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Updated: Dec 16, 2025

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Brain structure changes over time in normal and mildly impaired aged persons.

Charles D Smith1,2, Linda J Van Eldik3,4, Gregory A Jicha1,3

  • 1Department of Neurology, University of Kentucky College of Medicine, Lexington, Kentucky, USA.

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Brain aging involves grey matter loss and cerebrospinal fluid expansion, with the hippocampus particularly affected in normal aging. Mild cognitive impairment accelerates this hippocampal loss.

Keywords:
CSF expansionagingcognitiongrey matter losshippocampal volume loss

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Area of Science:

  • Neuroimaging
  • Gerontology
  • Brain Aging Research

Background:

  • Structural brain changes are characteristic of aging, even without dementia.
  • Previous studies show variability in the rate and location of age-related brain changes.
  • Understanding these changes is crucial for differentiating normal aging from neurodegenerative conditions.

Purpose of the Study:

  • To quantify longitudinal changes in brain structure in healthy older adults.
  • To identify specific brain regions most affected by aging.
  • To compare brain changes in healthy aging with those in individuals with mild cognitive impairment (MCI).

Main Methods:

  • Analysis of paired magnetic resonance imaging (MRI) scans from 78 healthy older adults (aged 70-78) over a median of 5.8 years.
  • Annual cognitive and health assessments to ensure participants maintained normal cognition.
  • Comparison with a smaller group of 6 individuals diagnosed with MCI at baseline.

Main Results:

  • Healthy elders exhibited a grey matter (GM) loss rate of 2.56 ml/year and cerebrospinal fluid (CSF) expansion of 2.97 ml/year.
  • Hippocampal volume loss was accelerated at 0.0114 ml/year, exceeding global rates.
  • Greatest GM loss occurred in the posterior inferior frontal lobe, medial parietal lobe, and dorsal cerebellum.
  • The MCI group showed a significantly increased rate of GM loss in the hippocampus compared to the healthy group.

Conclusions:

  • Longitudinal MRI reveals consistent patterns of GM loss and CSF expansion in healthy aging, with the hippocampus being particularly vulnerable.
  • The observed rates are within the lower range reported in literature, possibly reflecting the good health of the study cohort.
  • Individuals with MCI exhibit accelerated hippocampal atrophy, highlighting its role in early cognitive decline.