. 2023 Apr 17;12:e81067. doi: 10.7554/eLife.81067

Table 5. Relationships between validation variables and brain-age delta stratified by sex for all CU and MCI individuals.

			Females						Males
Model			β (SE)	P-Value	[0.025, 0.075]	N	Effect size	FDR corr P-Value corr	β	P-Value	[0.025, 0.075]	N	Effect size	FDR corr P-Value
	CU Individuals
Amyloid-β pathology (ref: A-)			0.286 (0.065)	<0.001	[0.160, 0.413]	966	0.288	<0.001	0.341 (0.076)	<0.001	[0.192, 0.490]	668	0.344	<0.001
Amyloid-β / Tau pathology (ref: A-T-)		A+T-	0.250 (0.082)	0.003	[0.088, 0.411]	688	0.252	0.008	0.2978 (0.096)	0.002	[0.110, 0.486]	474	0.301	0.006
Amyloid-β / Tau pathology (ref: A-T-)		A+T +	0.391 (0.131)	0.003	[0.134, 0.648]	688	0.385	0.008	0.173 (0.163)	0.290	[–0.148, 0.494]	474	0.175	0.424
APOE status (ref: APOE-ε33)		APOE-ε2	–0.175 (0.110)	0.112	[–0.391, 0.041]	966	0.172	0.209	–0.061 (0.122)	0.615	[–0.301, 0.178]	668	0.062	0.766
		APOE-ε4	0.117 (0.067)	0.081	[–0.014, 0.248]		0.116	0.162	0.249 (0.082)	0.003	[0.087, 0.410]		0.249	0.008
		APOE-ε24	–0.011 (0.197)	0.958	[–0.337, 0.358]		0.011	0.999	0.044 (0.212)	0.836	[–0.372, 0.461]		0.045	0.976
WMH volume ^*			0.263 (0.041)	<0.001	[0.183, 0.342]	580	0.072	<0.001	0.179 (0.050)	<0.001	[0.790, 0.278]	392	0.032	<0.001
CSF NfL ¥			0.129 (0.064)	0.046	[0.002, 0.256]	228	0.019	0.102	0.006 (0.078)	0.939	[–0.149, 0.161]	150	0.000	0.999
Plasma NfL ^†			0.191 (0.059)	0.001	[0.076, 0.306]	298	0.037	0.003	0.110 (0.069)	0.119	[–0.029, 0.248]	210	0.012	0.217
Brain Atrophy ^†			0.045 (0.063)	0.475	[–0.079, 0.169]	171	0.002	0.635	0.082 (0.074)	0.268	[–0.064, 0.228]	102	0.007	0.418
	MCI Individuals
Amyloid-β pathology			0.713 (0.131)	<0.001	[0.455, 0.970]	217	0.751	<0.001	0.581 (0.124)	<0.001	[0.337, 0.824]	286	0.597	<0.001
Amyloid-β / Tau pathology (ref: A-T-)		A+T-	0.556 (0.176)	0.002	[0.210, 0.903]	214	0.590	0.006	0.543 (0.144)	<0.001	[0.260, 0.827]	284	0.558	<0.001
Amyloid-β / Tau pathology (ref: A-T-)		A+T +	0.809 (0.146)	<0.001	[0.52, 1.098]	214	0.812	<0.001	0.626 (0.145)	<0.001	[0.342, 0.911]	284	0.633	<0.001
APOE status (ref: APOE-ε33)		APOE-ε2	0.034 (0.295)	0.908	[–0.546, 0.614]	217	0.033	0.999	–0.008 (0.206)	0.992	[–0.408, 0.404]	286	0.002	0.999
		APOE-ε4	0.254 (0.142)	0.0676	[–0.026, 0.535]		0.267	0.155	0.287 (0.125)	0.023	[0.040, 0.534]		0.289	0.052
		APOE-ε24	0.290 (0.418)	0.489	[–0.535,1.115]		0.309	0.649	0.399 (0.507)	0.431	[–0.598, 1.398]		0.389	0.584
WMH volume			0.158 (0.085)	0.063	[–0.009, 0.325]	181	0.020	0.133	0.300 (0.069)	<0.001	[0.164, 0.437]	252	0.075	<0.001
Plasma NfL ^‡			0.342 (0.098)	0.001	[0.147, 0.536]	128	0.097	0.003	0.164 (0.091)	0.068	[–0.012, 0.341]	173	0.020	0.137

Notes: Relationships between validation variables and Brain-Age delta from all CU pooled subjects (including ALFA+, ADNI, EPAD and OASIS) and all MCI pooled subjects (including ADNI and EPAD). Results given by the linear model: brain-age delta ~each variable +chronological age+sex. The standardized regression coefficients (β), standard errors (SE), P-value, 95% Confidence Interval, number of individuals (N) and effect size are depicted for each variable.

Significant values after FDR correction (p<0.05) are marked in bold. Effect size in categorical variables was calculated as Cohen’s D, while Cohens f² was calculated for continuous measurements. Amyloid-β status was defined by CSF (ALFA+, ADNI, and EPAD) or amyloid PET (OASIS).

APOE, apolipoprotein E; WMH, White Matter Hyperintensities; CSF, cerebrospinal fluid; NfL, neurofilament light; ref, reference.

Contains data from ALFA+, ADNI and EPAD.

^†

Contains data from ALFA +and ADNI.

^‡

Contains data from ADNI.