Sex differences in the association between lipids and cognitive function in older adults

Figures & data

Figure 1. Flow chart outlining the process for selecting participants.

Table 1. General characteristics of all participants.

Characteristics	All participants (n = 2170)	Female (n = 1106)	Male (n = 1064)	p value
Age, years	69.83 ± 7.18	69.81 ± 7.28	69.86 ± 7.08	0.696
Race/Ethnicity, n (%)				0.774
Non-Hispanic white	1204 (55.48%)	615 (55.61%)	589 (55.36%)
Non-Hispanic black	356 (16.41%)	177 (16.00%)	179 (16.82%)
Mexican American	316 (14.56%)	159 (14.38%)	157 (14.76%)
Other Hispanic	166 (7.65%)	89 (8.05%)	77 (7.24%)
Other Races	128 (5.90%)	66 (5.97%)	62 (5.83%)
Education, n (%)				0.053
Less than high school	495 (22.81%)	258 (23.33%)	237 (22.27%)
High school	668 (30.78%)	362 (32.73%)	306 (28.76%)
College or above	1007 (46.41%)	486 (43.94%)	521 (48.97%)
Obesity, n (%)				0.226
Underweight or normal	615 (28.34%)	333 (30.11%)	282 (26.50%)
Overweight	810 (37.33%)	354 (32.01%)	456 (42.86%)
Obese	745 (34.33%)	419 (37.88%)	326 (30.64%)
Fat intake, g	68.37 ± 37.43	59.45 ± 32.98	77.65 ± 39.48	< 0.001
Smoked at least 100 cigarettes in life, n (%)	1122 (51.71%)	421 (38.07%)	701 (65.88%)	< 0.001
Had at least 12 alcohol drinks every year, n (%)	1437 (66.22%)	582 (52.62%)	855 (80.36%)	< 0.001
Hypertension, n (%)	1208 (55.67%)	651 (58.86%)	557 (52.35%)	0.002
Diabetes, n (%)	441 (20.32%)	215 (19.44%)	226 (21.24%)	0.297
TC, mg/dL	200.15 ± 41.89	211.33 ± 40.40	188.53 ± 40.24	< 0.001
TC level, n (%)				< 0.001
Low levels	542 (24.98%)	172 (15.55%)	370 (34.77%)
Middle levels	1080 (49.77%)	566 (51.18%)	514 (48.31%)
High levels	548 (25.25%)	368 (33.27%)	180 (16.92%)
TG, mg/dL	131.64 ± 64.23	134.23 ± 64.54	128.95 ± 63.84	0.022
TG level, n (%)				0.183
Low levels	540 (24.88%)	262 (23.69%)	278 (26.13%)
Middle levels	1084 (49.95%)	557 (50.36%)	527 (49.53%)
High levels	546 (25.16%)	287 (25.95%)	259 (24.34%)
LDL-C, mg/dL	119.11 ± 36.80	124.46 ± 36.29	113.55 ± 36.53	< 0.001
LDL-C level, n (%)				< 0.001
Low levels	534 (24.61%)	201 (18.17%)	333 (31.30%)
Middle levels	1080 (49.77%)	575 (51.99%)	505 (47.46%)
High levels	556 (25.62%)	330 (29.84%)	226 (21.24%)
HDL-C, mg/dL	54.73 ± 16.54	60.03 ± 16.78	49.21 ± 14.34	< 0.001
HDL-C level, n (%)				< 0.001
Low levels	505 (23.27%)	128 (11.57%)	377 (35.43%)
Middle levels	1096 (50.51%)	563 (50.90%)	533 (50.09%)
High levels	569 (26.22%)	415 (37.52%)	154 (14.47%)
DSST scores	45.47 ± 17.95	47.77 ± 18.32	43.09 ± 17.25	< 0.001

Abbreviations: TC, total cholesterol; TG, triglyceride; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; DSST, digit symbol substitution test.

Table 2. Serum lipids profile and Digit Symbol Substitution Test score: multivariate linear regression analysis.

	Model 1		Model 2		Model 3
	OR (95% CI)	p value	OR (95% CI)	p value	OR (95% CI)	p value
Total
TC levels
Low levels	−2.969	0.034	−1.115	0.290	−0.920	0.383
	(−5.707, – 0.232)		(−3.181, 0.952)		(−2.987, 1.147)
High levels	0.601	0.672	−1.004	0.350	−1.132	0.288
	(−2.181, 3.382)		(−3.109, 1.101)		(−3.224, 0.959)
TG levels
Low levels	1.733	0.078	1.079	0.152	0.857	0.255
	(−0.191, 3.658)		(−0.398, 2.556)		(−0.620, 2.333)
High levels	2.760	0.007	1.426	0.067	1.473	0.057
	(0.763, 4.757)		(−0.101, 2.952)		(−0.046, 2.992)
LDL-C levels
Low levels	−0.147	0.912	−0.831	0.410	−0.491	0.627
	(−2.764, 2.470)		(−2.810, 1.147)		(−2.468, 1.487)
High levels	−1.241	0.367	0.732	0.481	0.666	0.519
	(−3.936, 1.455)		(−1.304, 2.768)		(−1.361, 2.694)
HDL-C levels
Low levels	−5.683	<0.001	−3.625	<0.001	−3.425	<0.001
	(−7.684, – 3.682)		(−5.175, – 2.074)		(−4.971, – 1.879)
High levels	1.501	0.138	−0.254	0.745	−0.453	0.565
	(−0.485, 3.487)		(−1.785, 1.277)		(−1.996, 1.091)
Female
TC levels
Low levels	−5.042	0.022	−0.741	0.657	−0.661	0.691
	(−9.367, – 0.717)		(−4.010, 2.529)		(−3.925, 2.603)
High levels	−1.859	0.320	−3.431	0.016	−3.590	0.011
	(−5.527, 1.809)		(−6.210, – 0.651)		(−6.343, – 0.837)
TG levels
Low levels	2.206	0.119	0.432	0.692	0.048	0.964
	(−0.568, 4.981)		(−1.706, 2.570)		(−2.080, 2.177)
High levels	2.879	0.048	2.433	0.029	2.323	0.035
	(0.020, 5.737)		(0.251, 4.614)		(0.159, 4.488)
LDL-C levels
Low levels	−1.572	0.437	−2.899	0.058	−2.269	0.135
	(−5.537, 2.394)		(−5.891, 0.093)		(−5.248, 0.711)
High levels	−0.328	0.860	2.146	0.126	2.118	0.129
	(−3.968, 3.312)		(−0.601, 4.892)		(−0.616, 4.851)
HDL-C levels
Low levels	−4.790	0.010	−4.591	0.001	−4.422	0.002
	(−8.434, – 1.146)		(−7.339, – 1.843)		(−7.152, – 1.692)
High levels	1.800	0.174	0.499	0.620	−0.084	0.934
	(−0.795, 4.395)		(−1.478, 2.476)		(−2.072, 1.904)
Male
TC levels
Low levels	−1.802	0.319	−1.873	0.172	−1.701	0.216
	(−5.352, 1.748)		(−4.560, 0.814)		(−4.395, 0.993)
High levels	3.033	0.172	2.147	0.202	2.223	0.185
	(−1.323, 7.388)		(−1.153, 5.447)		(−1.063, 5.508)
TG levels
Low levels	1.831	0.181	2.061	0.049	1.846	0.079
	(−0.851, 4.513)		(0.010, 4.112)		(−0.213, 3.905)
High levels	2.011	0.159	0.592	0.587	0.589	0.588
	(−0.786, 4.808)		(−1.542, 2.726)		(−1.542, 2.720)
LDL-C levels
Low levels	1.466	0.404	0.884	0.507	1.037	0.438
	(−1.981,4. 912)		(−1.731, 3.500)		(−1.584, 3.657)
High levels	−2.163	0.292	−0.993	0.523	−1.022	0.510
	(−6.191, 1.865)		(−4.046, 2.060)		(−4.065, 2.021)
HDL-C levels
Low levels	−4.902	<0.001	−2.781	0.004	−2.657	0.006
	(−7.411, – 2.394)		(−4.688, – 0.874)		(−4.568, – 0.746)
High levels	−0.958	0.574	−1.123	0.384	−0.891	0.494
	(−4.301, 2.385)		(−3.655, 1.408)		(−3.447, 1.666)

Model 1: total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein.

Model 2: model 1 plus sex (not included in female/male group), age, race, education.

Model 3: model 2 plus obesity, fat intake, hypertension, diabetes, smoking status, drinking status.

Table 3. Female serum lipids profile and Digit Symbol Substitution Test scores: multivariate linear regression analysis adjusting for numbers of conceptions and live births.

	Multivariate linear regression analyses ^A
	OR (95% CI)	p value
Pregnancies	−0.482 (−1.286, 0.321)	0.239
Live birth	−0.411 (−1.38, 0.559)	0.406
TC levels
Low levels	−0.265 (−3.566, 3.036)	0.875
High levels	−3.133 (−6.010, – 0.257)	0.033
TG levels
Low levels	0.770 (−1.465, 3.006)	0.499
High levels	2.961 (0.740, 5.181)	0.009
LDL-C
Low levels	−2.521 (−5.533, 0.490)	0.101
High levels	2.002 (−0.855, 4.859)	0.169
HDL-C
Low levels	−4.690 (−7.507, – 1.874)	0.001
High levels	−0.143 (−2.204, 1.917)	0.891

A: The model included total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, age, race, education, obesity, fat intake, hypertension, diabetes, smoking status, drinking status, pregnancies, and live births.

Figure 2. The nonlinear association between serum lipids and DSST scores through GAM natural cubic spline fitting. The gray area around the curve represents the 95% confidence interval. Group A showed the nonlinear association between serum lipids and DSST scores in the total population. Group B showed the nonlinear association between serum lipids and DSST scores in sex-stratified analyses. The degrees of freedom of the RCS curve are set to 3. Abbreviations: TC, total cholesterol; TG, triglyceride; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; DSST, digit symbol substitution test.

Data availability

The NHANES raw data is available at https://wwwn.cdc.gov/nchs/nhanes/default.aspx.

Data that support the findings of this study are available in the Zenodo repository as ‘NHANES DATASET05162024’ at http://doi.org/10.5281/zenodo.11199721

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