Alzheimer’s disease genetic risk and cognitive reserve in relationship to long-term cognitive trajectories among cognitively normal individuals

Table 4 Mixed-effects model results for AD-PRS_w/oAPOE, APOE-ε4, and CR in relationship to cognitive trajectories (N = 1175)

	Global factor score			Memory factor score			Executive function factor score
	Estimate (95% CI)	p-value	Effect size	Estimate (95% CI)	p-value	Effect size	Estimate (95% CI)	p-value	Effect size
Time	0.003 (− 0.015, 0.020)	0.77	-	0.025 (0.003, 0.048)	0.03 *	-	− 0.014 (− 0.033, 0.004)	0.13	-
Time²	− 0.004 (− 0.005, − 0.004)	< 0.001 ***	-	− 0.003 (− 0.003, − 0.002)	< 0.001 ***	-	− 0.004 (− 0.005, − 0.004)	< 0.001 ***	-
CR index	0.330 (0.282, 0.378)	< 0.001 ***	0.38	0.325 (0.269, 0.381)	< 0.001 ***	0.37	0.307 (0.256, 0.357)	< 0.001 ***	0.37
AD-PRS_w/oAPOE	0.009 (− 0.034, 0.051)	0.69	0.01	− 0.018 (− 0.068, 0.031)	0.46	0.02	0.028 (− 0.017, 0.072)	0.23	0.03
APOE-ε4	0.022 (− 0.065, 0.109)	0.62	0.03	0.040 (− 0.061, 0.141)	0.44	0.05	− 0.047 (− 0.138, 0.045)	0.32	0.06
CR index × time	0.005 (− 0.001, 0.010)	0.09	0.07	0.008 (0.002, 0.015)	0.01 *	0.11	0.002 (− 0.003, 0.007)	0.42	0.03
AD-PRS_w/oAPOE × time	− 0.005 (− 0.010, 0.000)	0.04 *	0.07	− 0.004 (− 0.009, 0.002)	0.21	0.05	− 0.005 (− 0.010, − 0.001)	0.02 *	0.09
APOE-ε4 × time	− 0.025 (− 0.034, − 0.015)	< 0.001 ***	0.35	− 0.029 (− 0.040, − 0.017)	< 0.001 ***	0.38	− 0.012 (− 0.021, − 0.004)	0.005 **	0.21
CR index × AD-PRS_w/oAPOE	0.031 (− 0.019, 0.082)	0.23	0.04	0.040 (− 0.018, 0.099)	0.18	0.05	0.029 (− 0.024, 0.082)	0.28	0.04
CR index × AD-PRS_w/oAPOE × time	− 0.004 (− 0.009, 0.002)	0.21	0.05	− 0.005 (− 0.011, 0.002)	0.20	0.06	− 0.002 (− 0.007, 0.004)	0.56	0.03

AD-PRS_w/oAPOE sensitivity analyses evaluating whether the relationship between the AD-PRS_w/oAPOE and cognitive trajectories remained when terms for APOE-ε4 genetic status (i.e., APOE-ε4 and APOE-ε4 × time) were included as additional model predictors. Separate models were estimated for the global, episodic memory, and executive function factor scores. Results of the full models including the 3-way interaction terms are shown; the patterns of results shown were the same when non-significant 3-way interaction terms were excluded. Models were additionally adjusted for baseline age, sex and cohort (ACS, AIBL, BIOCARD, BLSA, WRAP), and their interactions with time. ***p < 0.001; **p < 0.01; *p < 0.05

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