The association between hippocampal subfield volumes and education in cognitively normal older adults and amnestic mild cognitive impairment patients

Figures & data

Figure 1 Illustration of parcellation scheme used for automated hippocampal subfield segmentation: axial view, coronal view, sagittal view. Images are from a control subject.

Abbreviations: CA, cornus ammonis; GC-DG, granule cell layer of dentate gyrus; HATA, the hippocampus–amygdala transition area.

Table 1 Demographic and clinical characteristics of the study participants

	Control group (n=39)	aMCI group (n=38)	p-value
Age (years)	71.8±5.8 (62–87)	75.5±5.4 (63–89)	0.006
Sex (M:F, %)	46:54	26:74	0.116
Education (years)	9.1±6.3 (0–21)	10.2±4.7 (0–20)	0.368
APOE4 carrier (n, %)	6 (18.2%)	9 (25.7%)	0.648
MMSE-K	26.5±2.4 (23–30)	23.1±3.9 (11–29)	<0.001
CERAD-K WLM	17.3±3.9 (10–28)	12.9±3.9 (6–20)	<0.001
CERAD-K WLR	5.5±1.6 (3–9)	2.7±1.8 (0–8)	<0.001
CERAD-K WLRc	8.9±1.2 (6–11)	6.5±2.4 (1–10)	<0.001
CERAD-K CR	7.1±2.9 (2–11)	3.7±2.5 (0–8)	<0.001
TICV (mm^3)	1,445,879.9±162,780.2 (1,099,427–1,727,122)	1,453,963.5±166,234.4 (1,151,643–1,786,046)	0.830

Note: Data are means ± SD (minimum–maximum) unless indicated otherwise.

Abbreviations: aMCI, amnestic mild cognitive impairment; CERAD-K, the Korean version of Consortium to Establish a Registry for Alzheimer’s Disease; CR, constructional recall; MMSE-K, the Korean version of mini mental status examination; TICV, total intracranial volume; WLM, word list memory; WLR, word list recall; WLRc, word list recognition.

Table 2 Relationship between hippocampal subfield volumes and education

Hippocampus	Education yearsa (both groups)			Education yearsb (control group)			Education yearsb (aMCI group)
	Std. β	t	p-value	Std. β	t	p-value	Std. β	t	p-value
Left
CA1	−0.06	−0.53	0.6	0.22	1.12	0.27	−0.22	−1.29	0.206
CA3	−0.13	−1.04	0.305	0.05	0.23	0.823	−0.16	−0.91	0.372
CA4	−0.1	−0.84	0.404	0.15	0.70	0.489	−0.21	−1.28	0.211
GC-DG	−0.11	−0.95	0.348	0.14	0.67	0.507	−0.23	−1.43	0.163
Parasubiculum	−0.31	−2.70	0.009c,^#	−0.29	−1.36	0.185	−0.37	−2.43	0.021c,^*
Presubiculum	−0.26	−2.38	0.02c,^*	−0.15	−0.71	0.485	−0.28	−2.00	0.055c
Subiculum	−0.23	−2.19	0.032c,^*	−0.11	−0.56	0.579	−0.31	−2.12	0.042c,^*
Total	−0.19	−1.72	0.09c	0.05	0.26	0.797	−0.26	−1.68	0.102c
Right
CA1	−0.11	−1.13	0.371	0.18	0.92	0.365	−0.13	−0.82	0.42
CA3	−0.11	−0.84	0.403	0.12	0.61	0.547	−0.08	−0.98	0.336
CA4	−0.05	−0.39	0.698	0.29	1.43	0.164	−0.18	−1.04	0.305
GC-DG	−0.05	−0.64	0.705	0.34	1.83	0.077c	−0.17	−1.06	0.296
Parasubiculum	−0.2	−1.69	0.095c	−0.13	−0.61	0.549	−0.29	−1.83	0.077c
Presubiculum	−0.15	−1.22	0.229	0.01	0.02	0.98	−0.21	−1.29	0.208
Subiculum	−0.17	−1.53	0.132c	0.02	0.12	0.907	−0.22	−1.48	0.149c
Total	−0.1	−0.83	0.41	0.19	0.99	0.329	−0.19	−1.16	0.257

Notes:

a Subjects’ age, sex, diagnosis and APOE ε4 genotype were used as covariates.

b Subjects’ age, sex, and APOE ε4 genotype were used as covariates,

c Education was finally selected as an independent variable after performing stepwise regression (^*p<0.05; ^#p<0.01).

Abbreviations: aMCI, amnestic mild cognitive impairment; CA, cornus ammonis; GC-DG, granule cell layer of dentate gyrus; std. β, standardized beta.

Table 3 (A–E) Relationships between cognitive functions and hippocam pal subfield volumes

A
MMSE-K
Hippocampus	MMSE-Ka (control group)			MMSE-Ka (aMCI group)
	Std. β	t	p-value	Std. β	t	p-value
Left
CA1	0.01	0.05	0.963	−0.07	−0.37	0.717
CA3	−0.13	−0.55	0.59	0.01	0.07	0.943
CA4	−0.13	−0.55	0.585	0.02	0.11	0.911
GC-DG	−0.14	−0.61	0.546	0	0.01	0.989
Parasubiculum	0.07	0.27	0.788	0.06	0.35	0.732
Presubiculum	−0.36	−1.81	0.08b	0.04	0.24	0.816
Subiculum	−0.38	−2.04	0.05b	0.01	0.09	0.928
Total	−0.19	−0.83	0.415	−0.03	−0.16	0.876
Right
CA1	−0.09	−0.39	0.701	−0.13	−0.73	0.472
CA3	0.24	1.03	0.313	−0.02	−0.09	0.927
CA4	0.1	0.45	0.655	−0.04	−0.19	0.851
GC-DG	0.07	0.33	0.744	−0.03	−0.19	0.849
Parasubiculum	−0.1	−0.39	0.701	−0.07	−0.38	0.708
Presubiculum	−0.28	−1.15	0.259	−0.04	−0.21	0.835
Subiculum	−0.3	−1.30	0.206	−0.03	−0.16	0.878
Total	−0.15	−0.67	0.51	−0.11	−0.58	0.567

B
CERAD-K word list memory
Hippocampus	CERAD-K WLMa (control group)			CERAD-K WLMa (aMCI group)
	Std. β	t	p-value	Std. β	t	p-value
Left
CA1	0.26	1.48	0.149c	−0.07	−0.38	0.705
CA3	0.04	0.19	0.848	−0.1	−0.51	0.617
CA4	0.33	1.95	0.06c	−0.08	−0.44	0.66
GC-DG	0.29	1.68	0.104c	−0.05	−0.26	0.796
Parasubiculum	−0.11	−0.53	0.601	−0.1	−0.60	0.555
Presubiculum	0.01	0.04	0.97	−0.02	−0.10	0.917
Subiculum	0.26	1.58	0.124c	0	0	0.997
Total	0.14	0.74	0.464	−0.05	−0.32	0.752
Right
CA1	0.08	0.45	0.655	0.01	0.05	0.959
CA3	−0.09	−0.47	0.643	0.24	1.47	0.151c
CA4	−0.01	−0.06	0.953	0.13	0.73	0.474
GC-DG	−0.01	−0.08	0.936	0.14	0.82	0.421
Parasubiculum	0.04	0.18	0.858	0.05	0.29	0.778
Presubiculum	−0.05	−0.25	0.805	0.2	1.18	0.247
Subiculum	−0.01	−0.04	0.97	0.08	0.50	0.62
Total	0	0.02	0.986	0.07	0.39	0.696

C
CERAD-K word list recall
Hippocampus	CERAD-K WLRa (control group)			CERAD-K WLRa (aMCI group)
	Std. β	t	p-value	Std. β	t	p-value
Left
CA1	0.15	0.66	0.516	0.02	0.12	0.909
CA3	−0.12	−0.50	0.621	0.13	0.66	0.514
CA4	−0.08	−0.35	0.726	0	0.00	1
GC-DG	−0.06	−0.28	0.779	0.05	0.29	0.775
Parasubiculum	−0.65	−3.53	0.001d,‡	0.05	0.29	0.771
Presubiculum	−0.64	−3.58	0.001d,‡	−0.09	−0.57	0.576
Subiculum	−0.42	−2.15	0.039d,*	−0.11	−0.70	0.488
Total	−0.27	−1.37	0.183d	−0.05	−0.28	0.778
Right
CA1	−0.09	−0.41	0.688	−0.16	−0.93	0.362
CA3	−0.15	−0.69	0.497	−0.11	−0.58	0.566
CA4	−0.16	−0.72	0.477	−0.15	−0.79	0.435
GC-DG	−0.13	−0.62	0.54	−0.11	−0.60	0.556
Parasubiculum	−0.32	−1.86	0.072d	−0.18	−1.02	0.317
Presubiculum	−0.43	−2.17	0.038e,*	−0.17	−0.98	0.333
Subiculum	−0.41	−2.16	0.039d,*	−0.14	−0.80	0.431
Total	−0.34	−1.72	0.096d	−0.17	−0.95	0.35

D
CERAD-K word list recognition
Hippocampus	CERAD-K WLRca (control group)			CERAD-K WLRca (aMCI group)
	Std. β	t	p-value	Std. β	t	p-value
Left
CA1	0.48	3.20	0.003f,‡	0.1	0.55	0.584
CA3	0.57	3.84	0.001f,‡	0.06	0.33	0.747
CA4	0.54	3.60	0.001f,‡	0.07	0.43	0.671
GC-DG	0.5	3.23	0.003f,‡	0.06	0.35	0.726
Parasubiculum	−0.01	−0.07	0.948	0.06	0.40	0.69
Presubiculum	0.12	0.2	0.548	−0.02	−0.16	0.878
Subiculum	0.34	2.06	0.048f,*	−0.03	−0.20	0.843
Total	0.48	3.03	0.005f,#	0.01	0.04	0.966
Right
CA1	0.32	1.97	0.059f	0.02	0.15	0.883
CA3	0.28	1.60	0.121f	−0.03	0.18	0.883
CA4	0.36	2.26	0.032f,*	−0.01	−0.05	0.961
GC-DG	0.27	1.66	0.108f	0	0.02	0.982
Parasubiculum	0.25	1.46	0.154f	−0.03	−0.20	0.844
Presubiculum	0.32	1.91	0.065f	−0.08	−0.46	0.646
Subiculum	0.29	1.70	0.1f	−0.08	−0.50	0.622
Total	0.37	2.30	0.028f,*	−0.06	−0.37	0.712

E
CERAD-K constructional recall
Hippocampus	CERAD-K CRa (control group)			CERAD-K CRa (aMCI group)
	Std. β	t	p-value	Std. β	t	p-value
Left
CA1	0.14	0.54	0.596	0.01	0.06	0.952
CA3	−0.18	−0.66	0.514	0.16	0.71	0.481
CA4	−0.11	−0.42	0.677	0.18	0.84	0.405
GC-DG	−0.11	−0.42	0.675	0.43	2.75	0.01g,*
Parasubiculum	−0.24	−0.87	0.391	−0.06	−0.28	0.779
Presubiculum	−0.16	−0.56	0.579	0.05	0.28	0.78
Subiculum	−0.02	−0.07	0.945	0.18	0.95	0.349
Total	−0.13	−0.48	0.638	0.13	0.65	0.518
Right
CA1	−0.05	−0.21	0.834	0.07	0.32	0.755
CA3	−0.27	−1.02	0.315	0.23	1.05	0.303
CA4	−0.3	−1.16	0.255	0.41	2.59	0.014g,*
GC-DG	−0.26	−1.08	0.288	0.4	2.47	0.019g,*
Parasubiculum	−0.26	−0.91	0.369	0.03	0.12	0.904
Presubiculum	−0.19	−0.70	0.493	0.45	2.98	0.005g,#
Subiculum	−0.07	−0.26	0.797	0.26	1.30	0.205
Total	−0.2	−0.79	0.434	0.41	2.60	0.014g,*

Notes:

a Subjects’ age, sex, education, and APOE ε4 genotype were used as covariates.

b MMSE-K was finally selected as an independent variable after performing stepwise regression.

c CERAD-K word list memory was finally selected as an independent variable after performing stepwise regression.

d CERAD-K word list recall was finally selected as an independent variable after performing stepwise regression.

e Insignificant finally selected model after performing stepwise regression.

f CERAD-K word list recognition was finally selected as an independent variable after performing stepwise regression.

g CERAD-K constructional recall was finally selected as an independent variable after performing stepwise regression.

* p<0.05;

# p<0.01;

‡ p<0.005.

Abbreviations: aMCI, amnestic mild cognitive impairment; CA, cornus ammonis; GC-DG, granule cell layer of dentate gyrus; MMSE-K, the Korean version of mini mental status examination; std. β, standardized beta; CERAD-K, the Korean version of Consortium to Establish a Registry for Alzheimer’s Disease; WLRc, word list recognition; WLR, word list recall.

Table 4 Relationships between cognitive functions and education

Cognitive function	Education yearsa (control group)			Education yearsa (aMCI group)
	Std. β	t	p-value	Std. β	t	p-value
MMSE-K	0.45	3.08	0.004b,^‡	0.46	2.85	0.008b,^#
CERAD-K word list memory	0.32	1.60	0.121b	0.16	0.96	0.346
CERAD-K word list recall	0.23	1.21	0.237	0.09	0.53	0.602
CERAD-K word list recognition	0.02	0.08	0.936	0.04	0.25	0.807
CERAD-K constructional recall	0.74	6.04	<0.001b,^‡	0.3	2.14	0.041b,^*

Notes:

a Subjects’ age, sex, and APOE ε4 genotype were used as covariates.

b Education years were finally selected as an independent variable after performing stepwise regression (^*p<0.05; ^#p<0.01; ^‡p<0.005).

Abbreviations: aMCI, amnestic mild cognitive impairment; CERAD-K, the Korean version of Consortium to Establish a Registry for Alzheimer’s Disease; MMSE-K, the Korean version of mini mental status examination; std. β, standardized beta.