Original Article

Pathological correlates of dementia in a longitudinal, population-based sample of aging

  1. Joshua A. Sonnen MD1,*,
  2. Eric B. Larson MD, MPH2,
  3. Paul K. Crane MD, MPH3,
  4. Sebastien Haneuse PhD2,
  5. Ge Li MD, PhD4,5,
  6. Gerald D. Schellenberg PhD3,6,
  7. Suzanne Craft PhD4,6,
  8. James B. Leverenz MD5,7,8,
  9. Thomas J. Montine MD, PhD1

Article first published online: 20 AUG 2007

DOI: 10.1002/ana.21208

Issue

Annals of Neurology

Annals of Neurology

Volume 62, Issue 4, pages 406–413, October 2007

Additional Information

How to Cite

Sonnen, J. A., Larson, E. B., Crane, P. K., Haneuse, S., Li, G., Schellenberg, G. D., Craft, S., Leverenz, J. B. and Montine, T. J. (2007), Pathological correlates of dementia in a longitudinal, population-based sample of aging. Annals of Neurology, 62: 406–413. doi: 10.1002/ana.21208

Author Information

  1. 1

    Department of Pathology, University of Washington, Seattle, WA

  2. 2

    Center for Health Studies, Group Health Cooperative, Seattle, WA

  3. 3

    Department of Medicine and, Seattle, WA

  4. 4

    Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA

  5. 5

    Departments of Mental Illness, Seattle, WA

  6. 6

    Departments of Geriatrics, Veterans Affairs Puget Sound Health Care System, Seattle, WA

  7. 7

    Department of Neurology, University of Washington, Seattle, WA

  8. 8

    Departments of Parkinson's Research, Education Clinical Centers, Veterans Affairs Puget Sound Health Care System, Seattle, WA

*325 Ninth Avenue, Department of Pathology, Box 359791, Seattle, WA 98104-2499

Publication History

  1. Issue published online: 29 OCT 2007
  2. Article first published online: 20 AUG 2007
  3. Manuscript Revised: 6 JUL 2007
  4. Manuscript Accepted: 6 JUL 2007
  5. Manuscript Received: 29 MAR 2007

Funded by

  • NIH (National Institute on Aging). Grant Numbers: AG06781, AG023801, AG000258
  • National Institute of Neurological Disorders and Stroke. Grant Number: NS48595

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Abstract

Objective

Previously published community- or population-based studies of brain aging and dementia with autopsy were restricted to a single sex, a single ethnic group, Roman Catholic clergy, or focused pathological assessments. Our goal was to determine the independent pathological correlates associated with dementia in a typical US population.

Methods

We evaluated autopsy data from the Adult Changes in Thought study, an ongoing longitudinal, population-based study of brain aging and dementia. Analyses were based on data collected from about 3,400 people 65 years or older who were cognitively intact at the time of enrollment in the Group Health Cooperative in King County, Washington. All consecutive autopsies (n = 221; 20% of deaths) from this cohort were evaluated and analyzed by weighted multivariate analysis to account for potential participation bias.

Results

After adjusting for age, sex, education, and APOE, independent correlates of dementia (relative risk, 95% confidence interval; overall p value) included Braak stage (V/VI vs 0/I/II: 5.89, 1.62–17.60; p < 0.05), number of cerebral microinfarcts in standardized sections (>2 vs none: 4.80, 1.91–10.26; p < 0.001), and neocortical Lewy bodies (any vs none: 5.08, 1.37–18.96; p < 0.05). Estimates of adjusted population attributable risk for these three processes were 45% for Braak stage, 33% for microinfarcts, and 10% for neocortical Lewy bodies.

Interpretation

Our results underscore the therapeutic imperative for Alzheimer's and Lewy body diseases, and provide evidence to support the immediate use of strategies that target cerebral microinfarcts as a means to partially prevent or delay the onset of dementia. Ann Neurol 2007

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