The dynamic response to a stimulus such as exercise can reveal valuable insights into systems control in health and disease that are not evident from the steady-state perturbation. However, the dynamic response profile and kinetics of cerebrovascular function have not been determined to date. We tested the hypotheses that bilateral middle cerebral artery blood flow mean velocity (MCA) increases exponentially following the onset of moderate-intensity exercise in 10 healthy young subjects. The MCA response profiles were well fit to a delay (TD) + exponential (time constant, τ) model with substantial agreement for baseline [left (L): 69, right (R): 64 cm/s, coefficient of variation (CV) 11%], response amplitude (L: 16, R: 13 cm/s, CV 23%), TD (L: 54, R: 52 s, CV 9%), τ (L: 30, R: 30 s, CV 22%), and mean response time (MRT) (L: 83, R: 82 s, CV 8%) between left and right MCA as supported by the high correlations (e.g., MRT = 0.82, < 0.05) and low CVs. Test-retest reliability was high with CVs for the baseline, amplitude, and MRT of 3, 14, and 12%, respectively. These responses contrasted markedly with those of three healthy older subjects in whom the MCA baseline and exercise response amplitude were far lower and the kinetics slowed. A single older stroke patient showed baseline ipsilateral MCA that was lower still and devoid of any exercise response whatsoever. We conclude that kinetics analysis of MCA during exercise has significant potential to unveil novel aspects of cerebrovascular function in health and disease. Resolution of the dynamic stimulus-response profile provides a greater understanding of the underlying the physiological control processes than steady-state measurements alone. We report a novel method of measuring cerebrovascular blood velocity (MCAv) kinetics under ecologically valid conditions from rest to moderate-intensity exercise. This technique reveals that brain blood flow increases exponentially following the onset of exercise with ) a strong bilateral coherence in young healthy individuals, and) a potential for unique age- and disease-specific profiles.

Blood velocity measured in the middle cerebral artery (MCA) increases with finite kinetics during moderate-intensity exercise, and the amplitude and dynamics of the response provide invaluable insights into the controlling mechanisms. The MCA response after exercise onset is well fit to an exponential model in young individuals but remains to be characterized in their older counterparts. The responsiveness of vasomotor control degrades with advancing age, especially in skeletal muscle. We tested the hypothesis that older subjects would evince a slower and reduced MCA response to exercise. Twenty-nine healthy young (25 ± 1 yr old) and older (69 ± 1 yr old) adults each performed a rapid transition from rest to moderate-intensity exercise on a recumbent stepper. Resting MCA was lower in older than young subjects (47 ± 2 vs. 64 ± 3 cm/s, P < 0.001), and amplitude from rest to steady-state exercise was lower in older than young subjects (12 ± 2 vs. 18 ± 3 cm/s, P = 0.04), even after subjects were matched for work rate. As hypothesized, the time constant was significantly longer (slower) in the older than young subjects (51 ± 10 vs. 31 ± 4 s, P = 0.03), driven primarily by older women. Neither age-related differences in fitness, end-tidal CO, nor blood pressure could account for this effect. Thus, MCA kinetic analyses revealed a marked impairment in the cerebrovascular response to exercise in older individuals. Kinetic analysis offers a novel approach to evaluate the efficacy of therapeutic interventions for improving cerebrovascular function in elderly and patient populations. NEW & NOTEWORTHY Understanding the dynamic cerebrovascular response to exercise has provided insights into sex-related cerebrovascular control mechanisms throughout the aging process. We report novel differences in the kinetics response of cerebrovascular blood velocity after the onset of moderate-intensity exercise. The exponential increase in brain blood flow from rest to exercise revealed that 1) the kinetics profile of the older group was blunted compared with their young counterparts and 2) the older women demonstrated a slowed response.

Understanding grasping control after stroke is important for relearning motor skills. The authors examined 10 individuals (5 males; 5 females; ages 32-86) with chronic unilateral middle cerebral artery (MCA) stroke (4 right lesions; 6 left lesions) when lifting a novel test object using skilled precision grip with their ipsilesional ("unaffected") hand compared to healthy controls (n = 14; 6 males; 8 females; ages 19-86). All subjects possessed normal range of motion, cutaneous sensation, and proprioception in the hand tested and had no apraxia or cognitive deficits. Subjects lifted the object 10 times at each object weight (260 g, 500 g, 780 g) using a moderately paced self-selected lifting speed. The normal horizontal ("grip") force and vertical tangential ("lift") force were separately measured at the thumb and index finger. Regardless of the object weight or stroke location, the stroke group generated greater grip forces at liftoff of the object (> or =39%; P < or = 0.05) and across the dynamic (P < or = 0.05) and static portions (P < or = 0.05) of the lifts compared to the healthy group. Peak lift forces were equivalent between groups, suggesting accurate load force information processing occurred. These results warrant further investigation of altered sensorimotor processing or compensatory biomechanical strategies that may lead to inaccurate grip force execution after strokes.

The goal of this study was to explore the association of beta-amyloid accumulation and cerebrovascular response (CVR) in cognitively normal older adults. Beta-amyloid accumulation was characterized with [18F] Florbetapir positron emission tomography scans. CVR was calculated as middle cerebral artery blood flow velocity change from rest to moderate intensity exercise. We found that individuals with elevated beta-amyloid aggregation had a blunted CVR ( n = 25, age 70.1 ± 4.8; 3.3 ± 3.7 cm/s) compared to non-elevated individuals ( n = 45, age 72.0 ± 4.9; 7.2 ± 5.0 cm/s, p < 0.001). Further, greater beta-amyloid burden was linearly associated with less CVR across all participants (b = -11.7, p < 0.001). Greater CVR and less beta-amyloid burden were associated with processing speed ( p < 0.05). This study is the first to show that CVR from rest to exercise is blunted across increased global beta-amyloid burden.

These results suggest that rehabilitation efforts to improve distance walking should focus on different factors depending on initial distance walked.