Alterations in cerebral metabolic rate and blood supply across the adult lifespan

Abstract

With age, the brain undergoes comprehensive changes in its function and physiology. Cerebral metabolism and blood supply are among the key physiologic processes supporting the daily function of the brain and may play an important role in age-related cognitive decline. Using MRI, it is now possible to make quantitative assessment of these parameters in a noninvasive manner. In the present study, we concurrently measured cerebral metabolic rate of oxygen (CMRO(2)), cerebral blood flow (CBF), and venous blood oxygenation in a well-characterized healthy adult cohort from 20 to 89 years old (N = 232). Our data showed that CMRO(2) increased significantly with age, while CBF decreased with age. This combination of higher demand and diminished supply resulted in a reduction of venous blood oxygenation with age. Regional CBF was also determined, and it was found that the spatial pattern of CBF decline was heterogeneous across the brain with prefrontal cortex, insular cortex, and caudate being the most affected regions. Aside from the resting state parameters, the blood vessels' ability to dilate, measured by cerebrovascular reactivity to 5% CO(2) inhalation, was assessed and was reduced with age, the extent of which was more prominent than that of the resting state CBF.

Figure 1.

Diagram illustrating the homeostasis of oxygen delivery and consumption in the brain. Arterial (Y_a) and venous (Y_v) oxygenation levels are the percentage of hemoglobin in the blood that is bound to oxygen. Y_a is close to unity and, relative to Y_v, does not vary much across individuals. Arterial vessels deliver blood to brain tissue, the flow rate of which is denoted by CBF. When the blood transits through capillary beds, a portion of the carried oxygen is extracted by brain tissue for its metabolism, the rate of which is denoted by CMRO₂. The portion that remains in the blood will determine the value of Y_v and is drained through veins.

Figure 2.

Scatter plot between global venous oxygenation (Y_v) and age (total N = 232). Each dot represents data from one subject. The data from women and men are shown with different symbols. The dashed line is a linear fitting of the experimental data from both sexes. Regression analysis showed that age has a significant effect on Y_v (P < 0.0001), but a quadratic model did not improve the fitting. Women showed higher Y_v compared with men (P = 0.0205).

Figure 3.

Global CBF alterations with age. (a) Illustration of the imaging slice (yellow) with regards to the major feeding arteries. (b) Scatter plot between global CBF and age (total N = 232). The data from women and men are shown with different symbols. The dashed line is a linear fitting of the experimental data from both sexes. Regression analysis showed that age has a significant effect on CBF (P = 0.0065). Women showed higher CBF compared with men (P < 0.0001).

Figure 4.

Scatter plot between global CMRO₂ and age (total N = 232). The data from women and men are shown with different symbols. The dashed line is a linear fitting of the experimental data. Regression analysis showed that age has a positive effect on CMRO₂ (P = 0.0101). Women showed higher CMRO2 compared with men (P < 0.0001).

Figure 5.

Regional CBF maps as a function of age. Subjects from each decade were grouped, and their CBF maps were averaged for display. Six representative brain sections are shown.

Figure 6.

Results of voxel-based analysis of CBF decreases with age. The left panel (a) shows the glass brain overlay, and the right panel (b) shows the rendering on the Montreal Neurological Institute brain template. Colored voxels indicate brain regions with age-related CBF decrease (P < 0.005, cluster size = 200 voxels). The differences are most pronounced in the rostral half of the brain and are more prominent in the right hemisphere.

Figure 7.

Results of voxel-based analysis of CVR decrease with age. The left panel (a) shows the glass brain overlay, and the right panel (b) shows the rendering on the Montreal Neurological Institute (MNI) brain template. Colored voxels indicate brain regions with age-related CVR decrease (P < 0.005, cluster size = 200 voxels). The CVR alterations cover the majority of the brain with the exception of occipital pole and are more prevalent than the CBF alterations.

Figure 8.

Decade-by-decade alterations in prefrontal CVR and CBF. Display scales for CVR and CBF are shown on the left and right axis, respectively. The display scales were set such that the first points of the 2 curves overlapped. It can be seen that CVR manifests a more rapid decay with age compared with CBF. The subjects in each decade were grouped, and the data shown are the mean and standard error of the group.