The Brain in Motion II Study: study protocol for a randomized controlled trial of an aerobic exercise intervention for older adults at increased risk of dementia.

BACKGROUND: There remains no effective intervention capable of reversing most cases of dementia. Current research is focused on prevention by addressing risk factors that are shared between cardiovascular disease and dementia (e.g., hypertension) before the cognitive, functional, and behavioural symptoms of dementia manifest. A promising preventive treatment is exercise. This study describes the methods of a randomized controlled trial (RCT) that assesses the effects of aerobic exercise and behavioural support interventions in older adults at increased risk of dementia due to genetic and/or cardiovascular risk factors. The specific aims are to determine the effect of aerobic exercise on cognitive performance, explore the biological mechanisms that influence cognitive performance after exercise training, and determine if changes in cerebrovascular physiology and function persist 1 year after a 6-month aerobic exercise intervention followed by a 1-year behavioural support programme (at 18 months). METHODS: We will recruit 264 participants (aged 50-80 years) at elevated risk of dementia. Participants will be randomly allocated into one of four treatment arms: (1) aerobic exercise and health behaviour support, (2) aerobic exercise and no health behaviour support, (3) stretching-toning and health behaviour support, and (4) stretching-toning and no health behaviour support. The aerobic exercise intervention will consist of three supervised walking/jogging sessions per week for 6 months, whereas the stretching-toning control intervention will consist of three supervised stretching-toning sessions per week also for 6 months. Following the exercise interventions, participants will receive either 1 year of ongoing telephone behavioural support or no telephone support. The primary aim is to determine the independent effect of aerobic exercise on a cognitive composite score in participants allocated to this intervention compared to participants allocated to the stretching-toning group. The secondary aims are to examine the effects of aerobic exercise on a number of secondary outcomes and determine whether aerobic exercise-related changes persist after a 1-year behavioural support programme (at 18 months). DISCUSSION: This study will address knowledge gaps regarding the underlying mechanisms of the pro-cognitive effects of exercise by examining the potential mediating factors, including cerebrovascular/physiological, neuroimaging, sleep, and genetic factors that will provide novel biologic evidence on how aerobic exercise can prevent declines in cognition with ageing. TRIAL REGISTRATION: ClinicalTrials.gov NCT03035851 . Registered on 30 January 2017.

Effect of aerobic exercise on white matter microstructure in the aging brain.

Aging is associated with decline in white matter (WM) microstructure, decreased cognitive functioning, and increased risk of Alzheimer's disease and related dementias. Recent research has identified aerobic physical exercise as a promising intervention for increasing white matter microstructure in aging, with the aim of increasing cognitive abilities, and protecting against neurodegenerative processes. However, the degree to which white matter microstructure can be protected or improved with exercise remains incompletely understood. Here, a sub-group of 25 healthy, sedentary participants (aged 57 to 86 years; M = 67.1; SD = 7.9; 11 female, 14 male) from the larger Brain in Motion Study (Tyndall et al., 2013) underwent diffusion tensor imaging (DTI) before and after a six-month aerobic exercise intervention. DTI data were analysed with FSL's Tract-Based Spatial Statistics (TBSS) to determine whether WM microstructure improved, as defined by increased fractional anisotropy (FA) and/or decreased mean diffusivity (MD), after the aerobic exercise intervention. Neither FA nor MD of the cerebral WM were significantly correlated with either age or cardiovascular fitness at baseline. Whole-brain WM mean FA decreased over the intervention while mean MD showed no significant change. Longitudinal TBSS analyses revealed decreased FA in the left uncinate fasciculus, left anterior corona radiata, left inferior fronto-occipital fasciculus, and left anterior thalamic radiation. MD increased in the left forceps major, left inferior longitudinal fasciculus, and left superior longitudinal fasciculus. Results indicate that six months of aerobic exercise in healthy, sedentary older adults was not associated with improvements in FA or MD measures of cerebral WM microstructure.

Novel Approach to Characterize Heterogeneity in an Aerobic Exercise Intervention.

PURPOSE: Exercise intervention studies for brain health can be difficult to interpret due to heterogeneity in exercise intensity, exercise duration, and in adherence to the exercise intervention. This study aimed to characterize heterogeneity in these components in a cohort of healthy middle-age and older adults who participated in a prescribed 6-month supervised aerobic exercise intervention as part of the Brain in Motion study. METHODS AND RESULTS: Group-based multitrajectory analysis (GBMTA) was used to characterize variation in the trajectory of exercise intensity and duration for male and female participants in the first 3 months of the exercise program. The GBMTA for males and females revealed two distinct trajectory subgroups, namely, "high-increasing" (HI) and "low-increasing" (LI). Logistic regression was used to assess the association between the identified latent subgroups and (i) demographic characteristics; (ii) physiological characteristics, including cardiovascular and cerebrovascular function; (iii) genetic characteristics; and (iv) adherence with American College of Sports Medicine guidelines on exercise for older adults. Of the 196 participants, 54.1% met the American College of Sports Medicine aerobic exercise targets for intensity and duration during the intervention. Aerobic fitness (maximal oxygen uptake; odds ratio, 1.27; P < 0.01) was significantly different between these trajectory subgroups in males, and cerebrovascular function (cerebrovascular resistance; odds ratio, 0.14; P < 0.01) was significantly different between these trajectory subgroups in females. CONCLUSION: This novel approach to tracking a prespecified exercise program highlights that there are individual and group-specific variations within a prescribed exercise intervention. Characterizing exercise adherence in this way holds promise in developing optimized exercise prescriptions tailored to individual baseline characteristics, and additionally highlighting those participants at greatest risk of not meeting minimum dosage requirements for physiological and/or cognitive health.

No evidence that working memory training alters gray matter structure: A MRI surface -based analysis.

Attempts to determine the cognitive benefits of adaptive working memory training in healthy adults has resulted in a polarized and stagnating field. Heterogeneous approaches and problematic methodological choices have contributed to the controversy. Structural neuroimaging has the potential to identify biological changes present after working memory training, which could go undetected by cognitive outcome tasks. In this study, 24 healthy community dwelling adults aged 18 - 40 years underwent structural magnetic resonance neuroimaging (MRI) before and after completing a 6-week n-back working memory training program. An active control group (n = 24) completed 6-weeks of processing speed training using the same computerized platform and neuroimaging protocol. Cortical surface area, thickness, and volume measurements were collected in a-priori regions of interest in the frontal and parietal lobes. Subcortical and total gray matter volumes were also measured. Group by time repeated measures Analyses of Variance (RM-ANOVAs) were conducted to identify changes in surface area, thickness, or volume measurements associated with training type over time. Null results were present across all neuroanatomical metrics after correction for multiple comparisons. Findings of this study, in concert with recently published investigations, support the idea that adaptive n-back working memory training is not an effective method for inducing neuroanatomical change. Further investigation into other forms of training may help advance the field.

Protective Effects of Exercise on Cognition and Brain Health in Older Adults.

Accelerated trajectories of cognitive decline in older adults may increase the risk of developing Alzheimer disease and related dementias (ADRD). Physical activity has potential modifying effects on these changes that could prevent or delay ADRD. This review explores the hypothesis that multiple, mutually complimentary, and interacting factors explain the positive association between exercise and the optimization of cognition in older adults.

Effects of Six-Month Aerobic Exercise Intervention on Sleep in Healthy Older Adults in the Brain in Motion Study: A Pilot Study.

BACKGROUND: Sleep disturbances have been shown to be associated with the presence of the apolipoprotein (APOE) ɛ4 allele, the well-known genetic risk factor for late-onset sporadic Alzheimer's disease (AD). OBJECTIVE: This study quantifies the effects of a six-month aerobic exercise intervention on objective and subjective sleep quality in middle-aged to older individuals including those at increased genetic risk for late-onset sporadic Alzheimer's disease (AD), who carry the apolipoprotein (APOE) ɛ4 risk allele. METHODS: 199 sedentary men and women without significant cognitive impairments were enrolled in the Brain in Motion study, a quasi-experimental single group pre-test/post-test study with no control group. Participants completed a six-month aerobic exercise intervention and consented to genetic testing. Genotyping of APOE confirmed that 54 individuals were carriers of the ɛ4 allele. Participants' subjective quality of sleep was assessed with the Pittsburgh Sleep Quality Index (PSQI) pre- and post-intervention. A convenience sample of participants (n = 29, APOE ɛ4+ = 7) consented to undergo two nights of in-home polysomnography (PSG) pre- and post intervention. Sleep architecture and respiratory variables were assessed. RESULTS: The six-month aerobic exercise intervention significantly improved participants' total PSQI score, sleep efficiency, and sleep latency in the full sample (n = 199). PSG results showed that total sleep time and sleep onset latency significantly improved over the course of the exercise intervention only in individuals who carried the APOE ɛ4 allele. These results are, however, exploratory and need to be carefully interpreted due to the rather small number of APOE ɛ4+ in the PSG subgroup. CONCLUSIONS: The six-month aerobic exercise intervention significantly improved participants' sleep quality with beneficial effects on PSG shown in individuals at increased genetic risk for late-onset sporadic AD.

Functional brain activation associated with working memory training and transfer.

While behavioural trials of working memory (WM) training have received much attention in recent years, a lesser explored parallel approach is functional neuroimaging. A small literature has suggested a complex time course for functional activation pattern changes following WM training (i.e. not simply increasing or decreasing due to training); however, no study to date has examined such neuroplastic effects in both the training task (dual n-back) and the fluid intelligence transfer task to which the training is purported to transfer (Raven's Matrices). This study investigated neural correlates of WM training in healthy young adults randomized to six weeks of WM training, or an active control condition (processing speed training) with a pre- and post-training fMRI design. Results indicated significant reductions in activation for the WM trained group in key WM-task related areas for trained WM tasks after training compared to the processing speed active control group. The same pattern of training related decreases in activation for the WM trained group was not observed for the transfer task, which is consistent with null results for all cognitive outcomes of the present trial. The observed pattern of results suggests that repetitive practice with a complex task does indeed lead to neuroplastic processes that very likely represent the reduced demand for attentional control while sub-components of the task become more routinized with practice. We suggest that future research investigate neural correlates of WM training in populations for which WM itself is impaired and/or behavioural trials of WM training have returned more promising results.

Working memory training in healthy young adults: Support for the null from a randomized comparison to active and passive control groups.

Training of working memory as a method of increasing working memory capacity and fluid intelligence has received much attention in recent years. This burgeoning field remains highly controversial with empirically-backed disagreements at all levels of evidence, including individual studies, systematic reviews, and even meta-analyses. The current study investigated the effect of a randomized six week online working memory intervention on untrained cognitive abilities in a community-recruited sample of healthy young adults, in relation to both a processing speed training active control condition, as well as a no-contact control condition. Results of traditional null hypothesis significance testing, as well as Bayesian factor analyses, revealed support for the null hypothesis across all cognitive tests administered before and after training. Importantly, all three groups were similar at pre-training for a variety of individual variables purported to moderate transfer of training to fluid intelligence, including personality traits, motivation to train, and expectations of cognitive improvement from training. Because these results are consistent with experimental trials of equal or greater methodological rigor, we suggest that future research re-focus on: 1) other promising interventions known to increase memory performance in healthy young adults, and; 2) examining sub-populations or alternative populations in which working memory training may be efficacious.

A qualitative analysis of the effects of a comorbid disordered gambling diagnosis with schizophrenia.

Little research has examined the association between disordered gambling and psychosis. In addition, clinicians treating schizophrenia or schizoaffective disorders rarely screen for or treat comorbid gambling problems due to diagnostic overshadowing. Thus, the effects of disordered gambling on symptoms of schizophrenia and vice versa remain largely unexplored and unidentified in research and clinical practice. The goal of the present study was to explore qualitatively the reciprocal associations between schizophrenia/schizoaffective disorder and disordered gambling through content and functional analyses from the perspective of the affected individual. Eight participants who met DSM-IV criteria for schizophrenia or schizoaffective disorder and disordered gambling participated in a qualitative interview examining key antecedents associated with their gambling, as well as perceived functional consequences of gambling. Content analysis revealed unique patterns of responses specific to individuals with schizophrenia or schizoaffective disorder that are not typically observed in individuals with disordered gambling alone. Specifically, gambling as filling a need for activity, and gambling as a means of connecting with society/world were the notable reasons for engaging in problematic gambling. Furthermore, some, but not all participants described a direct exacerbation of their psychosis by gambling and a greater involvement in gambling due to their symptoms of schizophrenia.

Psychosocial Treatments for Schizophrenia: An Evaluation of Theoretically Divergent Treatment Paradigms, and Their Efficacy.

UNLABELLED: General Purpose: This paper chronologically examines four theoretically divergent psychosocial treatments for schizophrenia, each intended to augment pharmacological treatment. The goal is to familiarize readers with a sample of well-established psychosocial treatments to provide an enhanced perspective on newer and future psychosocial treatments for schizophrenia. Clinical implications and future research directions are discussed. METHODOLOGY: Social skills training, cognitive behavioral therapy, cognitive remediation, and social cognitive training therapy paradigms were searched and the extant literature is summarized for each, with particular focus on: 1) the rationale for treatment methodology; 2) particular methods of treatment; and, 3) meta-analytic data regarding their efficacy and/or effectiveness. RESULTS/CONCLUSIONS: Each of the four treatment methodologies discussed evinces particular strengths and specific weaknesses for clinical practice, with no clear superior methodology across all clinical populations/situations. Future research must continue to examine social cognitive treatments, as well as the effects of combined psychosocial treatments.

Intact anger recognition in depression despite aberrant visual facial information usage.

BACKGROUND: Previous literature has indicated abnormalities in facial emotion recognition abilities, as well as deficits in basic visual processes in major depression. However, the literature is unclear on a number of important factors including whether or not these abnormalities represent deficient or enhanced emotion recognition abilities compared to control populations, and the degree to which basic visual deficits might impact this process. METHODS: The present study investigated emotion recognition abilities for angry versus neutral facial expressions in a sample of undergraduate students with Beck Depression Inventory-II (BDI-II) scores indicative of moderate depression (i.e., ≥20), compared to matched low-BDI-II score (i.e., ≤2) controls via the Bubbles Facial Emotion Perception Task. RESULTS: Results indicated unimpaired behavioural performance in discriminating angry from neutral expressions in the high depressive symptoms group relative to the minimal depressive symptoms group, despite evidence of an abnormal pattern of visual facial information usage. LIMITATIONS: The generalizability of the current findings is limited by the highly structured nature of the facial emotion recognition task used, as well as the use of an analog sample undergraduates scoring high in self-rated symptoms of depression rather than a clinical sample. CONCLUSIONS: Our findings suggest that basic visual processes are involved in emotion recognition abnormalities in depression, demonstrating consistency with the emotion recognition literature in other psychopathologies (e.g., schizophrenia, autism, social anxiety). Future research should seek to replicate these findings in clinical populations with major depression, and assess the association between aberrant face gaze behaviours and symptom severity and social functioning.

Aberrant patterns of visual facial information usage in schizophrenia.

Deficits in facial emotion perception have been linked to poorer functional outcome in schizophrenia. However, the relationship between abnormal emotion perception and functional outcome remains poorly understood. To better understand the nature of facial emotion perception deficits in schizophrenia, we used the Bubbles Facial Emotion Perception Task to identify differences in usage of visual facial information in schizophrenia patients (n = 20) and controls (n = 20), when differentiating between angry and neutral facial expressions. As hypothesized, schizophrenia patients required more facial information than controls to accurately differentiate between angry and neutral facial expressions, and they relied on different facial features and spatial frequencies to differentiate these facial expressions. Specifically, schizophrenia patients underutilized the eye regions, overutilized the nose and mouth regions, and virtually ignored information presented at the lowest levels of spatial frequency. In addition, a post hoc one-tailed t test revealed a positive relationship of moderate strength between the degree of divergence from "normal" visual facial information usage in the eye region and lower overall social functioning. These findings provide direct support for aberrant patterns of visual facial information usage in schizophrenia in differentiating between socially salient emotional states.