The Aging Brain

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The studies of brain and cognition reveal that in both domains, age-related changes are differential as well as generalized. The results of postmortem and in vivo investigations of the human brain demonstrate that although advanced age is associated with reduced total brain weight, nonspecific sulcal expansion, ventricular enlargement (Fig. 1), and a decline in global brain

Figure 1 Examples of brain aging as seen on MR images (a 23-year-old female and a 77-year-old female). The images represent a cross section of the brain in a horizontal plane. The parameters used to acquire these images emphasize changes in brain water state and content, thus highlighting the spaces surrounding blood vessels and the cerebral sulci and ventricles filled with cerebrospinal fluid. In this type of MR scan, fluid appears white and myelinated fibers are at the darkest end of the gray scale. Note enlarged ventricles, widened sulci, and the presence of subcortical white matter hyperintensities in the aging brain.

Young Old

Figure 1 Examples of brain aging as seen on MR images (a 23-year-old female and a 77-year-old female). The images represent a cross section of the brain in a horizontal plane. The parameters used to acquire these images emphasize changes in brain water state and content, thus highlighting the spaces surrounding blood vessels and the cerebral sulci and ventricles filled with cerebrospinal fluid. In this type of MR scan, fluid appears white and myelinated fibers are at the darkest end of the gray scale. Note enlarged ventricles, widened sulci, and the presence of subcortical white matter hyperintensities in the aging brain.

blood flow, the greatest negative impact of aging is evidenced by the prefrontal cortex (PFC) and the neostriatum (Figs. 2A and 2B). Age-related changes in the hippocampus (Fig. 2C) are also significant, although some of them may be attributed to the early signs of age-related pathology and are more prevalent in the oldest old. The cerebellum and the primary sensory cortices show only mild age-related decline, and the lower brain regions such as the ventral pons appear insensitive to the impact of senescence.

Figure 2 Regional age-related differences in the brain comparison of MR images. (A) Prefrontal cortex in a coronal plane perpendicular to the plane cutting through the anterior and posterior commissures (AC-PC). (B) Basal ganglia (striatum) in a horizontal plane approximately parallel to the AC-PC. (C) Hippocampus (HC; in a sagittal plane, perpendicular to the AC-PC). The images of a 23-year-old female are on the left, and the images of a 77-year-old female are on the right. The image acquisition parameters were selected to emphasize anatomical details and the white-gray matter differences. On these images, the white matter and blood vessels appear in high-intensity white, the gray matter is rendered in a darker end of the gray scale, and the cerebrospinal fluid is black.

Figure 2 Regional age-related differences in the brain comparison of MR images. (A) Prefrontal cortex in a coronal plane perpendicular to the plane cutting through the anterior and posterior commissures (AC-PC). (B) Basal ganglia (striatum) in a horizontal plane approximately parallel to the AC-PC. (C) Hippocampus (HC; in a sagittal plane, perpendicular to the AC-PC). The images of a 23-year-old female are on the left, and the images of a 77-year-old female are on the right. The image acquisition parameters were selected to emphasize anatomical details and the white-gray matter differences. On these images, the white matter and blood vessels appear in high-intensity white, the gray matter is rendered in a darker end of the gray scale, and the cerebrospinal fluid is black.

The reasons for the observed differential distribution of age-related vulnerabilities are unclear. The pattern of differential brain aging reflects to some extent the outline of age-sensitive neurotransmitter systems and may be associated with age-related changes in the intracellular distribution of calcium ions. The regions and cell ensembles that have higher propensity to calcium-driven plasticity may be more vulnerable to excitotoxic events that cause age-related damage. Although there is a tendency of phylogeneti-cally newer and ontogenetically late to mature regions to show greater negative effects of age, interspecies and even interstrain differences in brain response to aging are plentiful. Most of the age-sensitive regions are also located in the areas of the brain that are prone to suffer negative effects of subclinical ischemia. Although those are only clues, and biological mechanisms that drive differential brain aging remain to be elucidated, the connection between brain aging and cognitive changes of late adulthood is undeniable. The main challenge for cognitive neuroscience is to establish specific relations between age-related transformations of the brain circuitry and altered performance of cognitive operations that depend on those circuits.

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