Brain structural alterations before mild cognitive impairment.
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.


CONCLUSIONS
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.
Smith
C D
CD
MRISC, Room 62, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536. csmith@mri.uky.edu
Chebrolu
H
H
Wekstein
D R
DR
Schmitt
F A
FA
Jicha
G A
GA
Cooper
G
G
Markesbery
W R
WR
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D003071:Cognition / Q000502:physiology; D003072:Cognition Disorders / Q000473:pathology* / Q000503:physiopathology; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology; D010296:Parietal Lobe / Q000473:pathology / Q000503:physiopathology; D011237:Predictive Value of Tests; D013702:Temporal Lobe / Q000473:pathology / Q000503:physiopathology