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Increasing precision in exercise prescription to promote cognitive and brain health. The neural interplay between cognitive function and mobility. The relationship between sleep and cognitive function. Preventing falls in high-risk older adults.
Individuals with a background in: 1) kinesiology; 2) psychology; 3) geriatrics; and/or 4) neuroimaging - with experience in clinical research and working directly with older adults.
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Dissertations completed in 2010 or later are listed below. Please note that there is a 6-12 month delay to add the latest dissertations.
White matter hyperintensities (WMH) are a prominent feature of cerebral small vessel disease and are associated with cognitive and mobility impairment. These deficits may be caused by the disruption of large-scale functional networks due to the presence of WMHs. However, knowledge regarding the relevance of these lesions on functional networks remains inconclusive. In this thesis I used lesion network mapping to: 1) investigate the functional connectivity specifically associated with WMHs; and 2) determine whether WMH-related disruption to major functional networks is associated with impairments in cognition and mobility. In addition, physical activity (PA) is a possible countermeasure to reduce both WMHs and falls risk. However, no study has yet investigated whether PA attenuates the association between WMHs, falls risk, and cognition. I conducted a secondary cross-sectional analysis to investigate whether PA moderates the association between WMH volume, falls risk, and cognition. Finally, resistance training (RT) is a promising lifestyle intervention to reduce WMH progression, improve executive functions, and reduce falls. However, the underlying neurobiological process by which RT improves executive functions and falls risk remain unclear. Thus, I conducted an exploratory analyses of a randomized controlled trial to: 1) identify whether RT is able to mitigate WMH-related network disruption; and 2) determine whether changes in network disruption are associated with changes in cognition and falls risk. My research showed that WMH-related disruption to the sensorimotor, and ventral attention network was associated with poorer global cognition and postural sway, while disruption to the dorsal attention network was associated with increased falls risk. I showed that PA moderates the association between WMHs and falls risk and that 12 months of twice-weekly RT slowed WMH-related disruption to the sensorimotor, dorsal attention, and ventral attention networks. Reduced disruption to the dorsal and ventral attention networks was associated with improved executive functions and reduced falls risk respectively. The findings from this thesis highlight the functional networks disrupted by WMHs that may underlie the cognitive impairment and increased falls risk evident in older adults with cerebral small vessel disease. Further, interventions targeting disease progression should aim to increase physical activity, with a potential emphasis on RT.
Effective lifestyle and behavioural strategies which maintain the cognitive health of older adults with Mild Cognitive Impairment (MCI) – a transition stage between healthy cognition and dementia – are greatly needed. There are three time-use activity behaviours which all humans engage in daily: physical activity (PA), sedentary behaviour (SB), and sleep. Each time-use activity behaviour is linked to cognitive health, although the magnitude of these relationships are still uncertain. There is also preliminary evidence that these time-use activity behaviours share a complex and dynamic relationship with each other and cognitive health. Thus, the aim of this dissertation was two-fold: 1) to advance the current knowledge about the dynamic relationships between time-use activity behaviours and cognitive health; and 2) to characterize potential time-use activity behaviour intervention strategies for promoting cognitive health. Using a systematic review of observational studies, I showed SB is associated with poorer cognitive function. I next conducted three cross-sectional studies which found 1) the relationships of PA and SB with cognitive function differ by MCI status; 2) PA is associated with better cognitive function independent of any sleep index, while only sleep efficiency is associated with cognitive performance independent of PA; and 3) PA is associated with greater brain cortical thickness independent of SB, but SB is not associated with cortical thickness independent of PA. I then conducted a secondary analysis of a randomized controlled trial (RCT), where I found that while the intervention significantly increased older adult PA, it did not improve cognitive function. My final thesis study was a proof-of-concept RCT to examine the effects of multimodal chronotherapy to promote better sleep among older adults with MCI and poor sleep; I found the intervention improved subjective sleep, but did not improve objective sleep or cognitive function. The results of my thesis contribute to a better understanding of how time-use activity behaviours impact older adult cognitive health, and helps to refine the public health message for best promoting healthy cognitive aging through lifestyle.
Since the world is aging at an unprecedented rate, it is important to identify and evaluate strategies that promote healthy cognitive aging. In addition to exercise, computerized cognitive training (CCT) is an emerging and promising strategy to promote cognitive function. Therefore, the aim of my dissertation is four-fold: 1) To provide a detailed review of literature examining the underlying neural changes of CCT in older adults; 2) To examine the effects of CCT, alone and when immediately preceded by a 15-minute brisk walk, on cognitive function; 3) To identify the neural correlates of CCT-induced cognitive benefits; and 4) To examine whether CCT impacts these neural correlates. Firstly, a systematic review examining the underlying neural mechanisms of CCT showed that, despite promising benefits on for example functional connectivity, there is a need for more high-quality studies in order to draw sound conclusions. Secondly, I addressed the remaining three aims by developing an 8-week randomized controlled trial of CCT examining the impact of CCT, alone and when immediately preceded by a single bout of aerobic exercise, on cognitive function compared with an active control in community-dwelling older adults. Results demonstrated that those assigned to CCT showed cognitive benefits compared with those assigned to the active control. More widespread cognitive benefits were seen for those assigned to the combined exercise and CCT group. In addition, using resting-state functional magnetic resonance imaging, I examined inter-network functional connectivity over the course of the eight weeks. I was able to identify inter-network functional connectivity correlates of change in cognitive performance observed after the 8-week intervention. Moreover, those assigned to purely CCT improved regional inter-network functional connectivity compared with the active control. My work confirms and extends on previous work, suggesting that CCT benefits cognitive function. A novel finding is the additional cognitive benefit elicited when preceding CCT with a single bout of exercise. Additionally, new insights into the potential neural mechanisms underlying CCT-induced benefits on cognitive function are presented. Overall, results from my dissertation contribute to this emerging field, suggesting CCT as a promising strategy to promote healthy cognitive aging.
Cerebral small vessel disease (cSVD) is a key contributor to vascular cognitive impairment and Alzheimer’s disease (AD), the two most common causes of cognitive impairment and dementia. Given the pervasiveness of cSVD in older adults, it is critical that we better understand the cognitive and physical outcomes of cerebrovascular damage and identify strategies to mitigate its progression. Moreover, it is important to assess the effect AD pathology in cSVD, as the two often co-exist and share common pathogenic mechanisms. Specifically, I investigated the role of Aβ plaques, a pathological hallmark of AD, on cognitive and physical outcomes in older adults with cSVD. Another feature of cSVD is myelin loss and currently its role is poorly understood; as such, I examined the contribution of myelin to cognition in older adults with cSVD. There is mounting evidence to suggest that aerobic training (AT) is a promising strategy to combat cSVD as key vascular risk factors (i.e., hypertension, hypercholesteremia, and type 2 diabetes) are modifiable by exercise; critically, the efficacy of exercise may vary by biological sex. Thus, I conducted an exploratory analysis of a randomized controlled trial to examine: 1) the impact of AT in mitigating white matter hyperintensity (WMH) progression, a predominant cSVD lesion; and 2) whether AT efficacy varied by sex. My research showed that Aβ plaque deposition was negatively associated with both cognitive and physical outcomes. In addition, less myelin was associated with impaired processing speed and working memory. My exploratory analysis did not find that AT significantly reduced WMH progression. However, there was a sex difference in response to AT; AT trained males demonstrated reduced progression compared with AT trained females. Overall, the results of this thesis suggest that therapeutic trials in people with cSVD should consider the effects of both cerebral Aβ plaque deposition and myelin loss on cognitive or physical function and future studies should account for sex differences to better understand the efficacy of exercise training. There has been limited pharmacological progress in treating cSVD; thus, it is critical that we continue to investigate lifestyle strategies to prevent or slow the progression of cSVD.
As the world’s population ages, mobility and cognitive impairments are major health-care priorities. Given the particular relevance of the brain in the manifestation of both conditions, the aims of my dissertation are two-fold: 1) to advance our knowledge of the intrinsic relationship between mobility and cognitive impairments; and 2) to characterize the underlying functional neural mechanisms by which exercise promotes cognitive and mobility outcomes in older adults with mild cognitive impairment. Using magnetic resonance imaging, I focused on characterizing brain structures and brain function – as measured by functional neural activity as well as regional and network connectivity – associated with falls and slow gait. Additionally, I investigated how aerobic exercise may exert influence on mobility and cognitive function via pathways indicated by magnetic resonance imaging derived neural correlates. My research showed that while falls are associated with lower total and regional gray and white matter volume, slow gait, in conjunction with mild cognitive impairment, is reflected by disrupted neural network connectivity. Moreover, my work aligns with emerging concept of neural efficiency by generating evidence that suggests aerobic exercise training may promote mobility and cognitive function by maintaining or improving neural efficiency. Overall, these results contribute to a better understanding of the neural underpinnings of mobility and cognitive impairments, as well as provide new insight into the neural mechanisms by which exercise promotes mobility and cognitive function.
Introduction: The world’s population is aging at an unprecedented rate. By 2050, the number of adults older than 60 years will double from 10% to 20%. This trend has immense implications, due to the prevalence of impaired physical and cognitive functions among older adults. Therefore, it is important to understand the underlying mechanisms for these impairments and identify effective prevention strategies. White matter hyperintensities (WMHs) are common findings on MRI scans of older adults, and are associated with both physical and cognitive decline. Key risk factors for WMHs are related to metabolic and cardiovascular health. Thus, due to the established and significant benefit of targeted exercise training on metabolic and cardiovascular health in older adults, we hypothesized that one mechanism by which exercise, and specifically resistance training (RT), promotes physical and cognitive functions is by reducing WMH progression among older adults. Methods: We explored the associations between WMHs and physical and cognitive functions in Chapters 2 to 4. In Chapter 5, we presented a randomized controlled trial of 52-week RT. Participants were randomized to either once-weekly RT, twice-weekly RT, or twice-weekly balance and tone. We investigated the effect of RT on WMH progression. Results: Results from Chapters 2 and 3 suggest that reduced WMH progression may translate to maintained, or improved, physical and cognitive functions. Chapter 4 demonstrated that physical function is important for cognitive health. Chapter 5 provided proof-of-concept evidence that RT has beneficial effects on WMH progression, which may translate to improved physical and cognitive function. Specifically, we found that reduced WMH progression was significantly iii associated with improved gait speed. Moreover, our results suggest this effect may be dose-dependent, as the significant reduction in WMH progression was only observed among those in the twice-weekly RT group, and not in the once-weekly RT group. Conclusion: We provided converging evidence from four separate studies leading to the conclusion that RT has beneficial effects on WMH progression. Since WMHs are demonstrated to have significant associations with physical and cognitive dysfunctions, we believe that exercise-induced reductions of WMHs progression might translate to improvements in physical and cognitive functions in older adults.
Falls are a leading health care issue in our rapidly aging society. While impaired cognitive functioning has previously been linked to falls, my dissertation aims to understand the specific relationship between attentional processing and falls/falls risk. My dissertation is comprised of four separate studies, each examining a specific facet of attention and its corresponding association with falls. The specific domains of attention that I examine include: 1. Visual-spatial attention in the context of task-irrelevant peripheral stimuli; 2. Dual-task ability under cognitive load using a virtual reality system intended to simulate real-world experiences; 3. Time spent engaged in task-unrelated thoughts (i.e., mind-wandering); and 4. The neural correlates that subserve selective attention and executive control. Using multi-modal measures, including event-related potentials, functional magnetic resonance imaging, and behavioural performance, my research examines how each area of attention is impaired as a function of falls history and/or physiological falls risk. Based on the attentional resource model, my research converges on the notion that falls risk is associated with a reduction in the level of available attentional resources, in addition to an impaired ability to appropriately allocate resources to the primary task. Importantly, such deficits in attentional processing may contribute to postural instability, given that the control of balance and posture require a greater proportion of cognitive resources with age. Taken together, these findings have critical implications for developing novel intervention strategies aimed towards improving quality of life and independence among older adults.
Master's Student Supervision
Theses completed in 2010 or later are listed below. Please note that there is a 6-12 month delay to add the latest theses.
As the population of older adults is expected to rise exponentially, the necessity for a clearer understanding of the components that contribute to age-related changes in cognitive function cannot be overstated. It is critical to understand the risk factors for cognitive decline and dementia in order to improve early detection and prevention. Females are disproportionately affected by Alzheimer’s Disease and other dementias due to contributing factors such as age and sex hormones. Pregnancy is a significant hormonal event in a female’s life and has been found to be associated with increased cardiovascular risk. While the relationship between pregnancy and cardiovascular risk in later life is well-established, whether the number of pregnancies influences this risk still requires further exploration. In this cross-sectional study, the differences in cardiovascular risk as well as executive function among levels of parity in older females with mild cognitive impairment were assessed. Further, the influence physical fitness has on the relationships between parity and cardiovascular risk as well as parity and executive function in older females with mild cognitive impairment was explored. Baseline data were compiled from two ongoing randomized controlled trials within the Aging, Mobility, and Cognitive Health Lab. Results showed that cardiovascular risk was lowest among primiparous females compared with multiparous females and yet, executive function was lowest among primiparous females and highest among females having given birth twice. In addition, physical fitness did not moderate the relationship between cardiovascular risk and parity nor did it moderate the relationship between parity and executive function. The findings from this highlight the importance of taking reproductive health into consideration when evaluating cardiovascular and cognitive health in females in later life.
Cognitive impairment is a common consequence of stroke that is largely overlooked in post-stroke care. To improve care for cognitive health in stroke, records of lived experience are needed to understand patient priorities. Post-stroke cognition is interrelated with other forms of post-stroke impairment. Specifically, executive performance is cross-sectionally related to mobility post-stroke but it is unknown if this relationship persists over time. This thesis examined: 1) the lived experience of cognitive changes post-stroke and 2) the relationship between executive performance and changes in mobility and balance over time in chronic stroke. Aim 1 was addressed through a qualitative study which captured the experience of post-stroke cognitive changes. This study showed that subjective post-stroke cognitive changes carried meaningful consequences for participants, and identified potential gaps in stroke care. Aim 2 was addressed in sub-analyses of data from a randomized control trial examining the effects of exercise and social and cognitive enrichment on cognition against a control (balance and tone exercises) in community-dwelling older adults (aged 55+ years) with chronic stroke (n=120). Four MANCOVA models were constructed wherein change in mobility was the dependent variable and executive performance and intraindividual variability at baseline were the independent variables; group allocation, age, sex, and education were included as covariates. Change in mobility was quantified through change scores calculated from baseline and 6-month performance on the Timed Up and Go test, the Short Physical Performance Battery and usual gait speed. Separate models were constructed for each independent variable: Digit Span test, Trail-Making Test Ratio, Stroop Colour Word test and intraindividual variability of the Stroop Colour Word test, using Pillai’s Trace. If a significant multivariate test was identified for any independent variable, the univariate F tests were examined. Given the known effect of two study groups: the control group and exercise training, on mobility, the 4 MANCOVA models were run within a sample of all 3 study groups (n=103/120), and a sample of the exercise and control groups (n=74/120). Future studies are needed to better understand whether executive performance or intraindividual variability predicts change in mobility and balance in chronic stroke.
PURPOSE:Current evidence suggests chronic resistance exercise training (RET) improves older adults’ executive function; however, the effects of a single session of resistance exercise (RE) and dose (i.e., frequency, intensity, volume) on executive performance remains unclear. Thus, we investigated the effect of RE, at three different volumes, on executive function in healthy older women. METHODS:This was a within-subjects, crossover study design of 21 untrained, older women (65-75 years). At baseline, participants were familiarized with four RE machines (leg press, chest press, knee-extension and lat pull down) and performed a 10RM. Following a minimum of 7 days, participants randomly completed 3 RE conditions: 1, 3, or 5 sets of 10 repetitions (70%1RM; 120 sec rest between sets) for each exercise, and a control (CON) condition. We measured two executive processes: 1) inhibitory control using the Flanker task, and 2) cognitive flexibility using the Dimensional Change Card Sort (DCCS) task. We also measured the affective response to RE using the Feelings Scale. Using a linear mixed model, we determined the effect of different RE volumes (i.e., condition) and time (i.e., visit number), adjusting for baseline performance, on change in inhibitory control (i.e., after RE – before RE) and cognitive flexibility. We also examined the effect of both RE volume and time on change in affect (i.e., after RE – before RE) using a linear mixed model. RESULTS:At baseline, participants were physically healthy and did not have cognitive impairment (Montreal Cognitive Assessment (MoCA) scores > 26/30). There were no significant differences found for acute changes in flanker performance by condition performed (i.e., 1, 3, 5, or CON) (p=0.12) and by time (i.e., visit number) (p=0.84). Similarly, there was no effect of condition on acute changes in DCCS performance (p=0.66) or time (p=0.57). Change in affect was not significantly different by both condition (p=0.56) and time (p=0.09).CONCLUSION:Contrary to evidence showing RE can promote executive performance, our results suggest a single bout of RE did not improve executive function in healthy older women, irrespective of volume.
Background: Sub-cortical ischemic vascular cognitive impairment (SIVCI) is the most prevalent form of Vascular Cognitive Impairment (VCI). Previous studies have shown that Carotid-Femoral Pulse Wave Velocity (CF-PWV), cognitive function, mobility performance and blood pressure are related to White Matter Lesions (WMLs) volume, but whether these associations exist in those with mild SIVCI is unclear. Thus, in this study of older adults with mild SIVCI, I examined four questions:1) What is the association between total, deep and periventricular WMLs volume on Magnetic Resonance Imaging (MRI) with CF-PWV?2) What are the associations between total, deep and periventricular WMLs volume and measures of global cognitive function and executive function?3) What is the association between total, deep and periventricular WMLs volume with mobility performance? 4) What is the association between total, deep and periventricular WMLs volume with systolic and diastolic blood pressure?Methods: The data of 34 participants diagnosed with mild SIVCI were used for this cross-sectional analysis. Measures of interest included global cognitive function tests, such as Alzheimer’s disease Assessment Scale Cognitive Subscale (ADAS-cog) and Montreal Cognitive Assessment (MoCA). Executive functions were assessed with paper Stroop test, Trails Making Tests (A&B) and animal fluency. Mobility performance was assessed with the Time Up and Go test (TUG) and usual gait speed. CF-PWV was measured using the Complior System (ALAM Medical, France). WMLs volume was quantified for the total, deep and periventricular WMLs with a semi-automated technique.Results: We did not find an association between total or periventricular WMLs volume with CF-PWV, executive function, global cognitive function, mobility performance or blood pressure. Deep WMLs volume was associated with Trails B-A and animal category fluency but not associated with measures of global cognitive function. Deep WMLs volume was significantly associated with diastolic blood pressure. Conclusion: In this exploratory analysis, deep WMLs volume is associated with executive function and diastolic blood pressure. While systolic hypertension has been strongly linked to large vessel stroke events which are commonly complicated by post stroke cognitive impairment and dementia, our findings provide possible mechanistic insight to previous studies that found association between diastolic blood pressure and cognitive decline.
Introduction:Deficits in balance, mobility and executive functions are common among chronic stroke survivors and contribute to increased falls risk. Targeted exercise training reduces falls risk among older adults with chronic stroke and is a promising strategy to promote cognitive function. Specifically, the Otago exercise program (OEP) reduces falls risk and improves executive functions in older adults with a history of falls. Mindful based meditation (MBM) may be a complementary approach to the OEP for promoting balance and mobility and cognitive outcomes among older adults with chronic stroke. Purpose:The purpose of this proof-of-concept study was three-folds: 1) To examine whether MBM combined with OEP (OEP+MBM) is more efficacious than OEP alone (OEP-only) on improving balance, mobility and cognitive outcomes among older adults with chronic stroke. 2) To explore whether OEP-only or OEP+MBM has benefits for mindful attention, as measured by the Five Factor Mindfulness Questionnaire. 3) To assess components of feasibility to optimize larger repeat trials. Methods:Subjects: Twenty-three community dwelling adults aged > 55 years, who experienced a single ischemic or hemorrhagic stroke at least 12 months prior to studyStudy Design: 12-week proof-of-concept, assessor single-blinded randomized controlled trial Results:There is preliminary evidence for meditation practice as a safe intervention for older adults with chronic stroke. Although no statistically significant effects were found, two cognitive variables with marginally significant improvements for the OEP+MBM group provide support for MBM to improve attention and processing speed. Examination of the between-group differences on the outcome variables standardized to standard deviation values provide tentative support for the OEP+MBM intervention and rationale for further research. Self-reported levels of mindfulness did not increase for either group. The feasibility of conducting future repeat studies was verified with 27 subjects recruited to attend information sessions within six weeks, 24/27 (.89) consenting to study participation and strong adherence (>.80) to interventions for all participants.Conclusions: This proof-of-concept study provides an early indication that future studies are warranted to examine whether the addition of MBM to therapeutic exercise has the potential to positively impacts balance, mobility, and cognitive outcomes in older adults with chronic stroke.
Background Traditionally, Alzheimer’s disease (AD) and vascular cognitive impairment (VCI) were considered to be distinct and unrelated; however, increasing evidence is demonstrating an overlap between AD and VCI pathology. As such, the current criteria for the clinical diagnosis of VCI may not distinguish those with cognitive impairment exclusively due to subcortical ischemic small vessel disease from those with mixed vascular and AD pathology. Furthermore, it is unclear how co-existing amyloid pathology may affect cognitive function in people with VCI. Objectives: 1) To determine the frequency of mixed VCI-amyloid pathology (mixed VCI) in patients clinically diagnosed with VCI. 2) To explore the impact of co-existing amyloid pathology on cognitive function in people with VCI. MethodsThis is a cross sectional analysis of data acquired from a randomized controlled trial investigating the effects of aerobic exercise training on cognitive function in people with VCI. Twenty-four participants – 18 participants with VCI and 6 normal controls – completed PET imaging using Pittsburgh Compund-B (PiB) to quantify amyloid burden. Participants with VCI who exhibited PiB uptake 2 standard deviations above the mean of controls were considered to have significant PiB binding and were classified as PiB-positive and to have mixed VCI.To determine the effect of amyloid pathology on cognitive function we collected the following cognitive measures: 1) ADAS-Cog; 2) EXIT-25; and 3) Three executive processes including a) Digits Forward and Backward Test, b) Stroop Test, c) Trail Making Test (Parts A & B). A Pearson correlation coefficient was used to determine the association between PiB uptake and cognitive function.ResultsEight out of 18 (44%) participants were PiB-positive and 10 (56%) participants were PiB-negative. PiB-positive and PiB-negative groups did not differ in cognitive functioning (p>0.05), however, increased PiB uptake was associated with greater cognitive dysfunction as measured by the MOCA (r=-0.63, p
Background: Falls among seniors are a major health issue. About 30% of community-dwelling adults aged 65 years and older experience one or more falls per year. Although not all falls lead to injury, 20% require medical attention and 5% result in fracture. Fall-related injuries are the leading cause of mortality due to unintentional injuries among those 65 and older. Key falls risk factors are categorized into physical factors (e.g. gait speed, balance, muscle strength, etc.) and neurocognitive factors (e.g. cognitive performance, brain volume, etc.). To date, few studies have examined the brain function on falls risk. My thesis explores this question through functional connectivity MRI analysis. Method: A cross-sectional functional magnetic resonance imaging study consisted of 44 (23 non-fallers and 21 fallers) community dwelling older adults. Participants performed the finger tapping motor task and I examined for differences in functional connectivity of four age-related neural networks: default mode network (DMN), fronto-executive network (FE), fronto-parietal network (FP), and motor network (Mot). Results: Significant between-group differences were identified in between-network functional connectivity. Fallers showed decreased connectivity between the FP network and Mot network (p
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