Effects of age on tissues and regions of the cerebrum and cerebellum
Introduction
Early autopsy studies of neurologically normal cases revealed age-related decreases in brain weight [10], [17] and brain volume [9], [18]; and provided evidence that such decreases were accompanied by some degree of neuronal loss in cerebral cortex, brain stem structures, and basal ganglia [5], [6], [32]. Magnetic resonance imaging (MRI) of the brain was the first method with sufficient resolution to permit investigation of age-related change in individual cortical and subcortical structures in living human subjects. MRI reveals evidence of volume loss, in the form of increased cerebrospinal fluid (CSF) spaces, in many older, medically-normal individuals. We previously described age-related brain morphologic changes measured with MR morphometric techniques in subjects ranging in age from 30 to 79 years. Increasing age was associated with increasing ventricular and cortical sulcal CSF and with substantial reduction in both cortical and subcortical compartments of the gray matter. Cortical gray matter losses occurred in widespread regions, including the structures on the mesial surface of the temporal lobe. Subcortical gray matter losses were also observed, particularly in the striatum. The prevalence of signal hyperintensities within the white matter increased in the older subjects; however, we did not observe a significant decrease in the volume of the cerebral white matter [19], [22].
Numerous other studies have applied MR morphometric techniques in studies of normal aging. These have confirmed volume decreases in cortical gray matter [2], [31], [33], [34], [39], cerebral hemispheres [7], [8], and basal ganglia structures [27], [30], [35], and increases in volumes of [15], [28], or odds of [8], signal hyperintensities in the white matter. In some studies, such as our previous study, white matter volume did not appear to change with age [2], [19], [33]. However, results of some recent studies suggest that significant white matter volume loss does occur, at least in some cerebral regions [15], [34], [36]. The present study extends our earlier work by: examining a larger age range; providing detailed volumetric characterization of multiple subcortical and limbic structures; providing lobar measures of cortical gray matter, underlying white matter, and signal abnormalities; providing measures of cerebellar gray and white matter; and applying statistical techniques for comparing the age-effects in different regions. In addition, specific problems associated with tissue segmentation in older individuals are highlighted and discussed.
Section snippets
Subjects
Seventy-eight normal adult volunteers (41 women and 37 men, ranging in age from 30 to 99 years—mean 64, s.d. 17.4) were examined for age-associated changes in regional brain volumes. Of the seventy-eight individuals, 71 identified themselves as Caucasian, 3 as Hispanic, 3 as African-American, and 1 individual has unknown racial/ethnic identity. All subjects were screened for any current and significant medical, psychiatric, intellectual, or neurological disorders. Middle-aged and elderly
Results
Estimates of the strength of (monotone) association between age and the gray matter volumes are given in Table 3. There is strong evidence for age-related decline in the volume of the cerebral cortex, and this appears to be particularly pronounced in frontal cortex. Indeed the secondary analyses comparing rates of decline in cortical regions suggest that the decline in frontal cortex volume is significantly faster than is the decline in parietal lobe or insular cortex (rho’s: frontal vs.
Discussion
Although, ideally, models of the effects of advancing age on the brain would be based on observed changes over time in individual subjects, in practice, longitudinal methods are attended by a number of significant logistical complications. The cross-sectional data presented here describe differences between subjects of different ages, not age changes per se. We are therefore attempting to extrapolate age-changes from age-differences. The validity of such functions based on age-differences
Summary and conclusions
The major novel findings of the present study are: that age-related losses in the hippocampus are significantly accelerated relative to gray matter losses elsewhere in the brain; that there are disproportionate effects on the frontal lobes in terms of cortical volume loss and increases in white matter signal hyperintensity; and that the later occurring loss of cerebral and cerebellar white matter is ultimately greater than loss of gray matter in very elderly normal individuals. Differing sample
Acknowledgements
This research was supported by Medical Research Service of the Department of Veterans Affairs; the Alzheimer’s Disease Research Center, NIA 2P50AG05131 (PI: L. Thal, M.D.); the HIV Neurobehavioral Research Center, NIMH 1P50MH45294 (PI: I. Grant, M.D.); and the Geropsychiatry Clinical Research Center, NIMH 1P30MH49671 (PI: D. Jeste, M.D.).
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