Longitudinal progression of subclinical structural brain disease in normal aging

Ian A Cook, Andrew F Leuchter, Melinda L Morgan, Jennifer J Dunkin, Elise Witte, Steven David, Laura Mickes, Ruth O'Hara, Sara Simon, Robert Lufkin, Michelle Abrams, Susan Rosenberg

Research output: Contribution to journalArticle (Academic Journal)peer-review

43 Citations (Scopus)


OBJECTIVE: The authors describe four types of brain structural change in "normal aging:" cortical atrophy, central atrophy, deep white-matter hyperintensities (DWMH), and periventricular hyperintensities (PVH). Cross-sectional investigations have reported that greater volumes of these forms of "subclinical structural brain disease" (SSBD) were found with increasing age. Greater volumes were also associated with poorer cognition, even though subjects performed within the normal range. The natural history of these forms of SSBD and their functional impact are not well established.

METHODS: Twenty-nine normal subjects, ages 60-89, were examined longitudinally by volumetric magnetic resonance imagery, with two assessments performed at least 2 years apart; 26 also completed neuropsychological testing to evaluate processing speed, executive functions, language, and other cognitive functions. Associations between structure and function were evaluated with regression models.

RESULTS: For most subjects, the volumes for signs of all types of SSBD were found to have increased; for many subjects, increases were small, and a few showed no change or small decreases. PVH and DWMH increases were predicted by baseline cerebrovascular risk factors. Cognitive test performance changed little over time for these normal subjects.

CONCLUSIONS: SSBD volumes increased for most subjects over time, with small average increases for most types. Pretreatment cerebrovascular risk factors were associated with greater increases of PVH and DWMH, suggesting that progression of these types of SSBD may be amenable to intervention.

Original languageEnglish
Pages (from-to)190-200
Number of pages11
JournalAmerican Journal of Geriatric Psychiatry
Issue number2
Publication statusPublished - 11 Mar 2004


  • Aged
  • Aged, 80 and over
  • Aging/physiology
  • Atrophy/pathology
  • Cerebral Cortex/abnormalities
  • Cerebral Ventricles/abnormalities
  • Cognition Disorders/diagnosis
  • Cross-Sectional Studies
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Severity of Illness Index


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