Laurence Desjardins-Crépeau

Age dependence of hemodynamic response characteristics in human functional magnetic resonance imaging

Functional magnetic resonance imaging (fMRI) studies of cognitive aging have generally compared the amplitude and extent of blood oxygen level-dependent (BOLD) signal increases evoked by a task in older and younger groups. BOLD is thus used as a direct index of neuronal activation and it is assumed that the relationship between neuronal activity and the hemodynamic response is unchanged across the lifespan. However, even in healthy aging, differences in vascular and metabolic function have been observed that could affect the coupling between neuronal activity and the BOLD signal. Here we use a calibrated fMRI method to explore vascular and metabolic changes that might bias such BOLD comparisons. Though BOLD signal changes evoked by a cognitive task were found to be similar between a group of younger and older adults (e.g., 0.50 ± 0.04% vs. 0.50 ± 0.05% in right frontal areas), comparison of BOLD and arterial spin labelling (ASL) responses elicited in the same set of structures by a controlled global hypercapnic manipulation revealed significant differences between the 2 groups. Older adults were found to have lower responses in BOLD and flow responses to hypercapnia (e.g., 1.48 ± 0.07% vs. 1.01 ± 0.06% over gray matter for BOLD and 24.92 ± 1.37% vs. 20.67 ± 2.58% for blood flow), and a generally lower maximal BOLD response M (5.76 ± 0.2% vs. 5.00 ± 0.3%). This suggests that a given BOLD response in the elderly might represent a larger change in neuronal activity than the same BOLD response in a younger cohort. The results of this study highlight the importance of ancillary measures such as ASL for the correct interpretation of BOLD responses when fMRI responses are compared across populations who might exhibit differences in vascular physiology.

Absolute quantification of resting oxygen metabolism and metabolic reactivity during functional activation using QUO2 MRI

We have recently described an extension of calibrated MRI, which we term QUO2 (for QUantitative O(2) imaging), providing absolute quantification of resting oxidative metabolism (CMRO(2)) and oxygen extraction fraction (OEF(0)). By combining BOLD, arterial spin labeling (ASL) and end-tidal O(2) measurements in response to hypercapnia, hyperoxia and combined hyperoxia/hypercapnia manipulations, and the same MRI measurements during a task, a comprehensive set of vascular and metabolic measurements can be obtained using a generalized calibration model (GCM). These include the baseline absolute CBF in units of ml/100g/min, cerebrovascular reactivity (CVR) in units of %Δ CBF/mm Hg, M in units of percent, OEF(0) and CMRO(2) at rest in units of μmol/100g/min, percent evoked CMRO(2) during the task and n, the value for flow-metabolic coupling associated with the task. The M parameter is a calibration constant corresponding to the maximal BOLD signal that would occur upon removal of all deoxyhemoglobin. We have previously shown that the GCM provides estimates of the above resting parameters in grey matter that are in excellent agreement with literature. Here we demonstrate the method using functionally-defined regions-of-interest in the context of an activation study. We applied the method under high and low signal-to-noise conditions, corresponding respectively to a robust visual stimulus and a modified Stroop task. The estimates fall within the physiological range of literature values, showing the general validity of the GCM approach to yield non-invasively an extensive array of relevant vascular and metabolic parameters.

Hearts and minds: linking vascular rigidity and aerobic fitness with cognitive aging

Human aging is accompanied by both vascular and cognitive changes. Although arteries throughout the body are known to become stiffer with age, this vessel hardening is believed to start at the level of the aorta and progress to other organs, including the brain. Progression of this vascular impairment may contribute to cognitive changes that arise with a similar time course during aging. Conversely, it has been proposed that regular exercise plays a protective role, attenuating the impact of age on vascular and metabolic physiology. Here, the impact of vascular degradation in the absence of disease was investigated within 2 groups of healthy younger and older adults. Age-related changes in executive function, elasticity of the aortic arch, cardiorespiratory fitness, and cerebrovascular reactivity were quantified, as well as the association between these parameters within the older group. In the cohort studied, older adults exhibited a decline in executive functions, measured as a slower performance in a modified Stroop task (1247.90 ± 204.50 vs. 898.20 ± 211.10 ms on the inhibition and/or switching component, respectively) than younger adults. Older participants also showed higher aortic pulse wave velocity (8.98 ± 3.56 vs. 3.95 ± 0.82 m/s, respectively) and lower VO₂ max (29.04 ± 6.92 vs. 42.32 ± 7.31 mL O2/kg/min, respectively) than younger adults. Within the older group, faster performance of the modified Stroop task was associated with preserved aortic elasticity (lower aortic pulse wave velocity; p = 0.046) and higher cardiorespiratory fitness (VO₂ max; p = 0.036). Furthermore, VO₂ max was found to be negatively associated with blood oxygenation level dependent cerebrovascular reactivity to CO₂ in frontal regions involved in the task (p = 0.038) but positively associated with cerebrovascular reactivity in periventricular watershed regions and within the postcentral gyrus. Overall, the results of this study support the hypothesis that cognitive status in aging is linked to vascular health, and that preservation of vessel elasticity may be one of the key mechanisms by which physical exercise helps to alleviate cognitive aging.

Higher levels of cardiovascular fitness are associated with better executive function and prefrontal oxygenation in younger and older women

Aim: Many studies have suggested that physical exercise training improves cognition and more selectively executive functions. There is a growing interest to clarify the neurophysiological mechanisms that underlie this effect. The aim of the current study was to evaluate the neurophysiological changes in cerebral oxygenation associated with physical fitness level and executive functions. Method: In this study, 22 younger and 36 older women underwent a maximal graded continuous test (i.e., V˙O2max) in order to classify them into a fitness group (higher vs. lower fit). All participants completed neuropsychological paper and pencil testing and a computerized Stroop task (which contained executive and non-executive conditions) in which the change in prefrontal cortex oxygenation was evaluated with near infrared spectroscopy (NIRS). Results: Our findings revealed a Fitness × Condition interaction (p < 0.05) such that higher fit women scored better on measures of executive functions than lower fit women. In comparison to lower fit women, higher fit women had faster reaction times in the Executive condition of the computerized Stroop task. No significant effect was observed in the non-executive condition of the test and no interactions were found with age. In measures of cerebral oxygenation (ΔHbT and ΔHbO2), we found a main effect of fitness on cerebral oxygenation during the Stroop task such that only high fit women demonstrated a significant increase in the right inferior frontal gyrus. Discussion/Conclusion: Higher fit individuals who demonstrate better cardiorespiratory functions (as measured by V˙O2max) show faster reaction times and greater cerebral oxygenation in the right inferior frontal gyrus than women with lower fitness levels. The lack of interaction with age, suggests that good cardiorespiratory functions can have a positive impact on cognition, regardless of age.

Effects of combined physical and cognitive training on fitness and neuropsychological outcomes in healthy older adults.

Purpose Physical exercise and cognitive training have been shown to enhance cognition among older adults. However, few studies have looked at the potential synergetic effects of combining physical and cognitive training in a single study. Prior trials on combined training have led to interesting yet equivocal results. The aim of this study was to examine the effects of combined physical and cognitive interventions on physical fitness and neuropsychological performance in healthy older adults. Methods Seventy-six participants were randomly assigned to one of four training combinations using a 2×2 factorial design. The physical intervention was a mixed aerobic and resistance training program, and the cognitive intervention was a dual-task (DT) training program. Stretching and toning exercises and computer lessons were used as active control conditions. Physical and cognitive measures were collected pre- and postintervention. Results All groups showed equivalent improvements in measures of functional mobility. The aerobic–strength condition led to larger effect size in lower body strength, independently of cognitive training. All groups showed improved speed of processing and inhibition abilities, but only participants who took part in the DT training, independently of physical training, showed increased task-switching abilities. The level of functional mobility after intervention was significantly associated with task-switching abilities. Conclusion Combined training did not yield synergetic effects. However, DT training did lead to transfer effects on executive performance in neuropsychological tests. Both aerobic-resistance training and stretching-toning exercises can improve functional mobility in older adults.

Physical Functioning Is Associated With Processing Speed and Executive Functions in Community-Dwelling Older Adults

OBJECTIVES The aim of this study was to examine the association between physical functioning and cardiovascular burden on the cognitive performance of community-dwelling older adults. METHOD Ninety-three adults aged 60 and older completed a medical evaluation by a geriatrician, performance-based physical tests, and neuropsychological assessments. Cognitive composite scores (memory, speed, and executive) as well as a physical functioning score were created by averaging standardized z-scores of selected tests. A cardiovascular burden index was also computed by totalling the number of cardiovascular risk factors and diseases. RESULTS Multiple hierarchical regression analyses reveal that higher level of physical functioning was significantly associated with greater processing speed and better executive functions but was not associated with memory performance. These relations were independent of age, sex, and level of education. Cardiovascular burden was not significantly associated with any cognitive domain. DISCUSSION These results suggest that cognition is related to simple performance-based physical tests and highlight the importance of intervention studies aimed at enhancing cognitive and physical functioning in older adults.

Shedding light on the effect of priority instructions during dual-task performance in younger and older adults: A fNIRS study

Age-related differences in the ability to perform two tasks simultaneously (or dual-task) have become a major concern in aging neurosciences and have often been assessed with two distinct paradigms; the Psychological Refractory Period (PRP) and the Dual-Task (DT) paradigms. PRP studies assess participants when they give Priority to one task over the other (complete A then B), whereas in DT studies participants give Equal priority to both tasks (complete A and B). The Equal condition could be viewed as adding an executive control component to the task since the participants must spontaneously monitor attention between tasks. In the current study, we assessed the effect of priority instructions (Priority vs. Equal) on the dual-task performance and brain activity of younger (n = 16) and older adults (n = 19) with functional near infra-red spectroscopy (fNIRS). In younger adults, the Priority condition showed right-sided activation in the prefrontal cortex during DT execution. Older adults showed bilateral frontal activation, yet restrained to specific areas. They showed increased activation in DT vs. single task condition in the left dorsolateral prefrontal cortex (DLPFC) and the bilateral ventrolateral prefrontal cortex (VLPFC). In the Equal condition, the DT condition showed isolated left DLPFC and VLPFC activation in younger adults and widespread bilateral DLPFC activation in older adults. These results suggest that for both older and younger adults, priority effects are associated with distinct patterns of prefrontal activation. Age-related differences also exist in these patterns such that prefrontal activation seems to be more spread out at different sites in older adults when they are instructed to give Equal priority to both tasks.

Does Combined Physical and Cognitive Training Improve Dual-Task Balance and Gait Outcomes in Sedentary Older Adults?

Everyday activities like walking and talking can put an older adult at risk for a fall if they have difficulty dividing their attention between motor and cognitive tasks. Training studies have demonstrated that both cognitive and physical training regimens can improve motor and cognitive task performance. Few studies have examined the benefits of combined training (cognitive and physical) and whether or not this type of combined training would transfer to walking or balancing dual-tasks. This study examines the dual-task benefits of combined training in a sample of sedentary older adults. Seventy-two older adults (≥60 years) were randomly assigned to one of four training groups: Aerobic + Cognitive training (CT), Aerobic + Computer lessons (CL), Stretch + CT and Stretch + CL. It was expected that the Aerobic + CT group would demonstrate the largest benefits and that the active placebo control (Stretch + CL) would show the least benefits after training. Walking and standing balance were paired with an auditory n-back with two levels of difficulty (0- and 1-back). Dual-task walking and balance were assessed with: walk speed (m/s), cognitive accuracy (% correct) and several mediolateral sway measures for pre- to post-test improvements. All groups demonstrated improvements in walk speed from pre- (M = 1.33 m/s) to post-test (M = 1.42 m/s, p < 0.001) and in accuracy from pre- (M = 97.57%) to post-test (M = 98.57%, p = 0.005).They also increased their walk speed in the more difficult 1-back (M = 1.38 m/s) in comparison to the 0-back (M = 1.36 m/s, p < 0.001) but reduced their accuracy in the 1-back (M = 96.39%) in comparison to the 0-back (M = 99.92%, p < 0.001). Three out of the five mediolateral sway variables (Peak, SD, RMS) demonstrated significant reductions in sway from pre to post test (p-values < 0.05). With the exception of a group difference between Aerobic + CT and Stretch + CT in accuracy, there were no significant group differences after training. Results suggest that there can be dual-task benefits from training but that in this sedentary sample Aerobic + CT training was not more beneficial than other types of combined training.

Enhanced fitness relates to reduced cerebrovascular reactivity and perfusion in a sample of very healthy older adults

Aging is accompanied by decreased grey matter volume (GMV), cerebral blood flow (CBF), and cerebrovascular reactivity (CVR), where the latter tends to decline the earliest in aging. Enhanced fitness in aging has been related to preservation of GMV and CBF, and in some cases CVR, although there are contradictory relationships reported between CVR and fitness. Therefore, to gain a better understanding of the complex interplay with fitness and GMV, CBF and CVR, it is necessary to study them concurrently. Here, we aimed to disentangle the interactions between these outcomes in healthy older adults. MRI acquisitions collected anatomical, CBF and CVR information in all participants, as well as VO2,max. Results revealed decreased CVR was associated with increased fitness throughout large areas of the cerebral cortex. Within these regions it was found that lower fitness was associated with higher CBF and a slower hemodynamic response to hypercapnia. Overall, results indicate that the relationship between age, cerebral health and cerebral hemodynamics are complex. Future studies should collect other physiological outcomes in parallel with quantitative imaging, such as measures of carbon dioxide sensitivity and autoregulation, to further understand the intricacy of the effects fitness has on the aging brain, and how this may bias quantitative measures of cerebral health.

Hypertension and Age-Related Cognitive Decline

As the population is aging rapidly worldwide, there is an increasing need to better understand chronic conditions associated with aging such as vascular and metabolic diseases, and cognitive decline. Hypertension is one of the most prevalent chronic conditions associated with age and its impact on cognitive decline has often been put forth. Overall, both longitudinal and cross-sectional investigations suggest that hypertension can increase the risk of cognitive decline, and that the negative impact is more salient in processing speed and executive control tests. However, memory deficits associated with hypertension can also be observed. While hypertension has consistently been shown to increase the risk of dementia in middle-aged or young-old adults, some studies suggest that it could have a protective effect on cognition in very old populations. Studies looking at the effect of antihypertensive drug treatments report diverging results, but tend to suggest that treatment might be effective in preventing cognitive decline associated with age. Together, findings summarized here suggest that hypertension is an important factor that has a worsening effect on cognition as people age, and that antihypertensive approaches could help control or alleviate the impact of elevated blood pressure on cognition. Future studies will help identify effective ways to control hypertension and potentially emphasize preventive approaches as complementary avenues to the more traditional pharmacological approach.