The Australian Research Council Longevity Intervention (ARCLI) study protocol (ANZCTR12611000487910) addendum: neuroimaging and gut microbiota protocol.

BACKGROUND: The Australian Research Council Longevity Intervention (ARCLI) was designed to investigate the effects of two active supplements, Pycnogenol and Bacopa monnieri (CDRI08) on cognitive performance in a cohort of elderly participants. An additional antioxidant supplement has been included into the trial. A neuroimaging component has also been added to the ARCLI study to investigate the neurochemical biomarkers of oxidative stress in vivo, as well as structural and functional changes associated with ageing and oxidative stress. Faecal biomarkers of gut microflora will also be analysed to investigate if gut microbiota are associated with domains of cognition (e.g., attention, processing speed, memory), mood or other ARCLI outcome variables. The aim of this paper is to update the published methods of the ARCLI clinical trial before it is completed, and data analysis commences. METHODS: ARCLI is a randomised, placebo controlled, double-blind, now 4-arm clinical trial including neuroimaging and gut microflora sub-studies. Along with the demographic, haematological, mood, cardiovascular and cognitive assessments described in the initial protocol, 80 eligible participants from the overall study pool of ~ 400 will be recruited into the neuroimaging study and undergo scans at baseline, 3 months and 12 months. Proton magnetic resonance spectroscopy, resting state functional connectivity and arterial spin labelled perfusion sequences are neuroimaging techniques included for each MRI visit in the study. Similarly, approximately 300 participants from the main study pool will be recruited to provide faecal samples at baseline, 3 months and 12 months so that the gut microbiome can be studied. DISCUSSION: ARCLI is 12-month intervention study, currently underway with a group of older adults, investigating a range of outcomes and their association with ageing. The additional measurements in the ARCLI trial will further the understanding of the underlying mechanisms associated with healthy ageing and may provide insights into novel preventative therapeutic strategies for maintaining cognitive and brain health into old age. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12611000487970 .

Increases in total cholesterol and low density lipoprotein associated with decreased cognitive performance in healthy elderly adults.

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.

Evaluating an online self-distancing intervention to promote emotional regulation and posttraumatic growth during the COVID-19 pandemic.

OBJECTIVES: Three online studies were conducted to elucidate the role of emotional regulation (ER) in posttraumatic growth (PTG), evaluate the ability of an online self-distancing intervention to achieve ER, and test whether increasing the use of ER strategies promotes PTG. DESIGN: Cross-sectional (Study 1) and longitudinal randomized controlled trials (RCT) (Studies 2 and 3). METHOD: In Study 1, 626 adults completed measures of ER, PTG, and psychosocial functioning during the COVID-19 pandemic. In Study 2, 149 adults participated in a five-week RCT comparing self-immersed, spatially self-distanced, and temporally self-distanced reflection in their ability to regulate negative affect. In Study 3, 117 adults replicated the RCT of Study 2 and completed the measures from Study 1 a week pre- and post-intervention. RESULTS: Path analyses confirmed that ER strategies were relevant to COVID-19-related PTG. MANOVAs revealed that self-distancing was effective in regulating state negative affect. However, ANOVAs suggest that this was not due to increased use of ER strategies and did not improve PTG or psychosocial functioning. CONCLUSIONS: These findings support further research into the relevance of ER to PTG, and provide a foundation to understand PTG and develop PTG-promoting interventions within a broader stress-coping framework.

The Relationship between F2-Isoprostanes Plasma Levels and Depression Symptoms in Healthy Older Adults.

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.

The Relationship between Gut Microbiome and Cognition in Older Australians.

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.

Higher plasma levels of F2-isoprostanes are associated with slower psychomotor speed in healthy older adults.

Oxidative stress has been identified as a process which is detrimental to brain health, and associated with age-related cognitive declines. Few studies to-date have examined the relationship between in vivo oxidative stress biomarkers and cognitive performance within healthy elderly populations. The current study investigated the relationship between reaction time and oxidative stress, as measured by blood plasma concentrations of F2-isoprostanes using a sample of 251 healthy, non-demented, elderly volunteers (Male; 111: Female 140) aged 60-75 years from the Australian Research Council Longevity Intervention (ARCLI) study cohort. A Jensen Box was used in conjunction with the Hick paradigm in order to differentiate simple from choice reaction time (two, four and eight-choice conditions) as well as movement (MT) and decision times (DT). MT, but not DT, was found to be significantly slower for participants in the high F2-isoprostane group compared to the low F2-isoprostane group, across all stimulus choices. F2-isoprostanes, age and Wechsler Abbreviated Scale of Intelligence (WASI) full scale intelligence quotient (IQ) were found to be significant predictors of average MT in the sample as a whole. These findings provide preliminary evidence to suggest that higher levels of oxidative stress may be associated with impaired psychomotor speed in the healthy elderly population.

Impaired verbal episodic memory in healthy older adults is marked by increased F2-Isoprostanes.

Age-associated cognitive decline amongst otherwise healthy older individuals is a multifaceted characteristic of ageing. The role of oxidative stress biomarkers has been increasingly examined in the context of pathological aging conditions that affect cognition. Plasma F2-Isoprostane levels are a reliable index of systemic oxidative stress (specifically lipid peroxidation) and are elevated in dementia patients. Less is known about their role in healthy cognitive ageing. This study evaluated the relationship between F2-Isoprostanes and cognitive functioning in a cohort of 211 healthy elderly adults (60-75 years: Male; 88, Female; 123). Cognitive assessment included the Cognitive Drug Research (CDR) computerised assessment battery, which produces five validated factor scores (corresponding to 'Quality of Episodic Memory', 'Speed of Memory', Quality of Working Memory', Power of Attention' and 'Continuity of Attention'). Participants with higher F2-Isoprostane levels had significantly lower Quality of Episodic Memory scores (suggesting inferior abilities in retaining and retrieving verbal information in episodic memory). This is, to our knowledge, the first report of compromised verbal episodic memory in healthy ageing humans being linked to increased levels of F2-Isoprostanes. These results have relevance for interventions aimed at improving cognitive performance in the healthy elderly.