Effects of aging on cerebral blood flow, oxygen metabolism, and blood oxygenation level dependent responses to visual stimulation

Department of Neurosciences, University of California, San Diego, USA.
Human Brain Mapping (Impact Factor: 5.97). 04/2009; 30(4):1120-32. DOI: 10.1002/hbm.20574
Source: PubMed


Calibrated functional magnetic resonance imaging (fMRI) provides a noninvasive technique to assess functional metabolic changes associated with normal aging. We simultaneously measured both the magnitude of the blood oxygenation level dependent (BOLD) and cerebral blood flow (CBF) responses in the visual cortex for separate conditions of mild hypercapnia (5% CO(2)) and a simple checkerboard stimulus in healthy younger (n = 10, mean: 28-years-old) and older (n = 10, mean: 53-years-old) adults. From these data we derived baseline CBF, the BOLD scaling parameter M, the fractional change in the cerebral metabolic rate of oxygen consumption (CMRO(2)) with activation, and the coupling ratio n of the fractional changes in CBF and CMRO(2). For the functional activation paradigm, the magnitude of the BOLD response was significantly lower for the older group (0.57 +/- 0.07%) compared to the younger group (0.95 +/- 0.14%), despite the finding that the fractional CBF and CMRO(2) changes were similar for both groups. The weaker BOLD response for the older group was due to a reduction in the parameter M, which was significantly lower for older (4.6 +/- 0.4%) than younger subjects (6.5 +/- 0.8%), most likely reflecting a reduction in baseline CBF for older (41.7 +/- 4.8 mL/100 mL/min) compared to younger (59.6 +/- 9.1 mL/100 mL/min) subjects. In addition to these primary responses, for both groups the BOLD response exhibited a post-stimulus undershoot with no significant difference in this magnitude. However, the post-undershoot period of the CBF response was significantly greater for older compared to younger subjects. We conclude that when comparing two populations, the BOLD response can provide misleading reflections of underlying physiological changes. A calibrated approach provides a more quantitative reflection of underlying metabolic changes than the BOLD response alone.

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Available from: Amy Lansing, Oct 31, 2014
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    • "Reduced levels of deactivation are associated with Alzheimer's disease (Petrella et al., 2007; Persson et al., 2008; Sperling et al., 2009) further supporting the idea that the task-negative network may be selectively linked to cognitive health. In addition, amyloid plaques in DMN regions may cause functional disruption even in older adults classified as normal (Hedden et al., 2009). Agerelated structural damage in these regions may therefore be the substrate for drops in local connectivity as a function of age, which may in turn result in drops in the spread of the BOLD signal. "
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    ABSTRACT: Cross-sectional aging functional MRI results are sometimes difficult to interpret, as standard measures of activation and deactivation may confound variations in signal amplitude and spread, which however, may be differentially affected by age-related changes in various anatomical and physiological factors. To disentangle these two types of measures, here we propose a novel method to obtain independent estimates of the peak amplitude and spread of the BOLD signal in areas activated (task-positive) and deactivated (task-negative) by a Sternberg task, in 14 younger and 28 older adults. The peak measures indicated that, compared to younger adults, older adults had increased activation of the task-positive network, but similar levels of deactivation in the task-negative network. Measures of signal spread revealed that older adults had an increased spread of activation in task-positive areas, but a starkly reduced spread of deactivation in task-negative areas. These effects were consistent across regions within each network. Further, there was greater variability in the anatomical localization of peak points in older adults, leading to reduced cross-subject overlap. These results reveal factors that may confound the interpretation of studies of aging. Additionally, spread measures may be linked to local connectivity phenomena and could be particularly useful to analyze age-related deactivation patterns, complementing the results obtained with standard peak and region of interest analyses.
    Frontiers in Aging Neuroscience 10/2014; 6:288. DOI:10.3389/fnagi.2014.00288 · 4.00 Impact Factor
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    • "The latter, simpler, approach thus continues to be widely adopted in quantitative neuroimaging and other areas. A common practice has been to administer fixed fractional concentrations of O2 and CO2 for inhalation [3,5,6,17], delivering O2/CO2 enriched mixtures through low-cost nonrebreathing masks commonly used in clinical oxygen therapy, which usually incorporate a reservoir bag to increase dosage efficiency (the bag reservoir stores the gases delivered during expiration to make it available for next inspiration(s), making better use of administered gases and alleviating dropouts in FiO2 and FiCO2 during early phases of inspiration) [18]. However, either due to variations in the shape of the subject’s face or to incomplete sealing of one-way valves used to release excess gas flow, such oxygen masks are often very leaky [18], hampering precise adjustments in fractional inspired concentrations and thus limiting the reproducibility of the hyperoxic/hypercapnic stimuli. "
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    BMC Research Notes 04/2014; 7(1):235. DOI:10.1186/1756-0500-7-235
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    • "2579; Fax: +1 858 642 1218; E-mail: cwierenga@ucsd.edu. activity; however, resting cerebral blood flow (CBF) progressively declines with age after the third decade of life [1] [2] [3]. Moreover, vascular dysregulation has been implicated in the pathogenesis of Alzheimer's disease (AD) as evidenced by alterations in cerebral capillaries, white matter lesions, and reductions in CBF and glucose utilization [4]. "
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    ABSTRACT: Resting cerebral blood flow (CBF) decreases with age; however regulatory increases in hippocampal CBF have been associated with genetic risk (Apolipoprotein E [APOE] ε4 carriers) for Alzheimer's disease (AD). Although physical activity exerts beneficial effects on CBF in healthy elderly, the effects of sedentary behaviors on CBF remain unknown. We measured resting hippocampal CBF (via arterial spin labeling magnetic resonance imaging) and sedentary time/physical activity (via accelerometry) on 33 cognitively healthy adults (ages 52-81), 9 of which were APOE ε4 carriers. Results indicate that the relationship between sedentary time and CBF in the left hippocampus differs by APOE status, whereby APOE ε4 carriers show higher CBF as a function of longer sedentary time (B = 10.8, β = 0.74, t = 3.41, p < 0.01) compared to noncarriers (B = 1.4, SE = 2.7, β = 0.096, t = 0.51, p = 0.61), possibly suggesting a CBF regulatory response to compensate for metabolic alterations in dementia risk. These preliminary data suggest that the relationship between CBF and sedentary time is different in APOE carriers and noncarriers and that sedentary time may act as a behavioral risk factor for CBF dysregulation in those at genetic risk for developing AD. More research is needed to further understand the role of sedentary behaviors and physical activity on CBF, especially in individuals at genetic risk of developing AD.
    Journal of Alzheimer's disease: JAD 03/2014; 41(3). DOI:10.3233/JAD-132252 · 4.15 Impact Factor
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