Brain deficits in prediabetic adults: A systematic review.

Previous findings on the relationship between prediabetes (the precursor stage of type 2 diabetes) and brain health in humans are inconsistent. Thus, this systematic review of cross-sectional and longitudinal studies aimed to summarize what is currently known about brain deficits in prediabetic adults. Following the PRISMA reporting standards for systematic reviews, we conducted a comprehensive review of peer-reviewed journal articles published from 2009 to present, focusing on studies that assessed brain volume, structural connectivity, and cerebrovascular health in prediabetic adults and older adults (i.e., 18 years or older). We systematically searched PsychINFO, Scopus, Web of Science, Ovid MEDLINE, CINAHL, and EMbase databases. Quality assessment was based on the NIH Quality Assessment Tool for Observational and Cross-sectional Studies. In total, 19 studies were included in our review. Results from these studies show that prediabetes may be associated with deficits in brain structure and pathology, however, several studies also refute these findings. Moreover, we identified clear inconsistencies in study methodologies, including diabetes measures and classification, across studies that may account for these conflicting findings.

Sex differences in exercise efficacy to improve cognition: A systematic review and meta-analysis of randomized controlled trials in older humans.

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.

Sex differences in aerobic exercise efficacy to improve cognition: A systematic review and meta-analysis of studies in older rodents.

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.

Aerobic exercise promotes executive functions and impacts functional neural activity among older adults with vascular cognitive impairment.

BACKGROUND: Vascular cognitive impairment (VCI) results from cerebrovascular disease, and worldwide, it is the second most common type of cognitive dysfunction. While targeted aerobic training is a promising approach to delay the progression of VCI by reducing cardiometabolic risk factors, few randomised controlled trials to date have specifically assessed the efficacy of aerobic training on cognitive and brain outcomes in this group at risk for functional decline. AIM: To examine the effect of moderate-intensity aerobic training on executive functions and functional neural activity among older adults with mild subcortical ischaemic VCI (SIVCI). METHODS: Older adults with mild SIVCI were randomly assigned to: (1) 6-month, 3×/week aerobic training (n=10) or (2) usual care (control; n=11). Participants completed functional MRI (fMRI) at baseline and trial completion. During the fMRI sessions, behavioural performance on the Eriksen flanker task and task-evoked neural activity were assessed. RESULTS: At trial completion, after adjusting for baseline general cognition, total white matter lesion volume and flanker performance, compared with the control group, the aerobic training group significantly improved flanker task reaction time. Moreover, compared with the controls, the aerobic training group demonstrated reduced activation in the left lateral occipital cortex and right superior temporal gyrus. Reduced activity in these brain regions was significantly associated with improved (ie, faster) flanker task performance at trial completion. SUMMARY: Aerobic training among older adults with mild SIVCI can improve executive functions and neural efficiency of associated brain areas. Future studies with greater sample size should be completed to replicate and extend these findings.

Personalising exercise recommendations for brain health: considerations and future directions.

The societal value of strategies that delay the onset and progression of dementia cannot be overstated. Physical activity-unstructured and structured-is a promising, cost-effective strategy for the promotion of brain health. However, a large degree of variation exists in its efficacy. Therefore, to increase its utility as 'medication' for healthy cognitive ageing, it is imperative to identify key moderators and mediators of the positive effects of targeted exercise training on brain health. In this commentary, we focus on the type of targeted exercise training, the determinants of individual variation, including biological sex and genotypic factors, and the mechanisms by which exercise exerts its influence on the brain. We argue that a better understanding of these factors will allow for evidence-based, personalised, tailored exercise recommendations that go beyond the one-size-fits-all approach to successfully combat dementia.

White Matter Volume Mediates the Relationship Between Self-Efficacy and Mobility in Older Women.

Background/Study Context: With our aging population, understanding determinants of healthy aging is a priority. One essential component of healthy aging is mobility. Although self-efficacy can directly impact mobility in older adults, it is unknown what role brain health may play in this relationship. METHODS: The authors conducted a cross-sectional pilot analysis of community-dwelling women (N = 80, mean age = 69 years) to examine whether brain volume mediates the relationship between falls-related self-efficacy, as measured by the Activities-specific Balance Confidence (ABC) scale, and mobility, as measured by the Timed Up and Go (TUG) test. Age, depression, education, functional comorbidities, and Montreal Cognitive Assessment (MoCA) were included in the model as covariates. RESULTS: The authors report that total white matter volume, specifically, significantly mediates the relationship between self-efficacy and mobility, where higher self-efficacy was associated with greater white matter volume (r = .28), which, in turn, was associated with better mobility (r = -.30). CONCLUSION: This pilot study extends our understanding of the psychosocial and neurological factors that contribute to mobility and provides insight into effective strategies that may be used to improve functional independence among older adults. Future prospective and intervention studies are required to further elucidate the nature of the relationship between self-efficacy, mobility, and brain health.

Long-Term Effects of Resistance Exercise Training on Cognition and Brain Volume in Older Women: Results from a Randomized Controlled Trial.

Aerobic exercise training has been shown to attenuate cognitive decline and reduce brain atrophy with advancing age. The extent to which resistance exercise training improves cognition and prevents brain atrophy is less known, and few studies include long-term follow-up cognitive and neuroimaging assessments. We report data from a randomized controlled trial of 155 older women, who engaged in 52 weeks of resistance training (either once- or twice-weekly) or balance-and-toning (twice-weekly). Executive functioning and memory were assessed at baseline, 1-year follow-up (i.e., immediately post-intervention), and 2-year follow-up. A subset underwent structural magnetic resonance imaging scans at those time points. At 2-year follow-up, both frequencies of resistance training promoted executive function compared to balance-and-toning (standardized difference [d]=.31-.48). Additionally, twice-weekly resistance training promoted memory (d=.45), reduced cortical white matter atrophy (d=.45), and increased peak muscle power (d=.27) at 2-year follow-up relative to balance-and-toning. These effects were independent of one another. These findings suggest resistance training may have a long-term impact on cognition and white matter volume in older women.

Aerobic exercise increases hippocampal volume in older women with probable mild cognitive impairment: a 6-month randomised controlled trial.

BACKGROUND: Mild cognitive impairment (MCI) is a well-recognised risk factor for dementia and represents a vital opportunity for intervening. Exercise is a promising strategy for combating cognitive decline by improving brain structure and function. Specifically, aerobic training (AT) improved spatial memory and hippocampal volume in healthy community-dwelling older adults. In older women with probable MCI, we previously demonstrated that resistance training (RT) and AT improved memory. In this secondary analysis, we investigated: (1) the effect of RT and AT on hippocampal volume and (2) the association between change in hippocampal volume and change in memory. METHODS: 86 women aged 70-80 years with probable MCI were randomly assigned to a 6-month, twice-weekly programme of: (1) AT, (2) RT or (3) balance and tone training (BAT; ie, control). At baseline and trial completion, participants performed a 3T MRI scan to determine hippocampal volume. Verbal memory and learning were assessed by Rey's Auditory Verbal Learning Test. RESULTS: Compared with the BAT group, AT significantly improved left, right and total hippocampal volumes (p≤0.03). After accounting for baseline cognitive function and experimental group, increased left hippocampal volume was independently associated with reduced verbal memory and learning performance as indexed by loss after interference (r=0.42, p=0.03). CONCLUSIONS: Aerobic training significantly increased hippocampal volume in older women with probable MCI. More research is needed to ascertain the relevance of exercise-induced changes in hippocampal volume on memory performance in older adults with MCI. TRAIL REGISTRATION NUMBER: NCT00958867.

Visual asymmetry revisited: Mind wandering preferentially disrupts processing in the left visual field.

An emerging theory proposes that visual attention operates in parallel at two distinct time scales - a shorter one (<1s) associated with moment-to-moment orienting of selective visuospatial attention, and a longer one (>10s) associated with more global aspects of attention-to-task. Given their parallel nature, here we examined whether these comparatively slower fluctuations in task-related attention show the same visual field asymmetry - namely, a right visual field bias - as often reported for selective visual-spatial attention. Participants performed a target detection task at fixation while event-related potentials (ERP) time-locked to task-irrelevant visual probes presented in the left and right visual fields were recorded. At random intervals, participants were asked to report whether they were "on-task" or "mind wandering". Our results demonstrated that sensory attenuation during periods of "mind wandering" relative to "on-task", as measured by the visual P1 ERP component at electrodes sites contralateral to the stimulus, was only observed for probes presented in the left visual field. In contrast, the magnitude of sensory gain in the right visual field was insensitive to whether participants were "on-task" or "mind wandering". Taken together, our results support the notion that task-related attention at longer time scales and spatial attention at shorter time scales affect the same underlying mechanism in visual cortex.

Four weeks of meditation training improves sustained attention in community-dwelling older adults: a proof-of-concept randomized controlled trial.

Introduction: With our rapidly expanding population of older adults, identifying effective intervention strategies to improve cognitive functioning is an increasing priority. This study sought to examine whether 4 weeks of thrice-weekly meditation training can improve attention in older adults, as well as whether such benefits may extend to other domains of cognition as well as mobility. Methods: Forty-three participants (mean age 68 years) were randomized into either the focused attention meditation group or the music listening control group (Clinicaltrials.gov ID NCT03417635). Participants completed three 20-minute guided group sessions per week for four consecutive weeks. Our primary outcome measure was behavioural performance on the Sustained Attention to Response Task (SART). Secondary and tertiary outcome measures included event-related potentials (ERPs) during the SART task, measures of executive functioning, and measures of mobility. Results: We found that meditation training significantly improved attention, as demonstrated by improved SART accuracy and changes in N2 ERP amplitude and latency. Discussion: These findings suggest that meditation may lead to changes in attention and underlying cognitive processing in older adults, although a full-scale definitive trial is needed. Future research on the long-term benefits with real world applications is warranted.

Emerging concept: 'central benefit model' of exercise in falls prevention.

Falls are a common geriatric syndrome and are the third leading cause of chonic disability worldwide. Falls are not random events and occur, at least in part, due to impaired physiological function, such as impaired balance, and cognitive impairment. The clinical syndrome of falls is important for Sports and Exercise Medicine Clinicians as there is Level 1 evidence that targeted exercise prescription is an effective intervention strategy. The widely accepted dogma is that improved physical function, balance and muscle strength, underlies the effectiveness of the exercise in reducing falls. However, findings from randomised controlled trials suggest that exercise reduce falls via mechanisms other than improved physiological function. The authors propose that improved cognitive function - specifically, executive functions - and associated functional plasticity may be an important yet underappreciated mechanism by which the exercise reduces falls in older adults.

What do functional neuroimaging studies tell us about the association between falls and cognition in older adults? A systematic review.

Impaired cognition is a known risk factor for falls in older adults. To enhance prevention strategies and treatment of falls among an aging global population, an understanding of the neural processes and networks involved is required. We present a systematic review investigating how functional neuroimaging techniques have been used to examine the association between falls and cognition in seniors. Peer-reviewed articles were identified through searching five electronic databases: 1) Medline, 2) PsycINFO, 3) CINAHL, 4) EMBASE, and 5) Pubmed. Key author, key paper, and reference searching was also conducted. Nine studies were included in this review. A questionnaire composed of seven questions was used to assess the quality of each study. EEG, fMRI, and PET were utilized across studies to examine brain function in older adults. Consistent evidence demonstrates that cognition is associated with measures of falls/falls risk, specifically visual attention and executive function. Our results show that falls/falls risk may be implicated with specific brain regions and networks. Future studies should be prospective and long-term in nature, with standardized outcome measures. Mobile neuroimaging techniques may also provide insight into brain activity as it pertains to cognition and falls in older adults in real-world settings.

Changes in Cognition and Brain Function After 26 Weeks of Progressive Resistance Training in Older Adults at Risk for Diabetes: A Pilot Randomized Controlled Trial.

OBJECTIVES: Type 2 diabetes is associated with deficits in cognition and brain health. Individuals with at least 1 risk factor for diabetes (i.e. obesity, prediabetes) already experience some neurocognitive impairment and are at risk for further decline. One way to combat these deficits is through exercise, but it is unknown whether resistance exercise can improve these functions in this at-risk group. METHODS: This study was a pilot randomized controlled trial. Participants were 60 to 80 years of age and had prediabetes (fasting capillary glucose 6.1 to 6.9 mmol/L) and/or were living with overweight or obesity (body mass index ≥25 kg/m2). Participants completed resistance training or balance and stretching exercises (control) thrice weekly for 6 months. Neuropsychological tests were used to assess cognitive ability, whereas functional magnetic resonance imaging was used to examine brain activation patterns. RESULTS: Resistance training led to improvements in task-switching, attention, and conflict resolution, as well as improved patterns of brain activation that may mimic healthy older adults. CONCLUSIONS: Resistance exercise may serve as an effective behavioural strategy to improve neurocognition in older adults at risk for type 2 diabetes. A large-scale powered trial is needed to further explore these findings.

Frailty and functional brain connectivity (FBC) in older adults with mild cognitive impairment (MCI): baseline results from the SYNERGIC Trial.

Functional brain connectivity (FBC), or areas that are anatomically separate but temporally synchronized in their activation, represent a sensitive biomarker for monitoring dementia progression. It is unclear whether frailty is associated with FBC in those at higher risk of progression to dementia (e.g., mild cognitive impairment -MCI-) and if sex plays a role. We used baseline data from the SYNERGIC trial, including participants with MCI that received brain MRI. In this cross-sectional analyses (n = 100), we measured frailty using a deficit accumulation frailty index. Using the CONN toolbox, we assessed FBC of networks and regions of interest across the entire connectome. We used Pearson's correlation to investigate the relationship between FBC and frailty index in the full sample and by sex. We also divided the full sample and each sex into tertiles based upon their frailty index score and then assessed between-tertile differences in FBC. The full sample (cluster: size = 291 p-FDR < 0.05) and males (cluster: size = 993 and 451 p-FDR < 0.01) demonstrated that increasing (stronger) connectivity between the right hippocampus and clusters in the temporal gyrus was positively correlated with increasing (worse) frailty. Males also demonstrated between-tertile differences in right hippocampus connectivity to clusters in the lateral occipital cortex (cluster: size = 289 p-FDR < 0.05). Regardless of frailty status, females demonstrated stronger within-network connectivity of the Default-Mode (p = 0.024). Our results suggest that increasing (worse) frailty was associated with increasing (stronger) connectivity between regions not typically linked, which may reflect a compensation tactic by the plastic brain. Furthermore, the relationship between the two variables appears to differ by sex. Our results may help elucidate why specific individuals progress to a dementia syndrome. NCT02808676. https://www.clinicaltrials.gov/ct2/show/NCT02808676.

Combining exercise with cognitive training and vitamin D3 to improve functional brain connectivity (FBC) in older adults with mild cognitive impairment (MCI). Results from the SYNERGIC trial.

Changes in functional brain connectivity (FBC) may indicate how lifestyle modifications can prevent the progression to dementia; FBC identifies areas that are spatially separate but temporally synchronized in their activation and is altered in those with mild cognitive impairment (MCI), a prodromal state between healthy cognitive aging and dementia. Participants with MCI were randomly assigned to one of five study arms. Three times per week for 20-weeks, participants performed 30-min of (control) cognitive training, followed by 60-min of (control) physical exercise. Additionally, a vitamin D3 (10,000 IU/pill) or a placebo capsule was ingested three times per week for 20-weeks. Using the CONN toolbox, we measured FBC change (Post-Pre) across four statistical models that collapsed for and/or included some or all study arms. We conducted Pearson correlations between FBC change and changes in physical and cognitive functioning. Our sample included 120 participants (mean age: 73.89 ± 6.50). Compared to the pure control, physical exercise (model one; p-False Discovery Rate (FDR) < 0.01 & < 0.05) with cognitive training (model two; p-FDR = < 0.001), and all three interventions combined (model four; p-FDR = < 0.01) demonstrated an increase in FBC between regions of the Default-Mode Network (i.e., hippocampus and angular gyrus). After controlling for false discovery rate, there were no significant correlations between change in connectivity and change in cognitive or physical function. Physical exercise alone appears to be as efficacious as combined interventional strategies in altering FBC, but implications for behavioral outcomes remain unclear.

Self-efficacy is independently associated with brain volume in older women.

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.

Reshaping the path of mild cognitive impairment by refining exercise prescription: a study protocol of a randomized controlled trial to understand the "what," "for whom," and "how" of exercise to promote cognitive function.

BACKGROUND: Targeted exercise training is a promising strategy for promoting cognitive function and preventing dementia in older age. Despite the utility of exercise as an intervention, variation still exists in exercise-induced cognitive gains and questions remain regarding the type of training (i.e., what), as well as moderators (i.e., for whom) and mechanisms (i.e., how) of benefit. Both aerobic training (AT) and resistance training (RT) enhance cognitive function in older adults without cognitive impairment; however, the vast majority of trials have focused exclusively on AT. Thus, more research is needed on RT, as well as on the combination of AT and RT, in older adults with mild cognitive impairment (MCI), a prodromal stage of dementia. Therefore, we aim to conduct a 6-month, 2 × 2 factorial randomized controlled trial in older adults with MCI to assess the individual effects of AT and RT, and the combined effect of AT and RT on cognitive function and to determine the possible underlying biological mechanisms. METHODS: Two hundred and sixteen community-dwelling adults, aged 65 to 85 years, with MCI from metropolitan Vancouver will be recruited to participate in this study. Randomization will be stratified by biological sex and participants will be randomly allocated to one of the four experimental groups: (1) 4×/week balance and tone (BAT; i.e., active control); (2) combined 2×/week AT + 2×/week RT; (3) 2×/week AT + 2×/week BAT; or (4) 2×/week RT + 2×/week BAT. The primary outcome is cognitive function as measured by the Alzheimer's Disease Assessment Scale-Cognitive-Plus. Secondary outcomes include cognitive function, health-related quality of life, physical function, actigraphy measures, questionnaires, and falls. Outcomes will be measured at baseline, 6 months (i.e., trial completion), and 18 months (i.e., 12-month follow-up). DISCUSSION: Establishing the efficacy of different types and combinations of exercise training to minimize cognitive decline will advance our ability to prescribe exercise as "medicine" to treat MCI and delay the onset and progression of dementia. This trial is extremely timely as cognitive impairment and dementia pose a growing threat to global public health. TRIAL REGISTRATION: ClinicalTrials.gov NCT02737878 . Registered on April 14, 2016.

Bootstrap analysis of the single subject with event related potentials.

Neural correlates of cognitive states in event-related potentials (ERPs) serve as markers for related cerebral processes. Although these are usually evaluated in subject groups, the ability to evaluate such markers statistically in single subjects is essential for case studies in neuropsychology. Here we investigated the use of a simple test based on nonparametric bootstrap confidence intervals for this purpose, by evaluating three different ERP phenomena: the face-selectivity of the N170, error-related negativity, and the P3 component in a Posner cueing paradigm. In each case, we compare single-subject analysis with statistical significance determined using bootstrap to conventional group analysis using analysis of variance (ANOVA). We found that the proportion of subjects who show a significant effect at the individual level based on bootstrap varied, being greatest for the N170 and least for the P3. Furthermore, it correlated with significance at the group level. We conclude that the bootstrap methodology can be a viable option for interpreting single-case ERP amplitude effects in the right setting, probably with well-defined stereotyped peaks that show robust differences at the group level, which may be more characteristic of early sensory components than late cognitive effects.