Table 1 Demographics, clinical characteristics and neuropsychological assessment of the study sample
Characteristics
|
AD
(n=57)
|
aMCI
(n=57)
|
HC
(n=48)
|
p Value
|
Women (%)
|
31 (54)
|
35 (61)
|
30(63)
|
0.645b
|
Age (years)
|
67.74 (8.28)
|
66.33 (7.47)
|
66.75 (7.41)
|
0.613a
|
Years of education
|
6.14 (5.38)
|
9.53 (4.71)
|
11.69(3.48)
|
<0.001a
|
MMSE score
|
15.28 (5.22)
|
26.35 (1.58)
|
28.60(1.11)
|
<0.001a
|
Clinical Dementia Rating Scale
|
|
|
|
|
1 (%)
|
21 (37)
|
|
|
|
2 (%)
|
22 (39)
|
|
|
|
3 (%)
|
14 (25)
|
|
|
|
TIV (mm3)
|
1314.27 (109.09)
|
1352.93
(99.70)
|
1368.67
(103.03)
|
0.023a
|
Frame-wise displacement (mm)
|
0.21(0.14)
|
0.22(0.16)
|
0.18(0.11)
|
0.466a
|
neuropsychological tests
|
|
|
|
|
AVLT (immediate)
|
2.01(1.62)
|
5.89(2)
|
9.04(1.76)
|
<0.001a
|
AVLT (delay)
|
0(0-0)
|
4.46(3.08)
|
10.13(2.77)
|
<0.001c
|
AVLT (recognize)
|
10(6-12)
|
12(11-14)
|
14(13.5-15)
|
<0.001c
|
VFT (Animals)
|
9(7-10)
|
13(10.5-14.5)
|
18.13(3.93)
|
<0.001c
|
DSpF
|
5(4-6)
|
7(6-8)
|
8(7-8)
|
<0.001c
|
DSpB
|
3(2-3)
|
4(3-5)
|
5(4-6)
|
<0.001c
|
cognitive functionscore
|
|
|
|
|
Episodic memoryd
|
-2.70(1.65)
|
0.27(1.58)
|
2.88(1.22)
|
<0.001a
|
Semantic memoryd
|
-0.85(0.63)
|
0.04(-0.43-0.32)
|
1.0(0.74)
|
<0.001c
|
Working memoryd
|
-1.48(1.63)
|
0.29(1.24)
|
1.42(1.32)
|
<0.001a
|
|
|
|
|
|
|
Datas with normal distribution are expressed as mean (SD) or as percentage.
Datas with non-normal distribution are expressed as median (interquartile range).
aGroup difference was tested by using one-way analysis of variance (ANOVA).
bGroup difference was tested by using Pearson’s Chi-square test.
cGroup difference was tested by using Kruskal-Wallis test.
dEach cognitive composite score was computed by converting raw scores on each component of neuropsychological tests to z scores, using the mean and SD for all participants in the study, and averaging the z scores to yield the composite score.
Abbreviations: AD, Alzheimer’s disease; aMCI, amnestic mild cognitive impairment; HC, healthy control; MMSE, Mini-Mental State Examination; TIV, total intracranial volume; SD, standard deviations; AVLT, auditory verbal learning test; VFT, verbal fluency test; DSpF, Digit Span Forward; DSpB, Digit Span Backward.
Table 2 Results of voxel-based regression analyses between neuroimaging parameters and years of education
Region
|
Number of voxels
|
t-score
|
MNI coordinates
|
x
|
y
|
z
|
Negative correlations between years of education and GMV
|
dorsal anterior cingulate cortex
|
291
|
-5.25
|
0
|
20
|
33
|
Negative correlations between years of education and ReHo
|
left anterior part of inferior temporal cortex
|
65
|
-6
|
-57
|
-12
|
-33
|
left posterior part of inferior temporal cortex
|
59
|
-4.69
|
-51
|
-30
|
-21
|
Negative correlations between years of education and left aITC rsFC
|
right angular gyrus
|
32
|
-4.79
|
45
|
-66
|
42
|
left mid frontal cortex
|
27
|
-5.57
|
-39
|
15
|
57
|
right superior frontal cortex
|
16
|
-4.95
|
24
|
27
|
54
|
Structural MR (GMV): Adjusted for age, sex, MMSE, and TIV.
Resting-state fMRI (ReHo and rsFC): Adjusted for age, sex, MMSE, and head motion parameters.
Coordinates (x,y,z) are given in MNI standard space. All regions listed are statistically significant at p<0.05 level (FDR corrected).
Abbreviations: GMV, gray matter volume; ReHo, Regional Homogeneity; rsFC, resting-state functional connectivity; MNI, Montreal Neurological Institute; aITC, anterior part of inferior temporal cortex; MMSE, Mini-Mental State Examination; TIV, total intracranial volume.
Table 3 Correlations between years of education and biomarkers of AD-related pathology: linear regression analysis
AD-related pathology biomarkers
|
Relationships with years of education
|
HC
|
aMCI
|
CDR1
(mild dementia)
|
CDR2
(moderate dementia)
|
CDR3
(severe dementia)
|
β
(SE)
|
p
|
B
|
β
(SE)
|
p
|
B
|
β
(SE)
|
p
|
B
|
β
(SE)
|
p
|
B
|
β
(SE)
|
p
|
B
|
GMV of dACC
|
-0.001
(0.002)
|
0.7
|
-0.062
|
-0.003
(0.002)
|
0.038
*
|
-0.258
|
-0.007
(0.002)
|
0.006**
|
-0.753
|
-0.006
(0.005)
|
0.233
|
-0.569
|
-0.005
(0.004)
|
0.239
|
-0.568
|
ReHo of left aITC
|
0.008
(0.005)
|
0.108
|
0.261
|
-0.003
(0.003)
|
0.372
|
-0.127
|
-0.018
(0.004)
|
0.000***
|
-0.739
|
-0.038
(0.012)
|
0.006**
|
-1.485
|
-0.007
(0.005)
|
0.247
|
-0.62
|
ReHo of left pITC
|
0.003
(0.006)
|
0.649
|
0.076
|
-0.008
(0.004)
|
0.037
*
|
-0.284
|
-0.025
(0.006)
|
0.002**
|
-0.831
|
-0.003
(0.014)
|
0.829
|
-0.101
|
-0.011
(0.01)
|
0.305
|
-0.586
|
left aITC rsFC
|
right angular gyrus
|
0.002
(0.01)
|
0.814
|
0.038
|
-0.004
(0.009)
|
0.662
|
-0.061
|
-0.034
(0.01)
|
0.004**
|
-0.72
|
-0.041
(0.026)
|
0.127
|
-0.899
|
-0.036
(0.012)
|
0.017
*
|
-1.043
|
left mid frontal cortex
|
0.013
(0.008)
|
0.098
|
0.271
|
0.002
(0.008)
|
0.763
|
0.039
|
-0.031
(0.008)
|
0.002**
|
-0.717
|
-0.035
(0.019)
|
0.081
|
-0.873
|
0.003
(0.011)
|
0.78
|
0.103
|
right superior frontal cortex
|
0.002
(0.009)
|
0.835
|
0.032
|
-0.002
(0.007)
|
0.786
|
-0.038
|
-0.029
(0.009)
|
0.007**
|
-0.658
|
-0.05
(0.021)
|
0.029*
|
-1.244
|
0.013
(0.012)
|
0.317
|
0.372
|
Structural MR (GMV): Adjusted for age, sex, MMSE, and TIV.
Resting-state fMRI (ReHo and rsFC): Adjusted for age, sex, MMSE, and head motion parameters.
Abbreviations: AD, Alzheimer’s disease; aMCI, amnestic mild cognitive impairment; HC, healthy control; CDR, Clinical Dementia Rating; SE, standard error; GMV, gray matter volume; ReHo, Regional Homogeneity; rsFC, resting-state functional connectivity; dACC, dorsal anterior cingulate cortex; aITC, anterior part of inferior temporal cortex; pITC, posterior part of inferior temporal cortex; MMSE, Mini-Mental State Examination; TIV, total intracranial volume.
β stand for unstandardized coefficients, B stand for standardized coefficients (Beta).
P< 0.05*, P< 0.01**, P< 0.001***
Table 4 Correlations between ROI-based neuroimaging variables and clinical cognitive function scores in AD group
Cognitive system
|
Episodic memory
|
Semantic memory
|
Working memory
|
r
|
p
|
r
|
p
|
r
|
p
|
aGMV of dACC
|
0.334
|
0.015*
|
0.453
|
0.001**
|
0.205
|
0.141
|
bReHo of left aITC
|
0.172
|
0.217
|
0.049
|
0.728
|
0.021
|
0.884
|
bReHo of left pITC
|
0.391
|
0.004**
|
0.2
|
0.151
|
0.102
|
0.466
|
Left aITC rsFCb
|
|
|
|
|
|
|
right angular gyrus
|
0.312
|
0.023*
|
0.082
|
0.562
|
0.089
|
0.525
|
Left middle frontal cortex
|
0.338
|
0.013*
|
0.277
|
0.045*
|
0.084
|
0.552
|
right superior frontal cortex
|
0.108
|
0.44
|
-0.035
|
0.805
|
-0.128
|
0.36
|
The relationship between neuroimaging variables and clinical cognitive function scores were assessed by using Pearson correlation analysis.
aAdjusted for age, sex, education, and TIV.
bAdjusted for age, sex, education, and head motion parameters.
P< 0.05*, P< 0.01**, P< 0.001***
Abbreviations: AD, Alzheimer’s disease; GMV, gray matter volume; ReHo, Regional Homogeneity; rsFC, resting-state functional connectivity; dACC, dorsal anterior cingulate cortex; aITC, anterior part of inferior temporal cortex; pITC, posterior part of inferior temporal cortex; TIV, total intracranial volume; ROI, region of interest.