The influence of baseline sleep on exercise-induced cognitive change in cognitively unimpaired older adults: A randomised clinical trial

Objectives: Observational studies consistently demonstrate that physical activity is associated with elevated cognitive function, however, there remains significant heterogeneity in cognitive outcomes from randomized exercise interventions. Individual variation in sleep behaviours may be a source of variability in the effectiveness of exercise-induced cognitive change, however this has not yet been investigated. The current study aimed to (1) investigate the influence of a 6-month exercise intervention on sleep, assessed pre- and post-intervention and, (2) investigate whether baseline sleep measures moderate exercise-induced cognitive changes. Methods: We utilised data from the Intense Physical Activity and Cognition (IPAC) study (n = 89), a 6-month moderate intensity and high intensity exercise intervention, in cognitively unimpaired community-dwelling older adults aged 60–80 (68.76 ± 5.32). Exercise was supervised and completed on a stationary exercise bicycle, and cognitive function was measured using a comprehensive neuropsychological battery administered pre- and post-intervention. Sleep was measured using the Pittsburgh sleep quality index. There was no effect of the exercise intervention on any sleep outcomes from pre- to post-intervention. Results: There was a significant moderating effect of baseline sleep efficiency on both episodic memory and global cognition within the moderate intensity exercise group, such that those with poorer sleep efficiency at baseline showed greater exercise-induced improvements in episodic memory. Conclusions: These results suggest that those with poorer sleep may have the greatest exercise-induced cognitive benefits and that baseline sleep behaviours may be an important source of heterogeneity in previous exercise interventions targeting cognitive outcomes

Study protocol of the intense physical activity and cognition study: The effect of high-intensity exercise training on cognitive function in older adults

Introduction: Inconsistent results from previous studies of exercise and cognitive function suggest that rigorously designed randomized controlled trials are urgently needed. Here, we describe the design of the Intense Physical Activity and Cognition (IPAC) study, which will assess the impact of a 6-month high-intensity exercise intervention on cognitive function and biomarkers of dementia risk, compared with a 6-month moderate-intensity exercise intervention and control group (no study-related exercise). Methods: One-hundred and five cognitively healthy men and women aged between 60 and 80 years are randomized into a high-intensity exercise, moderate-intensity exercise, or control group. Individuals randomized to an exercise intervention undertake 6 months of cycle-based exercise twice a week, at 50 minutes per session. All participants undergo comprehensive neuropsychological testing, blood sampling, brain magnetic resonance imaging, fitness testing, and a body composition scan at baseline, 6 months (immediately after intervention), and 18 months (12 months after intervention). Discussion: The IPAC study takes a multidisciplinary approach to investigating the role of exercise in maintaining a healthy brain throughout aging. Rigorous monitoring of exertion and adherence throughout the intervention, combined with repeated measures of fitness, is vital in ensuring an optimum exercise dose is reached. Results from the IPAC study will be used to inform a large-scale multicentre randomized controlled trial, with the ultimate aim of pinpointing the frequency, duration, and intensity of exercise that provides the most benefit to the brain, in terms of enhancing cognitive function and reducing dementia risk in older adults

High-intensity exercise and cognitive function in cognitively normal older adults: A pilot randomised clinical trial

© 2021, The Author(s). Background: Physical inactivity has been consistently linked to increased risk of cognitive decline; however, studies examining the impact of exercise interventions on cognition have produced inconsistent findings. Some observational studies suggest exercise intensity may be important for inducing cognitive improvements; however, this has yet to be thoroughly examined in older adult cohorts. The objective of the current study was to evaluate the effect of systematically manipulated high-intensity and moderate-intensity exercise interventions on cognition. Methods: This multi-arm pilot randomised clinical trial investigated the effects of 6 months of high-intensity exercise and moderate-intensity exercise, compared with an inactive control, on cognition. Outcome measures were assessed at pre- (baseline), post- (6 months), and 12 months post-intervention. Ninety-nine cognitively normal men and women (aged 60–80 years) were enrolled from October 2016 to November 2017. Participants that were allocated to an exercise group (i.e. high-intensity or moderate-intensity) engaged in cycle-based exercise two times per week for 6 months. Cognition was assessed using a comprehensive neuropsychological test battery. Cardiorespiratory fitness was evaluated by a graded exercise test. Results: There was a dose-dependent effect of exercise intensity on cardiorespiratory fitness, whereby the high-intensity group experienced greater increases in fitness than the moderate-intensity and control groups. However, there was no direct effect of exercise on cognition. Conclusions: We did not observe a direct effect of exercise on cognition. Future work in this field should be appropriately designed and powered to examine factors that may contribute to individual variability in response to intervention. Trial registration: This study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12617000643370). Registered on 3 May 2017—retrospectively registered. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=37278

High-intensity exercise and cognitive function in cognitively normal older adults: A pilot randomised clinical trial

© 2021, The Author(s). Background: Physical inactivity has been consistently linked to increased risk of cognitive decline; however, studies examining the impact of exercise interventions on cognition have produced inconsistent findings. Some observational studies suggest exercise intensity may be important for inducing cognitive improvements; however, this has yet to be thoroughly examined in older adult cohorts. The objective of the current study was to evaluate the effect of systematically manipulated high-intensity and moderate-intensity exercise interventions on cognition. Methods: This multi-arm pilot randomised clinical trial investigated the effects of 6 months of high-intensity exercise and moderate-intensity exercise, compared with an inactive control, on cognition. Outcome measures were assessed at pre- (baseline), post- (6 months), and 12 months post-intervention. Ninety-nine cognitively normal men and women (aged 60–80 years) were enrolled from October 2016 to November 2017. Participants that were allocated to an exercise group (i.e. high-intensity or moderate-intensity) engaged in cycle-based exercise two times per week for 6 months. Cognition was assessed using a comprehensive neuropsychological test battery. Cardiorespiratory fitness was evaluated by a graded exercise test. Results: There was a dose-dependent effect of exercise intensity on cardiorespiratory fitness, whereby the high-intensity group experienced greater increases in fitness than the moderate-intensity and control groups. However, there was no direct effect of exercise on cognition. Conclusions: We did not observe a direct effect of exercise on cognition. Future work in this field should be appropriately designed and powered to examine factors that may contribute to individual variability in response to intervention. Trial registration: This study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12617000643370). Registered on 3 May 2017—retrospectively registered. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=37278

How does apolipoprotein E genotype influence the relationship between physical activity and Alzheimer’s disease risk? A novel integrative model

Background: Wide evidence suggests that physical activity (PA) confers protection against Alzheimer’s disease (AD). On the other hand, the apolipoprotein E gene (APOE) ε4 allele represents the greatest genetic risk factor for developing AD. Extensive research has been conducted to determine whether frequent PA can mitigate the increased AD risk associated with APOE ε4. However, thus far, these attempts have produced inconclusive results. In this context, one possible explanation could be that the influence of the combined effect of PA and APOE ε4 carriage might be dependent on the specific outcome measure utilised. Main body: In order to bridge these discrepancies, the aim of this theoretical article is to propose a novel model on the interactive effects of PA and APOE ε4 carriage on well-established mechanisms underlying AD. Available literature was searched to investigate how PA and APOE ε4 carriage, independently and in combination, may alter several molecular pathways involved in AD pathogenesis. The reviewed mechanisms include amyloid beta (Aβ) and tau deposition and clearance, neuronal resilience and neurogenesis, lipid function and cerebrovascular alterations, brain immune response and glucose metabolism. Finally, combining all this information, we have built an integrative model, which includes evidence-based and theoretical synergistic interactions across mechanisms. Moreover, we have identified key knowledge gaps in the literature, providing a list of testable hypotheses that future studies need to address. Conclusions: We conclude that PA influences a wide array of molecular targets involved in AD neuropathology. A deeper understanding of where, when and, most importantly, how PA decreases AD risk even in the presence of the APOE ε4 allele will enable the creation of new protocols using exercise along pharmaceuticals in combined therapeutic approaches

The impact of exercise, sleep, and diet on neurocognitive recovery from mild traumatic brain injury in older adults: A narrative review

Mild traumatic brain injury (mTBI) accounts for a large majority of traumatic brain injuries sustained globally each year. Older adults, who are already susceptible to age-related declines to neurocognitive health, appear to be at an increased risk of both sustaining an mTBI and experiencing slower or impaired recovery. There is also growing evidence that mTBI is a potential risk factor for accelerated cognitive decline and neurodegeneration. Lifestyle-based interventions are gaining prominence as a cost-effective means of maintaining cognition and brain health with age. Consequently, inter-individual variations in exercise, sleep, and dietary patterns could influence the trajectory of post-mTBI neurocognitive recovery, particularly in older adults. This review synthesises the current animal and human literature centred on the mechanisms through which lifestyle-related habits and behaviours could influence acute and longer-term neurocognitive functioning following mTBI. Numerous neuroprotective processes which are impacted by lifestyle factors have been established in animal models of TBI. However, the literature is characterised by a lack of translation to human samples and limited appraisal of the interaction between ageing and brain injury. Further research is needed to better establish the therapeutic utility of applying lifestyle-based modifications to improve post-mTBI neurocognitive outcomes in older adults

Fluid biomarkers in cerebral amyloid angiopathy

Cerebral amyloid angiopathy (CAA) is a type of cerebrovascular disorder characterised by the accumulation of amyloid within the leptomeninges and small/medium-sized cerebral blood vessels. Typically, cerebral haemorrhages are one of the first clinical manifestations of CAA, posing a considerable challenge to the timely diagnosis of CAA as the bleedings only occur during the later disease stages. Fluid biomarkers may change prior to imaging biomarkers, and therefore, they could be the future of CAA diagnosis. Additionally, they can be used as primary outcome markers in prospective clinical trials. Among fluid biomarkers, blood-based biomarkers offer a distinct advantage over cerebrospinal fluid biomarkers as they do not require a procedure as invasive as a lumbar puncture. This article aimed to provide an overview of the present clinical data concerning fluid biomarkers associated with CAA and point out the direction of future studies. Among all the biomarkers discussed, amyloid β, neurofilament light chain, matrix metalloproteinases, complement 3, uric acid, and lactadherin demonstrated the most promising evidence. However, the field of fluid biomarkers for CAA is an under-researched area, and in most cases, there are only one or two studies on each of the biomarkers mentioned in this review. Additionally, a small sample size is a common limitation of the discussed studies. Hence, it is hard to reach a solid conclusion on the clinical significance of each biomarker at different stages of the disease or in various subpopulations of CAA. In order to overcome this issue, larger longitudinal and multicentered studies are needed.</p