Table 2.

Relationship between brain volumes and age as well as significance of nonlinearity using generalized additive modeling

Brain Regions	Control		sMCI		cMCI		AD		Nonlinearity

	eDF	F_age	eDF	F_age	eDF	F_age	eDF	F_age	F_nonlinear	p_nonlinear
Lateral ventricles	1.9	22.2^‡	2.3	45.2^‡	1.3	33.5^‡	1.5	35.7^‡	7.1	8.0 × 10^-3
Total white matter	1.7	23.5^‡	2.2	40.2^‡	1.9	18.7^†	2.0	18.3^†	5.5	9.2 × 10^-3
Total gray matter	1.8	45.9^‡	2.0	30.7^‡	1.9	9.1^$	1.2	0.6^ns	5.3	1.1 × 10^-2

Parahippocampal gyrus	1.9	9.3^$	1.6	18.7^$	1.3	2.4^ns	1.4	14.4^†	14.9	3.6 × 10^-5
Fusiform gyrus	1.6	31.2^‡	1.3	17.1^†	1.2	16.8^†	1.0	2.6^ns	14.1	7.0 × 10^-4
Hippocampus	1.7	44.5^‡	2.4	37.8^‡	1.8	25.6^‡	2.1	27.3^‡	12.2	4.6 × 10^-4
Transverse temporal GM^(a)	1.9	20.5^‡	2.2	9.7^†	2.0	20.7^‡	1.3	12.2^†	9.9	1.9 × 10^-3
Entorhinal cortex	1.7	5.5^ns	1.4	18.8^†	1.3	12.9^†	1.4	22.6^‡	9.2	1.0 × 10^-2
Superior temporal GM^(a)	1.9	33.6^‡	1.4	9.6^†	1.9	27.0^‡	1.3	6.9^ns	4.3	ns

Posterior cingulate	1.9	31.1^‡	1.4	13.7^‡	1.9	9.4^†	1.0	0.1^ns	5.0	ns
Precentral GM^(a)	1.8	60.0^‡	2.1	50.1^‡	1.8	14.6^‡	1.7	10.1^†	5.0	ns
Lateral orbitofrontal GM^(a)	1.3	25.9^‡	1.7	82.3^‡	1.4	21.7^‡	1.4	13.2^†	4.9	ns
Medial orbitofrontal GM^(a)	1.3	12.1^†	1.6	58.2^‡	1.4	13.6^†	1.4	19.3^†	4.5	ns
Inferior parietal GM^(a)	1.2	48.9^‡	1.6	14.6^†	1.3	3.2^ns	1.0	2.0^ns	1.5	ns
Superior frontal GM^(a)	1.8	41.1^‡	1.9	22.2^‡	1.8	23.7^‡	1.7	11.9^†	0.9	ns

eDF: extra degrees of freedom, an index of nonlinearity where a value larger than unity indicates the deviation from linearity.

F_age: F-value of age dependence test;

P-value levels of age tests: ns = not significant;

p = 0.05;

^†

p = 0.01;

^‡

p = 0.001;

F_nonlinear: F-value of nonlinearity test;

p_nonlinear = p-value of nonlinearity test;

GM: Gray matter;