Strategies to enhance the response of liver cancer to pharmacological treatments.

In contrast to other types of cancers, there is no available efficient pharmacological treatment to improve the outcomes of patients suffering from major primary liver cancers, i.e., hepatocellular carcinoma and cholangiocarcinoma. This dismal situation is partly due to the existence in these tumors of many different and synergistic mechanisms of resistance, accounting for the lack of response of these patients, not only to classical chemotherapy but also to more modern pharmacological agents based on the inhibition of tyrosine kinase receptors (TKIs) and the stimulation of the immune response against the tumor using immune checkpoint inhibitors (ICIs). This review summarizes the efforts to develop strategies to overcome this severe limitation, including searching for novel drugs derived from synthetic, semisynthetic, or natural products with vectorial properties against therapeutic targets to increase drug uptake or reduce drug export from cancer cells. Besides, immunotherapy is a promising line of research that is already starting to be implemented in clinical practice. Although less successful than in other cancers, the foreseen future for this strategy in treating liver cancers is considerable. Similarly, the pharmacological inhibition of epigenetic targets is highly promising. Many novel "epidrugs," able to act on "writer," "reader," and "eraser" epigenetic players, are currently being evaluated in preclinical and clinical studies. Finally, gene therapy is a broad field of research in the fight against liver cancer chemoresistance, based on the impressive advances recently achieved in gene manipulation. In sum, although the present is still dismal, there is reason for hope in the non-too-distant future.

Areca catechu-From farm to food and biomedical applications.

The family Arecaceae includes 181 genera and 2,600 species with a high diversity in physical characteristics. Areca plants, commonly palms, which are able to grow in nearly every type of habitat, prefer tropical and subtropical climates. The most studied species Areca catechu L. contains phytochemicals as phenolics and alkaloids with biological properties. The phenolics are mainly distributed in roots followed by fresh unripe fruits, leaves, spikes, and veins, while the contents of alkaloids are in the order of roots, fresh unripe fruits, spikes, leaves, and veins. This species has been reputed to provide health effects on the cardiovascular, respiratory, nervous, metabolic, gastrointestinal, and reproductive systems. However, in many developing countries, quid from this species has been associated with side effects, which include the destruction of the teeth, impairment of oral hygiene, bronchial asthma, or oral cancer. Despite these side effects, which are also mentioned in this work, the present review collects the main results of biological properties of the phytochemicals in A. catechu. This study emphasizes the in vitro and in vivo antioxidant, antimicrobial, anticancer, and clinical effectiveness in humans. In this sense, A. catechu have demonstrated effectiveness in several reports through in vitro and in vivo experiments on disorders such as antimicrobial, antioxidant, or anticancer. Moreover, our findings demonstrate that this species presents clinical effectiveness on neurological disorders. Hence, A. catechu extracts could be used as a bioactive ingredient for functional food, nutraceuticals, or cosmeceuticals. However, further studies, especially extensive and comprehensive clinical trials, are recommended for the use of Areca in the treatment of diseases.

Tablet-Based Hearing Test Among Child Clinical Populations: Performance and Preference.

Background and Introduction: Tablet-based automated audiometry applications are a recent alternative method to perform pure-tone hearing testing. Children, in particular, might benefit from such apps because of the game-like interface. However, how children perceive this alternative approach has not been well studied. This study examined children's preference of hearing test and a relationship between their test preference and hearing test results. Materials and Methods: Forty children 6-12 years of age completed a pure-tone hearing test in both the tablet-based automated (tablet) method and the conventional method. Hearing thresholds were measured at 0.5, 1, 2, 4, 6, and 8 kHz in each ear. An exit interview was conducted to obtain each child's test preference. Results: We found that 59% of the children preferred the tablet method when compared to the conventional method. Preference to the tablet method was stronger in the younger children (6 years) than older children (7-12 years). The linear regression analyses suggest that test preference does not affect the hearing test results in the conventional method, but does negatively affect the results in the tablet method. In addition, poor performance was found among children with a clinical diagnosis, in particular, in the tablet method. Discussion: These results suggest that hearing thresholds may be overestimated in children, especially those with clinical diagnosis such as attention or behavioral issues in the tablet method. Future work is needed to determine which clinical populations have potential benefit from a tablet method. Conclusions: Children's test preference is not a good index of hearing test accuracy.

Phytochemical Composition and Bioactive Effects of Salvia africana, Salvia officinalis 'Icterina' and Salvia mexicana Aqueous Extracts.

In the present study, aqueous extracts of Salvia africana, Salvia officinalis 'Icterina' and Savia mexicana origin were screened for their phenolic composition and for antibacterial, antioxidant, anti-inflammatory and cytotoxic properties. The three aqueous extracts contained distinct phenolic compounds, with S. africana presenting the highest total levels (231.6 ± 7.5 µg/mg). Rosmarinic acid was the dominant phenolic compound in all extracts, yet that of S. africana origin was characterized by the present of yunnaneic acid isomers, which overall accounted for about 40% of total phenolics. In turn, S. officinalis 'Icterina' extract presented glycosidic forms of apigenin, luteolin and scuttelarein, and the one obtained from S. mexicana contained several simple caffeic acid derivatives. S. africana aqueous extract exhibited high antioxidant potential in four methods, namely the DPPH• (2,2-diphenyl-1-picrylhydrazyl) scavenging ability, iron-reducing power, inhibition of ß-carotene bleaching and of thiobarbituric acid reactive substances (TBARS), for which EC50 values were equal or only 1.3-3.1 higher than those of the standard compounds. Moreover, this extract was able to lower the levels of nitric oxide (NO) production in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages (EC50 = 47.8 ± 2.1 µg/mL). In addition, the three sage aqueous extracts showed promising cytotoxic effect towards hepatocellular HepG2, cervical HeLa, and breast carcinoma cells MCF-7. Overall this study highlights the potential of three little-exploited Salvia species, with commercial value for applications in food or pharmaceutical industries.

Salvia elegans, Salvia greggii and Salvia officinalis Decoctions: Antioxidant Activities and Inhibition of Carbohydrate and Lipid Metabolic Enzymes.

Salvia elegans Vahl., Salvia greggii A. Gray, and Salvia officinalis L. decoctions were investigated for their health-benefit properties, in particular with respect to antioxidant activity and inhibitory ability towards key enzymes with impact in diabetes and obesity (α-glucosidase, α-amylase and pancreatic lipase). Additionally, the phenolic profiles of the three decoctions were determined and correlated with the beneficial properties. The S. elegans decoction was the most promising in regard to the antioxidant effects, namely in the scavenging capacity of the free radicals DPPH•, NO• and O2•⁻, and the ability to reduce Fe3+, as well as the most effective inhibitor of α-glucosidase (EC50 = 36.0 ± 2.7 µg/mL vs. EC50 = 345.3 ± 6.4 µg/mL and 71.2 ± 5.0 µg/mL for S. greggii and S. officinalis, respectively). This superior activity of the S. elegans decoction over those of S. greggii and S. officinalis was, overall, highly correlated with its richness in caffeic acid and derivatives. In turn, the S. officinalis decoction exhibited good inhibitory capacity against xanthine oxidase activity, a fact that could be associated with its high content of flavones, in particular the glycosidic forms of apigenin, scutellarein and luteolin.

Metabolites and Biological Activities of Thymus zygis, Thymus pulegioides, and Thymus fragrantissimus Grown under Organic Cultivation.

Thymus plants are marketed for diverse usages because of their pleasant odor, as well as high nutritional value and wealth of health-promoting phytochemicals. In this study, Thymuszygis, Thymuspulegioides, and Thymusfragrantissimus grown under organic cultivation regime were characterized regarding nutrients and phenolic compounds. In addition, the antioxidant and antibacterial properties of these species were screened. The plants were particularly notable for their high K/Na ratio, polyunsaturated fatty acids content and low omega-6/omega-3 fatty acids ratios, which are valuable features of a healthy diet. Caffeic acid and/or its derivatives, mainly rosmarinic acid and caffeoyl rosmarinic acid, represented the majority of the phenolic constituents of these plants, although they were less representative in T. pulegioides, which in turn was the richest in flavones. The latter species also exhibited the highest antioxidant capacity (DPPH● EC50 of 9.50 ± 1.98 µg/mL and reducing power EC50 of 30.73 ± 1.48 µg/mL), while T. zygis was the most active towards Gram-positive and Gram-negative bacteria. Overall, the results suggest that the three thyme plants grown in organic farming are endowed with valuable metabolites that give them high commercial value for applications in different industries.

Health-Promoting Effects of Thymus herba-barona, Thymus pseudolanuginosus, and Thymus caespititius Decoctions.

Thymus herba-barona, Thymus pseudolanuginosus, and Thymus caespititius decoctions were screened for their phenolic constituents, along with their potential antioxidant, anti-inflammatory, and antibacterial activities. The total phenolic compounds in the extracts of the three plants ranged from 236.0 ± 26.6 mgGAE/g (T. caespititus) to 293.0 ± 30.5 mgGAE/g of extract (T. pseudolanuginosus), being particularly rich in caffeic acid derivatives, namely rosmarinic acid and its structural isomers, as well as flavones, such as luteolin-O-glucuronide. The T. pseudolanuginosus extract presented the best DPPH radical scavenging ability (EC50 = 10.9 ± 0.7 µg/mL), a high reducing power (EC50 = 32.2 ± 8.2 µg/mL), and effectively inhibited the oxidation of ß-carotene (EC50 = 2.4 ± 0.2 µg/mL). The extracts also showed NO● scavenging activity close to that of ascorbic acid, and thus might be useful as anti-inflammatory agents. In addition, they exhibited antibacterial activity against gram-negative and gram-positive bacteria. Staphylococcus aureus strains were the most sensitive bacteria to thyme extracts, with minimum inhibitory concentration and minimum bactericidal concentration values in the range of 0.6-3.5 mg/mL. Overall, this work is an important contribution for the phytochemical characterization and the potential antioxidant, anti-inflammatory, and antimicrobial activities of these three Thymus species, which have been poorly explored.

Seaweeds as Preventive Agents for Cardiovascular Diseases: From Nutrients to Functional Foods.

Being naturally enriched in key nutrients and in various health-promoting compounds, seaweeds represent promising candidates for the design of functional foods. Soluble dietary fibers, peptides, phlorotannins, lipids and minerals are macroalgae's major compounds that can hold potential in high-value food products derived from macroalgae, including those directed to the cardiovascular-health promotion. This manuscript revises available reported data focusing the role of diet supplementation of macroalgae, or extracts enriched in bioactive compounds from macroalgae origin, in targeting modifiable markers of cardiovascular diseases (CVDs), like dyslipidemia, oxidative stress, vascular inflammation, hypertension, hypercoagulability and activation of the sympathetic and renin-angiotensin systems, among others. At last, the review also describes several products that have been formulated with the use of whole macroalgae or extracts, along with their claimed cardiovascular-associated benefits.

Does substrate matter in the deep sea? A comparison of bone, wood, and carbonate rock colonizers.

Continental margins host methane seeps, animal falls and wood falls, with chemosynthetic communities that may share or exchange species. The goal of this study was to examine the existence and nature of linkages among chemosynthesis-based ecosystems by deploying organic fall mimics (bone and wood) alongside defaunated carbonate rocks within high and lesser levels of seepage activity for 7.4 years. We compared community composition, density, and trophic structure of invertebrates on these hard substrates at active methane seepage and transition (less seepage) sites at Mound 12 at ~1,000 m depth, a methane seep off the Pacific coast of Costa Rica. At transition sites, the community composition on wood and bone was characteristic of natural wood- and whale-fall community composition, which rely on decay of the organic substrates. However, at active sites, seepage activity modified the relationship between fauna and substrate, seepage activity had a stronger effect in defining and homogenizing these communities and they depend less on organic decay. In contrast to community structure, macrofaunal trophic niche overlap between substrates, based on standard ellipse areas, was greater at transition sites than at active sites, except between rock and wood. Our observations suggest that whale- and wood-fall substrates can function as stepping stones for seep fauna even at later successional stages, providing hard substrate for attachment and chemosynthetic food.

Pharmacological Properties of Bergapten: Mechanistic and Therapeutic Aspects.

Bergapten (BP) or 5-methoxypsoralen (5-MOP) is a furocoumarin compound mainly found in bergamot essential oil but also in other citrus essential oils and grapefruit juice. This compound presents antibacterial, anti-inflammatory, hypolipemic, and anticancer effects and is successfully used as a photosensitizing agent. The present review focuses on the research evidence related to the therapeutic properties of bergapten collected in recent years. Many preclinical and in vitro studies have been evidenced the therapeutic action of BP; however, few clinical trials have been carried out to evaluate its efficacy. These clinical trials with BP are mainly focused on patients suffering from skin disorders such as psoriasis or vitiligo. In these trials, the administration of BP (oral or topical) combined with UV irradiation induces relevant lesion clearance rates. In addition, beneficial effects of bergamot extract were also observed in patients with altered serum lipid profiles and in people with nonalcoholic fatty liver. On the contrary, there are no clinical trials that investigate the possible effects on cancer. Although the bioavailability of BP is lower than that of its 8-methoxypsoralen (8-MOP) isomer, it has fewer side effects allowing higher concentrations to be administered. In conclusion, although the use of BP has therapeutic applications on skin disorders as a sensitizing agent and as components of bergamot extract as hypolipemic therapy, more trials are necessary to define the doses and treatment guidelines and its usefulness against other pathologies such as cancer or bacterial infections.

Psychoactive substance consumption: A Portuguese cross-sectional study.

BACKGROUND: Increasing consumption of psychoactive substances is a major social concern worldwide. OBJECTIVES: To investigate the prevalence of psychoactive substances consumption in the Portuguese, throughout their life as well as recently, and the main reasons for the consumption and associated factors. METHODS: This cross-sectional study was based on the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) applied to a sample of 385 Portuguese obtained for convenience. It was used descriptive statistics, the Cui-square, Mann-Whitney U and Kruskal-Wallis tests, with a significance level of 5%. RESULTS: Alcohol was the most consumed throughout life (86%), followed by xanthines (79%) and tobacco (60%). In the last 3 months, xanthines (49%) were the most consumed daily, followed by tobacco (22%) and alcohol (9%). Socializing was the main reason for consumption of alcohol (67%), tobacco (36%) and cannabis (34%) while anxiolytics have been used to sleep (50%) and xanthines to increase cognitive capacity (35%). Tobacco (p = 0.016), alcohol (p = 0.03) and illicit substances (p < 0.001) were more consumed by men and anxiolytics by women (p = 0.027). Alcohol (p = 0.008), cannabis (p = 0.027), and xanthines (p = 0.009) were mostly consumed by young adults. CONCLUSIONS: The results reveal sporadic and recreational use of illicit substances, and regular use of alcohol, tobacco and xanthines, mostly by young adults and men, and anxiolytics by women. Socializing was the main reason for psychoactive substances consumption.

Chemical Composition, Antioxidant Potential, and Blood Glucose Lowering Effect of Aqueous Extract and Essential Oil of Thymus Serrulatus Hochst. Ex Benth.

Thymus serrulatus, an endemic plant of Ethiopia, is traditionally used to cure various diseases and as a food ingredient. In the Ethiopian folk medicine, the decoction is orally taken as a remedy to treat diabetes and high blood pressure. The purpose of the present study was to evaluate the antioxidant and antihyperglycemic effects of the aqueous extract and of the essential oil of Thymus serrulatus. The chemical composition of the aqueous extract was determined by LC-MS and the essential oil was characterized by GC-MS analysis. Radical scavenging assays, namely scavenging of 2,2-diphenyl-1-picrylhydrazyl (DPPH•), hydroxyl (•OH), and nitric oxide (•NO), were used as a first approach to screen the potential antioxidant abilities of the samples. Alpha-amylase and α-glucosidase inhibitory studies were also employed to evaluate the in vitro antihyperglycemic potential of the plant. The in vivo blood glucose lowering effect of the extracts was assessed using hypoglycemic activity and the oral glucose tolerance test in normal and in streptozotocin induced diabetic mice. When compared to the aqueous extract, the essential oil showed superior radical scavenging activity, particularly for •NO, as well as greater inhibitory potency against α-amylase and α-glucosidase (IC50 = 0.01 mg/ml and 0.11 mg/ml, respectively). Both tested samples showed a statistically significant antihyperglycemic effect. The aqueous extract at 600 mg/kg exerted maximum antihyperglycemic activity (44.14%), followed by the essential oil (30.82%). Body weight and glucose tolerance parameters were also improved by the samples both in normal and diabetic mice. The findings of this study support the hypothesis that aqueous extract and essential oil of T. serrulatus are promising therapeutic agents.

Phenolic Bioactives as Antiplatelet Aggregation Factors: The Pivotal Ingredients in Maintaining Cardiovascular Health.

Cardiovascular diseases (CVD) are one of the main causes of mortality in the world. The development of these diseases has a specific factor-alteration in blood platelet activation. It has been shown that phenolic compounds have antiplatelet aggregation abilities and a positive impact in the management of CVD, exerting prominent antioxidant, anti-inflammatory, antitumor, cardioprotective, antihyperglycemic, and antimicrobial effects. Thus, this review is intended to address the antiplatelet activity of phenolic compounds with special emphasis in preventing CVD, along with the mechanisms of action through which they are able to prevent and treat CVD. In vitro and in vivo studies have shown beneficial effects of phenolic compound-rich plant extracts and isolated compounds against CVD, despite that the scientific literature available on the antiplatelet aggregation ability of phenolic compounds in vivo is scarce. Thus, despite the current advances, further studies are needed to confirm the cardioprotective potential of phenolic compounds towards their use alone or in combination with conventional drugs for effective therapeutic interventions.

Health-Promoting Effects of Thymus Phenolic-Rich Extracts: Antioxidant, Anti-Inflammatory and Antitumoral Properties.

Thymus genus comprises numerous species that are particularly abundant in the West Mediterranean region. A growing body of evidence suggests that many of these species are a rich source of bioactive compounds, including phenolic compounds such as rosmarinic acid, salvianolic acids and luteolin glycosides, able to render them potential applications in a range of industrial fields. This review collects the most relevant studies focused on the antioxidant, anti-inflammatory and anti-cancer of phenolic-rich extracts from Thymus plants, highlighting correlations made by the authors with respect to the main phenolic players in such activities.

Hepatoprotection of Mentha aquatica L., Lavandula dentata L. and Leonurus cardiaca L.

The phenolic composition of hydroethanolic extracts of Mentha aquatica L., Lavandula dentata L. and Leonurus cardiaca L., obtained from plants grown under organic cultivation, was determined and their hepatoprotective effects were investigated in vitro. L. cardiaca extract was rich in phenylethenoid glycosides, especially lavandolifolioside (254 ± 36 µg/mg), whereas rosmarinic acid and eriodictyol-O-rutinoside were the major phenolic compounds of L. dentata and M. aquatica extracts, accounting for 68 ± 7 µg/mg and 145 ± 22 µg/mg, respectively. These differential phenolic components presumably account for their dissimilar antioxidant properties. While L. cardiaca extract showed moderate biological effects, M. aquatica extract displayed high antioxidant activity in chemical models, and that of L. dentata was effective in counteracting potassium dichromate-induced ROS generation in human hepatocarcinoma cells. Moreover, M. aquatica extract (50 µg/mL) and its mixture (50%/50%) with L. dentata extract displayed an effective cytoprotective effect.

The Health-Benefits and Phytochemical Profile of Salvia apiana and Salvia farinacea var. Victoria Blue Decoctions.

Salvia apiana and Salvia farinacea var. Victoria Blue decoctions were screened for diverse bioactivities, including the ability to counteract oxidative and inflammatory events, as well as to act as cytotoxic and antimicrobial agents. Both extracts showed good activities and that of S. apiana origin was particularly effective regarding the ability to prevent lipid peroxidation and to prevent nitric oxide (NO●) production in lipopolysaccharide (LPS)-activated murine macrophage RAW 264.7 cell line (EC50 = 50 µg/mL). Moreover, it displayed high cytotoxic capacity against hepatocellular carcinoma HepG2, cervical carcinoma HeLa, and breast carcinoma cells MCF-7, but comparatively low effects in porcine liver primary cells, which highlights its selectivity (GI50 = 41-60 µg/mL vs. 362 µg/mL, respectively). Further, it exhibited inhibitory and lethal potential against a panel of Gram-positive and Gram-negative bacteria. It is possible that the bioactive properties of the two Salvia extracts are associated to their phenolic components and, in the particular case of S. apiana, to its richness in phenolic terpenes, namely in rosmanol, hydroxycarnosic acid and a derivative of sageone, which were found in the extract.

Rubus ulmifolius Schott fruits: A detailed study of its nutritional, chemical and bioactive properties.

There is a growing interest in wild edible species that represent a source of several health-promoting compounds, providing a potential strategy to diversify and enrich the daily diet. The aim of the present work was to characterize the nutritional and chemical composition of Rubus ulmifolius Schott fruits. Furthermore, their antimicrobial activity, non-anthocyanin and anthocyanin phenolic profile were also determined. According to the obtained results, R. ulmifolius fruits exhibited a high concentration in carbohydrates and a low fat content, in comparison with the other nutrients and non-nutrients detected in this sample. The colour parameters demonstrated differences in a* and b* parameters after lyophilisation process. Glucose and fructose were the most abundant free sugars detected and quinic acid showed the highest content compared to the other five organic acids identified. The fatty acids profile revealed 25 compounds, being mostly represented by polyunsaturated fatty acids and evidencing linolenic and α-linolenic acid as the most abundant. All tocopherol isoforms were detected, revealing γ-tocopherol with highest amount. Cyanidin-3-O-glucoside, ellagic acid pentoside, ellagic acid glucuronide and sanguiin H-10 were the main phenolic compounds present, which could be related to the antimicrobial activity (MIC values ranging between 5 and 20 mg/mL) revealed by R. ulmifolius fruits. These results showed that this fruit is a good source of nutrients as also non-nutrient compounds, with human health benefits.

Is there a clinical application for tablet-based automated audiometry in children?

INTRODUCTION: Recent research supports the clinical use of automated audiometry for pediatric hearing screenings. However, very few studies have tested whether tablet-based automated audiometry can offer a valid alternative to traditional manual audiometry for estimation of hearing thresholds in children. This study examined the validity and efficiency of automated audiometry in school-aged children. METHODS: Hearing thresholds for 0.5, 1, 2, 4, 6, and 8 kHz were collected in 32 children ages 6-12 years using standard audiometry and tablet-based automated audiometry in a soundproof booth. Test administration time, test preference, and medical history were also collected. RESULTS: Results exhibited that the majority (67%) of threshold differences between automated and standard were within the clinically acceptable range (10 dB). The threshold difference between the two tests showed that automated audiometry thresholds were higher by 12 dB in 6-year-olds, 7 dB in 7- to 9-year-olds, and 3 dB in 10- to 12-year-olds. In addition, test administration times were similar, such that standard audiometry took an average of 12.3 min and automated audiometry took 11.9 min. CONCLUSIONS: These results support the use of tablet-based automated audiometry in children from ages 7-12 years. However, the results suggest that the clinical use of at least some types of tablet-based automated audiometry may not be feasible in children 6 years of age.

Is annual surveillance of all treated hypothyroid patients necessary?

BACKGROUND: Annual surveillance (with thyroid function testing) is widely recommended for the long-term follow-up of treated hypothyroid patients. It is based largely on consensus opinion and there is limited evidence to support the frequency of monitoring. The majority of patients in our hospital based thyroid register are on 18 monthly follow-up. METHODS: We carried out a retrospective analysis to see if there is evidence to support more frequent testing. We used a logistic regression model to assess whether any baseline characteristics could be applied to predict an abnormal test. RESULTS: We identified 2,125 patients with a minimum of 10 years follow-up (89% female, 65% autoimmune hypothyroidism, and mean age at registration 51 years). There were 2 groups: 1182 (56%) had been allocated to 18 monthly follow-up and the rest had annual surveillance. The groups were well matched at baseline. Overall, during follow-up the 12 monthly group had more abnormal tests requiring dose adjustment. However, on logistic regression analysis, people aged less than 60 years, individuals taking < 150 mug thyroxine per day and people on 18 monthly follow-up had less abnormal tests. CONCLUSION: 18 monthly surveillance may be adequate in the long term follow-up of hypothyroid patients less than 60 years of age on a stable thyroxine dose of 100-150 mug/day where there are robust follow-up mechanisms in place. Implementing this strategy has potential for cost saving.

The Impact of Age and Cognitive Reserve on Resting-State Brain Connectivity.

Cognitive reserve (CR) is a protective mechanism that supports sustained cognitive function following damage to the physical brain associated with age, injury, or disease. The goal of the research was to identify relationships between age, CR, and brain connectivity. A sample of 90 cognitively normal adults, ages 45-64 years, had their resting-state brain activity recorded with electroencephalography (EEG) and completed a series of memory and executive function assessments. CR was estimated using years of education and verbal IQ scores. Participants were divided into younger and older age groups and low- and high-CR groups. We observed greater left- than right-hemisphere coherence in younger participants, and greater right- than left-hemisphere coherence in older participants. In addition, greater coherence was observed under eyes-closed than eyes-open recording conditions for both low-CR and high-CR participants, with a more substantial difference between recording conditions in individuals high in CR regardless of age. Finally, younger participants low in CR exhibited greater mean coherence than younger participants high in CR, whereas the opposite pattern was observed in older participants, with greater coherence in older participants high in CR. Together, these findings suggest the possibility of a shift in the relationship between CR and brain connectivity during aging.