Brain energy metabolism and blood flow differences in healthy aging

Abstract

Cerebral metabolic rate of oxygen consumption (CMRO(2)), cerebral blood flow (CBF), and oxygen extraction fraction (OEF) are important indices of healthy aging of the brain. Although a frequent topic of study, changes of CBF and CMRO(2) during normal aging are still controversial, as some authors find decreases of both CBF and CMRO(2) but increased OEF, while others find no change, and yet other find divergent changes. In this reanalysis of previously published results from positron emission tomography of healthy volunteers, we determined CMRO(2) and CBF in 66 healthy volunteers aged 21 to 81 years. The magnitudes of CMRO(2) and CBF declined in large parts of the cerebral cortex, including association areas, but the primary motor and sensory areas were relatively spared. We found significant increases of OEF in frontal and parietal cortices, excluding primary motor and somatosensory regions, and in the temporal cortex. Because of the inverse relation between OEF and capillary oxygen tension, increased OEF can compromise oxygen delivery to neurons, with possible perturbation of energy turnover. The results establish a possible mechanism of progression from healthy to unhealthy brain aging, as the regions most affected by age are the areas that are most vulnerable to neurodegeneration.

Figure 1

Illustration of the volume-of-interest (VOI) generation. On the left is shown a gray matter segmentation (gray) for a young subject with the generic mask for F-M1 (frontal lobe without primary motor area) (shown in red) overlaid. These binary masks are multiplied to create the VOI and are shown on the right (white). This customized VOI is superimposed on the parametric cerebral blood flow (CBF) image of the same subject.

Figure 2

Top row shows mean cerebral blood flow (CBF) (mL/100 g per minute) images where cortical decreases are apparent both between young and middle age, and between middle age and old (blue arrows show examples). Subcortical structures are relatively conserved with aging (black arrows). Cerebral metabolic rate of oxygen (μmol/100 g per minute) images are shown in the bottom row, and although there is some cortical decline with aging, the effect is relatively small compared with the change in CBF. Left in the figure corresponds to left side of the brain.

Figure 3

Scatter plots of cerebral blood flow (CBF), cerebral metabolic rate of oxygen consumption (CMRO₂), and oxygen extraction fraction (OEF) by volume-of-interest (VOI). Statistics for the regression lines are shown in Table 1. CBF (mL/100 g per minute), CMRO₂ (μmol/100 g per minute), OEF is a ratio.

Figure 4

T-maps of cerebral blood flow (CBF) (top) and cerebral metabolic rate of oxygen consumption (CMRO₂) (bottom) relative decreases as a function of age. T-values are shown on the right, threshold P=0.05, corrected. The most significant decreases in both CBF and CMRO₂ are seen in the superior frontal gyrus. Small insets display masks used in ratio normalization, these masks represent areas that are preserved during aging. Gray arrows indicate medial superior part of the central sulcus, which is surrounded by primary motor and somatosensory areas and is preserved during aging (blue arrows).

Figure 5

Illustration of sulcal widening in old age. Magnetic resonance (MR) images of two men are shown, on the left is a 26 year old and on the right an 81 year old. If large, fixed-sized volumes-of-interest (VOIs) or regions of interest (ROIs) (14 to 20 mm in earlier studies) are used to sample values from the corresponding positron emission tomography (PET) images, a larger proportion of the sampling area would include sulcal cerebrospinal fluid (CSF) in older subjects.