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1.
Nutrients ; 13(7)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209677

RESUMO

In recent years, neurological and neurodegenerative disorders research has focused on altered molecular mechanisms in search of potential pharmacological targets, e.g., imbalances in mechanisms of response to oxidative stress, inflammation, apoptosis, autophagy, proliferation, differentiation, migration, and neuronal plasticity, which occur in less common neurological and neurodegenerative pathologies (Huntington disease, multiple sclerosis, fetal alcohol spectrum disorders, and Down syndrome). Here, we assess the effects of different catechins (particularly of epigalocatechin-3-gallate, EGCG) on these disorders, as well as their use in attenuating age-related cognitive decline in healthy individuals. Antioxidant and free radical scavenging properties of EGCG -due to their phenolic hydroxyl groups-, as well as its immunomodulatory, neuritogenic, and autophagic characteristics, makes this catechin a promising tool against neuroinflammation and microglia activation, common in these pathologies. Although EGCG promotes the inhibition of protein aggregation in experimental Huntington disease studies and improves the clinical severity in multiple sclerosis in animal models, its efficacy in humans remains controversial. EGCG may normalize DYRK1A (involved in neural plasticity) overproduction in Down syndrome, improving behavioral and neural phenotypes. In neurological pathologies caused by environmental agents, such as FASD, EGCG enhances antioxidant defense and regulates placental angiogenesis and neurodevelopmental processes. As demonstrated in animal models, catechins attenuate age-related cognitive decline, which results in improvements in long-term outcomes and working memory, reduction of hippocampal neuroinflammation, and enhancement of neuronal plasticity; however, further studies are needed. Catechins are valuable compounds for treating and preventing certain neurodegenerative and neurological diseases of genetic and environmental origin. However, the use of different doses of green tea extracts and EGCG makes it difficult to reach consistent conclusions for different populations.


Assuntos
Antioxidantes/farmacologia , Catequina/farmacologia , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças Neurodegenerativas/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Envelhecimento Cognitivo/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Plasticidade Neuronal/efeitos dos fármacos
2.
Nutrients ; 13(7)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34201969

RESUMO

Decreased concentration of phospholipids were observed in brain tissue from individuals with dementia compared with controls, indicating phospholipids might be a key variable in development of age-related cognitive impairment. The reflection of these phospholipid changes in blood might provide both reference for diagnosis/monitoring and potential targets for intervention through peripheral circulation. Using a full-scale targeted phospholipidomic approach, 229 molecular species of plasma phospholipid were identified and quantified among 626 senile residents; the association of plasma phospholipids with MoCA score was also comprehensively discussed. Significant association was confirmed between phospholipid matrix and MoCA score by a distance-based linear model. Additionally, the network analysis further observed that two modules containing PEs were positively associated with MoCA score, and one module containing LPLs had a trend of negative correlation with MoCA score. Furthermore, 23 phospholipid molecular species were found to be significantly associated with MoCA score independent of fasting glucose, lipidemia, lipoproteins, inflammatory variables and homocysteine. Thus, the decreased levels of pPEs containing LC-PUFA and the augmented levels of LPLs were the most prominent plasma phospholipid changes correlated with the cognitive decline, while alterations in plasma PC, PS and SM levels accompanying cognitive decline might be due to variation of lipidemia and inflammatory levels.


Assuntos
Envelhecimento Cognitivo/fisiologia , Disfunção Cognitiva/sangue , Fosfolipídeos/sangue , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Modelos Lineares , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Redes Neurais de Computação
3.
J Alzheimers Dis ; 82(4): 1703-1713, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34219722

RESUMO

BACKGROUND: Several early-life factors have been associated with higher risk of developing dementia. It is unclear whether season of birth (SOB) can affect cognitive aging in older adults or not. OBJECTIVE: We aimed to study the association of SOB with the level of cognitive performance as well as with the rate of cognitive decline. METHODS: We studied 70,203 individuals who participated in the Survey of Health, Aging and Retirement in Europe. Cognition was measured with tests on verbal fluency and immediate and delayed recall. We assessed the association of SOB with the level of cognitive performance using multiple linear regression and with the rate of cognitive decline using linear mixed-effects models. RESULTS: When compared to individuals born in winter and adjusted for sociodemographic and health-related characteristics, being born in summer was associated with a higher level of delayed recall (B 0.05; 95%CI 0.01 to 0.09) and verbal fluency (B 0.15; 95%CI 0.00 to 0.29) and being born in fall with a higher level of immediate recall (B 0.04; 95%CI 0.01 to 0.08) and verbal fluency (B 0.15; 95%CI 0.01 to 0.29). Individuals born in summer had a higher yearly decline in delayed recall (B -0.005; 95%CI -0.009 to 0.000), while the scores in delayed recall in participants born in spring showed an inverse trend (B 0.005; 95%CI 0.000 to 0.010). CONCLUSION: Individuals born in winter seem to carry a life-long disadvantage in a lower level of cognitive performance; however, being born in winter does not seem to affect the rate of cognitive decline.


Assuntos
Envelhecimento Cognitivo/fisiologia , Disfunção Cognitiva/psicologia , Estações do Ano , Estudos Transversais , Europa (Continente) , Feminino , Inquéritos Epidemiológicos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
4.
PLoS One ; 16(7): e0254038, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34197534

RESUMO

BACKGROUND: Life expectancy is increasing in most high-income countries, but gains in life years are maximized if spent in good health and if cognitive abilities are maintained until old age. Age-related decline of cognitive abilities does nevertheless occur, but the pace of decline is decisive. This was the starting point for our study that aims to examine cohort effects of cognitive aging in women and men in Germany, Spain and Sweden by analyzing changes from 2004 to 2013 by estimating cohort effects within age groups starting from the age of 50 years. METHODS: A cohort study was conducted that was based on data of the surveys 2004 (N = 6,081) and 2013 (N = 8,650) from the Survey of Health, Ageing and Retirement in Europe (SHARE). The analyses were based on data of female and male respondents aged 50 years and older. Age-specific means of verbal fluency and delayed recall from the German, Spanish and Swedish samples were the cognitive domains considered in the study. RESULTS: In both domains of cognitive ability the achievements in the later surveys were higher than in the earlier ones. This was found in all countries, abut achievement levels increased markedly in the German and the Spanish samples, while the scores of the Swedish samples were not significantly different. While the highest scores were found for Sweden, Germany ranked in the middle and the lowest scores were found in the Spanish samples. Over time, the scores of the German samples approached those of Sweden. CONCLUSIONS: From the first to the second survey, improvements of older adults' cognitive abilities were found for all countries considered. This may indicate improvements of the underlying educational systems, but also increasingly stimulating general living conditions.


Assuntos
Cognição/fisiologia , Envelhecimento Cognitivo/fisiologia , Expectativa de Vida , Aposentadoria , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Alemanha/epidemiologia , Inquéritos Epidemiológicos , Humanos , Masculino , Espanha/epidemiologia , Suécia/epidemiologia
5.
Nutrients ; 13(6)2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34063827

RESUMO

A previous systematic review revealed that lutein intake leads to improved cognitive function among older adults. However, the association between lutein intake and brain health remains unclear. METHODS: We searched the Web of Science, PubMed, PsycInfo, and Cochrane Library for research papers. The criteria were (1) an intervention study using oral lutein intake or a cross-sectional study that examined lutein levels and the brain, (2) participants were older adults, and (3) brain activities or structures were measured using a brain imaging technique (magnetic resonance imaging (MRI) or electroencephalography (EEG)). RESULTS: Seven studies using MRI (brain activities during rest, cognitive tasks, and brain structure) and two studies using EEG were included. We mainly focused on MRI studies. Three intervention studies using MRI indicated that 10 mg lutein intake over 12 months had a positive impact on healthy older adults' brain activities during learning, resting-state connectivity, and gray matter volumes. Four cross-sectional studies using MRI suggested that lutein was positively associated with brain structure and neural efficiency during cognitive tasks. CONCLUSION: Although only nine studies that used similar datasets were reviewed, this systematic review indicates that lutein has beneficial effects on healthy older adults' brain health.


Assuntos
Encéfalo/efeitos dos fármacos , Cognição/efeitos dos fármacos , Ingestão de Alimentos/psicologia , Luteína/farmacologia , Idoso , Encéfalo/diagnóstico por imagem , Envelhecimento Cognitivo/fisiologia , Estudos Transversais , Feminino , Frutas/química , Voluntários Saudáveis , Humanos , Imageamento por Ressonância Magnética , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise e Desempenho de Tarefas , Verduras/química
6.
J Alzheimers Dis ; 82(3): 1203-1218, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34151803

RESUMO

BACKGROUND: The relationships between obesity and cognitive decline in aging are mixed and understudied among Hispanics/Latinos. OBJECTIVE: To understand associations between central obesity, cognitive aging, and the role of concomitant cardiometabolic abnormalities among Hispanics/Latinos. METHODS: Participants included 6,377 diverse Hispanics/Latinos enrolled in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and SOL-Investigation for Neurocognitive Aging (SOL-INCA). Participants were 45 years and older at the first cognitive testing session (Visit 1). Cognitive outcomes (z-score units) included global composite and domain specific (learning, memory, executive functioning, processing speed) measures at a second visit (SOL-INCA, on average, 7 years later), and 7-year change. We used survey linear regression to examine associations between central obesity (waist circumference≥88 cm and≥102 cm for women and men, respectively) and cognition. We also tested whether the relationships between obesity and cognition differed by cardiometabolic status (indication of/treatment for 2 + of the following: high triglycerides, hypertension, hyperglycemia, low high-density lipoprotein cholesterol). RESULTS: Central obesity was largely unassociated with cognitive outcomes, adjusting for covariates. However, among individuals with central obesity, cardiometabolic abnormality was linked to poorer cognitive function at SOL-INCA (ΔGlobalCognition =-0.165, p < 0.001) and to more pronounced cognitive declines over the average 7 years (ΔGlobalCognition = -0.109, p < 0.05); this was consistent across cognitive domains. CONCLUSION: Central obesity alone was not associated with cognitive function. However, presence of both central obesity and cardiometabolic abnormalities was robustly predictive of cognition and 7-year cognitive declines, suggesting that in combination these factors may alter the cognitive trajectories of middle-aged and older Hispanics/Latinos.


Assuntos
Fatores de Risco Cardiometabólico , Envelhecimento Cognitivo/fisiologia , Disfunção Cognitiva/metabolismo , Hispano-Americanos , Testes Neuropsicológicos , Obesidade Abdominal/metabolismo , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/metabolismo , Envelhecimento/psicologia , Envelhecimento Cognitivo/psicologia , Disfunção Cognitiva/etnologia , Disfunção Cognitiva/psicologia , Estudos de Coortes , Feminino , Hispano-Americanos/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Abdominal/etnologia , Obesidade Abdominal/psicologia , Estudos Prospectivos
7.
Sci Rep ; 11(1): 12552, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-34131185

RESUMO

An association between cognitive impairment and tripping over obstacles during locomotion in older adults has been suggested. However, owing to its memory-guided movement, whether this is more pronounced in the trailing limb is poorly known. We examined age-related changes in stepping over, focusing on trailing limb movements, and their association with cognitive performance. Age-related changes in obstacle avoidance were examined by comparing the foot kinematics of 105 older and 103 younger adults when stepping over an obstacle. The difference in the clearance between the leading and trailing limbs (Δ clearance) was calculated to determine the degree of decrement in the clearance of the trailing limb. A cognitive test battery was used to evaluate cognitive function among older adults to assess their association with Δ clearance. Older adults showed a significantly lower clearance of the trailing limb than young adults, resulting in greater Δ clearance. Significant correlations were observed between greater Δ clearance and scores on the Montreal Cognitive Assessment and immediate recall of the Wechsler Memory Scale-Revised Logical Memory test. Therefore, memory functions may contribute to the control of trailing limb movements, which can secure a safety margin to avoid stumbling over an obstacle during obstacle avoidance locomotion.


Assuntos
Envelhecimento Cognitivo/fisiologia , Disfunção Cognitiva/fisiopatologia , Marcha/fisiologia , Locomoção/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Articulação do Tornozelo/fisiologia , Aprendizagem da Esquiva/fisiologia , Fenômenos Biomecânicos , Cognição/fisiologia , Feminino , Pé/fisiologia , Humanos , Cinética , Masculino , Caminhada/fisiologia , Adulto Jovem
8.
J Am Geriatr Soc ; 69(7): 1826-1835, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33954985

RESUMO

OBJECTIVE: We examined whether sarcopenia is associated with the occurrence of late-life cognitive impairment. METHODS: Nondemented older adults (N = 1175) underwent annual testing with 17 cognitive tests summarized as a global cognitive score. A composite sarcopenia score was constructed based on muscle mass measured with bioelectrical impedance and muscle function based on grip strength. Cox proportional hazard models were employed to examine associations of sarcopenia with incident Alzheimer's dementia (AD) and incident mild cognitive impairment (MCI). Linear mixed-effect models determined the association of sarcopenia with cognitive decline. All models controlled for age, sex, education, race, and height squared. RESULTS: Average follow-up was 5.6 years. More severe sarcopenia at baseline was associated with a higher risk of incident AD (hazard ratio [HR], 1.50 [95% confidence interval 1.20-1.86]; p < 0.001) and of MCI (1.21 [1.01-1.45]; 0.04) and a faster rate of cognitive decline (estimate = -0.013; p = 0.01). Analyses of the individual components of sarcopenia showed that muscle function was associated with incident AD, incident MCI, and cognitive decline with and without a term for lean muscle mass in the model. In contrast, lean muscle mass was not associated with incident cognitive impairment or cognitive decline when a term for muscle function was included in the model. CONCLUSIONS: Poor muscle function, but not reduced lean muscle mass, drives the association of sarcopenia with late-life cognitive impairment. Further work is needed to identify features of muscle structure, which may increase the specificity of sarcopenia for identifying older adults at risk for late-life cognitive impairment.


Assuntos
Doença de Alzheimer/epidemiologia , Envelhecimento Cognitivo/fisiologia , Disfunção Cognitiva/epidemiologia , Sarcopenia/psicologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/etiologia , Disfunção Cognitiva/etiologia , Impedância Elétrica , Feminino , Força da Mão , Humanos , Incidência , Modelos Lineares , Masculino , Músculo Esquelético/fisiopatologia , Testes Neuropsicológicos , Modelos de Riscos Proporcionais , Sarcopenia/fisiopatologia
9.
J Alzheimers Dis ; 81(3): 871-920, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33935078

RESUMO

A decade has passed since we published a comprehensive review in this journal addressing the topic of promoting successful cognitive aging, making this a good time to take stock of the field. Because there have been limited large-scale, randomized controlled trials, especially following individuals from middle age to late life, some experts have questioned whether recommendations can be legitimately offered about reducing the risk of cognitive decline and dementia. Despite uncertainties, clinicians often need to at least make provisional recommendations to patients based on the highest quality data available. Converging lines of evidence from epidemiological/cohort studies, animal/basic science studies, human proof-of-concept studies, and human intervention studies can provide guidance, highlighting strategies for enhancing cognitive reserve and preventing loss of cognitive capacity. Many of the suggestions made in 2010 have been supported by additional research. Importantly, there is a growing consensus among major health organizations about recommendations to mitigate cognitive decline and promote healthy cognitive aging. Regular physical activity and treatment of cardiovascular risk factors have been supported by all of these organizations. Most organizations have also embraced cognitively stimulating activities, a heart-healthy diet, smoking cessation, and countering metabolic syndrome. Other behaviors like regular social engagement, limiting alcohol use, stress management, getting adequate sleep, avoiding anticholinergic medications, addressing sensory deficits, and protecting the brain against physical and toxic damage also have been endorsed, although less consistently. In this update, we review the evidence for each of these recommendations and offer practical advice about behavior-change techniques to help patients adopt brain-healthy behaviors.


Assuntos
Cognição/fisiologia , Envelhecimento Cognitivo/fisiologia , Envelhecimento Saudável/fisiologia , Estilo de Vida Saudável/fisiologia , Dieta Saudável , Exercício Físico/fisiologia , Exercício Físico/psicologia , Envelhecimento Saudável/psicologia , Humanos
10.
Mod Trends Psychiatry ; 32: 12-25, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34032642

RESUMO

Since the beginning of life on earth, microorganisms have played a significant role in evolution. Throughout the history of Homo sapiens and its precursor humanoid forms, microorganisms have been present at birth and proliferated until death. It is at these extremes of life that the microbiome, especially that within the gastrointestinal tract, is most dynamic and perhaps has its greatest influence on host health. Here, we focus on the role of the gut microbiome as a regulator of brain and behaviour through key points in the human lifespan. We first describe trajectories of the microbiome in early life and ageing, before providing evidence for the existence of sensitive periods in the microbiome-gut-brain axis at these extremes of the lifespan. Finally, we briefly examine potential mechanisms for interactions between the microbiome and the brain during development and ageing.


Assuntos
Encéfalo , Envelhecimento Cognitivo , Microbioma Gastrointestinal/fisiologia , Desenvolvimento Humano/fisiologia , Encéfalo/crescimento & desenvolvimento , Encéfalo/microbiologia , Cognição/fisiologia , Envelhecimento Cognitivo/fisiologia , Envelhecimento Cognitivo/psicologia , Humanos
11.
J Alzheimers Dis ; 81(2): 751-768, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33843672

RESUMO

BACKGROUND: There is growing consensus that non-genetic determinants of dementia can be linked to various risk- and resiliency-enhancing factors accumulating throughout the lifespan, including socioeconomic conditions, early life experiences, educational attainment, lifestyle behaviors, and physical/mental health. Yet, the causal impact of these diverse factors on dementia risk remain poorly understood due to few longitudinal studies prospectively characterizing these influences across the lifespan. OBJECTIVE: The Initial Lifespan's Impact on Alzheimer's Disease and Related Dementia (ILIAD) study aims to characterize dementia prevalence in the Wisconsin Longitudinal Study (WLS), a 60-year longitudinal study documenting life course trajectories of educational, family, occupational, psychological, cognitive, and health measures. METHODS: Participants are surveyed using the modified Telephone Interview for Cognitive Status (TICS-m) to identify dementia risk. Those scoring below cutoff undergo home-based neuropsychological, physical/neurological, and functional assessments. Dementia diagnosis is determined by consensus panel and merged with existing WLS data for combined analysis. RESULTS: Preliminary findings demonstrate the initial success of the ILIAD protocol in detecting dementia prevalence in the WLS. Increasing age, hearing issues, lower IQ, male sex, APOE4 positivity, and a steeper annualized rate of memory decline assessed in the prior two study waves, all increased likelihood of falling below the TICS-m cutoff for dementia risk. TICS-m scores significantly correlated with standard neuropsychological performance and functional outcomes. CONCLUSION: We provide an overview of the WLS study, describe existing key lifespan variables relevant to studies of dementia and cognitive aging, detail the current WLS-ILIAD study protocol, and provide a first glimpse of preliminary study findings.


Assuntos
Transtornos Cognitivos/epidemiologia , Disfunção Cognitiva/epidemiologia , Demência/epidemiologia , Demência/psicologia , Transtornos Cognitivos/diagnóstico , Envelhecimento Cognitivo/fisiologia , Disfunção Cognitiva/diagnóstico , Escolaridade , Feminino , Humanos , Estudos Longitudinais , Masculino , Prevalência
12.
PLoS One ; 16(4): e0250222, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33861794

RESUMO

Accelerated cognitive ageing (ACA) is an ageing co-morbidity in epilepsy that is diagnosed through the observation of an evident IQ decline of more than 1 standard deviation (15 points) around the age of 50 years old. To understand the mechanism of action of this pathology, we assessed brain dynamics with the use of resting-state fMRI data. In this paper, we present novel and promising methods to extract brain dynamics between large-scale resting-state networks: the emulative power, wavelet coherence, and granger causality between the networks were extracted in two resting-state sessions of 24 participants (10 ACA, 14 controls). We also calculated the widely used static functional connectivity to compare the methods. To find the best biomarkers of ACA, and have a better understanding of this epilepsy co-morbidity we compared the aforementioned between-network neurodynamics using classifiers and known machine learning algorithms; and assessed their performance. Results show that features based on the evolutionary game theory on networks approach, the emulative powers, are the best descriptors of the co-morbidity, using dynamics associated with the default mode and dorsal attention networks. With these dynamic markers, linear discriminant analysis could identify ACA patients at 82.9% accuracy. Using wavelet coherence features with decision-tree algorithm, and static functional connectivity features with support vector machine, ACA could be identified at 77.1% and 77.9% accuracy respectively. Granger causality fell short of being a relevant biomarker with best classifiers having an average accuracy of 67.9%. Combining the features based on the game theory, wavelet coherence, Granger-causality, and static functional connectivity- approaches increased the classification performance up to 90.0% average accuracy using support vector machine with a peak accuracy of 95.8%. The dynamics of the networks that lead to the best classifier performances are known to be challenged in elderly. Since our groups were age-matched, the results are in line with the idea of ACA patients having an accelerated cognitive decline. This classification pipeline is promising and could help to diagnose other neuropsychiatric disorders, and contribute to the field of psychoradiology.


Assuntos
Envelhecimento Cognitivo/fisiologia , Epilepsia/diagnóstico por imagem , Epilepsia/fisiopatologia , Idoso , Envelhecimento/fisiologia , Algoritmos , Biomarcadores/análise , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Causalidade , Cognição/fisiologia , Análise Discriminante , Feminino , Humanos , Aprendizado de Máquina , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Rede Nervosa/metabolismo , Rede Nervosa/fisiopatologia , Descanso/fisiologia , Máquina de Vetores de Suporte
13.
Neuroimage ; 235: 117963, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-33813007

RESUMO

A major goal of human neuroscience is to relate differences in brain function to differences in behavior across people. Recent work has established that whole-brain functional connectivity patterns are relatively stable within individuals and unique across individuals, and that features of these patterns predict various traits. However, while functional connectivity is most often measured at rest, certain tasks may enhance individual signals and improve sensitivity to behavior differences. Here, we show that compared to the resting state, functional connectivity measured during naturalistic viewing-i.e., movie watching-yields more accurate predictions of trait-like phenotypes in the domains of both cognition and emotion. Traits could be predicted using less than three minutes of data from single video clips, and clips with highly social content gave the most accurate predictions. Results suggest that naturalistic stimuli amplify individual differences in behaviorally relevant brain networks.


Assuntos
Percepção Auditiva/fisiologia , Envelhecimento Cognitivo/fisiologia , Conectoma , Emoções/fisiologia , Filmes Cinematográficos , Rede Nervosa/fisiologia , Personalidade/fisiologia , Percepção Social , Percepção Visual/fisiologia , Adulto , Tecnologia de Rastreamento Ocular , Feminino , Humanos , Individualidade , Imageamento por Ressonância Magnética , Masculino , Rede Nervosa/diagnóstico por imagem , Adulto Jovem
14.
Minerva Med ; 112(4): 441-447, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33709673

RESUMO

Cognitive reserve is originally an epidemiological concept that encompasses individual abilities to cope with changes. It is considered the result of a balance between processes of cellular damage and repair, and its description raised much interest in predicting and preventing cognitive decline in aging and Alzheimer's disease (AD). In this study, we discussed the concept of cognitive reserve considering the recent definition of AD as a biological continuum and suggest that the protection of cognitive reserve may result from efficient synaptic plasticity mechanisms. Despite pathological changes of AD appearing very early during life, long before the onset of cognitive symptoms, different variables act together to keep repair mechanisms effective guaranteeing successful aging if environmental enrichment is maintained.


Assuntos
Doença de Alzheimer/diagnóstico , Doença de Alzheimer/prevenção & controle , Reserva Cognitiva/fisiologia , Plasticidade Neuronal/fisiologia , Doença de Alzheimer/etiologia , Envelhecimento Cognitivo/fisiologia , Dano ao DNA/fisiologia , Reparo do DNA/fisiologia , Metabolismo Energético/fisiologia , Humanos , Mitocôndrias/fisiologia , Degeneração Neural/fisiopatologia
15.
Mayo Clin Proc ; 96(3): 788-814, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33673927

RESUMO

Increased life expectancy combined with the aging baby boomer generation has resulted in an unprecedented global expansion of the elderly population. The growing population of older adults and increased rate of age-related chronic illness has caused a substantial socioeconomic burden. The gradual and progressive age-related decline in hormone production and action has a detrimental impact on human health by increasing risk for chronic disease and reducing life span. This article reviews the age-related decline in hormone production, as well as age-related biochemical and body composition changes that reduce the bioavailability and actions of some hormones. The impact of hormonal changes on various chronic conditions including frailty, diabetes, cardiovascular disease, and dementia are also discussed. Hormone replacement therapy has been attempted in many clinical trials to reverse and/or prevent the hormonal decline in aging to combat the progression of age-related diseases. Unfortunately, hormone replacement therapy is not a panacea, as it often results in various adverse events that outweigh its potential health benefits. Therefore, except in some specific individual cases, hormone replacement is not recommended. Rather, positive lifestyle modifications such as regular aerobic and resistance exercise programs and/or healthy calorically restricted diet can favorably affect endocrine and metabolic functions and act as countermeasures to various age-related diseases. We provide a critical review of the available data and offer recommendations that hopefully will form the groundwork for physicians/scientists to develop and optimize new endocrine-targeted therapies and lifestyle modifications that can better address age-related decline in heath.


Assuntos
Envelhecimento Cognitivo/fisiologia , Disfunção Cognitiva/prevenção & controle , Envelhecimento Saudável/fisiologia , Terapia de Reposição Hormonal/estatística & dados numéricos , Estilo de Vida , Idoso , Terapia Comportamental/estatística & dados numéricos , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo
16.
Neuroimage ; 232: 117875, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33639257

RESUMO

The concept of cognitive reserve proposes that specific life experiences result in more flexible or resilient cognitive processing allowing some people to cope better with age- or disease-related brain changes than others. Imaging studies seeking to understand the neural implementation of cognitive reserve have most often used task-related fMRI studies. Using that approach, we recently described a task-invariant cognitive-reserve network whose expression correlated with IQ and that moderated between cortical thickness and cognitive performance. Here we sought to identify a pattern of resting BOLD connectivity related to cognitive reserve. We identified a connectome pattern whose connectivity correlated with IQ in both the derivation sample and a separate replication sample. The majority of the edges showing positive relationships with IQ implicate frontal regions. In the derivation sample, connectivity either moderated the relationship between mean cortical thickness and a set of cognitive outcomes or accounted for unique variance in cognitive performance after accounting for cortical thickness. In a replication sample we found that expression of this connectome correlated significantly with the primary endpoint of IQ, and also accounted for unique variance in cognitive performance beyond cortical thickness. Our findings represent an intermediate level of replication and are unlikely to have arisen purely by type-I error. This connectivity pattern therefore meets some of our theoretical criteria for a cognitive reserve-related network and provides insight into the neural implementation of cognitive reserve. Further, expression of this connectome could potentially be used as a direct measure of cognitive reserve, and as an outcome measure for intervention studies that seek to influence cognitive reserve. Future validation of and re-derivation of the pattern in expanded data sets by our and other groups will lead to further improved estimates of cognitive reserve in resting functional connectivity.


Assuntos
Encéfalo/fisiologia , Reserva Cognitiva/fisiologia , Conectoma/métodos , Imageamento por Ressonância Magnética/métodos , Rede Nervosa/fisiologia , Descanso/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Cognição/fisiologia , Envelhecimento Cognitivo/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Consumo de Oxigênio/fisiologia , Adulto Jovem
17.
Mech Ageing Dev ; 195: 111463, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33607172

RESUMO

Cognitive function is a substantially heritable trait related to numerous important life outcomes. Several genome-wide association studies of cognitive function have in recent years led to the identification of thousands of significantly associated loci and genes. Individuals included in these studies have rarely been nonagenarians and centenarians, and since cognitive function is an important component of quality of life for this rapidly expanding demographic group, there is a need to explore genetic factors associated with individual differences in cognitive function at advanced ages. In this study, we pursued this by performing a genome-wide association study of cognitive function in 490 long-lived Danes (age range 90.1-100.8 years). While no genome-wide significant SNPs were identified, suggestively significant SNPs (P < 1 × 10-5) were mapped to several interesting genes, including ZWINT, CELF2, and DNAH5, and the glutamate receptor genes GRID2 and GRM7. Additionally, results from a gene set over-representation analysis indicated potential roles of gene sets related to G protein-coupled receptor (GPCR) signaling, interaction between L1 and ankyrins, mitogen-activated protein kinase (MAPK) signaling, RNA degradation, and cell cycle. Larger studies are needed to shed further light on the possible importance of these suggestive genes and pathways in cognitive function in nonagenarians and centenarians.


Assuntos
Cognição/fisiologia , Envelhecimento Cognitivo/fisiologia , Qualidade de Vida , Transdução de Sinais/fisiologia , Idoso de 80 Anos ou mais , Dineínas do Axonema/genética , Proteínas CELF/genética , Ciclo Celular/fisiologia , Dinamarca/epidemiologia , Feminino , Estudos de Associação Genética , Estudo de Associação Genômica Ampla , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Proteínas do Tecido Nervoso/genética , Proteínas Nucleares/genética , Polimorfismo de Nucleotídeo Único , Estabilidade de RNA
18.
Aging (Albany NY) ; 13(3): 3218-3238, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33510046

RESUMO

Normal brain aging is characterized by declining neuronal integrity, yet it remains unclear how microstructural injury influences cognitive aging and whether such mechanisms differ between sexes. Using restriction spectrum imaging (RSI), we examined sex differences in associations between brain microstructure and cognitive function in 147 community-dwelling older men and women (56-99 years). Gray and white matter microstructure correlated with global cognition, executive function, visuospatial memory, episodic memory, and logical memory, with the strongest associations for restricted, hindered and free isotropic diffusion. Associations were stronger for women than for men, a difference likely due to greater age-related variability in cognitive scores and microstructure in women. Isotropic diffusion mediated effects of age on cognition for both sexes, though distinct mediation patterns were present for women and men. For women, hippocampal and corpus callosum microstructure mediated age effects on verbal and visuospatial memory, respectively, whereas for men fiber microstructure (mainly fornix and corpus callosum) mediated age effects on executive function and visuospatial memory. These findings implicate sex-specific pathways by which changing brain cytoarchitecture contributes to cognitive aging, and suggest that RSI may be useful for evaluating risk for cognitive decline or monitoring efficacy of interventions to preserve brain health in later life.


Assuntos
Encéfalo , Envelhecimento Cognitivo/fisiologia , Idoso , Idoso de 80 Anos ou mais , Encéfalo/anatomia & histologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais
19.
Sci Rep ; 11(1): 943, 2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441584

RESUMO

Epigenetic imprinting is important for neurogenesis and brain function. Hippocampal volumes and brain hyperintensities in late life have been associated with early life circumstances. Epigenetic imprinting may underpin these associations. Methylation was measured at 982 sites in 13 imprinted locations in blood samples from a longitudinal cohort by bisulphite amplicon sequencing. Hippocampal volumes and hyperintensities were determined at age 64y and 72y using MRI. Hyperintensities were determined in white matter, grey matter and infratentorial regions. Permutation methods were used to adjust for multiple testing. At 64y, H19/IGF2 and NESPAS methylation predicted hippocampal volumes. PEG3 predicted hyperintensities in hippocampal grey matter, and white matter. GNASXL predicted grey matter hyperintensities. Changes with age were predicted for hippocampal volume (MEST1, KvDMR, L3MBTL, GNASXL), white matter (MEST1, PEG3) and hippocampal grey matter hyperintensities (MCTS2, GNASXL, NESPAS, L3MBTL, MCTS2, SNRPN, MEST1). Including childhood cognitive ability, years in education, or socioeconomic status as additional explanatory variables in regression analyses did not change the overall findings. Imprinting methylation in multiple genes predicts brain structures, and their change over time. These findings are potentially relevant to the development of novel tests of brain structure and function across the life-course, strategies to improve cognitive outcomes, and our understanding of early influences on brain development and function.


Assuntos
Envelhecimento Cognitivo/fisiologia , Epigênese Genética/genética , Hipocampo/metabolismo , Fatores Etários , Idoso , Encéfalo/fisiologia , Estudos de Coortes , Metilação de DNA/genética , Epigênese Genética/fisiologia , Epigenômica/métodos , Feminino , Impressão Genômica/genética , Substância Cinzenta/fisiologia , Hipocampo/fisiologia , Humanos , Masculino , Metilação , Pessoa de Meia-Idade , Substância Branca/fisiologia
20.
Neuroimage ; 229: 117737, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33486125

RESUMO

Despite the necessity to understand how the brain endures the initial stages of age-associated cognitive decline, no brain mechanism has been quantitatively specified to date. The brain may withstand the effects of cognitive aging through redundancy, a design feature in engineered and biological systems, which entails the presence of substitute elements to protect it against failure. Here, we investigated the relationship between functional network redundancy and age over the human lifespan and their interaction with cognition, analyzing resting-state functional MRI images and cognitive measures from 579 subjects. Network-wide redundancy was significantly associated with age, showing a stronger link with age than other major topological measures, presenting a pattern of accumulation followed by old-age decline. Critically, redundancy significantly mediated the association between age and executive function, with lower anti-correlation between age and cognition in subjects with high redundancy. The results suggest that functional redundancy accrues throughout the lifespan, mitigating the effects of age on cognition.


Assuntos
Encéfalo/fisiologia , Cognição/fisiologia , Envelhecimento Cognitivo/fisiologia , Longevidade/fisiologia , Rede Nervosa/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Envelhecimento Cognitivo/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Adulto Jovem
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