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NEUROLOGY 2007;68:1268-1273
© 2007 American Academy of Neurology

Brain structural alterations before mild cognitive impairment

C. D. Smith, MD, H. Chebrolu, MSEE, D. R. Wekstein, PhD, F. A. Schmitt, PhD, G. A. Jicha, MD, PhD, G. Cooper, MD, PhD and W. R. Markesbery, MD

From the Departments of Neurology (C.D.S., H.C., F.A.S., G.A.J., W.R.M.), Anatomy and Neurobiology (C.D.S., W.R.M.), Pathology (W.R.M.), Behavioral Science (F.A.S.), Psychiatry (F.A.S.), and Psychology (F.A.S.), Magnetic Resonance Imaging and Spectroscopy Center (C.D.S., H.C.), and Alzheimer's Disease Center and Sanders-Brown Center on Aging (C.D.S., D.R.W., F.A.S., G.A.J., G.C., W.R.M.), University of Kentucky College of Medicine, Lexington.

Address correspondence and reprint requests to Dr. Charles D. Smith, MRISC, Room 62, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536; e-mail: csmith{at}mri.uky.edu

Objective: To determine whether alterations of brain structure in normal aged individuals precede the development of mild cognitive impairment (MCI) or Alzheimer disease (AD).

Background: Persons with MCI and AD demonstrate cortical volume losses vs asymptomatic aged individuals, particularly in the hippocampus, amygdala, and entorhinal cortex. It is unknown whether these losses or other volumetric changes are present, and to what degree, in cognitively normal individuals before the clinical diagnosis of MCI.

Methods: Structural MRI was performed on a cross-section of 136 longitudinally examined normal aged subjects. All subjects were cognitively normal at the time of their scan, but 23 later developed MCI, and 9 of these 23 went on to an AD diagnosis. Extracted volumes from voxel-based morphometric analysis were combined with clinical data to compare the 23 subjects who eventually developed MCI to 113 subjects who remained cognitively normal over an average follow-up of 5.4 years.

Results: Initially normal subjects who eventually developed MCI demonstrated decreased gray matter volumes in the anteromedial temporal lobes bilaterally and left angular gyrus while still cognitively normal.

Conclusion: Structural brain changes in anatomic areas involved in higher cognitive processes precede clinical signs and symptoms in longitudinally followed normal subjects destined to develop mild cognitive impairment.

Supported by National Institute of Neurological Disorders and Stroke Grant 5R01 NS-36660, C.D.S., NIA Grant 1P30-AG028383, W.R.M., and General Clinical Research Center grant 5M01 RR02602.

Disclosure: The authors report no conflicts of interest.

Received August 15, 2006. Accepted in final form December 11, 2006.


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