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Background: Physiological cascades of neurotrophic factors and inflammatory cytokines may mediate the exercise-induced amelioration of cognition in older adults. However, there is limited understanding on how different exercise modalities improving cognition alter biomarkers. Our aim was to evaluate the effects of different exercise modalities on blood biomarker concentrations in cognitive clinical trials of older adults., Methods: A systematic review (SR) and meta-analysis (MA) were performed using the databases PubMed, EMBASE, and SCOPUS. After exclusions, 17 trials with 18 distinct exercise interventions were included., Results: Aerobic training increased (n = 2) or did not significantly change BDNF (n = 5), and resistance training increased (n = 2) or did not significantly change (n = 2) IGF-1. Multimodal training significantly increased (n = 1) or did not change (n = 3) BDNF. Interventions that recruited sex-specific cohorts showed an advantage in males for blood marker concentrations and cognitive performance outcomes (n = 3) compared to females (n = 3). Only one of three interventions decreased concentrations of CRP. Eight studies examining BDNF changes were suited for MA and showed that higher BDNF concentrations were reached post intervention, although not reaching statistical significance (p = .26, I 2  = 44 %)., Discussion: Our results suggest that exercise has potential to ameliorate cognitive decline in older adults with divergent, modality-specific, neurotrophic mechanisms., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Exercise is a non-pharmacological strategy to mitigate the deleterious effects of aging on brain health. However, a large amount of variation exists in its efficacy. Sex of participants and exercise type are two possible factors contributing to this variation. To better understand this, we conducted a concurrent systematic review and meta-analysis of cognitively healthy older adults. Executive functions, episodic memory, visuospatial function, word fluency, processing speed and global cognitive function were examined for exercise- and sex-dependent effects. For executive functions, three types of exercise interventions - aerobic training, resistance training, and multimodal training (i.e., both aerobic and resistance training) - were associated with larger effect sizes in studies comprised of a higher percentage of women compared to studies with a lower percentage of women. This suggests that women's executive processes may benefit more from exercise than men. Regardless of sex, compared to control, all three exercise training approaches enhanced visuospatial function, but only multimodal training enhanced episodic memory. Overall, aerobic training led to greater benefits than resistance training in global cognitive function and executive functions, while multimodal combined training led to greater benefits than aerobic training for global cognitive function, episodic memory, and word fluency. Possible underlying mechanisms, including brain-derived neurotrophic factor and sex steroid hormones, are discussed., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Research in humans indicates that women may show greater cognitive benefits from aerobic training (AT) than men. To determine whether this sex difference extends to rodents, we conducted a systematic review and meta-analysis of studies in healthy, older rodents. Results indicate that compared to controls, AT improved hippocampus-dependent and -independent learning and memory. A sex difference was found with males showing larger benefits from AT on conditioned-avoidance and non-spatial memory tasks. AT also increased brain-derived neurotrophic factor compared to controls, with larger effects in females. As an exploratory analysis, sex differences in voluntary AT were examined separately from forced AT. Voluntary AT enhanced non-spatial memory to a greater extent in males. Forced AT enhanced hippocampus-dependent learning and memory more so in females. These findings suggest that sex is an important factor to consider, and studies directly assessing sex differences in the ability of exercise to improve brain function are needed., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Impaired mobility, such as falls, may be an early biomarker of subsequent cognitive decline and is associated with subclinical alterations in both brain structure and function. In this 12-month prospective study, we examined whether there are volumetric differences in gray matter and subcortical regions, as well as cerebral white matter, between older fallers and non-fallers. In addition, we assessed whether these baseline volumetric differences are associated with changes in cognitive function over 12months. A total of 66 community-dwelling older adults were recruited and categorized by their falls status. Magnetic resonance imaging occurred at baseline and participants' physical and cognitive performances were assessed at baseline and 12-months. At baseline, fallers showed significantly lower volumes in gray matter, subcortical regions, and cerebral white matter compared with non-fallers. Notably, fallers had significantly lower left lateral orbitofrontal white matter volume. Moreover, lower left lateral orbitofrontal white matter volume at baseline was associated with greater decline in set-shifting performance over 12months. Our data suggest that falls may indicate subclinical alterations in regional brain volume that are associated with subsequent decline in executive functions., (Copyright © 2016. Published by Elsevier Inc.)

Executive cognitive functions play a critical role in falls risk—a pressing health care issue in seniors. In particular, intact attentional processing is integral for safe mobility and navigation. However, the specific contribution of impaired visual–spatial attention in falls remains unclear. In this study, we examined the association between visual–spatial attention to task-irrelevant stimuli and falls risk in community-dwelling older adults. Participants completed a visual target discrimination task at fixation while task-irrelevant probes were presented in both visual fields. We assessed attention to left and right peripheral probes using event-related potentials (ERPs). Falls risk was determined using the valid and reliable Physiological Profile Assessment (PPA). We found a significantly positive association between reduced attentional facilitation, as measured by the N1 ERP component, and falls risk. This relationship was specific to probes presented in the left visual field and measured at ipsilateral electrode sites. Our results suggest that fallers exhibit reduced attention to the left side of visual space and provide evidence that impaired right hemispheric function and/or structure may contribute to falls.

Although mind-wandering is common, engaging in task-irrelevant thoughts can have negative functional consequences. We examined whether mind-wandering frequency may be related to falls-a major health-care problem. Seniors completed a sustained attention task and self-reported their current attentional states. Monthly falls reports were collected over 12 months. Falls were associated with an increased frequency of mind-wandering. In addition, poorer performance on the sustained attention task was associated with more falls over 12 months. Given that fallers are known to have impaired executive cognitive functioning, our results are consistent with the current theory that poor attentional control may contribute to the occurrence of mind-wandering.

Objectives: To investigate the independent contribution of change in sub-total body fat and lean mass to cognitive performance, specifically the executive processes of selective attention and conflict resolution, in community-dwelling older women., Methods: This secondary analysis included 114 women aged 65 to 75 years old. Participants were randomly allocated to once-weekly resistance training, twice-weekly resistance training, or twice-weekly balance and tone training. The primary outcome measure was the executive processes of selective attention and conflict resolution as assessed by the Stroop Test. Sub-total body fat and lean mass were measured by dual-energy x-ray absorptiometry (DXA) to determine the independent association of change in both sub-total body fat and sub-total body lean mass with Stroop Test performance at trial completion., Results: A multiple linear regression model showed reductions in sub-total body fat mass to be independently associated with better performance on the Stroop Test at trial completion after accounting for baseline Stroop performance, age, baseline global cognitive state, baseline number of comorbidities, baseline depression, and experimental group. The total variance explained was 39.5%; change in sub-total body fat mass explained 3.9% of the variance. Change in sub-total body lean mass was not independently associated with Stroop Test performance (P>0.05)., Conclusion: Our findings suggest that reductions in sub-total body fat mass - not sub-total lean mass - is associated with better performance of selective attention and conflict resolution.

Maintaining functional plasticity of the cortex is essential for healthy aging and aerobic exercise may be an effective behavioral intervention to promote functional plasticity among seniors. Whether resistance training has similar benefits on functional plasticity in seniors has received little investigation. Here we show that 12 months of twice-weekly resistance training led to functional changes in 2 regions of cortex previously associated with response inhibition processes-the anterior portion of the left middle temporal gyrus and the left anterior insula extending into lateral orbital frontal cortex-in community-dwelling senior women. These hemodynamic effects co-occurred with improved task performance. Our data suggest that resistance training improved flanker task performance in 2 ways: (1) an increased engagement of response inhibition processes when needed; and (2) a decreased tendency to prepare response inhibition as a default state. However, we highlight that this effect of resistance training was only observed among those who trained twice weekly; participants of the once-weekly resistance training did not demonstrate comparable response profiles, both in behavioral performance and hemodynamic activity in cortex. In sum, our findings suggest that twice-weekly resistance training in seniors can positively impact functional plasticity of response inhibition processes in cortex, and that it does so in a manner that complements the effects on selective attention that have previously been ascribed to aerobic exercise in seniors., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: ageing is highly associated with neurodegeneration and atrophy of the brain. Evidence suggests that personality variables are risk factors for reduced brain volume. We examine whether falls-related self-efficacy is independently associated with brain volume., Method: a cross-sectional analysis of whether falls-related self-efficacy is independently associated with brain volumes (total, grey and white matter). Three multivariate regression models were constructed. Covariates included in the models were age, global cognition, systolic blood pressure, functional comorbidity index and current physical activity level. MRI scans were acquired from 79 community-dwelling senior women aged 65-75 years old. Falls-related self-efficacy was assessed by the activities-specific balance confidence (ABC) scale., Results: after accounting for covariates, falls-related self-efficacy was independently associated with both total brain volume and total grey matter volume. The final model for total brain volume accounted for 17% of the variance, with the ABC score accounting for 8%. For total grey matter volume, the final model accounted for 24% of the variance, with the ABC score accounting for 10%., Conclusion: we provide novel evidence that falls-related self-efficacy, a modifiable risk factor for healthy ageing, is positively associated with total brain volume and total grey matter volume., Trial Registration: ClinicalTrials.gov Identifier: NCT00426881.

To what extent does our visual-spatial attention change with age? In this regard, it has been previously reported that relative to young controls, seniors show delays in attention-related sensory facilitation. Given this finding, our study was designed to examine two key questions regarding age-related changes in the effect of spatial attention on sensory-evoked responses in visual cortex--are there visual field differences in the age-related impairments in sensory processing, and do these impairments co-occur with changes in the executive control signals associated with visual spatial orienting? Therefore, our study examined both attentional control and attentional facilitation in seniors (aged 66-74 years) and young adults (aged 18-25 years) using a canonical spatial orienting task. Participants responded to attended and unattended peripheral targets while we recorded event-related potentials (ERPs) to both targets and attention-directing spatial cues. We found that not only were sensory-evoked responses delayed in seniors specifically for unattended events in the left visual field as measured via latency shifts in the lateral occipital P1 elicited by visual targets, but seniors also showed amplitude reductions in the anterior directing attentional negativity (ADAN) component elicited by cues directing attention to the left visual field. At the same time, seniors also had significantly higher error rates for targets presented in the left vs. right visual field. Taken together, our data thus converge on the conclusion that age-related changes in visual spatial attention involve both sensory-level and executive attentional control processes, and that these effects appear to be strongly associated with the left visual field., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Improved usual gait speed predicts substantial reduction in mortality. A better understanding of the modifiable factors that are independently associated with improved gait speed would ensure that intervention strategies are developed based on a valid theoretical framework. Thus, we examined the independent association of change in executive functions and change in falls-related self-efficacy with improved gait speed among community-dwelling senior women., Methods: A secondary analysis of the 135 senior women aged 65 to 75 years old who completed a 12-month randomized controlled trial of resistance training. Usual gait speed was assessed using a 4-meter walk. Three executive processes were assessed by standard neuropsychological tests: 1) set shifting; 2) working memory; and 3) selective attention and response inhibition. A linear regression model was constructed to determine the independent association of change in executive functions and falls-related self-efficacy with change in gait speed., Results: Improved selective attention and conflict resolution, and falls-related self-efficacy, were independently associated with improved gait speed after accounting for age, global cognition, baseline gait speed, and change in quadriceps strength. The total variance explained was 24%., Conclusions: Interventions that target executive functions and falls-related self-efficacy, in addition to physical functions, to improve gait speed may be more efficacious than those that do not., Trial Registration: ClinicalTrials.gov Identifier: NCT00426881.