Original Article

Brain imaging evidence of preclinical Alzheimer's disease in normal aging

  1. William Jagust MD1,2,3,*,
  2. Amy Gitcho BA2,
  3. Felice Sun PhD2,
  4. Beth Kuczynski PhD2,
  5. Dan Mungas PhD4,
  6. Mary Haan DrPH5

Article first published online: 8 FEB 2006

DOI: 10.1002/ana.20799

Issue

Annals of Neurology

Annals of Neurology

Volume 59, Issue 4, pages 673–681, April 2006

Additional Information

How to Cite

Jagust, W., Gitcho, A., Sun, F., Kuczynski, B., Mungas, D. and Haan, M. (2006), Brain imaging evidence of preclinical Alzheimer's disease in normal aging. Annals of Neurology, 59: 673–681. doi: 10.1002/ana.20799

Author Information

  1. 1

    School of Public Health, University of California, Berkeley

  2. 2

    Helen Wills Neuroscience Institute, University of California, Berkeley

  3. 3

    Lawrence Berkeley National Laboratory, University of California, Berkeley

  4. 4

    Department of Neurology, School of Medicine, University of California, Davis, CA

  5. 5

    Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI

*Helen Wills Neuroscience Institute, 132 Barker Hall, University of California, Berkeley, CA 94720

Publication History

  1. Issue published online: 24 MAR 2006
  2. Article first published online: 8 FEB 2006
  3. Manuscript Accepted: 13 DEC 2005
  4. Manuscript Revised: 1 DEC 2005
  5. Manuscript Received: 15 JUL 2005

Funded by

  • NIH (National Institute on Aging). Grant Numbers: AG12975, AG10220
  • National Institute of Diabetes and Digestive and Kidney Diseases. Grant Number: DK60753

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Abstract

Objective

This study was designed to test the hypothesis that baseline glucose metabolism and medial temporal lobe brain volumes are predictive of cognitive decline in normal older people.

Methods

We performed positron emission tomography using [18F]fluorodeoxyglucose and structural magnetic resonance imaging at baseline in 60 cognitively normal community-dwelling older subjects who were part of a longitudinal cohort study. Subjects were followed for a mean of 3.8 years, with approximately annual evaluation of global cognition (the Modified Mini-Mental State Examination) and episodic memory (delayed recall). Baseline brain volumes and glucose metabolism were evaluated in relation to the rate of change in cognitive test scores.

Results

Six subjects developed incident dementia or cognitive impairment (converters). Baseline positron emission tomography scans showed regions in left and right angular gyrus, left mid-temporal gyrus, and left middle frontal gyrus that predicted the rate of change on the Modified Mini-Mental State Examination (p < 0.001). The left hemisphere temporal and parietal regions remained significant when converters were excluded. Both hippocampal (p = 0.03) and entorhinal cortical volumes (p = 0.01) predicted decline on delayed recall over time, and entorhinal cortical volumes remained significant when converters were excluded (p = 0.02). These brain volumes did not predict Modified Mini-Mental State Examination decline.

Interpretation

These results indicate that temporal and parietal glucose metabolism predict decline in global cognitive function, and medial temporal brain volumes predict memory decline in normal older people. The anatomical location of these findings suggests detection of preclinical Alzheimer's disease pathology. Ann Neurol 2006

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