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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.
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Graduate Student Supervision
Doctoral Student Supervision (Jan 2008 - Nov 2020)
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 (2010 - 2018)
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