Classification of Alzheimer disease, mild cognitive impairment, and normal cognitive status with large-scale network analysis based on resting-state functional MR imaging.
OBJECTIVE
To use large-scale network (LSN) analysis to classify subjects with Alzheimer disease (AD), those with amnestic mild cognitive impairment (aMCI), and cognitively normal (CN) subjects.


METHODS
The study was conducted with institutional review board approval and was in compliance with HIPAA regulations. Written informed consent was obtained from each participant. Resting-state functional magnetic resonance (MR) imaging was used to acquire the voxelwise time series in 55 subjects with clinically diagnosed AD (n = 20), aMCI (n =15), and normal cognitive function (n = 20). The brains were divided into 116 regions of interest (ROIs). The Pearson product moment correlation coefficients of pairwise ROIs were used to classify these subjects. Error estimation of the classifications was performed with the leave-one-out cross-validation method. Linear regression analysis was performed to analyze the relationship between changes in network connectivity strengths and behavioral scores.


RESULTS
The area under the receiver operating characteristic curve (AUC) yielded 87% classification power, 85% sensitivity, and 80% specificity between the AD group and the non-AD group (subjects with aMCI and CN subjects) in the first-step classification. For differentiation between subjects with aMCI and CN subjects, AUC was 95%; sensitivity, 93%; and specificity, 90%. The decreased network indexes were significantly correlated with the Mini-Mental State Examination score in all tested subjects. Similarly, changes in network indexes significantly correlated with Rey Auditory Verbal Leaning Test delayed recall scores in subjects with aMCI and CN subjects.


CONCLUSIONS
LSN analysis revealed that interconnectivity patterns of brain regions can be used to classify subjects with AD, those with aMCI, and CN subjects. In addition, the altered connectivity networks were significantly correlated with the results of cognitive tests.
Department of Biophysics, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA.
Gang
G
Chen
B Douglas
BD
Ward
Chunming
C
Xie
Wenjun
W
Li
Zhilin
Z
Wu
Jennifer L
JL
Jones
Malgorzata
M
Franczak
Piero
P
Antuono
Shi-Jiang
SJ
Li
D000368:Aged; D000465:Algorithms; D000544:Alzheimer Disease / Q000150:complications* / Q000175:diagnosis*; D001931:Brain Mapping / Q000379:methods*; D003072:Cognition Disorders / Q000175:diagnosis* / Q000209:etiology*; D005260:Female; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D016571:Neural Networks, Computer; D015203:Reproducibility of Results; D012146:Rest; D012680:Sensitivity and Specificity
Int J Psychophysiol. 2008 Mar;67(3):252-61
17669531
Brain. 2009 Jan;132(Pt 1):213-24
18952674
Neuroimage. 2006 Jul 15;31(4):1536-48
16632379
Magn Reson Med. 2000 Jul;44(1):162-7
10893535
Radiology. 2009 Apr;251(1):195-205
19201945
Proc Natl Acad Sci U S A. 1978 Jul;75(7):3034-6
16592540
J Neurosci. 2009 Oct 14;29(41):12729-34
19828783
Nature. 2006 Oct 19;443(7113):768-73
17051202
Neuroimage. 2006 Jun;31(2):496-504
16473024
Nat Neurosci. 2006 Jan;9(1):23-5
16341210
Nature. 2008 Jun 12;453(7197):869-78
18548064
Proc Natl Acad Sci U S A. 2007 Nov 13;104(46):18265-9
17991778
Magn Reson Imaging. 2008 Apr;26(3):379-92
18164158
Science. 2005 Aug 5;309(5736):948-51
16081740
Cereb Cortex. 2009 Jan;19(1):72-8
18403396
Neuroimage. 2007 Oct 1;37(4):1083-90; discussion 1097-9
17719799
Neuron. 2009 Apr 16;62(1):42-52
19376066
Neuroimage. 2002 Jan;15(1):273-89
11771995
Neuroimage. 2008 Feb 15;39(4):1731-43
18053747
Radiology. 2002 Oct;225(1):253-9
12355013
Neurobiol Aging. 2008 Jan;29(1):23-30
17097767
Magn Reson Med. 1995 Oct;34(4):537-41
8524021
Magn Reson Med. 2006 Jul;56(1):41-50
16767759
Neurology. 2009 Oct 13;73(15):1193-9
19822868
Neurology. 2007 Oct 23;69(17):1650-6
17954780
Neuroimage. 2008 Jun;41(2):277-85
18400519
Proc Natl Acad Sci U S A. 2008 Oct 14;105(41):16039-44
18843113
Hum Brain Mapp. 2007 Oct;28(10):967-78
17133390
Annu Rev Neurosci. 2009;32:209-24
19400723
Front Integr Neurosci. 2009 Jul 30;3:17
19668703
Annu Rev Neurosci. 2006;29:449-76
16776593
Neuroscientist. 2009 Aug;15(4):333-50
19458383
Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4637-42
15070770
Cereb Cortex. 2007 Jan;17(1):92-9
16452642
Natl Vital Stat Rep. 2009 Apr 17;57(14):1-134
19788058
PLoS Comput Biol. 2008 Jun 27;4(6):e1000100
18584043
J Neurosci. 2008 Apr 30;28(18):4756-66
18448652