Table 2.

Cognitive function/impairment and cognitive change/decline (all time points) by sex and ApoE4 status; Baltimore Longitudinal Study on Aging

	Men			Women
	ApoE4+	ApoeE4−		ApoE4+	ApoE4−
Predicted cognitive function/impairment at mean age at follow-up †
MMSE
N	76	243		69	142
Mean (SD)	28.0 (2.0)	28.4 (1.5)	~	27.7 (3.1)	28.6 (1.4)	*
	−0.21			−0.84* ¶
Multivariate-adjusted β‡ (95% CI)	(−0.56; 0.14)			(−1.30; −0.38)
% <20th percentile (score <27.4)	27.6	16.5	*	23.2	11.3	*
	2.47*			4.92*
Multivariate-adjusted OR§ (95% CI)	(1.17; 5.21)			(1.79; 13.56)
BVRT
N	88	281		83	188
Mean (SD)	5.4 (3.4)	5.0 (3.0)		6.7 (4.7)	5.1 (3.2)	*
	0.13			1.16* ¶
Multivariate-adjusted β (95% CI)	(−0.43; 0.68)			(0.43; 1.89)
% >80th percentile (score >7.4)	27.3	19.9		32.5	23.9
	1.59			2.36*
Multivariate-adjusted OR (95% CI)	(0.74; 3.42)			(1.08; 5.16)
CVLT (List A)
N	78	251		69	171
Mean (SD)	49.0 (10.5)	48.3 (10.5)		53.8 (12.2)	57.0 (10.4)	*
	1.30			−3.01* ¶
Multivariate-adjusted β (95% CI)	(−0.97; 3.57)			(−5.42; −0.59)
% <20th percentile (score <43.2)	30.8	33.1		20.3	11.1	~
	0.82			4.60* ¶
Multivariate-adjusted OR (95% CI)	(0.43; 1.58)			(1.65; 12.84)
CVLT (delayed recall)
N	78	251		69	171
Mean (SD)	10.3 (2.8)	10.0 (3.3)		11.3 (3.4)	12.1 (2.7)	~
	0.41			−0.88* ¶
Multivariate-adjusted β (95% CI)	(−0.29; 1.11)			(−1.57; −0.19)
% <20th percentile (score <8.6)	24.4	30.3		20.3	11.1	~
	0.60			3.62* ¶
Multivariate-adjusted OR (95% CI)	(0.30; 1.20)			(1.39; 9.45)
VFT-L
N	77	248		72	149
Mean (SD)	14.8 (3.9)	14.4 (3.9)		14.0 (3.9)	14.6 (3.5)
	0.44			−0.44
Multivariate-adjusted β (95% CI)	(−0.53; 1.42)			(−1.43; 0.55)
% <20th percentile (score <10.9)	11.7	20.6	~	16.7	14.1
	0.47~			1.13
Multivariate-adjusted OR (95% CI)	(0.20; 1.07)			(0.47; 2.72)
VFT-C
N	77	248		72	149
Mean (SD)	13.6 (3.5)	14.0 (3.4)		14.5 (3.9)	15.5 (3.4)	~
	−0.02			−0.89*
Multivariate-adjusted β (95% CI)	(−0.71; 0.67)			(1.65; −0.13)
% <20th percentile (score <11.4)	23.4	21.8		23.6	12.7	*
	0.93			3.96* ¶
Multivariate-adjusted OR (95% CI)	(0.41; 2.08)			(1.32; 11.88)
Trails A
N	76	237		67	136
Mean (SD)	41.2 (15.4)	39.2 (15.6)		41.4 (14.6)	41.7 (20.6)
	1.82			0.54
Multivariate-adjusted β (95% CI)	(−1.73; 5.36)			(−3.66; 4.74)
% >80th percentile (score >52.0)	21.0	12.7	~	14.9	20.6
	2.58*			0.69
Multivariate-adjusted OR (95% CI)	(1.11; 5.97)			(0.26; 1.93)
Trails B
N	76	237		67	135
Mean (SD)	107.3 (46.9)	98.1 (38.6)	~	119.5 (56.3)	103.7 (44.0)	*
	6.73			15.29*
Multivariate-adjusted β (95% CI)	(−1.83; 15.30)			(5.29; 26.00)
% >80th percentile (score >146.0)	23.7	13.9	*	28.4	15.6	*
	2.44*			4.14*
Multivariate-adjusted OR (95% CI)	(1.09; 5.48)			(1.54; 11.16)
Predicted cognitive annual rate change/decline at mean age of follow-up †
MMSE
N	76	243		69	142
Mean (SD)	−0.01 (0.13)	0.03 (0.08)	*	−0.01 (0.17)	0.05 (0.10)	*
	−0.03*			−0.06*
Multivariate-adjusted β (95% CI)	(−0.05; −0.01)			(−0.09; −0.04)
% <20th percentile (change <-0.03)	33.8	20.8	*	23.2	8.4	*
	2.03*			6.58*
Multivariate-adjusted OR (95% CI)	(1.08; 3.80)			(2.28; 18.89)
BVRT
N	88	281		83	188
Mean (SD)	0.13 (0.08)	0.12 (0.07)		0.14 (0.10)	0.11 (0.07)	*
	0.005			0.028* ¶
Multivariate-adjusted β (95% CI)	(−0.010; 0.020)			(0.011; 0.046)
% >80th percentile (change >0.18)	31.8	24.2		31.3	16.5	*
	1.42			3.14*
Multivariate-adjusted OR (95% CI)	(0.77; 2.64)			(1.51; 6.55)
CVLT (List A)
N	78	251		69	171
Mean (SD)	−0.33 (0.23)	−0.31 (0.26)		−0.34 (0.30)	−0.26 (0.23)	*
	−0.017			−0.071*
Multivariate-adjusted β (95% CI)	(−0.078; 0.043)			(−0.133; −0.008)
% <20th percentile (change <−0.47)	26.9	27.9		31.9	17.0	*
	0.96			3.80* ¶
Multivariate-adjusted OR (95% CI)	(0.50; 1.83)			(1.65; 8.72)
CVLT (delayed recall)
N	78	251		69	171
Mean (SD)	−0.09 (0.05)	−0.09 (0.06)		−0.09 (0.07)	−0.07 (0.05)	*
	0.006			−0.018* ¶
Multivariate-adjusted β (95% CI)	(−0.007; 0.020)			(−0.032; −0.004)
% <20th percentile (change <−0.13)	21.8	27.5		27.5	12.3	*
	0.63			5.78* ¶
Multivariate-adjusted OR (95% CI)	(0.32; 1.25)			(2.29; 14.54)
VFT-L
N	77	248		72	149
Mean (SD)	−0.01 (0.12)	−0.01 (0.11)		0.01 (0.14)	0.02 (0.11)
	−0.001			−0.009
Multivariate-adjusted β (95% CI)	(−0.029; 0.027)			(−0.041; 0.022)
% <20th percentile (change <−0.08)	23.4	24.6		19.4	20.1
	0.91			1.00
Multivariate-adjusted OR (95% CI)	(0.47; 1.77)			(0.43; 2.39)
VFT-C
N	77	248		72	149
Mean (SD)	−0.07 (0.15)	−0.04 (0.14)	~	−0.07(0.16)	−0.01 (0.13)	*
	−0.025			−0.057*
Multivariate-adjusted β (95% CI)	(−0.055; 0.005)			(−0.091; −0.023)
% <20th percentile (change <−0.13)	32.5	22.9	~	26.4	16.7	~
	1.81~			2.49*
Multivariate-adjusted OR (95% CI)	(0.90; 3.63)			(1.05; 5.90)
Trails A
N	76	237		67	136
Mean (SD)	0.34 (0.96)	0.12 (0.98)	~	0.23 (0.95)	0.23(0.80)
	0.233			0.031
Multivariate-adjusted β (95% CI)	(−0.017; 0.483)			(−0.201; 0.263)
% >80th percentile (change >0.85)	21.0	11.8	*	16.4	16.2
	2.19*			1.19
Multivariate-adjusted OR (95% CI)	(1.02; 4.70)			(0.44; 3.22)
Trails B
N	76	237		67	135
Mean (SD)	0.52 (2.21)	0.04 (1.77)	~	0.78 (2.40)	0.13 (1.85)	*
	0.391			0.673*
Multivariate-adjusted β (95% CI)	(−0.067; 0.848)			(0.173; 1.174)
% >80th percentile (change >1.92)	21.0	13.9		25.4	15.6
	1.70			2.70*
Multivariate-adjusted OR (95% CI)	(0.80; 3.58)			(1.09; 6.73)

Abbreviations: ApoE4=Apolipoprotein E ε4 allele carrier status; CI=Confidence Interval; BVRT=Benton Visual Retention Test; CVLT=California Verbal Learning Test; MMSE=Mini- Mental State Examination; OR=Odds Ratio; SD=Standard Deviation; VFT-C=Verbal Fluency Test, Categories or “Category Fluency” test; VFT-L=Verbal Fluency Test, Letters or “Letter Fluency” test.

^~p<0.10;

^*p<0.05 for the null hypothesis of no difference between ApoE status for means, proportions, β coefficient (OLS regression) or Log_e(OR) (logistic regression) within each sex group.

^†Cognitive scores were predicted at mean age at follow-up prior to onset of dementia using a multivariate linear mixed model controlling for sex, race/ethnicity, education (years), and smoking status, with age added among the fixed effect variables to allow for quadratic non-linear change. The lowest quintile in the total population with data on this test was considered as “cognitive impairment” for most tests except BVRT, Trails A and B where the highest quintile was considered as impairment. The slope or annual rate of change was also predicted from these models at the mean age at follow-up (i.e. between age 50 and individual mean age of follow-up for each cognitive test). The lowest quintile of the slope or rate of change was considered as “significant cognitive decline” for most tests except for BVRT, Trails A and B where the highest quintile was considered as decline ( See Appendix B for more details).

^‡Based on multivariate OLS regression models with outcome being cognitive function or cognitive annual rate of change and main exposure being ApoE4 status, stratified by sex. The model controlled for first-visit age, mean age at follow-up, education, first-visit smoking status, first-visit self-reported type 2 diabetes, hypertension, cardiovascular disease and body mass index.

^§Based on multivariate logistic regression models with outcome being cognitive impairment or cognitive decline and main exposure being ApoE4 status, stratified by sex. The model controlled for first-visit age, mean age at follow-up, education, first-visit smoking status, first-visit self-reported type 2 diabetes, hypertension, cardiovascular disease and body mass index.

^¶p<0.05 for null hypothesis that ApoE4×sex is significant in a multivariate OLS or logistic regression model with cognitive function/change or impairment/decline as the outcomes and ApoE4 status as the main exposure, with sex entered into the main effects and control made for first-visit age, mean age at follow-up, education, first-visit smoking status, first-visit self-reported type 2 diabetes, hypertension, cardiovascular disease and body mass index.