Albumin-corrected anion gap and cognitive function in older adults

doi:10.3969/j.issn.1004-583X.2026.10.005

Abstract

Abstract:

Objective To investigate the association between albumin-corrected anion gap (corrected AG) and cognitive performance among older adults in the United States. Methods Adults aged ≥60 years from the 2011-2014 National Health and Nutrition Examination Survey (NHANES) were included. Complex survey-weighted regression, quartile analyses, and restricted cubic spline analyses were performed to evaluate the associations of corrected AG with overall cognitive performance and performance across different cognitive domains. Results A total of 2, 530 participants were included. For each 1-standard-deviation increase in corrected AG, the overall cognitive Z score decreased by 0.055 (95%CI, -0.083 to -0.028; P<0.001). Four secondary cognitive outcomes remained statistically significant after false discovery rate correction, with no evidence of nonlinearity. Conclusion Higher corrected AG was associated with poorer overall cognitive performance in older adults. Longitudinal studies are warranted to further validate this association.

Key words: cognition, albumin-corrected anion gap, older adults, NHANES, kidney function

CLC Number:

R338.64

Wang Dongze, Wang Xiaohan, Wang Wenyuan, Zhang Shaoru, Wang Yanyong. Albumin-corrected anion gap and cognitive function in older adults[J]. Clinical Focus, 2026, 41(10): 901-909.

Add to citation manager EndNote|Ris|BibTeX

URL: https://www.lchc.cn/EN/10.3969/j.issn.1004-583X.2026.10.005

https://www.lchc.cn/EN/Y2026/V41/I10/901

Figures/Tables 8

References 28

[1]	Li T, Hu Z, Qiao L, et al. Chronic kidney disease and cognitive performance: NHANES 2011-2014[J]. BMC Geriatr, 2024, 24(1):351. doi: 10.1186/s12877-024-04917-2. pmid: 38637739
[2]	Zhang J, Wu L, Wang P, et al. Prevalence of cognitive impairment and its predictors among chronic kidney disease patients: A systematic review and meta-analysis[J]. PLoS One, 2024, 19(6):e0304762. doi: 10.1371/journal.pone.0304762.
[3]	Bolignano D, Simeoni M, Hafez G, et al. Cognitive impairment in CKD patients: A guidance document by the CONNECT network[J]. Clin Kidney J, 2025, 18(2):sfae294. doi: 10.1093/ckj/sfae294.
[4]	Merlino L, Rainone F, Chinnadurai R, et al. Health outcomes in chronic kidney disease patients with cognitive impairment or dementia: A global collaborative analysis[J]. Clin Kidney J, 2025, 18(1):sfae401. doi: 10.1093/ckj/sfae401.
[5]	Cheung KL, Arce Renteria M, Callas PW, et al. Kidney Function, cognitive impairment, and trajectories: A longitudinal biracial study[J]. J Gen Intern Med, 2025, 40(14):3403-3412. doi: 10.1007/s11606-025-09366-0.
[6]	Otobe Y. Current status of the cognitive impairment in chronic kidney disease[J]. Phys Ther Res, 2024, 27(3):115-120.doi: 10.1298/ptr.R0033. pmid: 39866390
[7]	Yan Q, Liu M, Xie Y, et al. Kidney-brain axis in the pathogenesis of cognitive impairment[J]. Neurobiol Dis, 2024, 200:106626. doi: 10.1016/j.nbd.2024.106626.
[8]	Wagner CA, Massy ZA, Capasso G, et al. Translational research on cognitive impairment in chronic kidney disease[J]. Nephrol Dial Transplant, 2025, 40(4):621-631. doi: 10.1093/ndt/gfae229.
[9]	Andrews TD, Day GS, Irani SR, et al. Uremic toxins, CKD, and cognitive dysfunction[J]. J Am Soc Nephrol, 2025, 36(6):1208-1226. doi: 10.1681/ASN.0000000675.
[10]	Bossola M, Picconi B. Uremic toxins and the brain in chronic kidney disease[J]. J Nephrol, 2024, 37(5):1391-1395. doi: 10.1007/s40620-024-01929-4. pmid: 38625502
[11]	Zimmermann S, Mathew A, Bondareva O, et al. Chronic kidney disease leads to microglial potassium efflux and inflammasome activation in the brain[J]. Kidney Int, 2024, 106(6):1101-1116. doi: 10.1016/j.kint.2024.06.028.
[12]	Bobot M, Guedj E, Resseguier N, et al. Increased blood-brain barrier permeability and cognitive impairment in patients With ESKD[J]. Kidney Int Rep, 2024, 9(10):2988-2995. doi: 10.1016/j.ekir.2024.07.021. pmid: 39430169
[13]	Rački V, Vujičić B, Komen V, et al. The kidney-brain axis in chronic kidney disease: Uremic toxins, cognitive decline, mechanistic pathways, biomarkers and therapeutic perspectives[J]. Biomedicines, 2026, 14(7):1579. doi: 10.3390/biomedicines14071579.
[14]	Alter DN, Zha L. The anion gap as a predictive tool for morbidity and mortality[J]. Crit Rev Clin Lab Sci, 2025, 62(8):568-584. doi: 10.1080/10408363.2025.2526346.
[15]	Ni ZB, Zhang HB, Huang LZ, et al. Albumin-corrected anion gap and risk of mortality among US adults[J]. Arch Public Health, 2025, 83:263. doi: 10.1186/s13690-025-01752-8.
[16]	Chen Y, You MY, Chu L. Association of albumin-corrected anion gap with severe consciousness disorders and outcomes in ischemic stroke: A retrospective MIMIC analysis[J]. Sci Rep, 2024, 14:26006. doi: 10.1038/s41598-024-76324-x. pmid: 39472602
[17]	Wang R, Rong J, Xu J, et al. A prognostic model incorporating the albumin-corrected anion gap in patients with aneurysmal subarachnoid hemorrhage[J]. Front Neurol, 2024, 15:1361888. doi: 10.3389/fneur.2024.1361888.
[18]	Figge J, Jabor A, Kazda A, et al. Anion gap and hypoalbuminemia[J]. Crit Care Med, 1998, 26(11):1807-1810.doi: 10.1097/00003246-199811000-00019. pmid: 9824071
[19]	Dobre M, Gaussoin SA, Bates JT, et al. Serum bicarbonate concentration and cognitive function in hypertensive adults[J]. Clin J Am Soc Nephrol, 2018, 13(4):596-603. doi: 10.2215/CJN.07050717.
[20]	Brody DJ, Kramarow EA, Taylor CA, et al. Cognitive performance in adults aged 60 and over: National Health and Nutrition Examination Survey, 2011-2014[J]. Natl Health Stat Report, 2019, (126):1-23. pmid: 31751207
[21]	Morris JC, Heyman A, Mohs RC, et al. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part I. Clinical and neuropsychological assessment of Alzheimer's disease[J]. Neurology, 1989, 39(9):1159-1165. doi: 10.1212/WNL.39.9.1159. pmid: 2771064
[22]	Jaeger J. Digit symbol substitution test: The case for sensitivity over specificity in neuropsychological testing[J]. J Clin Psychopharmacol, 2018, 38(5):513-519. doi: 10.1097/JCP.0000000000000941. pmid: 30124583
[23]	Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate[J]. Ann Intern Med, 2009, 150(9):604-612. doi: 10.7326/0003-4819-150-9-200905050-00006. pmid: 19414839
[24]	Inker LA, Eneanya ND, Coresh J, et al. New creatinine- and cystatin C-based equations to estimate GFR without race[J]. N Engl J Med, 2021, 385(19):1737-1749. doi: 10.1056/NEJMoa2102953.
[25]	Kroenke K, Spitzer RL, Williams JBW. The PHQ-9: Validity of a brief depression severity measure[J]. J Gen Intern Med, 2001, 16(9):606-613. doi: 10.1046/j.1525-1497.2001.016009606.x. pmid: 11556941
[26]	Lumley T. Analysis of complex survey samples[J]. J Stat Softw, 2004, 9(8):1-19. doi: 10.18637/jss.v009.i08.
[27]	von Elm E, Altman DG, Egger M, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: Guidelines for reporting observational studies[J]. Lancet, 2007, 370(9596):1453-1457. doi: 10.1016/S0140-6736(07)61602-X.
[28]	Lee KGR, Ghadge A, Raut B, et al. Cognitive impairment and health outcomes in non-dialysis chronic kidney disease: A systematic review and meta-analysis[J]. Clin Kidney J, 2025, 18(6):sfaf150.doi: 10.1093/ckj/sfaf150.

变量	Q1	Q2	Q3	Q4	F值	P值
非加权样本量	669	594	645	622
加权代表人口(百万)	12.99	11.18	12.02	10.69
年龄(岁)	68.23±6.37	68.92±6.65	69.7±6.75	69.95±6.85	6.334	0.002
PIR	3.55±1.56	3.07±1.52	3.01±1.55	2.82±1.59	9.464	<0.01
BMI(kg/m²)	27.79±5.55	28.83±5.71	29.43±6.57	30.5±7.03	6.880	0.001
体力活动(MET-min/周)	1 577.74±2 771.25	1 541.51±3 000.77	1 342.92±2 558.77	1 195.82±2 614.45	1.982	0.139
平均收缩压(mmHg)	130.58±17.8	130.87±18.62	131.52±19.02	133.03±19.54	1.579	0.216
平均舒张压(mmHg)	69.96±12.18	67.67±13.74	68.19±12.44	66.89±14.47	2.592	0.072
eGFR(ml·min^-1·1.73 m^-2)	77.17±15.31	74.45±15.79	72.14±18.68	68.77±20.92	24.341	<0.01
log UACR	2.41±0.88	2.47±1.03	2.58±0.98	2.90±1.30	14.551	<0.01
PHQ-9评分	2.42±3.39	2.47±3.39	3.03±4.16	3.56±4.63	11.570	<0.01
白蛋白校正AG(mmol/L)	7.66±0.80	9.13±0.28	10.22±0.35	12.29±1.28	3631.895	<0.01
整体认知Z评分	0.46±0.76	0.26±0.75	0.26±0.76	0.07±0.78	16.335	<0.01
CERAD即刻回忆Z评分	0.40±0.91	0.22±0.93	0.21±0.95	0.01±0.94	12.444	<0.01
CERAD延迟回忆Z评分	0.30±0.92	0.19±0.99	0.17±0.94	0.03±0.99	7.975	<0.01
动物命名流畅性Z评分	0.57±1.08	0.28±1.0	0.31±0.96	0.10±0.96	8.044	<0.01
DSST Z评分	0.59±0.94	0.39±0.89	0.40±0.94	0.17±0.97	11.553	<0.01
性别(%)—男	50.5	49.2	44.8	39.3	4.332	0.008
性别(%)—女	49.5	50.8	55.2	60.7
种族/族裔(%)—墨西哥裔美国人	2.6	3.2	3.0	4.9	0.659	0.682
种族/族裔(%)—非西班牙裔亚裔	3.1	3.6	3.4	2.8
种族/族裔(%)—非西班牙裔黑人	7.7	7.6	7.9	9.2
种族/族裔(%)—非西班牙裔白人	82.1	79.4	80.4	77.7
种族/族裔(%)—其他西班牙裔	3.4	4.2	3.1	3.6
种族/族裔(%)—其他/多种族	1.1	2.1	2.2	1.9
教育水平(%)—低于高中	12.2	16.6	15.2	21.0	3.370	0.007
教育水平(%)—高中/GED	18.2	20.9	24.7	22.3
教育水平(%)—大学及以上	69.6	62.5	60.1	56.7
婚姻状况(%)—已婚/同居	70.0	65.4	63.4	58.2	2.836	0.020
婚姻状况(%)—既往婚姻	25.5	28.7	33.2	37.9
婚姻状况(%)—从未结婚	4.5	5.9	3.4	3.9
吸烟状态(%)—从不	49.0	50.2	49.5	49.4	0.958	0.438
吸烟状态(%)—既往	42.6	38.1	38.0	37.5
吸烟状态(%)—当前	8.3	11.8	12.5	13.1
任一年度饮酒≥12杯史(%)—否	22.4	27.9	28.0	32.9	3.007	0.039
任一年度饮酒≥12杯史(%)—是	77.6	72.1	72.0	67.1
达到体力活动指南(%)—否	49.7	54.8	56.5	64.5	4.885	0.005
达到体力活动指南(%)—是	50.3	45.2	43.5	35.5
高血压(%)—否	42.6	37.1	26.2	23.4	12.083	<0.01
高血压(%)—是	57.4	62.9	73.8	76.6
糖尿病(%)—否	88.1	85.5	79.3	70.4	16.497	<0.01
糖尿病(%)—是	11.9	14.5	20.7	29.6
卒中史(%)—否	96.8	93.0	92.7	92.1	2.900	0.051
卒中史(%)—是	3.2	7.0	7.3	7.9
心血管疾病(%)—否	85.5	84.0	79.7	79.3	2.127	0.131
心血管疾病(%)—是	14.5	16.0	20.3	20.7

变量	Q1	Q2	Q3	Q4	F值	P值
非加权样本量	669	594	645	622
加权代表人口(百万)	12.99	11.18	12.02	10.69
年龄(岁)	68.23±6.37	68.92±6.65	69.7±6.75	69.95±6.85	6.334	0.002
PIR	3.55±1.56	3.07±1.52	3.01±1.55	2.82±1.59	9.464	<0.01
BMI(kg/m²)	27.79±5.55	28.83±5.71	29.43±6.57	30.5±7.03	6.880	0.001
体力活动(MET-min/周)	1 577.74±2 771.25	1 541.51±3 000.77	1 342.92±2 558.77	1 195.82±2 614.45	1.982	0.139
平均收缩压(mmHg)	130.58±17.8	130.87±18.62	131.52±19.02	133.03±19.54	1.579	0.216
平均舒张压(mmHg)	69.96±12.18	67.67±13.74	68.19±12.44	66.89±14.47	2.592	0.072
eGFR(ml·min^-1·1.73 m^-2)	77.17±15.31	74.45±15.79	72.14±18.68	68.77±20.92	24.341	<0.01
log UACR	2.41±0.88	2.47±1.03	2.58±0.98	2.90±1.30	14.551	<0.01
PHQ-9评分	2.42±3.39	2.47±3.39	3.03±4.16	3.56±4.63	11.570	<0.01
白蛋白校正AG(mmol/L)	7.66±0.80	9.13±0.28	10.22±0.35	12.29±1.28	3631.895	<0.01
整体认知Z评分	0.46±0.76	0.26±0.75	0.26±0.76	0.07±0.78	16.335	<0.01
CERAD即刻回忆Z评分	0.40±0.91	0.22±0.93	0.21±0.95	0.01±0.94	12.444	<0.01
CERAD延迟回忆Z评分	0.30±0.92	0.19±0.99	0.17±0.94	0.03±0.99	7.975	<0.01
动物命名流畅性Z评分	0.57±1.08	0.28±1.0	0.31±0.96	0.10±0.96	8.044	<0.01
DSST Z评分	0.59±0.94	0.39±0.89	0.40±0.94	0.17±0.97	11.553	<0.01
性别(%)—男	50.5	49.2	44.8	39.3	4.332	0.008
性别(%)—女	49.5	50.8	55.2	60.7
种族/族裔(%)—墨西哥裔美国人	2.6	3.2	3.0	4.9	0.659	0.682
种族/族裔(%)—非西班牙裔亚裔	3.1	3.6	3.4	2.8
种族/族裔(%)—非西班牙裔黑人	7.7	7.6	7.9	9.2
种族/族裔(%)—非西班牙裔白人	82.1	79.4	80.4	77.7
种族/族裔(%)—其他西班牙裔	3.4	4.2	3.1	3.6
种族/族裔(%)—其他/多种族	1.1	2.1	2.2	1.9
教育水平(%)—低于高中	12.2	16.6	15.2	21.0	3.370	0.007
教育水平(%)—高中/GED	18.2	20.9	24.7	22.3
教育水平(%)—大学及以上	69.6	62.5	60.1	56.7
婚姻状况(%)—已婚/同居	70.0	65.4	63.4	58.2	2.836	0.020
婚姻状况(%)—既往婚姻	25.5	28.7	33.2	37.9
婚姻状况(%)—从未结婚	4.5	5.9	3.4	3.9
吸烟状态(%)—从不	49.0	50.2	49.5	49.4	0.958	0.438
吸烟状态(%)—既往	42.6	38.1	38.0	37.5
吸烟状态(%)—当前	8.3	11.8	12.5	13.1
任一年度饮酒≥12杯史(%)—否	22.4	27.9	28.0	32.9	3.007	0.039
任一年度饮酒≥12杯史(%)—是	77.6	72.1	72.0	67.1
达到体力活动指南(%)—否	49.7	54.8	56.5	64.5	4.885	0.005
达到体力活动指南(%)—是	50.3	45.2	43.5	35.5
高血压(%)—否	42.6	37.1	26.2	23.4	12.083	<0.01
高血压(%)—是	57.4	62.9	73.8	76.6
糖尿病(%)—否	88.1	85.5	79.3	70.4	16.497	<0.01
糖尿病(%)—是	11.9	14.5	20.7	29.6
卒中史(%)—否	96.8	93.0	92.7	92.1	2.900	0.051
卒中史(%)—是	3.2	7.0	7.3	7.9
心血管疾病(%)—否	85.5	84.0	79.7	79.3	2.127	0.131
心血管疾病(%)—是	14.5	16.0	20.3	20.7

结局	例数	模型1			模型2			模型3			BH- FDR q
结局	例数	β	95%CI	P	β	95%CI	P	β	95%CI	P	BH- FDR q
整体认知Z评分	2 530	-0.108	-0.137, -0.080	<0.01	-0.078	-0.108, -0.048	<0.01	-0.055	-0.083, -0.028	<0.01
CERAD即刻回忆Z评分	2 533	-0.107	-0.150, -0.065	<0.01	-0.083	-0.130, -0.036	0.01	-0.068	-0.114, -0.021	0.006	0.023
CERAD延迟回忆Z评分	2 530	-0.073	-0.116,-0.030	0.002	-0.055	-0.099, -0.011	0.016	-0.043	-0.083, -0.004	0.032	0.032
动物命名流畅性Z评分	2 520	-0.126	-0.184, -0.067	<0.01	-0.092	-0.143, -0.040	0.001	-0.064	-0.114, -0.013	0.015	0.023
DSST Z评分	2 463	-0.126	-0.165, -0.087	<0.01	-0.081	-0.120, -0.042	<0.01	-0.045	-0.081, -0.008	0.017	0.023

结局	例数	模型1			模型2			模型3			BH- FDR q
结局	例数	β	95%CI	P	β	95%CI	P	β	95%CI	P	BH- FDR q
整体认知Z评分	2 530	-0.108	-0.137, -0.080	<0.01	-0.078	-0.108, -0.048	<0.01	-0.055	-0.083, -0.028	<0.01
CERAD即刻回忆Z评分	2 533	-0.107	-0.150, -0.065	<0.01	-0.083	-0.130, -0.036	0.01	-0.068	-0.114, -0.021	0.006	0.023
CERAD延迟回忆Z评分	2 530	-0.073	-0.116,-0.030	0.002	-0.055	-0.099, -0.011	0.016	-0.043	-0.083, -0.004	0.032	0.032
动物命名流畅性Z评分	2 520	-0.126	-0.184, -0.067	<0.01	-0.092	-0.143, -0.040	0.001	-0.064	-0.114, -0.013	0.015	0.023
DSST Z评分	2 463	-0.126	-0.165, -0.087	<0.01	-0.081	-0.120, -0.042	<0.01	-0.045	-0.081, -0.008	0.017	0.023

结局	例数		趋势P	Q2 vs Q1			Q3 vs Q1			Q4 vs Q1
结局	例数		趋势P	β	95%CI	P	β	95%CI	P	β	95%CI	P
整体认知Z评分	2 530	<0.01		-0.090	-0.206, 0.025	0.121	-0.041	-0.127, 0.045	0.337	-0.169	-0.253, -0.084	<0.01
CERAD即刻回忆Z评分	2 533	0.002		-0.095	-0.239, 0.049	0.187	-0.069	-0.188, 0.049	0.243	-0.227	-0.351, -0.103	<0.01
CERAD延迟回忆Z评分	2 530	0.025		-0.048	-0.217, 0.122	0.569	-0.026	-0.157, 0.104	0.683	-0.134	-0.251, -0.016	0.027
动物命名流畅性Z评分	2 520	0.034		-0.169	-0.320, -0.019	0.029	-0.081	-0.224, 0.061	0.253	-0.202	-0.357, -0.047	0.012
DSST Z评分	2 463	0.152		-0.062	-0.185, 0.061	0.312	0.014	-0.080, 0.109	0.761	-0.104	-0.210, 0.002	0.053