenues for prevention and intervention.


Assuntos
Árvores de Decisões , Humanos , Masculino , Feminino , China/epidemiologia , Idoso , Estudos Transversais , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Modelos Logísticos , Fatores de Risco , Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/psicologia , Transtornos Cognitivos/diagnóstico , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Inquéritos e Questionários , Atividades Cotidianas
14.
Cell Mol Life Sci ; 81(1): 215, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38739166

RESUMO

Down syndrome (DS) is a genetic disease characterized by a supernumerary chromosome 21. Intellectual deficiency (ID) is one of the most prominent features of DS. Central nervous system defects lead to learning disabilities, motor and language delays, and memory impairments. At present, a prenatal treatment for the ID in DS is lacking. Subcutaneous administration of synthetic preimplantation factor (sPIF, a peptide with a range of biological functions) in a model of severe brain damage has shown neuroprotective and anti-inflammatory properties by directly targeting neurons and microglia. Here, we evaluated the effect of PIF administration during gestation and until weaning on Dp(16)1Yey mice (a mouse model of DS). Possible effects at the juvenile stage were assessed using behavioral tests and molecular and histological analyses of the brain. To test the influence of perinatal sPIF treatment at the adult stage, hippocampus-dependent memory was evaluated on postnatal day 90. Dp(16)1Yey pups showed significant behavioral impairment, with impaired neurogenesis, microglial cell activation and a low microglial cell count, and the deregulated expression of genes linked to neuroinflammation and cell cycle regulation. Treatment with sPIF restored early postnatal hippocampal neurogenesis, with beneficial effects on astrocytes, microglia, inflammation, and cell cycle markers. Moreover, treatment with sPIF restored the level of DYRK1A, a protein that is involved in cognitive impairments in DS. In line with the beneficial effects on neurogenesis, perinatal treatment with sPIF was associated with an improvement in working memory in adult Dp(16)1Yey mice. Perinatal treatment with sPIF might be an option for mitigating cognitive impairments in people with DS.


Assuntos
Modelos Animais de Doenças , Síndrome de Down , Neurogênese , Animais , Síndrome de Down/tratamento farmacológico , Síndrome de Down/patologia , Síndrome de Down/metabolismo , Síndrome de Down/complicações , Síndrome de Down/genética , Neurogênese/efeitos dos fármacos , Camundongos , Feminino , Gravidez , Hipocampo/metabolismo , Hipocampo/patologia , Hipocampo/efeitos dos fármacos , Microglia/metabolismo , Microglia/efeitos dos fármacos , Microglia/patologia , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Tirosina Quinases/metabolismo , Proteínas Tirosina Quinases/genética , Quinases Dyrk , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Masculino , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/patologia
15.
BMJ Open ; 14(4): e083612, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38569699

RESUMO

INTRODUCTION: Annual cognitive screening in older adults is essential for early detection of cognitive impairment, yet primary care settings face time constraints that present barriers to routine screening. A remote cognitive screener completed on a patient's personal smartphone before a visit has the potential to save primary care clinics time, encourage broader screening practices and increase early detection of cognitive decline. MyCog Mobile is a promising new remote smartphone-based cognitive screening app for primary care settings. We propose a combined construct and clinical validation study of MyCog Mobile. METHODS AND ANALYSIS: We will recruit a total sample of 300 adult participants aged 65 years and older. A subsample of 200 healthy adult participants and a subsample of 100 adults with a cognitive impairment diagnosis (ie, dementia, mild cognitive impairment, cognitive deficits or other memory loss) will be recruited from the general population and specialty memory care centres, respectively. To evaluate the construct validity of MyCog Mobile, the healthy control sample will self-administer MyCog Mobile on study-provided smartphones and be administered a battery of gold-standard neuropsychological assessments. We will compare correlations between performance on MyCog Mobile and measures of similar and dissimilar constructs to evaluate convergent and discriminant validity. To assess clinical validity, participants in the clinical sample will self-administer MyCog Mobile on a smartphone and be administered a Mini-Cog screener and these data will be combined with the healthy control sample. We will then apply several supervised model types to determine the best predictors of cognitive impairment within the sample. Area under the receiver operating characteristic curve, accuracy, sensitivity and specificity will be the primary performance metrics for clinical validity. ETHICS AND DISSEMINATION: The Institutional Review Board at Northwestern University (STU00214921) approved this study protocol. Results will be published in peer-reviewed journals and summaries provided to the study's funders.


Assuntos
Transtornos Cognitivos , Disfunção Cognitiva , Demência , Humanos , Idoso , Smartphone , Demência/epidemiologia , Transtornos Cognitivos/diagnóstico , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Cognição
16.
Maturitas ; 184: 108003, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38649310

RESUMO

OBJECTIVE: The effects on the brain of hormone therapy after the onset of menopause remain uncertain. The effects may be beneficial, neutral, or harmful. We provide a conceptual review of the evidence. METHODS: We 1) provide a brief history of the evidence, 2) discuss some of the interpretations of the evidence, 3) discuss the importance of age at menopause, type of menopause, and presence of vasomotor symptoms, and 4) provide some clinical recommendations. RESULTS: The evidence and the beliefs about hormone therapy and dementia have changed over the last 30 years or more. Five recent observation studies suggested that hormone therapy is associated with an increased risk of dementia, and the association appears not to change with the timing of initiation of therapy. These harmful associations may be explained by a causal effect of hormone therapy on the brain or by several confounding mechanisms. We suggest that the use of hormone therapy should be customized for different subgroups of women. It may be important to subgroup women based on age at onset of menopause, type of menopause, and presence or absence of vasomotor symptoms. In addition, the effects may vary by type, dose, route, and duration of administration of estrogens and by the concurrent use of progestogens. DISCUSSION: The relation of hormone therapy with the risk of dementia is complex. Hormone therapy may have beneficial, neutral, or harmful effects on the brain. Hormone therapy should be guided by the clinical characteristics of the women being treated.


Assuntos
Demência , Terapia de Reposição de Estrogênios , Humanos , Feminino , Demência/induzido quimicamente , Demência/prevenção & controle , Demência/etiologia , Terapia de Reposição de Estrogênios/efeitos adversos , Terapia de Reposição de Estrogênios/métodos , Menopausa , Estrogênios/efeitos adversos , Estrogênios/uso terapêutico , Transtornos Cognitivos/prevenção & controle , Encéfalo/efeitos dos fármacos , Pós-Menopausa , Progestinas/efeitos adversos , Progestinas/administração & dosagem , Medição de Risco
17.
BMC Neurol ; 24(1): 111, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575854

RESUMO

BACKGROUND: Rapamycin is an inhibitor of the mechanistic target of rapamycin (mTOR) protein kinase, and preclinical data demonstrate that it is a promising candidate for a general gero- and neuroprotective treatment in humans. Results from mouse models of Alzheimer's disease have shown beneficial effects of rapamycin, including preventing or reversing cognitive deficits, reducing amyloid oligomers and tauopathies and normalizing synaptic plasticity and cerebral glucose uptake. The "Evaluating Rapamycin Treatment in Alzheimer's Disease using Positron Emission Tomography" (ERAP) trial aims to test if these results translate to humans through evaluating the change in cerebral glucose uptake following six months of rapamycin treatment in participants with early-stage Alzheimer's disease. METHODS: ERAP is a six-month-long, single-arm, open-label, phase IIa biomarker-driven study evaluating if the drug rapamycin can be repurposed to treat Alzheimer's disease. Fifteen patients will be included and treated with a weekly dose of 7 mg rapamycin for six months. The primary endpoint will be change in cerebral glucose uptake, measured using [18F]FDG positron emission tomography. Secondary endpoints include changes in cognitive measures, markers in cerebrospinal fluid as well as cerebral blood flow measured using magnetic resonance imaging. As exploratory outcomes, the study will assess change in multiple age-related pathological processes, such as periodontal inflammation, retinal degeneration, bone mineral density loss, atherosclerosis and decreased cardiac function. DISCUSSION: The ERAP study is a clinical trial using in vivo imaging biomarkers to assess the repurposing of rapamycin for the treatment of Alzheimer's disease. If successful, the study would provide a strong rationale for large-scale evaluation of mTOR-inhibitors as a potential disease-modifying treatment in Alzheimer's disease. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT06022068, date of registration 2023-08-30.


Assuntos
Doença de Alzheimer , Transtornos Cognitivos , Humanos , Envelhecimento , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/complicações , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Ensaios Clínicos Fase II como Assunto , Glucose/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Serina-Treonina Quinases TOR
18.
J Gerontol Nurs ; 50(4): 16-24, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38569106

RESUMO

PURPOSE: To systematically review the prevalence of motoric cognitive risk syndrome (MCR) among community-dwelling older adults and provide evidence-based support for policymakers planning health and social care policies. METHOD: Web of Science, PubMed, and Cochrane Library databases were searched for cross-sectional, prospective cohort, or population-based longitudinal studies of community-dwelling older adults aged ≥60 years with MCR from inception of the database through December 18, 2021. RESULTS: Seventeen studies were included. Pooled prevalence of MCR was found to be 10% (95% confidence interval [8%, 12%], I2 = 98.4%). Results of a subgroup analysis revealed a combined prevalence of MCR of 8.2% in males and 9.2% in females. Pooled prevalence of MCR was 9.7% in Asia and 10.2% in other regions. CONCLUSION: Prevalence of MCR in community-dwelling older adults is high. Our research may improve the epidemiological understanding of MCR, draw attention to older adults with MCR, and thus promote research of MCR and the formulation of relevant public health policies. With early identification and intervention of MCR, cognitive function can be improved, and the onset of dementia can be delayed or prevented. [Journal of Gerontological Nursing, 50(4), 16-24.].


Assuntos
Transtornos Cognitivos , Disfunção Cognitiva , Masculino , Feminino , Humanos , Idoso , Vida Independente , Estudos Prospectivos , Prevalência , Estudos Transversais , Cognição , Fatores de Risco
19.
Geriatr Psychol Neuropsychiatr Vieil ; 22(1): 76-84, 2024 Mar 01.
Artigo em Francês | MEDLINE | ID: mdl-38573147

RESUMO

Cognitive performance of older adults is very often inferior to that of younger adults on a variety of laboratory tests assessing basic functions such as memory, inhibition, or attention. Classic hypotheses and theories share the idea that these cognitive deficits are irreversible, due to profound cerebral changes. In this review article, we develop a more positive conception of aging, according to which cognitive deficits are not all irreversible, and can even be partially if not completely reversible. To this end, we present some of the most illustrative research on the reversibility of the effects of aging on cognition. We show how subtle contextual manipulations can change older adults' motivation and strategy, which improve their cognitive performance. We also show that guidance toward the selection of the most appropriate strategy, whether explicit as in selectivity paradigms or implicit as in dual-task procedures, can increase older adults' cognitive performance. We finally describe the hypotheses and theories that both account for low cognitive performance in old age and ways to reverse the effects of cognitive aging.


Assuntos
Transtornos Cognitivos , Envelhecimento Cognitivo , Disfunção Cognitiva , Humanos , Idoso , Cognição , Envelhecimento
20.
Wiad Lek ; 77(2): 225-232, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38592982

RESUMO

OBJECTIVE: Aim: To study the structure and characteristics of psychopathological symptoms in FM who left Ukraine as a result of the full-scale armed aggression of the Russian Federation against Ukraine, and internally displaced persons, in a comparative aspect. PATIENTS AND METHODS: Materials and Methods: Examination was performed in compliance with the principles of biomedical ethics, based on informed consent. Research was provided on the basis of the Ternopil Regional Clinical Psychoneurological Hospital. Inclusion criteria were women who were forced to leave the territory of Ukraine as a result of hostilities after February 24, 2022, and who left for temporary residence in the territory of the Republic of Poland (Poland) (FM), and women who were temporarily relocated within Ukraine in connection with connection with hostilities (IDP). Exclusion criteria from the study were presence of language disorders, pronounced cognitive disorders, severe somatic condition. The examination was organized by the method of a semi-structured clinical interview according to the developed by us protocol and was conducted remotely. During the examination, depressive, anxiety-phobic, asthenic and dyssomnic disorders, addictive behavior and symptoms of PTSDwere identified and verified. Statistical and mathematical processing a was carried out using Fisher's exact test. RESULTS: Results: The data we obtained indicate a significant spread of psychopathological symptoms in FM and IDP. CONCLUSION: Conclusions: FM and IDP are characterized by a high incidence of psychopathological symptoms. The most frequent were: depressed mood (FM - 67.2%, IDP - 58.5%), feelings of anxiety and fear (FM -52.5%, IDP - 43.6%), obsessive thoughts (FM - 58.9 %, IDP - 49.5%).


Assuntos
Transtornos Cognitivos , Refugiados , Migrantes , Humanos , Feminino , Masculino , Refugiados/psicologia , Transtornos de Ansiedade/epidemiologia , Ansiedade
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