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: 6.92). 04/2009; 30(4):1120-32. DOI: 10.1002/hbm.20574
Source: PubMed

ABSTRACT 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 · 2.84 Impact Factor
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    • "2579; Fax: +1 858 642 1218; E-mail: 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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    Journal of Alzheimer's disease: JAD 03/2014; 41(3). DOI:10.3233/JAD-132252 · 4.15 Impact Factor
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    • "Several reports have demonstrated age-related coupling changes between cerebral blood flow (CBF) and cerebral-metabolic rate of oxygen consumption (CMRO 2 ). Regional reductions in gray matter could lead to CMRO 2 decreases that could, combined with age-related CBF increases, lead to apparent increases in BOLD signal (e.g., Ances et al., 2009; Hutchison et al., 2012; Restom et al., 2007). Further studies using longitudinal designs and pharmacologic manipulations will be required to provide the kind of direct evidence required to infer causal structure–function relationships. "
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    ABSTRACT: Neurocognitive aging studies have focused on age-related changes in neural activity or neural structure but few studies have focused on relationships between the two. The present study quantitatively reviewed 24 studies of age-related changes in fMRI activation across a broad spectrum of executive function tasks using activation likelihood estimation (ALE) and 22 separate studies of age-related changes in gray matter using voxel-based morphometry (VBM). Conjunction analyses between functional and structural alteration maps were constructed. Overlaps were only observed in the conjunction of dorsalateral prefrontal cortex (DLPFC) gray matter reduction and functional hyperactivation but not hypoactivation. It was not evident that the conjunctions between gray matter and activation were related to task performance. Theoretical implications of these results are discussed.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 09/2013; 48. DOI:10.1016/j.pnpbp.2013.09.001 · 4.03 Impact Factor
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