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1.
Clin Geriatr Med ; 37(3): 457-467, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34210450

RESUMO

There is a strong association between obstructive sleep apnea (OSA) and cognitive dysfunction. Executive function, attention, verbal/visual long-term memory, visuospatial/constructional ability, and information processing are more likely to be affected, whereas language, psychomotor function, and short-term memory are less likely to be affected. Increased accumulation of Aß2-amyloid in the brain, episodic hypoxemia, oxidative stress, vascular inflammation, and systemic comorbidities may contribute to the pathogenesis. Patients with OSA should have cognitive screening or formal testing, and patients with cognitive decline should have testing for OSA. Treatment with continuous positive airway pressure may improve cognitive symptoms in the patient with OSA.


Assuntos
Transtornos Cognitivos/fisiopatologia , Cognição/fisiologia , Disfunção Cognitiva/etiologia , Pressão Positiva Contínua nas Vias Aéreas/efeitos adversos , Apneia Obstrutiva do Sono/terapia , Idoso , Função Executiva , Humanos , Apneia Obstrutiva do Sono/psicologia
2.
Minerva Med ; 112(4): 456-466, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34056888

RESUMO

Current investigations in pre-symptomatic dementia have suggested that depressive mood, a treatable condition, may play an important role in the development of the disorder. However, whether depression in adulthood constitute a risk factor, or a prodrome of dementia remains unclear. A major implication in such dispute is the analytic framework used to identify putative risk factors. Indeed, if evaluated in the years immediately prior to dementia diagnosis the association between depression and dementia may reflect depressive symptoms as a prodrome of yet-undiagnosed dementia. Unfortunately, long term prospective cohort investigations, reaching back into the preclinical phase of dementia are sparse. Here, we have surveyed high-quality evidence (systematic reviews and meta-analyses) on the association between depressive symptoms and increased odds of dementia. Meta-analytic findings are also presented and discussed regarding depression as a prodromal stage of dementia, or a consequence of underlying neurodegenerative processes. Additionally, the potential confounding effect of several variables on the risk association between depression and dementia, an aspect hardly investigated, is discussed. While early onset late-life depression - defined as starting before 60 years of age - increases the odds of developing dementia in predisposed subjects, late-onset depression appears to be a prodrome and a clear accelerating factor for cognitive deterioration. Since it is increasingly important to consider the potential of preemptive approaches to decrease the impact of dementia, evidence on potentially effective preventive strategies targeting depression as a risk factor, and next steps in further research are presented as concluding remarks.


Assuntos
Demência/etiologia , Depressão/complicações , Sintomas Prodrômicos , Fatores Etários , Transtornos Cognitivos/fisiopatologia , Transtornos Cognitivos/prevenção & controle , Demência/diagnóstico , Demência/epidemiologia , Demência/prevenção & controle , Depressão/epidemiologia , Depressão/psicologia , Progressão da Doença , Humanos , Metanálise como Assunto , Doenças Neurodegenerativas/complicações , Doenças Neurodegenerativas/psicologia , Fatores de Risco , Revisões Sistemáticas como Assunto
3.
Rev Neurol ; 72(11): 384-396, 2021 06 01.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-34042167

RESUMO

INTRODUCTION: Many patients with mild or severe COVID-19 do not make a full recovery and have a wide range of chronic symptoms for weeks or months after infection, often of a neurological, cognitive or psychiatric nature. The epidemiological evidence, diagnostic criteria and pathogenesis of post-COVID-19 syndrome are reviewed. DEVELOPMENT: Post-COVID-19 syndrome is defined by persistent clinical signs and symptoms that appear while or after suffering COVID-19, persist for more than 12 weeks and cannot be explained by an alternative diagnosis. The symptoms can fluctuate or cause relapses. It is a heterogeneous condition that includes post-viral chronic fatigue syndrome, sequelae in multiple organs and the effects of severe hospitalisation/post-intensive care syndrome. It has been reported in patients with mild or severe COVID-19 and irrespective of the severity of the symptoms in the acute phase. Between 10% and 65% of survivors who had mild/moderate COVID-19 present symptoms of post-COVID-19 syndrome for 12 weeks or more. At six months, subjects report an average of 14 persistent symptoms. The most common symptoms are fatigue, dyspnoea, anxiety, depression, and impaired attention, concentration, memory and sleep. The underlying biological mechanisms are unknown, although an abnormal or excessive autoimmune and inflammatory response may play an important role. CONCLUSIONS: Clinical manifestations are diverse, fluctuating and variable, although fatigue and neurocognitive complaints predominate. There is no defined consensus on post-COVID-19 syndrome and its diagnostic criteria have not been subjected to adequate psychometric evaluation.


Assuntos
COVID-19/complicações , SARS-CoV-2 , Autoimunidade , Encéfalo/metabolismo , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/fisiopatologia , Doenças Cardiovasculares/etiologia , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/fisiopatologia , Infecções por Coronavirus/complicações , Dispneia/etiologia , Síndrome de Fadiga Crônica/etiologia , Gastroenteropatias/etiologia , Hospitalização , Interações Hospedeiro-Patógeno , Humanos , Inflamação , Transtornos Mentais/etiologia , Doenças do Sistema Nervoso/etiologia , Especificidade de Órgãos , Pandemias , Disautonomias Primárias/etiologia , Fatores de Risco , Síndrome Respiratória Aguda Grave/complicações
4.
J Alzheimers Dis ; 81(2): 691-697, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33814451

RESUMO

BACKGROUND: The Clinical Dementia Rating (CDR) scale is commonly used to stage cognitive impairment, despite having educational limitations. In elderly with low education, a previous study has shown that intraindividual variability of reaction time (CV) and commission errors (CE), measured using a culture-free Go/No-Go task, can reliably distinguish early Alzheimer's disease (AD) from mild cognitive impairment (MCI) and healthy controls. OBJECTIVE: We aimed to extend the clinical utility of this culture-free Go/No-Go task in a sample with high educational disparity. METHODS: One hundred and ten participants with a wide range of years of formal education (0-14 years) were randomly selected from a geriatric unit and divided based on their CDR scores into cognitively unimpaired (CDR = 0), MCI (CDR = 0.5), and early AD (CDR = 1). All underwent a 90-s reaction-time test that measured the variables previously found to predict CDR in low educated elderly. Here we added years of formal education (educational level) to the model. Multivariate analyses compared differences in group means using educational level as confounding factor. A confirmatory discriminant analyses was performed, to assess if CDR scores could be predicted by the two Go/No-Go variables in a sample with high educational disparity. RESULTS: Over all three groups, differences in both CE and CV reached statistical significance (p < 0.05). The discriminant analysis demonstrated that CV and CE discriminated cognitively impaired from cognitively normal elderly. These results remained similar when discriminating MCI from cognitively unimpaired elderly. CONCLUSION: The Go/No-Go task reliably discriminates elderly with MCI from elderly without cognitive impairment independent of educational disparity.


Assuntos
Doença de Alzheimer/fisiopatologia , Atenção/fisiologia , Transtornos Cognitivos/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Análise e Desempenho de Tarefas , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Cognição/fisiologia , Transtornos Cognitivos/diagnóstico , Disfunção Cognitiva/diagnóstico , Progressão da Doença , Escolaridade , Feminino , Humanos , Masculino , Testes de Estado Mental e Demência , Índice de Gravidade de Doença
5.
JAMA Otolaryngol Head Neck Surg ; 147(6): 534-543, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33830194

RESUMO

Importance: In recent years, there have been several meaningful advances in the understanding of the cognitive effects of chronic rhinosinusitis. However, an investigation exploring the potential link between the underlying inflammatory disease and higher-order neural processing has not yet been performed. Objective: To describe the association of sinonasal inflammation with functional brain connectivity (Fc), which may underlie chronic rhinosinusitis-related cognitive changes. Design, Setting, and Participants: This is a case-control study using the Human Connectome Project (Washington University-University of Minnesota Consortium of the Human Connectome Project 1200 release), an open-access and publicly available data set that includes demographic, imaging, and behavioral data for 1206 healthy adults aged 22 to 35 years. Twenty-two participants demonstrated sinonasal inflammation (Lund-Mackay score [LMS] ≥ 10) and were compared with age-matched and sex-matched healthy controls (LMS = 0). These participants were further stratified into moderate (LMS < 14, n = 13) and severe (LMS ≥ 14, n = 9) inflammation groups. Participants were screened and excluded if they had a history of psychiatric disorder and/or neurological or genetic diseases. Participants with diabetes or cardiovascular disease were also excluded, as these conditions may affect neuroimaging quality. The data were accessed between October 2019 and August 2020. Data analysis was performed between May 2020 and August 2020. Main Outcomes and Measures: The primary outcome was the difference in resting state Fc within and between the default mode, frontoparietal, salience, and dorsal attention brain networks. Secondary outcomes included assessments of cognitive function using the National Institutes of Health Toolbox Cognition Battery. Results: A total of 22 patients with chronic rhinosinusitis and 22 healthy controls (2 [5%] were aged 22-25 years, 26 [59%] were aged 26-30 years, and 16 [36%] were aged 31-35 years; 30 [68%] were men) were included in the analysis. Participants with sinonasal inflammation showed decreased Fc within the frontoparietal network, in a region involving bilateral frontal medial cortices. This region demonstrated increased Fc to 2 nodes within the default-mode network and decreased Fc to 1 node within the salience network. The magnitude of these differences increased with inflammation severity (dose dependent). There were no significant associations seen on cognitive testing. Conclusions and Relevance: In this case-control study, participants with sinonasal inflammation showed decreased brain connectivity within a major functional hub with a central role in modulating cognition. This region also shows increased connectivity to areas that are activated during introspective and self-referential processing and decreased connectivity to areas involved in detection and response to stimuli. Future prospective studies are warranted to determine the applicability of these findings to a clinical chronic rhinosinusitis population.


Assuntos
Transtornos Cognitivos/fisiopatologia , Conectoma , Rinite/fisiopatologia , Sinusite/fisiopatologia , Adulto , Estudos de Casos e Controles , Doença Crônica , Feminino , Humanos , Inflamação/fisiopatologia , Masculino
6.
J Alzheimers Dis ; 81(2): 651-665, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33867359

RESUMO

BACKGROUND: The motoric cognitive risk (MCR) syndrome is a pre-clinical stage of dementia characterized by slow gait and cognitive complaint. Yet, the brain substrates of MCR are not well established. OBJECTIVE: To examine cortical thickness, volume, and surface area associated with MCR in the MCR-Neuroimaging Consortium, which harmonizes image processing/analysis of multiple cohorts. METHODS: Two-hundred MRIs (M age 72.62 years; 47.74%female; 33.17%MCR) from four different cohorts (50 each) were first processed with FreeSurfer 6.0, and then analyzed using multivariate and univariate general linear models with 1,000 bootstrapped samples (n-1; with resampling). All models adjusted for age, sex, education, white matter lesions, total intracranial volume, and study site. RESULTS: Overall, cortical thickness was lower in individuals with MCR than in those without MCR. There was a trend in the same direction for cortical volume (p = 0.051). Regional cortical thickness was also lower among individuals with MCR than individuals without MCR in prefrontal, insular, temporal, and parietal regions. CONCLUSION: Cortical atrophy in MCR is pervasive, and include regions previously associated with human locomotion, but also social, cognitive, affective, and motor functions. Cortical atrophy in MCR is easier to detect in cortical thickness than volume and surface area because thickness is more affected by healthy and pathological aging.


Assuntos
Envelhecimento/psicologia , Transtornos Cognitivos/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Demência/fisiopatologia , Velocidade de Caminhada/fisiologia , Idoso , Idoso de 80 Anos ou mais , Cognição/fisiologia , Transtornos Cognitivos/diagnóstico , Demência/diagnóstico , Feminino , Marcha/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Fatores de Risco
7.
JAMA Netw Open ; 4(3): e213227, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33787912

RESUMO

Importance: The increasing prevalence of cognitive decline, impairment, and dementia spurs intense interest in cognitive preservation strategies. Objective: To explore the longitudinal association between physical activity (PA) and cognitive performance among women at midlife. Design, Setting, and Participants: This cohort study is an analysis from the Study of Women's Health Across the Nation. Enrollment occurred from 1996 through 1997, and follow-up extended into 2017. Included individuals were those who had undergone cognitive measures during the first 3 cognitive test visits and had at least 1 additional cognitive measurement. Stroke prior to baseline was an exclusion, and observations were censored for subsequent stroke. Data were analyzed from June 2018 through August 2019. Exposures: Engaging in sport or exercise PA (self-reported). Main Outcomes and Measures: The Symbol Digit Modalities Test (SDMT) was used to assess cognitive processing speed. The East Boston Memory Test-Delayed (EBMT-D) was used to measure verbal episodic memory. The digit span backwards (DSB) test was used to evaluate working memory. Results: Among 1718 women with a median (range) observation time of 11.9 (0.60-13.5) years, the mean (SD) baseline age was 45.7 (2.5) years. From baseline through age 61 years, mean change in SDMT score was -0.20 annually (95% CI, -0.26 to -0.15; P < .001). After age 61 years, the mean change in SDMT was -0.51 yearly (95% CI, -0.54 to -0.41; P < .001). Beginning at age 58 years of the mean change in EBMT was -0.03 yearly (95% CI, -0.04 to -0.02; P < .001). Starting at age 61 years, mean (SD) change in DSB was -0.03 annually (95% CI, -0.04 to -0.01; P = .001). When adjusted for attrition and practice effect, PA was associated with higher concurrent SDMT and EBMT scores and a smaller decrease in SDMT score. For each unit increment in PA, there was a 0.36 increment in concurrent SDMT score (95% CI, 0.14 to 0.59; P = .002) and a 0.10 increment in concurrent EBMT score (95% CI, 0.05 to 0.15; P < .001). Greater PA was associated with a smaller annual mean decrease in SDMT score (0.06 yearly; 95% CI, 0.02 to 0.09; P = .001). After additional adjustment for demographic characteristics, menopause symptoms, hormone therapy use, and the presence of diabetes and hypertension, PA was not associated with trajectories (ie, levels or slopes) of any cognitive outcome. Conclusions and Relevance: This cohort study found no association between greater PA levels and cognitive outcomes among women in midlife, unlike cohort studies that begin observations at later ages, which may be associated with confounding by reverse causation (ie, cognitive decline associated with an outcome of lower PA levels).


Assuntos
Transtornos Cognitivos/psicologia , Cognição/fisiologia , Exercício Físico/fisiologia , Memória/fisiologia , Saúde da Mulher , Adulto , Transtornos Cognitivos/fisiopatologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos
8.
J Vis Exp ; (169)2021 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-33779592

RESUMO

An increasing amount of evidence shows that cognitive deficits and movement dysfunctions are not separated. Patients with mild cognitive impairment (MCI) can manifest fine motor disorders of the upper extremities. Handwriting is a complex and unique human activity involving both motor and cognitive coordination. Researchers from western countries have discovered that patients with MCI have abnormal handwriting features. However, no relevant studies have been conducted in the Chinese population. Owing to the cross-culture phenomenon of handwriting, the aim of this study is to find new handwriting tasks to demonstrate the differences in handwriting features between elderly patients with MCI and age-matched healthy individuals.


Assuntos
Transtornos Cognitivos/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Escrita Manual , Destreza Motora/fisiologia , Idoso , Fenômenos Biomecânicos , China , Feminino , Humanos , Masculino , Movimento , Testes Neuropsicológicos
10.
Nat Rev Neurosci ; 22(3): 167-179, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33536614

RESUMO

Cognitive and behavioural flexibility permit the appropriate adjustment of thoughts and behaviours in response to changing environmental demands. Brain mechanisms enabling flexibility have been examined using non-invasive neuroimaging and behavioural approaches in humans alongside pharmacological and lesion studies in animals. This work has identified large-scale functional brain networks encompassing lateral and orbital frontoparietal, midcingulo-insular and frontostriatal regions that support flexibility across the lifespan. Flexibility can be compromised in early-life neurodevelopmental disorders, clinical conditions that emerge during adolescence and late-life dementias. We critically evaluate evidence for the enhancement of flexibility through cognitive training, physical activity and bilingual experience.


Assuntos
Comportamento/fisiologia , Cognição/fisiologia , Rede Nervosa/fisiologia , Fenômenos Fisiológicos do Sistema Nervoso , Animais , Sintomas Comportamentais/fisiopatologia , Transtornos Cognitivos/fisiopatologia , Humanos , Rede Nervosa/fisiopatologia , Vias Neurais/fisiologia
11.
Gait Posture ; 85: 157-163, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33578308

RESUMO

BACKGROUND: Individuals with Parkinson's disease (PD) who report freezing of gait (FOG) have poorer sleep quality than those without FOG. Cognitive, anxiety, and mobility disability are components of the FOG phenotype, however, no study has investigated if poor sleep quality is associated with all three components that underlie FOG in PD. RESEARCH QUESTION: Are there associations among sleep quality and all three components of the FOG phenotype? METHODS: Forty and 39 individuals with and without FOG (PD + FOG and PD-FOG), respectively, and 31 age-matched healthy controls (HC) participated in this study. Self-reported FOG (new-FOG questionnaire-NFOGQ), sleep quality (Pittsburgh Sleep Quality Index-PSQI), cognitive function (Montreal Cognitive Assessment-MoCA), anxiety (subscale from Hospital Anxiety and Depression Scale-HADS-A), and mobility (timed-up-and-go test-TUG) were assessed. RESULTS AND SIGNIFICANCE: PSQI scores were correlated with the scores of NFOGQ, MoCA, HADS-A, and TUG time in PD + FOG (P ≤ 0.0038). The multiple regression analysis identified the PSQI scores as the only predictor of the variance of the NFOGQ scores (R2 = 0.46, P < .0001). The variance in the PSQI scores were explained (69 %) by MoCA scores, NFOGQ scores, TUG time, and HADS-A scores (P ≤ 0.05). Although PD + FOG had a higher disease severity compared to PD-FOG (P < 0.001), disease severity did not enter in the regression model to explain PSQI scores and NFOGQ scores. We also observed associations of PSQI scores with the MoCA scores and TUG time for HC (P ≤ 0.0038), whereas there was no association between PSQI scores and any variable in PD-FOG (P > 0.05). Finally, PD + FOG presented worse scores of PSQI, MoCA, HADS-A, and TUG time than PD-FOG and HC (P < 0.05). Thus, poor sleep quality is associated with FOG and all three components that underlie FOG, regardless of the disease severity. Therefore, treatments useful to decrease FOG should be targeted to ameliorate sleep quality, cognition, anxiety, and mobility.


Assuntos
Ansiedade/etiologia , Transtornos Cognitivos/etiologia , Transtornos Neurológicos da Marcha/etiologia , Limitação da Mobilidade , Doença de Parkinson/fisiopatologia , Doença de Parkinson/psicologia , Distúrbios do Início e da Manutenção do Sono/fisiopatologia , Idoso , Ansiedade/fisiopatologia , Ansiedade/psicologia , Estudos de Casos e Controles , Transtornos Cognitivos/fisiopatologia , Transtornos Cognitivos/psicologia , Avaliação da Deficiência , Feminino , Transtornos Neurológicos da Marcha/fisiopatologia , Transtornos Neurológicos da Marcha/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Fatores de Risco , Autorrelato , Índice de Gravidade de Doença , Distúrbios do Início e da Manutenção do Sono/etiologia , Distúrbios do Início e da Manutenção do Sono/psicologia
12.
Nutrients ; 13(2)2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33546219

RESUMO

Obesity is often associated with cognitive and mood disorders. Recent evidence suggests that obesity may cause hypothalamic inflammation. Our aim was to investigate the hypothesis that there is a causal link between obesity-induced hypothalamic inflammation and cognitive and mood disorders. Inflammation may influence hypothalamic inter-connections with regions important for cognition and mood, while it may cause dysregulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis and influence monoaminergic systems. Exercise, healthy diet, and glucagon-like peptide receptor agonists, which can reduce hypothalamic inflammation in obese models, could improve the deleterious effects on cognition and mood.


Assuntos
Transtornos Cognitivos/etiologia , Dieta/efeitos adversos , Doenças Hipotalâmicas/complicações , Inflamação/complicações , Transtornos do Humor/etiologia , Obesidade/complicações , Animais , Transtornos Cognitivos/fisiopatologia , Transtornos Cognitivos/prevenção & controle , Dieta Saudável , Exercício Físico , Receptores de Peptídeos Semelhantes ao Glucagon/agonistas , Humanos , Doenças Hipotalâmicas/terapia , Sistema Hipotálamo-Hipofisário/fisiopatologia , Inflamação/terapia , Transtornos do Humor/fisiopatologia , Transtornos do Humor/prevenção & controle , Obesidade/etiologia , Sistema Hipófise-Suprarrenal/fisiopatologia
13.
J Prev Alzheimers Dis ; 8(2): 142-150, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33569560

RESUMO

Importance/Objective: To describe the feasibility and acceptability of a 6-month web-based multidomain lifestyle training intervention for community-dwelling older people and to test the effects of the intervention on both function- and lifestyle-related outcomes. DESIGN: 6-month, parallel-group, randomized controlled trial (RCT). SETTING: Toulouse area, South-West, France. PARTICIPANTS: Community-dwelling men and women, ≥ 65 years-old, presenting subjective memory complaint, without dementia. INTERVENTION: The web-based multidomain intervention group (MIG) received a tablet to access the multidomain platform and a wrist-worn accelerometer measuring step counts; the control group (CG) received only the wrist-worn accelerometer. The multidomain platform was composed of nutritional advices, personalized exercise training, and cognitive training. Main outcomes and measures: Feasibility, defined as the proportion of people connecting to ≥75% of the prescribed sessions, and acceptability, investigated through content analysis from recorded semi-structured interviews. Secondary outcomes included clinical (eg, cognitive function, mobility, health-related quality of life (HRQOL)) and lifestyle (eg, step count, food intake) measurements. RESULTS: Among the 120 subjects (74.2 ±5.6 years-old; 57.5% women), 109 completed the study (n=54, MIG; n=55, CG). 58 MIG subjects connected to the multidomain platform at least once; among them, adherers of ≥75% of sessions varied across multidomain components: 37 people (63.8% of 58 participants) for cognitive training, 35 (60.3%) for nutrition, and three (5.2%) for exercise; these three persons adhered to all multidomain components. Participants considered study procedures and multidomain content in a positive way; the most cited weaknesses were related to exercise: too easy, repetitive, and slow progression. Compared to controls, the intervention had a positive effect on HRQOL; no significant effects were observed across the other clinical and lifestyle outcomes. CONCLUSIONS AND RELEVANCE: Providing multidomain lifestyle training through a web-platform is feasible and well-accepted, but the training should be challenging enough and adequately progress according to participants' capabilities to increase adherence. Recommendations for a larger on-line multidomain lifestyle training RCT are provided.


Assuntos
Envelhecimento , Cognição/fisiologia , Exercício Físico/fisiologia , Estilo de Vida , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Transtornos Cognitivos/fisiopatologia , Feminino , Humanos , Masculino
14.
Int J Mol Sci ; 22(1)2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33466445

RESUMO

The lack of effective disease-modifying therapeutics to tackle Alzheimer's disease (AD) is unsettling considering the actual prevalence of this devastating neurodegenerative disorder worldwide. Intermittent hypoxic conditioning (IHC) is a powerful non-pharmacological procedure known to enhance brain resilience. In this context, the aim of the present study was to investigate the potential long-term protective impact of IHC against AD-related phenotype, putting a special focus on cognition and mitochondrial bioenergetics and dynamics. For this purpose, six-month-old male triple transgenic AD mice (3×Tg-AD) were submitted to an IHC protocol for two weeks and the behavioral assessment was performed at 8.5 months of age, while the sacrifice of mice occurred at nine months of age and their brains were removed for the remaining analyses. Interestingly, IHC was able to prevent anxiety-like behavior and memory and learning deficits and significantly reduced brain cortical levels of amyloid-ß (Aß) in 3×Tg-AD mice. Concerning brain energy metabolism, IHC caused a significant increase in brain cortical levels of glucose and a robust improvement of the mitochondrial bioenergetic profile in 3×Tg-AD mice, as mirrored by the significant increase in mitochondrial membrane potential (ΔΨm) and respiratory control ratio (RCR). Notably, the improvement of mitochondrial bioenergetics seems to result from an adaptative coordination of the distinct but intertwined aspects of the mitochondrial quality control axis. Particularly, our results indicate that IHC favors mitochondrial fusion and promotes mitochondrial biogenesis and transport and mitophagy in the brain cortex of 3×Tg-AD mice. Lastly, IHC also induced a marked reduction in synaptosomal-associated protein 25 kDa (SNAP-25) levels and a significant increase in both glutamate and GABA levels in the brain cortex of 3×Tg-AD mice, suggesting a remodeling of the synaptic microenvironment. Overall, these results demonstrate the effectiveness of the IHC paradigm in forestalling the AD-related phenotype in the 3×Tg-AD mouse model, offering new insights to AD therapy and forcing a rethink concerning the potential value of non-pharmacological interventions in clinical practice.


Assuntos
Doença de Alzheimer/fisiopatologia , Transtornos Cognitivos/fisiopatologia , Cognição/fisiologia , Metabolismo Energético/fisiologia , Hipóxia/fisiopatologia , Camundongos Transgênicos/fisiologia , Mitocôndrias/fisiologia , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Ansiedade/metabolismo , Ansiedade/fisiopatologia , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Transtornos Cognitivos/metabolismo , Modelos Animais de Doenças , Hipóxia/metabolismo , Masculino , Camundongos , Camundongos Transgênicos/metabolismo , Mitocôndrias/metabolismo
15.
Hypertension ; 77(3): 972-979, 2021 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-33461314

RESUMO

Hypertension is related to increased risk of cognitive decline in a highly age-dependent manner. However, conflicting evidence exists on the relation between age of hypertension onset and cognition. Our goal was to investigate the association between early- versus late-onset hypertension and midlife cognitive performance in 2946 CARDIA study (Coronary Artery Risk Development in Young Adults) participants (mean age 55±4, 57% women). The participants underwent 9 repeat examinations, including blood pressure measurements, between 1985 to 1986 and 2015 to 2016. The participants underwent brain magnetic resonance imaging and completed Digit Symbol Substitution Test, Rey Auditory Verbal Learning Test, Stroop interference test, and the Montreal Cognitive Assessment to evaluate cognitive function at the year 30 exam. We assessed the relation between age of hypertension onset and cognitive function using linear regression models adjusted for cognitive decline risk factors, including systolic blood pressure. We observed that individuals with early-onset hypertension (onset at <35 years) had 0.24±0.09, 0.22±0.10, 0.27±0.09, and 0.19±0.07 lower standardized Z-scores in Digit Symbol Substitution Test, Stroop test, Montreal Cognitive Assessment, and a composite cognitive score than participants without hypertension (P<0.05 for all). In contrast, hypertension onset at ≥35 years was not associated with cognitive function (P >0.05 for all). In a subgroup of 559 participants, neither early- nor late-onset hypertension was related to macrostructural brain alterations (P >0.05 for all). Our results indicate that early-onset hypertension is a potent risk factor for midlife cognitive impairment. Thus, age of hypertension onset assessment in clinical practice could improve risk stratification of cognitive decline in patients with hypertension.


Assuntos
Pressão Sanguínea/fisiologia , Transtornos Cognitivos/fisiopatologia , Cognição/fisiologia , Função Executiva/fisiologia , Hipertensão/fisiopatologia , Adulto , Idade de Início , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Feminino , Humanos , Modelos Lineares , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
16.
Sci Rep ; 11(1): 1207, 2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441734

RESUMO

Working memory (WM) is a fundamental cognitive function that typically declines with age. Previous studies have shown that targeted WM training has the potential to improve WM performance in older adults. In the present study, we investigated whether a multi-domain cognitive training program that was not designed to specifically target WM could improve the behavioral performance and affect the neural activity during WM retrieval in healthy older adults. We assigned healthy older participants (70-78 years old) from a local community into a training group who completed a 3-month multi-domain cognitive training and a control group who only attended health education lectures during the same period. Behavioral and electroencephalography (EEG) data were recorded from participants while performing an untrained delayed match or non-match to category task and a control task at a pre-training baseline session and a post-training follow-up session. Behaviorally, we found that participants in the training group showed a trend toward greater WM performance gains than participants in the control group. Event-related potential (ERP) results suggest that the task-related modulation of P3 during WM retrieval was significantly enhanced at the follow-up session compared with the baseline session, and importantly, this enhancement of P3 modulation was only significant in the training group. Furthermore, no training-related effects were observed for the P2 or N2 component during WM retrieval. These results suggest that the multi-domain cognitive training program that was not designed to specifically target WM is a promising approach to improve WM performance in older adults, and that training-related gains in performance are likely mediated by an enhanced modulation of P3 which might reflect the process of WM updating.


Assuntos
Envelhecimento/fisiologia , Cognição/fisiologia , Potenciais Evocados/fisiologia , Aprendizagem/fisiologia , Memória de Curto Prazo/fisiologia , Idoso , Grupo com Ancestrais do Continente Asiático , Transtornos Cognitivos/fisiopatologia , Eletroencefalografia/métodos , Função Executiva/fisiologia , Feminino , Humanos , Masculino
17.
PLoS One ; 16(1): e0246008, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33503047

RESUMO

BACKGROUND: Preterm birth (PTB) and particularly late preterm PTB has become a research focus for obstetricians, perinatologists, neonatologists, pediatricians and policy makers alike. Translational models are useful tools to expedite and guide clinical but presently no model exists that contextualizes the late PTB scenario. Herein we aimed to develop a rabbit model that echo's the clinical neurocognitive phenotypes of early and late PTB. METHODS: Time mated rabbit does underwent caesarean delivery at a postconceptional age (PCA) of either 28 (n = 6), 29 (n = 5), 30 (n = 4) or 31 (n = 4) days, term = 31 d. Newborn rabbits were mixed and randomly allocated to be raised by cross fostering and underwent short term neurobehavioral testing on corrected post-natal day 1. Open field (OFT), spontaneous alteration (TMT) and novel object recognition (NORT) tests were subsequently performed at 4 and 8 weeks of age. RESULTS: PTB was associated with a significant gradient of short-term mortality and morbidity inversely related to the PCA. On postnatal day 1 PTB was associated with a significant sensory deficit in all groups but a clear motor insult was only noted in the PCA 29d and PCA 28d groups. Furthermore, PCA 29d and PCA 28d rabbits had a persistent neurobehavioral deficit with less exploration and hyperanxious state in the OFT, less alternation in TMT and lower discriminatory index in the NORT. While PCA 30d rabbits had some anxiety behavior and lower spontaneous alteration at 4 weeks, however at 8 weeks only mild anxiety driven behavior was observed in some of these rabbits. CONCLUSIONS: In this rabbit model, delivery at PCA 29d and PCA 28d mimics the clinical phenotype of early PTB while delivery at PCA 30d resembles that of late PTB. This could serve as a model to investigate perinatal insults during the early and late preterm period.


Assuntos
Transtornos Cognitivos/fisiopatologia , Cognição , Modelos Animais de Doenças , Nascimento Prematuro/fisiopatologia , Animais , Animais Recém-Nascidos , Transtornos Cognitivos/etiologia , Feminino , Masculino , Aprendizagem em Labirinto , Teste de Campo Aberto , Gravidez , Coelhos , Aprendizagem Espacial
18.
PLoS One ; 16(1): e0245425, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33481828

RESUMO

Spatial neglect (SN) is a common cognitive disorder after brain injury. Prism adaptation treatment (PAT) is one of the promising interventions for SN albeit inconsistent results from previous studies. We carried out a comparison intervention (PAT vs. Sham) and aimed to evaluate the efficacy of PAT on visuospatial symptoms of SN in an inpatient rehabilitation setting that offered a highly intensive comprehensive brain injury rehabilitation program. A total of 34 patients with moderate-to-severe SN secondary to stroke or traumatic brain injury were randomized to the PAT group and the Sham group (an active control group). Both groups received 10 sessions of treatment, over two weeks, in addition to the rehabilitation therapies provided by their rehabilitation care teams. Outcomes were measured using an ecological instrument (the Catherine Bergego Scale) and paper-and-pencil tests (the Bells Test, the Line Bisection Test and the Scene Copying Test). Patients were assessed at baseline, immediately after treatment, two weeks after treatment, and four weeks after treatment. 23 (67.6%) patients completed treatment and all the assessment sessions and were included in the final analyses using mixed linear modeling. While SN symptoms reduced in both groups, we found no difference between the two groups in the degree of improvement. In addition, the average SN recovery rates were 39.1% and 28.6% in the PAT and Sham groups, respectively, but this discrepancy did not reach statistical significance. Thus, the present study suggests that PAT may contribute little to SN care in the context of a highly intensive inpatient rehabilitation program. Further large-scale investigation is required to uncover the mechanisms underlying PAT and Sham in order to refine the treatment or create new interventions.


Assuntos
Transtornos Cognitivos/etiologia , Transtornos Cognitivos/terapia , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Transtornos Cognitivos/fisiopatologia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Acidente Vascular Cerebral/fisiopatologia , Reabilitação do Acidente Vascular Cerebral/métodos
19.
Exp Biol Med (Maywood) ; 246(1): 106-120, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32962408

RESUMO

IMPACT STATEMENT: This study provides crucial information that could be helpful in the development of new or repurposing of existing therapies for the treatment of cognitive deficit in individuals with sickle cell disease (SCD). Its impact is in demonstrating for the first time that neuroinflammation and along with abnormal neuroplasticity are among the underlying mechanism of cognitive and behavioral deficits in SCD and that drugs such as minocycline which targets these pathophysiological mechanisms could be repurposed for the treatment of this life altering complication of SCD.


Assuntos
Envelhecimento/patologia , Anemia Falciforme/complicações , Encéfalo/patologia , Transtornos Cognitivos/complicações , Inflamação/patologia , Anemia Falciforme/fisiopatologia , Animais , Comportamento Animal , Encéfalo/fisiopatologia , Transtornos Cognitivos/fisiopatologia , Espinhas Dendríticas/efeitos dos fármacos , Espinhas Dendríticas/metabolismo , Inflamação/fisiopatologia , Masculino , Camundongos , Minociclina/farmacologia , Neurogênese/efeitos dos fármacos , Plasticidade Neuronal/efeitos dos fármacos
20.
Psychopharmacology (Berl) ; 238(5): 1279-1289, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-30536081

RESUMO

RATIONALE: Schizophrenia is associated with impairments in cognitive functioning yet there are no approved drugs to treat these deficits. OBJECTIVES: Based on animal models, we investigated the potential for roflumilast, a selective inhibitor of phosphodiesterase type 4 (PDE4), to improve cognition, which may act by increasing intracellular cyclic adenosine monophosphate in brain regions underlying cognitive deficits in schizophrenia. METHODS: This study consisted of a randomised, double-blind, placebo-controlled, crossover design involving 15 schizophrenia patients. In 3 treatment periods, patients were given 8 days of placebo or one of the two doses of roflumilast (100 and 250 µg daily) with 14 days of washout between treatments. The primary endpoints were dorsolateral prefrontal cortex (DLPFC) activation during a visuospatial working memory task measured with fMRI on dosing day 8 and verbal memory and working memory performance change from baseline to day 8. Least square mean change scores were calculated for behavioural outcomes; fMRI data were analysed in SPM12 with bilateral DLPFC as regions of interest. RESULTS: Verbal memory was significantly improved under 250 µg roflumilast (effect size (ES) = 0.77) compared to placebo. fMRI analyses revealed that increasing dose of roflumilast was associated with reduction of bilateral DLPFC activation during working memory compared to placebo, although this was not statistically significant (ES = 0.31 for the higher dose). Working memory was not improved (ES = 0.03). CONCLUSIONS: Results support the mechanistic validation of potential novel strategies for improving cognitive dysfunction in schizophrenia and suggest that PDE4 inhibition may be beneficial for cognitive dysfunction in schizophrenia. TRIAL REGISTRATION: NCT02079844 .


Assuntos
Aminopiridinas/farmacologia , Benzamidas/farmacologia , Inibidores da Fosfodiesterase 4/farmacologia , Esquizofrenia/tratamento farmacológico , Adulto , Animais , Encéfalo/efeitos dos fármacos , Cognição/efeitos dos fármacos , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/fisiopatologia , Estudos Cross-Over , Ciclopropanos/farmacologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Memória Episódica , Memória de Curto Prazo/efeitos dos fármacos , Pessoa de Meia-Idade , Córtex Pré-Frontal/efeitos dos fármacos , Esquizofrenia/fisiopatologia
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