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Kava is a South Pacific plant-based medicine with anxiolytic properties, but little is known about the impact kava has on gene expression or whether gene expression can serve as a marker of kava response. This study aimed to determine whether kava treatment alters the expression of genes with physiological relevance to anxiety pathophysiology and whether the baseline expression of these physiologically relevant genes modifies the efficacy of kava treatment. In this post hoc analysis, we examined the expression of 48 genes relevant to the pathophysiology of anxiety collected from a double-blind randomized controlled trial that assessed the efficacy of kava treatment in generalized anxiety disorder. Peripheral blood gene expression was measured in 71 (34 kava, 37 placebo) adults at baseline and in 40 (19 kava, 21 placebo) after 8 weeks of treatment by reverse transcription polymerase chain reaction (PCR). Results revealed that kava decreased the expression of a subunit of the GABAA -rho receptor gene (GABRR2) and catechol-O-methyltransferase (COMT), a gene related to catecholamine metabolism. Kava efficacy was not found to be modified by baseline (pretreatment) expression of relevant genes. Although these results did not withstand statistical correction for multiple comparisons and require external validation, they support the notion that kava's mechanism of action includes interaction with GABAergic and catecholaminergic systems.
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Ansiolíticos , Kava , Humanos , Adulto , Catecol O-Metiltransferase/genética , Catecol O-Metiltransferase/uso terapêutico , Fitoterapia , Transtornos de Ansiedade/tratamento farmacológico , Transtornos de Ansiedade/genética , Ansiolíticos/farmacologia , Ansiolíticos/uso terapêutico , Ansiedade/tratamento farmacológico , Ansiedade/genética , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Expressão GênicaRESUMO
Flavonoids have shown anti-hypertensive and anti-atherosclerotic properties: the impact of habitual flavonoid intake on vascular function, central haemodynamics and arterial stiffness may be important. We investigated the relationship between habitual flavonoid consumption and measures of central blood pressure and arterial stiffness. We performed cross-sectional analysis of 381 non-smoking healthy older adults (mean age 66·0 (sd 4·1) years; BMI, 26·4 (sd 4·41) kg/m2; 41 % male) recruited as part of the Australian Research Council Longevity Intervention study. Flavonoid intake (i.e. flavonols, flavones, flavanones, anthocyanins, isoflavones, flavan-3-ol monomers, proanthocyanidins, theaflavins/thearubigins and total consumption) was estimated from FFQ using the US Department of Agriculture food composition databases. Measures of central haemodynamics and arterial stiffness included systolic blood pressure (cSBP), diastolic blood pressure (cDBP), mean arterial pressure (cMAP) and augmentation index (cAIx). After adjusting for demographic and lifestyle confounders, each sd/d higher intake of anthocyanins ((sd 44·3) mg/d) was associated with significantly lower cDBP (-1·56 mmHg, 95 % CI -2·65, -0·48) and cMAP (-1·62 mmHg, 95 % CI -2·82, -0·41). Similarly, each sd/d higher intake of flavanones ((sd 19·5) mg/d) was associated with ~1 % lower cAIx (-0·93 %, 95 % CI -1·77, -0·09). These associations remained signiï¬cant after additional adjustment for (1) a dietary quality score and (2) other major nutrients that may affect blood pressure or arterial stiffness (i.e. Na, K, Ca, Mg, n-3, total protein and fibre). This study suggests a possible benefit of dietary anthocyanin and flavanone intake on central haemodynamics and arterial stiffness; these findings require corroboration in further research.
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Background/study context: F2-Isoprostanes are putative markers of oxidative stress, one of the processes associated with biological senescence. Evidence exists for elevated F2-Isoprostanes in chronic conditions including psychiatric disorders. Few studies have examined the relationship between oxidative stress and mood in older healthy samples, to establish the influence on mental health. Given current aging demographics in many nations, management of brain and mental health is crucial for longevity, chronic disease management, and quality of life.Method: We investigated the relationship between F2-Isoprostanes, a marker for oxidative stress, and anxiety and mood in 262 healthy adults aged 60-75 years, using baseline data from the Australian Research Council Longevity Intervention (ARCLI; ANZCTR12611000487910), a 12-month nutraceutical intervention study.Results: Higher F2 levels significantly predicted increased Depression-dejection and Anger-hostility subscale scores from the Profile of Mood States (POMS). Fatigue-inertia subscale was predicted by increased Body Mass Index. Spielberger State-Trait Inventory (STAI) scores were significantly higher in females.Conclusion: While the primary outcome data did not find a definitive relationship between F2 and total mood or general anxiety levels, the sub-scale data adds weight toward growing literature that biological processes such as oxidative stress are in part related to mood. This is a modifiable risk factor contributing to physical and mental wellbeing that are crucial to healthy aging.
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F2-Isoprostanos , Qualidade de Vida , Idoso , Envelhecimento , Ansiedade/epidemiologia , Austrália , Feminino , Humanos , Estresse OxidativoRESUMO
OBJECTIVE: To investigate the effects of acute Panax quinquefolius (American ginseng) administration on steady state visually evoked potentials (SSVEPs) during completion of working memory and continuous performance tasks. METHODS: A randomised, double-blind, placebo controlled, balanced, cross-over trial was conducted in middle-aged volunteers aged between 40 and 60 years. Participants were administered 200 mg P. quinquefolius and placebo on two separate testing sessions. Six-h post-dose participants completed spatial working memory (SWM) and continuous performance (CP) tasks while SSVEP from a diffuse task-irrelevant 13 Hz flicker was recorded. RESULTS: During SWM retrieval, P. quinquefolius was associated with significantly reduced prefrontal SSVEP latency. There were no significant treatment effects on CP nor behavioural performance of either task. CONCLUSIONS: These findings provide preliminary evidence of increased recruitment of prefrontal brain regions during working memory processing following a single acute dose of P. quinquefolius.
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Cognição/efeitos dos fármacos , Potenciais Evocados Visuais/efeitos dos fármacos , Panax/química , Extratos Vegetais/farmacologia , Adulto , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Memória de Curto Prazo/efeitos dos fármacos , Pessoa de Meia-Idade , Testes NeuropsicológicosRESUMO
OBJECTIVE: Previous randomised, double-blind, placebo-controlled studies have shown that Kava (a South Pacific medicinal plant) reduced anxiety during short-term administration. The objective of this randomised, double-blind, placebo-controlled study was to perform a larger, longer-term trial assessing the efficacy and safety of Kava in the treatment of generalised anxiety disorder and to determine whether gamma-aminobutyric acid transporter (SLC6A1) single-nucleotide polymorphisms were moderators of response. METHODS: The trial was a phase III, multi-site, two-arm, 16-week, randomised, double-blind, placebo-controlled study investigating an aqueous extract of dried Kava root administered twice per day in tablet form (standardised to 120 mg of kavalactones twice/day) in 171 currently non-medicated anxious participants with diagnosed generalised anxiety disorder. The trial took place in Australia. RESULTS: An analysis of 171 participants revealed a non-significant difference in anxiety reduction between the Kava and placebo groups (a relative reduction favouring placebo of 1.37 points; p = 0.25). At the conclusion of the controlled phase, 17.4% of the Kava group were classified as remitted (Hamilton Anxiety Rating Scale score < 7) compared to 23.8% of the placebo group (p = 0.46). No SLC6A1 polymorphisms were associated with treatment response, while carriers of the rs2601126 T allele preferentially respond to placebo (p = 0.006). Kava was well tolerated aside from poorer memory (Kava = 36 vs placebo = 23; p = 0.044) and tremor/shakiness (Kava = 36 vs placebo = 23; p = 0.024) occurring more frequently in the Kava group. Liver function test abnormalities were significantly more frequent in the Kava group, although no participant met criteria for herb-induced hepatic injury. CONCLUSION: While research has generally supported Kava in non-clinical populations (potentially for more 'situational' anxiety as a short-term anxiolytic), this particular extract was not effective for diagnosed generalised anxiety disorder.
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Ansiolíticos/uso terapêutico , Transtornos de Ansiedade/tratamento farmacológico , Kava/química , Extratos Vegetais/uso terapêutico , Adulto , Ansiolíticos/efeitos adversos , Transtornos de Ansiedade/genética , Austrália , Método Duplo-Cego , Feminino , Proteínas da Membrana Plasmática de Transporte de GABA/genética , Humanos , Masculino , Pessoa de Meia-Idade , Fitoterapia , Extratos Vegetais/efeitos adversos , Raízes de Plantas/química , Polimorfismo de Nucleotídeo Único , Escalas de Graduação Psiquiátrica , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
The current study examined associations between blood lipid profiles and cognitive functioning using a healthy non-demented elderly sample. The sample comprised 196 healthy volunteers (male; 86: female 110) aged 60-75 years from the Australian Research Council Longevity Intervention (ARCLI) study cohort. Serum total cholesterol (T-C), low density lipoprotein cholesterol (LDL-c), high density lipoprotein cholesterol (HDL-c) and triglycerides (TGL) were collected, and participants completed the Swinburne University Computerized Cognitive Assessment Battery (SUCCAB). In line with prediction, higher levels of T-C and LDL-c were found to be associated with impaired speeds of response in tasks assessing recognition memory, working memory and inhibitory processing. However, contrary to prediction both TGL and HDL-c were found to be unrelated to cognitive functioning in the current sample. It is suggested that frontal lobe function may be differentially sensitive to the effects of T-C and LDL-c accumulation during the aging process. Future data collection as part of the larger ARCLI intervention study will provide important follow-up data regarding the ability of the baseline blood lipid data to predict subsequent cognitive change.
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Envelhecimento , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Cognição/fisiologia , Idoso , Austrália , Feminino , Humanos , Lipídeos , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangueRESUMO
Anxiety disorders are chronic and functionally disabling conditions with high psychological stress, characterised by cognitive symptoms of excessive worry and focus difficulties and physiological symptoms such as muscle tension and insomnia. Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter within the central nervous system and is a key target of pharmacotherapies in the treatment of anxiety. Although current pharmaceutical treatments are often efficacious, they may cause undesirable side effects including cognitive decrements and withdrawal symptoms. Plant-based "phytomedicines" may provide novel treatment options, to act as an adjunctive or alternative to existing anxiolytic medications. As such, we conducted a systematic review to assess the current body of literature on anxiolytic phytomedicines and/or phytoconstituents. An open-ended search to 5 July 2017 was conducted using MEDLINE (PubMed), Scopus, and Cochrane library online databases and performed in a stepped format from preclinical to clinical investigations. Eligible studies must have had (a) in vitro evidence of GABA-modulating activity, (b) animal studies using anxiety models to test an anxiolytic effect, and (c) human clinical trials. Ten phytomedicines were identified as having preclinical investigations showing interaction with the GABA system, in addition to human clinical trials: kava, valerian, pennywort, hops, chamomile, Ginkgo biloba, passionflower, ashwagandha, skullcap, and lemon balm. Collectively, the literature reveals preclinical and clinical evidence for various phytomedicines modulating GABA-pathways, with comparative anxiolytic effect to the current array of pharmaceuticals, along with good safety and tolerability profiles.
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Transtornos de Ansiedade/tratamento farmacológico , Agonistas de Receptores de GABA-A/uso terapêutico , Fitoterapia/métodos , Animais , Agonistas de Receptores de GABA-A/farmacologia , HumanosRESUMO
OBJECTIVE: A ginsenoside-rich extract of American ginseng (Panax quinquefolius L.), Cereboost(TM), was previously shown to improve working memory and mood in healthy young individuals. The present study represented a partial replication investigating whether these effects extended to healthy middle-aged individuals. METHODS: Fifty-two healthy volunteers (40-60 years old, mean age 51.63) received 200 mg of P. quinquefolius or a matching placebo according to a double-blind, placebo-controlled, balanced, crossover design. The Cognitive Drug Research battery and the Computerised Mental Performance Assessment System were used to evaluate cognitive performance at baseline then 1, 3 and 6 h following treatment. Blood glucose and mood were co-monitored. RESULTS: Compared with placebo, P. quinquefolius improved cognitive performance on 'Working Memory' factor at 3 h. Similar effects were observed in one of the two tasks making up this factor, spatial working memory. There were no significant effects on mood or blood glucose levels. CONCLUSIONS: These data confirm that P. quinquefolius can acutely benefit working memory and extend the age range of this effect to middle-aged individuals. These changes are unlikely to be underpinned by modulation of blood glucose in this population.
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Cognição/efeitos dos fármacos , Memória de Curto Prazo/efeitos dos fármacos , Panax/química , Extratos Vegetais/uso terapêutico , Adulto , Análise de Variância , Glicemia , Pressão Sanguínea/efeitos dos fármacos , Estudos Cross-Over , Método Duplo-Cego , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Entrevista Psiquiátrica Padronizada , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tempo de Reação/efeitos dos fármacos , Inquéritos e Questionários , Resultado do TratamentoRESUMO
BACKGROUND: This study assessed the effects of two doses of glucose and a caffeine-glucose combination on mood and performance of an ecologically valid, computerised multi-tasking platform. MATERIALS AND METHODS: Following a double-blind, placebo-controlled, randomised, parallel-groups design, 150 healthy adults (mean age 34.78 years) consumed drinks containing placebo, 25 g glucose, 60 g glucose or 60 g glucose with 40 mg caffeine. They completed a multi-tasking framework at baseline and then 30 min following drink consumption with mood assessments immediately before and after the multi-tasking framework. Blood glucose and salivary caffeine were co-monitored. RESULTS: The caffeine-glucose group had significantly better total multi-tasking scores than the placebo or 60 g glucose groups and were significantly faster at mental arithmetic tasks than either glucose drink group. There were no significant treatment effects on mood. Caffeine and glucose levels confirmed compliance with overnight abstinence/fasting, respectively, and followed the predicted post-drink patterns. CONCLUSION: These data suggest that co-administration of glucose and caffeine allows greater allocation of attentional resources than placebo or glucose alone. At present, we cannot rule out the possibility that the effects are due to caffeine alone Future studies should aim at disentangling caffeine and glucose effects.
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Afeto/efeitos dos fármacos , Cafeína/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Cognição/efeitos dos fármacos , Função Executiva/efeitos dos fármacos , Glucose/administração & dosagem , Adolescente , Adulto , Bebidas , Glicemia , Cafeína/análise , Estimulantes do Sistema Nervoso Central/análise , Método Duplo-Cego , Feminino , Humanos , Masculino , Conceitos Matemáticos , Pessoa de Meia-Idade , Testes Neuropsicológicos , Saliva/química , Adulto JovemRESUMO
Inflammation is repressed by interleukin 10 (IL10), a potent anti-inflammatory cytokine, and unchecked inflammation can have detrimental effects on cognition. In healthy older adults enrolled in the Australian Research Council Longevity Intervention (ARCLI) cohort we explored whether a known functional single nucleotide polymorphism (SNP) in the promoter region of IL10, -1082 G/A (rs1800896), was associated with reaction times on computerized cognitive testing that included elements of processing speed (i.e., reaction time). Participants were aged 60-75 years (240 females, 158 males), free of dementia and psychiatric disorders, and provide a blood sample. Processing speed was measured using the Swinburne University Computerized Cognitive Assessment Battery (SUCCAB), which includes measures of reaction time (in milliseconds, ms) on six tasks. Blood-derived DNA was genotyped for the IL10 rs1800896 SNP and presence of the APOE E4 allele. General linear models for each SUCCAB subtest were fitted, with age, sex, education (years), APOE E4 carrier status, and IL10 genotype as independent variables. Carriers of the IL10 AA genotype had significantly slower reaction times on multiple tests compared to carriers of the minor allele (AG, GG) and lower IL10 serum levels. Although IL10 SNPs have not been detected in Alzheimer's disease genome-wide associated studies, these results support further exploration of IL10 mechanisms as a possible resilience factor.
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Interleucina-10 , Velocidade de Processamento , Masculino , Feminino , Humanos , Idoso , Interleucina-10/genética , Vida Independente , Austrália , Polimorfismo de Nucleotídeo Único/genética , Genótipo , Regiões Promotoras Genéticas/genética , Inflamação/genética , Apolipoproteínas E/genética , Predisposição Genética para DoençaRESUMO
Kava (Piper methysticum) is a plant-based medicine, which has been previously shown to reduce anxiety. To date, however, no placebo-controlled trial assessing kava in the treatment of generalized anxiety disorder (GAD) has been completed. A total of 75 participants with GAD and no comorbid mood disorder were enrolled in a 6-week double-blind trial of an aqueous extract of kava (120/240 mg of kavalactones per day depending on response) versus placebo. γ-Aminobutyric acid (GABA) and noradrenaline transporter polymorphisms were also analyzed as potential pharmacogenetic markers of response. Reduction in anxiety was measured using the Hamilton Anxiety Rating Scale (HAMA) as the primary outcome. Intention-to-treat analysis was performed on 58 participants who met inclusion criteria after an initial 1 week placebo run-in phase. Results revealed a significant reduction in anxiety for the kava group compared with the placebo group with a moderate effect size (P = 0.046, Cohen d = 0.62). Among participants with moderate to severe Diagnostic and Statistical Manual of Mental Disorders-diagnosed GAD, this effect was larger (P = 0.02; d = 0.82). At conclusion of the controlled phase, 26% of the kava group were classified as remitted (HAMA ≤ 7) compared with 6% of the placebo group (P = 0.04). Within the kava group, GABA transporter polymorphisms rs2601126 (P = 0.021) and rs2697153 (P = 0.046) were associated with HAMA reduction. Kava was well tolerated, and aside from more headaches reported in the kava group (P = 0.05), no other significant differences between groups occurred for any other adverse effects, nor for liver function tests. Standardized kava may be a moderately effective short-term option for the treatment of GAD. Furthermore, specific GABA transporter polymorphisms appear to potentially modify anxiolytic response to kava.
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Ansiolíticos/uso terapêutico , Transtornos de Ansiedade/tratamento farmacológico , Kava , Extratos Vegetais/uso terapêutico , Adulto , Ansiolíticos/efeitos adversos , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/genética , Transtornos de Ansiedade/psicologia , Distribuição de Qui-Quadrado , Método Duplo-Cego , Feminino , Proteínas da Membrana Plasmática de Transporte de GABA/genética , Humanos , Masculino , Farmacogenética , Fitoterapia , Extratos Vegetais/efeitos adversos , Plantas Medicinais , Polimorfismo Genético , Escalas de Graduação Psiquiátrica , Fatores de Tempo , Resultado do Tratamento , Vitória , Adulto JovemRESUMO
Bacopa monniera (EBm), an Indian aquatic herb, has been used in traditional Ayurvedic medicine for centuries for indications related to memory and inflammation. More recently specific extracts of EBm have emerged that have been subjected to rigorous in vitro, animal and now human clinical trials. In this paper we discuss some of these studies with special reference to mechanisms and efficacy of a special extract of Bacopa (CDRI08). Studies using this extract indicate that CDRI08 has several modes of action on the human brain. Promising indications for use in humans include improving cognition in the elderly and in patients with neurodegenerative disorders.
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Bacopa , Nootrópicos/farmacologia , Extratos Vegetais/farmacologia , Animais , Austrália , Cognição/efeitos dos fármacos , Humanos , UniversidadesRESUMO
INTRODUCTION: Early identification and management of physical and mental illness is vital to maintain quality of life as we age. Markers of peripheral inflammation and liver function show elevations with aging, and are also associated with depression symptoms, suggesting a similar pattern in both aging and clinical groups. METHODS: The current study examined the relationship between such markers and measures of depression/negative mood in 284 healthy older adults using data from the Australian Research Council Longevity Intervention (ARCLI). Baseline data in adults aged 60-75 included mood symptoms via Profile of Mood States and Beck Depression Inventory II, and peripheral inflammatory (TNF-α, IL-6, hs-CRP) and liver markers (GGT, ALT, AST, AST:ALT ratio) derived from blood samples. RESULTS: The inflammation and liver enzyme relationship significantly predicted mood symptoms scores. Results showed that a significant relationship between C-reactive protein (CRP) and negative mood scores on Total Mood Disturbance and four of the six subscales (all p < .01) was dependent upon higher levels of gamma-glutamyl transferase (GGT). DISCUSSION: Higher levels of normal-range liver metabolic and peripheral inflammatory markers are observed with negative mood in a healthy older sample experiencing the biological impact of aging, but in the absence of clinical depression symptoms, suggesting a possible role of oxidative stress or other biological mechanisms occurring with aging in depression etiology. Lifestyle interventions are discussed.
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Depressão , Qualidade de Vida , Humanos , Idoso , Austrália , Fígado/metabolismo , Biomarcadores , Inflamação/metabolismo , Proteína C-Reativa/análise , gama-GlutamiltransferaseRESUMO
Generalised Anxiety Disorder (GAD) is a prevalent, chronic mental health disorder. The measurement of regional brain gamma-aminobutyric acid (GABA) offers insight into its role in anxiety and is a potential biomarker for treatment response. Research literature suggests Piper methysticum (Kava) is efficacious as an anxiety treatment, but no study has assessed its effects on central GABA levels. This study investigated dorsal anterior cingulate (dACC) GABA levels in 37 adult participants with GAD. GABA was measured using proton magnetic resonance spectroscopy (1H-MRS) at baseline and following an eight-week administration of Kava (standardised to 120 mg kavalactones twice daily) (n = 20) or placebo (n = 17). This study was part of the Kava for the Treatment of GAD (KGAD; ClinicalTrials.gov: NCT02219880), a 16-week intervention study. Compared with the placebo group, the Kava group had a significant reduction in dACC GABA (p = 0.049) at eight weeks. Baseline anxiety scores on the HAM-A were positively correlated with GABA levels but were not significantly related to treatment. Central GABA reductions following Kava treatment may signal an inhibitory effect, which, if considered efficacious, suggests that GABA levels are modulated by Kava, independent of reported anxiety symptoms. dACC GABA patterns suggest a functional role of higher levels in clinical anxiety but warrants further research for symptom benefit. Findings suggest that dACC GABA levels previously un-examined in GAD could serve as a biomarker for diagnosis and treatment response.
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Ansiolíticos , Kava , Adulto , Humanos , Transtornos de Ansiedade/tratamento farmacológico , Transtornos de Ansiedade/psicologia , Biomarcadores , Giro do Cíngulo/diagnóstico por imagem , Kava/química , Neuroimagem , Fitoterapia , Extratos Vegetais/farmacologiaRESUMO
Several cognitive domains show decline with increasing age, which is associated with poorer work performance and reduced quality of life. As many nations show a rise in the number of citizens aged over 60 years, the study of the mechanisms underlying age-related cognitive functional reductions, such as inflammation, is important. Inflammaging has been implicated in progressive minor decline through to dementia typologies, with peripheral cytokine patterns investigated for their potential role in cognitive function. Assessing the relationship between these markers and cognitive performance could elucidate mechanisms with aging beyond neuropathologies. The research literature suggests peripheral cytokines/chemokines such as interleukin-6 and c-reactive protein are associated with cognitive processing. In this systematic review, we examine the evidence for a relationship between a range of peripheral inflammatory markers and domains of cognitive function in healthy older adults. To do this, a literature search was conducted using the following databases: SCOPUS, PubMed, Web of Science, and PsycINFO. Risk of bias was assessed using the Cochrane Risk of Bias Tool. Twenty-nine studies met our inclusion criteria. Although a wide range of systemic inflammatory biomarkers were examined, IL-6 and CRP were the most studied. The evidence suggests an inverse inflammatory biomarker-cognitive function relationship whereby elevations in most cytokines were associated with poorer performance across cognitive domains. The findings contribute to our understanding of peripheral inflammation and domains of cognitive function, offering insight into inflammaging processes.
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Disfunção Cognitiva , Qualidade de Vida , Idoso , Biomarcadores , Proteína C-Reativa , Cognição , Citocinas , Humanos , Inflamação , Interleucina-6 , Pessoa de Meia-IdadeRESUMO
The increasing proportion of older citizens in our society reflects a need to better understand age-related biological underpinnings of mood, as depression in older age may be under-diagnosed. Pre-clinical and human studies evidence a relationship between oxidative stress (OS) biomarkers in depression symptoms, and an influence of biological factors such as Body Mass Index (BMI), but focus has been clinical or younger samples, and less is known about patterns in healthy older adults. We investigated these associations with data derived from the Australian Research Council Longevity Study (ARCLI; ANZCTR12611000487910), in 568 healthy adults aged 60-75 years using F2-Isoprostanes plasma levels, and controlling for demographic factors, in assessing mood via the Beck Depression Inventory-II, Chalder Fatigue Scale, and General Health Questionnaire 12. Elevated F2-Isoprostanes contributed to depressed mood on the BDI-II and reduced general health on the GHQ-12. BMI was positively associated with Chalder Fatigue scores, yet better ratings on the GHQ-12. Females had significantly higher F2-Isoprostanes than males. The results suggest that in otherwise healthy older adults, mood and mental health are reduced with increases in oxidative stress markers, exhibiting similar patterns observed in clinical groups. Sex as a factor should be considered when assessing OS levels in systemic pathologies. BMI as a modifiable risk factor for maintenance of mental health, and OS modification through nutrient supplementation, are discussed. The findings contribute to understanding oxidative stress marker patterns in healthy older adults and their potential role in mood symptoms and mental health.
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Ageing is associated with changes in biological processes, including reductions in cognitive functions and gut microbiome diversity. However, not much is known about the relationship between cognition and the microbiome with increasing age. Therefore, we examined the relationship between the gut microbiome and cognition in 69 healthy participants aged 60-75 years. The gut microbiome was analysed with the 16S rRNA sequencing method. The cognitive assessment included the Cognitive Drug Research computerised assessment battery, which produced five cognitive factors corresponding to 'Quality of Episodic Secondary Memory', 'Quality of Working Memory', 'Continuity of Attention, 'Speed of Memory' and 'Power of Concentration'. Multiple linear regression showed that the bacterial family Carnobacteriaceae explained 9% of the variance in predicting Quality of Episodic Secondary Memory. Alcaligenaceae and Clostridiaceae explained 15% of the variance in predicting Quality of Working Memory; Bacteroidaceae, Barnesiellaceae, Rikenellaceae and Gemellaceae explained 11% of the variance in Power of Concentration. The present study provides specific evidence of a relationship between specific families of bacteria and different domains of cognition.
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Envelhecimento/fisiologia , Cognição/fisiologia , Microbioma Gastrointestinal/fisiologia , Idoso , Atenção , Austrália , Feminino , Voluntários Saudáveis , Humanos , Modelos Lineares , Masculino , Memória Episódica , Memória de Curto Prazo , Pessoa de Meia-Idade , RNA Ribossômico 16S/genéticaRESUMO
BACKGROUND: The applicability of clinical trial findings (efficacy) to the routine care setting (effectiveness) may be limited because of study eligibility criteria and volunteer bias. Although well-chronicled in many conditions, the efficacy versus effectiveness of antiretroviral therapy (ART) remains understudied. METHODS: A retrospective study of the University of Alabama at Birmingham 1917 Clinic Cohort evaluated ART-naive patients who started ART from 1 January 2000 through 31 December 2006. Patients received ART through clinical trials or routine care. Multivariable logistic and linear regression models were fit to evaluate factors associated with virological failure (virological failure was defined as a viral load >50 copies/mL) and change from baseline CD4+ cell count 6 and 12 months after ART initiation. Sensitivity analyses evaluated the impact of missing data on outcomes. RESULTS: Among 570 patients starting ART during the study period, 121 (21%) enrolled in clinical trials, and 449 (79%) received ART via routine care. ART receipt through routine care was not associated with viral failure at either 6 months (odds ratio [OR], 1.00; 95% confidence interval [CI], 0.54-1.86) or 12 months (OR, 1.56; 95% CI, 0.80-3.05) in primary analyses. No statistically significant differences in CD4+ cell count responses at 6 and 12 months were observed. CONCLUSIONS: Although marked differences in efficacy versus effectiveness have been observed in the therapeutic outcomes of other conditions, our analyses found no evidence of such divergence among our patients who initiated antiretroviral therapy for human immunodeficiency virus infection.
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Antirretrovirais/administração & dosagem , Infecções por HIV/tratamento farmacológico , Adulto , Contagem de Linfócito CD4 , Feminino , HIV/isolamento & purificação , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , RNA Viral/sangue , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e Especificidade , Resultado do Tratamento , Carga ViralRESUMO
OBJECTIVE: Examine subjective sleep quality and inflammation among healthy older adults participating in the Australian Research Council Longevity Intervention (ARCLI). METHODS: Data was taken from a sub-set of 232 participants aged between 60-70 years (M = 65.88 ± SD 4.08 years) who participated in the baseline assessment phase of the Australian Research Council Longevity Intervention (ARCLI) study. Subjective sleep was assessed via the Leeds Sleep Evaluation Questionnaire (LSEQ). Inflammatory markers (TNF-α, IL-1ß, IL-6, IL-10, IL-2, IFN-γ, IL-4, hs-CRP) were derived from whole blood. Correlation and multiple regression analyses were used to examine associations between each of the four sleep outcome variables and inflammatory outcomes, examined as a group and following gender stratification. RESULTS: Difficulties getting to sleep were independently associated with higher IL-2 [F(1,156) = 4.62, adjusted R2 = 0.02, p = 0.03] and IL-1ß [F(1,141) = 8.52, adjusted R2 = 0.05, p = 0.004] (whole group). Difficulties getting to sleep were associated with greater IL-1ß [males: F(1,58) = 7.36, adjusted R2 = 0.097 p = 0.009; females: F (1,81) = 4.25, R2 = 0.038, p = 0.04], and negatively associated with hs-CRP (women) [F (1,129) = 4.71, R2 = 0.028, p = 0.032]. DISCUSSION: Subjective sleep-onset difficulties are associated with systemic inflammation.
Assuntos
Proteína C-Reativa/análise , Autoavaliação Diagnóstica , Interleucinas/sangue , Privação do Sono , Síndrome de Resposta Inflamatória Sistêmica , Idoso , Austrália/epidemiologia , Correlação de Dados , Estudos Transversais , Feminino , Humanos , Masculino , Fatores de Risco , Autorrelato/estatística & dados numéricos , Privação do Sono/diagnóstico , Privação do Sono/imunologia , Privação do Sono/psicologia , Higiene do Sono/fisiologia , Síndrome de Resposta Inflamatória Sistêmica/sangue , Síndrome de Resposta Inflamatória Sistêmica/diagnósticoRESUMO
RATIONALE: Dysregulation of the one carbon cycle is documented in depression. Thereby, S-adenosylmethionine (SAMe), a one-carbon cycle nutraceutical compound with a favourable side effect profile, has a theoretical rationale for efficacy. However, further controlled studies are required to confirm SAMe's efficacy. OBJECTIVES: To test the efficacy of SAMe versus placebo in unmedicated DSM-5 diagnosed (major depressive disorder) (MDD) patients with mild-to-moderate levels of depressive symptoms. METHODS: We conducted an 8-week, double-blind, randomised controlled trial testing 800 mg/day of SAMe monotherapy versus placebo in 49 patients with MDD (Montgomery-Åsberg Depression Rating Scale [MADRS] score 14-25) who were not currently taking antidepressants. One-carbon cycle biomarkers, brain-derived neurotropic factor (BDNF), and relevant single nucleotide polymorphisms (SNPs) were analysed as potential treatment moderators. RESULTS: A clinically relevant differential reduction from baseline to week 8 of 3.76 points occurred on the primary outcome (MADRS) in favour of SAMe. This however was not significant (p = 0.13) on an adjusted linear mixed model, notwithstanding a medium to large effect size of 0.72. A high placebo response rate of 53% occurred (> 50% reduction on MADRS). Exploratory analyses showed that SAMe was however effective in reducing depression amongst participants with milder depression severity (MADRS ≤ 22, p = 0.045). Response was not moderated by BDNF, SNPs, or one-carbon cycle biomarkers, although increased folate concentrations were correlated with improved symptoms in the SAMe group (r = - 0.57, p = 0.026). The treatment was safe and well tolerated. CONCLUSIONS: Although a differential reduction in depression symptoms between groups was observed in favour of SAMe, the results of this pilot study were not statistically significant. TRIAL REGISTRATION: ANZCTR-Australian New Zealand Clinical Trials Registry; No.: ACTRN12613001299796; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=364900.