A Mediterranean Diet and Walking Intervention to Reduce Cognitive Decline and Dementia Risk in Independently Living Older Australians: The MedWalk Randomized Controlled Trial Experimental Protocol, Including COVID-19 Related Modifications and Baseline Characteristics.

BACKGROUND: Several clinical trials have examined diet and physical activity lifestyle changes as mitigation strategies for risk factors linked to cognitive decline and dementias such as Alzheimer's disease. However, the ability to modify these behaviors longer term, to impact cognitive health has remained elusive. OBJECTIVE: The MedWalk trial's primary aim is to investigate whether longer-term adherence to a Mediterranean-style diet and regular walking, delivered through motivational interviewing and cognitive-behavioral therapy (MI-CBT), can reduce age-associated cognitive decline and other dementia risk factors in older, independently living individuals without cognitive impairment. METHODS: MedWalk, a one-year cluster-randomized controlled trial across two Australian states, recruited 60-90-year-old people from independent living retirement villages and the wider community. Participants were assigned to either the MedWalk intervention or a control group (maintaining their usual diet and physical activity). The primary outcome is 12-month change in visual memory and learning assessed from errors on the Paired Associates Learning Task of the Cambridge Neuropsychological Test Automated Battery. Secondary outcomes include cognition, mood, cardiovascular function, biomarkers related to nutrient status and cognitive decline, MI-CBT effectiveness, Mediterranean diet adherence, physical activity, quality of life, cost-effectiveness, and health economic evaluation.Progress and Discussion:Although COVID-19 impacts over two years necessitated a reduced timeline and sample size, MedWalk retains sufficient power to address its aims and hypotheses. Baseline testing has been completed with 157 participants, who will be followed over 12 months. If successful, MedWalk will inform interventions that could substantially reduce dementia incidence and ameliorate cognitive decline in the community. TRIAL REGISTRATION: Registered on the Australia New Zealand Clinical Trials Registry ANZCTR 12620000978965 (https://www.anzctr.org.au).

Findings of a Pilot Study Investigating the Effects of Mediterranean Diet and Aerobic Exercise on Cognition in Cognitively Healthy Older People Living Independently within Aged-Care Facilities: The Lifestyle Intervention in Independent Living Aged Care (LIILAC) Study.

BACKGROUND: Cognitive decline and Alzheimer disease are more prevalent in our aging population. Modifiable risk factors, such as diet and sedentary lifestyle, have been proposed as key to potentially ameliorating cognitive decline. Both exercise and Mediterranean diet (MedDiet) have been linked to reduced levels of cardiovascular disease and other comorbidities. Higher levels of exercise and MedDiet adherence may prove to be cognitively protective, both individually and synergistically. OBJECTIVES: The aim was to investigate the effect of a 6-mo program of MedDiet, exercise, and a combination of both, on cognition, mood, and general health in older persons living independently in aged-care communities. METHODS: The Lifestyle Intervention in Independent Living Aged Care (LIILAC) Study (ACTRN12614001133628) involved 102 participants, aged 60-90 y, who were randomly assigned to 1 of 4 intervention groups. Change in overall memory performance was assessed as the primary outcome. Additionally, changes in cognitive task performance, as well as mood, wellness, cardiovascular function, and blood biomarkers, were investigated. RESULTS: While there was no significant change in overall memory performance, there was a significant improvement in spatial working memory performance in the combined exercise and diet group, relative to controls. This combined intervention group also showed an overall improvement in their emotional state, as assessed by the Depression Anxiety Stress Scale, as did the exercise-only group. CONCLUSIONS: This research indicates that diet and exercise programs have the potential to improve aspects of cognition and mood in an aging population. However, given the lower than optimal sample size and lack of resources to reinforce the interventions during the trial, further larger randomized controlled trials are required to substantiate whether the introduction of diet and exercise programs into independent-living facilities is a viable method to preserve cognitive health in older people. This trial was registered at www.ANZCTR.org.au ACTRN 12614001133628 (LIILAC Study).

Modelling Modifiable Predictors of Age-Related Cognitive Decline: Exercise, Aortic Stiffness, and the Importance of Physical Fitness.

BACKGROUND: Previous modelling found that fitness and aortic stiffness both independently predicted spatial working memory (SWM) performance in older people. There is also evidence that greater engagement in moderate intensity exercise contributes to better cognitive performance, potentially working through improving fitness and aortic stiffness. OBJECTIVE: To investigate the effect of exercise on the previously established relationships between fitness, aortic stiffness, and SWM, and whether these associations differ between older adults of higher and lower fitness. METHODS: One hundred and two residents of independent living facilities, aged 60-90 (M = 77.5, SD = 6.9) participated in the study. Measures included computerized cognitive assessment, the Six-Minute Walk fitness test, the CHAMPS physical activity questionnaire, and aortic pulse wave analysis. Multiple structural equation models were used to test hypotheses. RESULTS: Overall, exercise levels had a small additional effect in predicting SWM, working exclusively through fitness, although this was only true for those of lower than average fitness. Additionally, it was found that while fitness was the most important factor in predicting SWM in those of lower fitness, aortic stiffness was the strongest predictor in those of higher fitness. CONCLUSION: Fitness and aortic stiffness are strong predictors of cognition in older people, and greater engagement in exercise predicted better cognition in those who were of lower fitness. Fitter older people may benefit more from interventions which target aortic stiffness in order to preserve cognitive performance as they age, while those who are less fit may benefit most from improving fitness first, including through increased physical activity.

Physical Fitness and Aortic Stiffness Explain the Reduced Cognitive Performance Associated with Increasing Age in Older People.

BACKGROUND: Greater physical fitness is associated with reduced rates of cognitive decline in older people; however, the mechanisms by which this occurs are still unclear. One potential mechanism is aortic stiffness, with increased stiffness resulting in higher pulsatile pressures reaching the brain and possibly causing progressive micro-damage. There is limited evidence that those who regularly exercise may have lower aortic stiffness. OBJECTIVE: To investigate whether greater fitness and lower aortic stiffness predict better cognitive performance in older people and, if so, whether aortic stiffness mediates the relationship between fitness and cognition. METHODS: Residents of independent living facilities, aged 60-90, participated in the study (N = 102). Primary measures included a computerized cognitive assessment battery, pulse wave velocity analysis to measure aortic stiffness, and the Six-Minute Walk test to assess fitness. Based on hierarchical regression analyses, structural equation modelling was used to test the mediation hypothesis. RESULTS: Both fitness and aortic stiffness independently predicted Spatial Working Memory (SWM) performance, however no mediating relationship was found. Additionally, the derived structural equation model shows that, in conjunction with BMI and sex, fitness and aortic stiffness explain 33% of the overall variation in SWM, with age no longer directly predicting any variation. CONCLUSIONS: Greater fitness and lower aortic stiffness both independently predict better SWM in older people. The strong effect of age on cognitive performance is totally mediated by fitness and aortic stiffness. This suggests that addressing both physical fitness and aortic stiffness may be important to reduce the rate of age associated cognitive decline.

The association between adherence to a Mediterranean style diet and cognition in older people: The impact of medication.

BACKGROUND: Recent reviews indicate that adherence to a Mediterranean diet may be associated with better cognitive functioning. In assessing these relationships in older individuals, previous studies have not taken into account medication usage that may support or compromise cognitive functioning. OBJECTIVE: To investigate the association between adherence to a Mediterranean style diet, cognition and medication usage in cognitively healthy older individuals. DESIGN: Data were assessed from individuals aged 60-90 years (mean = 77.8 years, SD = 6.7) from 15 independent living aged care villages around Melbourne, Australia. Participants' diets were assessed using a food frequency questionnaire (FFQ). Cognition was assessed using reaction times from the Swinburne University Computerised Cognitive Assessment Battery (SUCCAB). Prescribed medications were recorded and analysed using binary measures. Cluster analyses were used to group participants in terms of cognitive measures and medications taken. Analyses controlled for age, gender, average daily kilojoule (kJ) intake and medication cluster. RESULTS: The relationship between cognitive speed clusters and medication clusters was significant (Chi-squared = 10.63, df = 3, p = 0.014). The odds ratio of 1.533 for average daily food intake suggested that for each additional kilojoule of average daily intake, the odds of belonging to the slower reaction time cluster increased by 53% and odds ratio of 0.573 for Mediterranean diet score suggested that for every additional unit, the odds of belonging to the slower reaction time cluster declined by 43%. The relationship between Mediterranean diet score and cognition was only significant when medication use was taken into account. CONCLUSION: These data demonstrate that when medications are considered, a higher Mediterranean diet score is associated with a faster response on cognitive function tests. The present findings also indicate that it is pertinent to take into account medication use when investigating relationships between dietary status and cognitive performance.

How Does Exercise Reduce the Rate of Age-Associated Cognitive Decline? A Review of Potential Mechanisms.

The rate of age-associated cognitive decline varies considerably between individuals. It is important, both on a societal and individual level, to investigate factors that underlie these differences in order to identify those which might realistically slow cognitive decline. Physical activity is one such factor with substantial support in the literature. Regular exercise can positively influence cognitive ability, reduce the rate of cognitive aging, and even reduce the risk of Alzheimer's disease (AD) and other dementias. However, while there is substantial evidence in the extant literature for the effect of exercise on cognition, the processes that mediate this relationship are less clear. This review examines cardiovascular health, production of brain derived neurotrophic factor (BDNF), insulin sensitivity, stress, and inflammation as potential pathways, via which exercise may maintain or improve cognitive functioning, and may be particularly pertinent in the context of the aging brain. A greater understanding of these mechanisms and their potential relationships with exercise and cognition will be invaluable in providing biomarkers for investigating the efficacy of differing exercise regimes on cognitive outcomes.

Adherence to a Mediterranean-Style Diet and Effects on Cognition in Adults: A Qualitative Evaluation and Systematic Review of Longitudinal and Prospective Trials.

The Mediterranean-style diet (MedDiet) involves substantial intake of fruits, vegetables, and fish, and a lower consumption of dairy, red meat, and sugars. Over the past 15 years, much empirical evidence supports the suggestion that a MedDiet may be beneficial with respect to reducing the incidence of cardiovascular disease, cancer, metabolic syndrome, and dementia. A number of cross-sectional studies that have examined the impact of MedDiet on cognition have yielded largely positive results. The objective of this review is to evaluate longitudinal and prospective trials to gain an understanding of how a MedDiet may impact cognitive processes over time. The included studies were aimed at improving cognition or minimizing of cognitive decline. Studies reviewed included assessments of dietary status using either a food frequency questionnaire or a food diary assessment. Eighteen articles meeting our inclusion criteria were subjected to systematic review. These revealed that higher adherence to a MedDiet is associated with slower rates of cognitive decline, reduced conversion to Alzheimer's disease, and improvements in cognitive function. The specific cognitive domains that were found to benefit with improved Mediterranean Diet Score were memory (delayed recognition, long-term, and working memory), executive function, and visual constructs. The current review has also considered a number of methodological issues in making recommendations for future research. The utilization of a dietary pattern, such as the MedDiet, will be essential as part of the armamentarium to maintain quality of life and reduce the potential social and economic burden of dementia.

A randomised controlled trial investigating the effects of Mediterranean diet and aerobic exercise on cognition in cognitively healthy older people living independently within aged care facilities: the Lifestyle Intervention in Independent Living Aged Care (LIILAC) study protocol [ACTRN12614001133628].

BACKGROUND: The rapid ageing of the population is becoming an area of great concern, both globally and in Australia. On a societal level, the cost of supporting an ageing demographic, particularly with their associated medical requirements, is becoming an ever increasing burden that is only predicted to rise in the foreseeable future. The progressive decline in individuals' cognitive ability as they age, particularly with respect to the ever increasing incidence of Alzheimer's Disease (AD) and other cognitive complications, is in many respects one of the foundation stones of these concerns. There have been numerous observational studies reporting on the positive effects that aerobic exercise and the Mediterranean diet appear to have on improving cognitive ability. However, the ability of such interventions to improve cognitive ability, or even reduce the rate of cognitive ageing, has not been fully examined by substantial interventional studies within an ageing population. METHODS: The LIILAC trial will investigate the potential for cognitive change in a cohort of cognitively healthy individuals, between the ages of 60 and 90 years, living in independent accommodation within Australian aged care facilities. This four-arm trial will investigate the cognitive changes which may occur as a result of the introduction of aerobic exercise and/or Mediterranean diet into individuals' lifestyles, as well as the mechanisms by which these changes may be occurring. Participants will be tested at baseline and 6 months on a battery of computer based cognitive assessments, together with cardiovascular and blood biomarker assessments. The cardiovascular measures will assess changes in arterial stiffness and central pulse pressures, while the blood measures will examine changes in metabolic profiles, including brain derived neurotrophic factor (BDNF), inflammatory factors and insulin sensitivity. CONCLUSION: It is hypothesised that exercise and Mediterranean diet interventions, both individually and in combination, will result in improvements in cognitive performance compared with controls. Positive findings in this research will have potential implications for the management of aged care, particularly in respect to reducing the rate of cognitive decline and the associated impacts both on the individual and the broader community. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry- ACTRN12614001133628.