Table 2.

Decomposition of the total, direct, and indirect effects through neurodegenerative and cerebrovascular lesions of the association between Apolipoprotein E gene ε4 allele (APOE-ε4) and cognitive abilities (n = 648)

Outcome: Cognitive abilities measured by the clinical dementia rating sum of boxes
	Total effect		Direct effect		Indirect effect		Proportion mediated
	Estimate (95% CI)	p	Estimate (95% CI)	p	Estimate (95% CI)	P	Estimate (95% CI)	p
Neurodegenerative mediators
Neurofibrillary tangles (n = 648)	2.21(1.20; 3.29)	< 0.001	1.33(0.42; 2.38)	0.002	0.88(0.45; 1.38)	< 0.001	0.40(0.21; 0.70)	< 0.001
Neuritic plaques (n = 648)	2.21(1.10; 3.24)	< 0.001	0.85( − 0.26; 1.94)	0.13	1.36(0.86; 1.96)	< 0.001	0.62(0.35; 1.22)	< 0.001
TDP-43 (n = 310)	1.35( − 0.04; 2.82)	0.06	1.25( − 0.13; 2.63)	0.07	0.10( − 0.16; 0.52)	0.50	0.07( − 0.35; 0.54)	0.52
Lewy bodies disease (n = 617)	2.04(0.97; 3.11)	< 0.001	2.03(1.00; 3.08)	< 0.001	0.01( − 0.12; 0.17)	0.92	0.003( − 0.07; 0.08)	0.92
Cerebrovascular mediators
Lacunar infarcts (n = 648)	2.21(1.18; 3.31)	< 0.001	2.12(1.11; 3.23)	< 0.001	0.09( − 0.05; 0.26)	0.21	0.04( − 0.03; 0.13)	0.21
Hyaline arteriosclerosis (n = 648)	2.21(1.13; 3.24)	< 0.001	2.28(1.23; 3.33)	< 0.001	− 0.07( − 0.22; 0.05)	0.25	− 0.03( − 0.12; 0.02)	0.25
Cerebral Amyloid Angiopathy (n = 648)	2.21(1.13; 3.29)	< 0.001	2.08(0.93; 3.22)	< 0.001	0.12( − 0.07; 0.35)	0.20	0.06( − 0.03; 0.20)	0.20

Mediation analysis adjusted for age, sex, race, and education

APOE groups: Participants with at least one APOE-ε4 allele vs. APOE-ε4 non-carriers (reference group)