Participants
This research was approved by the Ethics Committee of Showa University Hospital, and was conducted in accordance with the principles of the Declaration of Helsinki (clinical trial identifier number: 2561). This study was registered for University hospital Medical Information Network (UMIN)-CTR (ID: UMIN000033776, 20/08/2018). The participants included in this study consisted of a subset of subjects from a previously published study [18], for whom both facial expression and structural MRI data were available. Participants were aged 23 to 59 years in the younger group and 60 to 85 years in the elderly group. All participants provided written informed consent. Twenty elderly participants (10 men and 10
Table 1. Participants characteristics
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Younger group
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Elderly group
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Average
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S.D.
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Average
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S.D.
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p value
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Age
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40.7
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11.5
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74.1
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4.3
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< 0.0001
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MoCA
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27.9
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2.1
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25.8
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2.2
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0.005
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Years of education
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17.1
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2.4
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13.4
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2.6
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< 0.0001
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Region volume
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ICV
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1568011
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135892
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1460717
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164837
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Left opercular part of inferior frontal gyrus
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3202
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522
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2810
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493
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0.492
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Left orbital part of inferior frontal gyrus
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1099
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169
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994
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203
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0.122
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Left triangular part of inferior frontal gyrus
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2474
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485
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2167
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320
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0.020
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Left middle frontal gyrus
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10348
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1699
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8239
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1301
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0.003
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Left superior frontal gyrus
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17598
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1647
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14854
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1780
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0.005
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Left hippocampus
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4172
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359
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3440
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358
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< 0.0001
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Right opercular part of inferior frontal gyrus
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3347
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479
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2856
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452
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0.040
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Right orbital part of inferior frontal gyrus
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1031
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199
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866
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208
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0.323
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Right triangular part of inferior frontal gyrus
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2127
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396
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1966
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420
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0.124
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Right middle frontal gyrus
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9044
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1047
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7517
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1183
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0.003
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Right superior frontal gyrus
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16644
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1573
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13646
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2005
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< 0.0001
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Right hippocampus
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4389
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332
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3609
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439
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< 0.0001
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MoCA: Montreal Cognitive Assessment. Years of Education: Years of education since entering elementary school. The standard deviations are shown in parentheses. Unpaired t test was used to age, MoCA, and years of education. RM-ANCOVA with MoCA and years of education as covariate was used to Wisconsin card sorting test. ICV: Intracranial volume. ANCOVA with intracranial volumes, MoCA, and years of education as covariate was used to brain volume. The unit of region volume is mm3.
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women) and 20 younger adults (11 women and 9 men) participated in this study (Table 1). The average age of all participants was 56.95 (SD = 18.95). Cerebral infarction was diagnosed in one man in the elderly group; his data were excluded from the analysis. Nineteen elderly and 18 younger participants were right-hand dominant, and all had normal visual acuity. The average age of the elderly group (mean age: 74.1) was higher than that in the younger group (mean age: 40.7; t37 =11.970, p < 0.0001). The average number of years of education in the elderly group was lower than that in the younger group (t37 = 4.610, p < 0.0001). The average MoCA score in the elderly group was lower than that in the younger group (t37 = 3.012, p = 0.005).
Wisconsin card sorting test
We used a modified and computerized version of the Keio Version WCST [19]. The WCST is a test that uses cards with printed figures consisting of one to four triangles, stars, crosses, and circles in red, green, yellow, and blue. Participants were required to place the response cards one by one under the four stimulus cards according to one of the three classification categories: color, shape, or number. The outcome measures were the number of categories achieved (CA), perseverative errors of Nelson (PEN), and difficulties in maintaining set (DMS). The CA is the number of categories for which six consecutive correct responses are achieved (eight is the maximum number of categories that can be achieved), and reflects the sum measure of the level of conceptual shifts. The index reflects the degree of concept formation and transformation. PEN reflects the number of incorrect responses in the same category as the immediately preceding incorrect response. The index indicates a tendency for false reactions to persist and a failure to suppress the previous reaction. DMS reflects the number of false responses after consecutive correct answers. The index refers to the degree to which the subject loses track of the classification category to which the participant is conforming.
MRI acquisition
MRI data were obtained at Ebara Hospital (Tokyo, Japan) using a Siemens Avanto 3 T Magnetom TIM Trio scanner. T1-weighted anatomical scan was measured following parameters (repetition time, 2250 ms; echo time, 3.06 ms; flip angle, 9 °; inversion time, 1000 ms; field of view, 256 × 256 mm; matrix size, 256 × 256; voxel size, 1 × 1 × 1 mm). The acquisition of high-resolution anatomical images
Were optimized with magnetization-prepared rapid gradient echo sequence.
Image processing
Image processing were performed with FreeSurfer version 6 [20, 21] including motion correction, removing nonbrain tissue, normalization with non-uniform intensity, affine registration to Montreal Neurological Institute (MNI) space, and Talairach transformation [22]. Volumetric segmentation [23], cortical surface reconstruction [24-26], and parcellation [27, 28] were automatically performed with the recon-all script on FreeSurfer after the image processing. Detailed descriptions have been provided elsewhere [29]. The 70 gray matter volumes determined by Desikan-Killiany brain atlas [28] were used in this study. All gray matter boundaries were confirmed by visual inspections of two trained neurologists with a graphic tool of Freeview after affine registration to MNI space. The two neurologists performed manual editing within the range of removing non-brain tissue included within the cortical boundary. Intracranial volume (ICV) was estimated using FreeSurfer version 6 [20, 21] for using as a covariate for statistical analysis.
Statistical analysis
An unpaired t-test was used to compare the age, years of education, and MoCA scores between the two groups. A one-way repeated measures analysis of covariance (RM-ANCOVA) was used to assess the age effect in the younger and elderly groups, with years of education and MoCA scores as covariates. Twelve regions were selected as the ROIs. An ANCOVA was used to compare the regional volumes between groups, with ICVs, years of education, and MoCA scores as covariates. Post-hoc t-tests with Bonferroni correction were performed for multiple comparisons for both the ANCOVA and RM-ANCOVA analyses. All tests were two-tailed. Results are presented as the mean ± standard error of the mean. SPSS version 26 was used for all statistical analyses. Relationships among age, years of education, 12 ROIs, 3 indices in WCST, and MoCA scores were determined using path analysis. The goodness of fit of index (GFI), root mean square error of approximation (RMSEA), comparative fit index (CFI), and Bollen-Stine bootstrap were calculated to check the model fitting. AMOS 27.0, was used for path analysis. Statistical significance was defined as an adjusted p-value of < 0.05.