Elsevier

Neurobiology of Aging

Volume 22, Issue 4, July–August 2001, Pages 581-594
Neurobiology of Aging

Effects of age on tissues and regions of the cerebrum and cerebellum

https://doi.org/10.1016/S0197-4580(01)00217-2Get rights and content

Abstract

Normal volunteers, aged 30 to 99 years, were studied with MRI. Age was related to estimated volumes of: gray matter, white matter, and CSF of the cerebrum and cerebellum; gray matter, white matter, white matter abnormality, and CSF within each cerebral lobe; and gray matter of eight subcortical structures. The results were: 1) Age-related losses in the hippocampus were significantly accelerated relative to gray matter losses elsewhere in the brain. 2) Among the cerebral lobes, the frontal lobes were disproportionately affected by cortical volume loss and increased white matter abnormality. 3) Loss of cerebral and cerebellar white matter occurred later than, but was ultimately greater than, loss of gray matter. It is estimated that between the ages of 30 and 90 volume loss averages 14% in the cerebral cortex, 35% in the hippocampus, and 26% in the cerebral white matter. Separate analyses were conducted in which genetic risk associated with the Apolipoprotein E ϵ4 allele was either overrepresented or underrepresented among elderly participants. Accelerated loss of hippocampal volume was observed with both analyses and thus does not appear to be due to the presence of at-risk subjects. MR signal alterations in the tissues of older individuals pose challenges to the validity of current methods of tissue segmentation, and should be considered in the interpretation of the results.

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.).

References (40)

  • C.E. Coffey et al.

    Sex differences in brain aginga quantitative magnetic resonance imaging study [published erratum appears in Arch Neurol 1998;55(5):627]

    Archives of Neurology

    (1998)
  • C.E. Coffey et al.

    Quantitative cerebral anatomy of the aging human braina cross-sectional study using magnetic resonance imaging

    Neurology

    (1992)
  • P.J.M. Davis et al.

    A new method for measuring cranial cavity volume and its application to the assessment of cerebral atrophy at autopsy

    Neuropathology and Applied Neurobiology

    (1977)
  • A.S. Dekaban et al.

    Changes in brain weights during the span of human liferelation of brain weights to body heights and body weights

    Ann Neurol

    (1978)
  • G. Fein et al.

    Preservation of normal cognitive functioning in elderly subjects with extensive white-matter lesions of long duration

    Arch Gen Psychiatry

    (1990)
  • C. Fennema-Notestine et al.

    Quantitative MRI in Alzheimer’s Disease and controls with and without the Apolipoprotein E epsilon 4 allele

    Society for Neuroscience Abstracts

    (1997)
  • J. Golomb et al.

    Hippocampal atrophy in normal aging. An association with recent memory impairment

    Archives of Neurology

    (1993)
  • F.M. Gunning-Dixon et al.

    The cognitive correlates of white matter abnormalities in normal aginga quantitative review

    Neuropsychology

    (2000)
  • C.R. Guttmann et al.

    White matter changes with normal aging

    Neurology

    (1998)
  • V.C. Hachinski et al.

    Cerebral blood flow in dementia

    Archives of Neurology

    (1975)
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