Age-related structural changes in the human midbrain: an MR image study
Introduction
The human brain changes quantitatively and qualitatively with normal aging. Brain volume decreases with increasing age. The chemical composition of the brain also changes with aging. Some of these age-related changes have been demonstrated in normal and pathologic conditions by magnetic resonance (MR) imaging [6], [22]. High resolution MR imaging can visualize subtle differences not only in the brain volume but also in tissue composition including water and iron. Several studies have focussed on structural changes in the midbrain that contains nuclei important for voluntary or involuntary movements and nerve fibers conducting sensory and motor information [6], [17]. These nuclei, e.g. the substantia nigra and the red nucleus, are delineated by MR imaging because they are rich in iron which attenuates the signal intensity of the T2-weighed MR imaging technique [18]. Thus, many studies have shown that iron concentration increases in pathologic conditions, especially in various neurodegenerative disorders [4] including Parkinson’s disease [3], [8], [10], [14], [17]. These clinicopathological studies have suggested that the increase in brain iron is associated with the decrease of neurons in the substantia nigra, which results in the decrease in motor function.
However, there is only limited knowledge of MR imaging in association with normal aging of the nigrostriatal system [6], [7], [17], [20]. Pathological and neurochemical studies have demonstrated that the number of dopaminergic neurons and the dopamine concentration in the substantia nigra decrease with normal aging [1], [2]. It is important to confirm this issue in vivo, using MR imaging-aided morphometry and signal intensity changes in the T2-weighted MR imaging technique, since information on the effects of normal aging on the midbrain is essential before evaluating pathological conditions. In the present study, we measured midbrain structures in a large number of healthy subjects to reveal their age-related changes on T2-weighed MR images.
Section snippets
Subjects
We recruited 274 volunteers without previous neurologic disorders, selected from non-neurological patients visiting the Outpatient Department of our hospital and from our hospital employees. After giving informed consent, the subjects underwent physical and neurological examinations. After excluding 48 subjects who showed neurological abnormalities (including paretic signs, extensor plantar responses, sensory disturbances, tremor and changes in muscle tone), or who had systemic diseases that
Results
The findings of the correlation studies between age and other variables are summarized in Table 1. MD was negatively correlated with age (r = −0.503 and p < 0.0001 for the left; r = −0.535 and p < 0.0001 for the right) as shown in Fig. 3. SNRND was also reduced with increasing age as shown in Fig. 4 (r = −0.606 and p < 0.0001 for the left; r = −0.573 and p < 0.0001 for the right). As indicated in Fig. 5, a positive correlation was found with SND (r = 0.513 and p < 0.0001 for the left; r =
Discussion
In the present study, we undertook a neurological evaluation of 274 subjects, then excluded inappropriate candidates, and finally adopted MR images of 194 subjects. To our knowledge, there is only one study on MR images with regard to morphometric changes in the human midbrain with normal aging, which studied 75 subjects without any neurologic disorders [6]. Therefore, the present study is the largest in scale to investigate age-related changes in the human midbrain using MR images. Although
Acknowledgements
We thank Mr. Masayoshi Miyashita for his technical support.
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