Conversion of mild cognitive impairment to Alzheimer disease predicted by hippocampal atrophy maps.
BACKGROUND
While most patients with mild cognitive impairment (MCI) transition to Alzheimer disease (AD), others develop non-AD dementia, remain in the MCI state, or improve.


OBJECTIVE
To test the following hypotheses: smaller hippocampal volumes predict conversion of MCI to AD, whereas larger hippocampal volumes predict cognitive stability and/or improvement; and patients with MCI who convert to AD have greater atrophy in the CA1 hippocampal subfield and subiculum.


METHODS
Prospective longitudinal cohort study.


METHODS
University of California-Los Angeles Alzheimer's Disease Research Center.


METHODS
We followed up 20 MCI subjects clinically and neuropsychologically for 3 years.


METHODS
Baseline regional hippocampal atrophy was analyzed with region-of-interest and 3-dimensional hippocampal mapping techniques.


RESULTS
During the 3-year study, 6 patients developed AD (MCI-c), 7 remained stable (MCI-nc), and 7 improved (MCI-i). Patients with MCI-c had 9% smaller left and 13% smaller right mean hippocampal volumes compared with MCI-nc patients. Radial atrophy maps showed greater atrophy of the CA1 subregion in MCI-c. Patients with MCI-c had significantly smaller hippocampi than MCI-i patients (left, 24%; right, 27%). Volumetric analyses showed a trend for greater hippocampal atrophy in MCI-nc relative to MCI-i patients (eg, 16% volume loss). After permutation tests corrected for multiple comparison, the atrophy maps showed a significant difference on the right. Subicular differences were seen between MCI-c and MCI-i patients, and MCI-nc and MCI-i patients. Multiple linear regression analysis confirmed the group effect to be highly significant and independent of age, hemisphere, and Mini-Mental State Examination scores at baseline.


CONCLUSIONS
Smaller hippocampi and specifically CA1 and subicular involvement are associated with increased risk for conversion from MCI to AD. Patients with MCI-i tend to have larger hippocampal volumes and relative preservation of both the subiculum and CA1.
Apostolova
Liana G
LG
Laboratory of Neuro Imaging, Department of Neurology, The David Geffen School of Medicine at UCLA, University of California-Los Angeles, Los Angeles, CA, USA. lapostolova@mednet.ucla.edu
Dutton
Rebecca A
RA
Dinov
Ivo D
ID
Hayashi
Kiralee M
KM
Toga
Arthur W
AW
Cummings
Jeffrey L
JL
Thompson
Paul M
PM