Serum Sodium and Cognition in Older Community-Dwelling Men

Kristen L. Nowak; Kristine Yaffe; Eric S. Orwoll; Joachim H. Ix; Zhiying You; Elizabeth Barrett-Connor; Andrew R. Hoffman; Michel Chonchol

doi:10.2215/CJN.07400717

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Table 1.

Baseline characteristics of study participants for prevalent cognitive impairment (cross-sectional) analysis by tertiles of baseline serum sodium levels

Variable	Tertile 1 (126–140 mmol/L) (n=1814)	Tertile 2 (141–142 mmol/L) (n=1818)	Tertile 3 (143–153 mmol/L) (n=1803)
Age, yr	74±6	74±6	74±6
Race (% white)^a	89	92	92
Education
High school or less	23	24	27
Some college	24	23	22
College	18	18	18
Some graduate school	11	11	11
Graduate school	25	24	23
Smoking^a
Never smoker	36	38	38
Current smoker	5	3	3
Former smoker	59	59	59
Alcohol intake, ≥12 drinks in past 12 mo^a	68	64	63
BMI category
Underweight	0.2	0.1	0.1
Normal weight	28	27	26
Overweight	51	50	52
Obese	21	23	22
Physical activity score	146±70	147±67	148±68
CKD-EPI eGFR, ml/min per 1.73 m²	76±16	75±15	75±15
Serum glucose, mg/dl^a	109±29	105±23	103±18
CVD	24	24	23
Diabetes^a	14	10	9
Hypertension^a	48	40	42
Stroke	6	5	6
COPD	11	10	11
Excellent or good health status	85	84	86
SF-12 MCS score	55.6±7.1	55.7±6.8	55.4±6.9
Thiazide diuretic use^a	17	11	10
3MS score	93±6	93±6	93±6
Trails B, time, s^a	138±62	133±57	134±58
Serum sodium, mmol/L^a	139±2 139; (138, 140)	142±1; 142 (141, 142)	144±1; 144 (143, 145)

Data are mean±SD, median (interquartile range), or %. Serum glucose is missing for n=141, thiazide diuretic use is missing for n=211, and Trails B time is missing for n=53. P values are comparisons across tertiles made using a chi-squared test for categoric data and ANOVA for continuous variables. BMI, body-mass index; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; CVD, cardiovascular disease; COPD, chronic obstructive pulmonary disease; SF-12 MCS score, Medical Outcomes Study 12-Item Short Form Mental Health Composite Score (health-related quality of life); 3MS, modified Mini-Mental Status examination; Trails B, Trail Making Test Part B.
↵a P<0.05 across tertiles by chi-squared test for categoric data and ANOVA for continuous variables.

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Table 2.

Associations (odds ratio [95% confidence interval]) between tertiles of serum sodium levels and prevalent cognitive impairment by logistic regression models (cross-sectional analysis)

Model	Tertile 1 (126–140 mmol/L) (n=1814)	Tertile 2 (141–142 mmol/L) (n=1818)	Tertile 3 (143–153 mmol/L) (n=1803)	Continuous (per 5 mmol/L lower serum sodium)
Unadjusted	1.26 (1.04 to 1.52)	Ref	1.10 (0.90 to 1.33)	1.19 (1.02 to 1.37)
Model 1	1.31 (1.07 to 1.61)	Ref	1.11 (0.90 to 1.36)	1.24 (1.06 to 1.45)
Model 2	1.32 (1.08 to 1.62)	Ref	1.11 (0.90 to 1.37)	1.25 (1.07 to 1.47)
Model 3	1.30 (1.05 to 1.59)	Ref	1.10 (0.90 to 1.36)	1.24 (1.05 to 1.45)
Model 4	1.30 (1.06 to 1.61)	Ref	1.09 (0.88 to 1.34)	1.24 (1.05 to 1.46)

The prevalence of cognitive impairment was 15% (n=274), 12% (n=225), and 13% (n=242) for tertile 1, tertile 2, and tertile 3. Model 1: adjusted for age, race/ethnicity, and education. Model 2: adjusted for model 1, smoking, alcohol intake, body-mass index category, and physical activity. Model 3: model 2+eGFR (Chronic Kidney Disease Epidemiology Collaboration equation), and history of cardiovascular disease, diabetes, hypertension, stroke, and chronic obstructive pulmonary disease. Model 4: model 3+quality-of-life measures and serum glucose level. Serum glucose level is missing in n=141.

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Table 3.

Baseline characteristics of study participants for cognitive decline (longitudinal) analysis by tertiles of baseline serum sodium levels

Variable	Tertile 1 (126–140 mmol/L) (n=1175)	Tertile 2 (141–142 mmol/L) (n=1214)	Tertile 3 (143–153 mmol/L) (n=1222)
Age, yr	72±5	72±5	73±5
Race (% white)^a	92	93	95
Education
High school or less	18	19	21
Some college	23	23	22
College	19	19	20
Some graduate school	12	13	12
Graduate school	28	26	26
Smoking
Never smoker	38	39	40
Current smoker	4	2	3
Former smoker	58	39	58
Alcohol, ≥12 drinks in past 12 mo	71	68	68
BMI category
Underweight	0.2	0.1	0.1
Normal weight	28	26	24
Overweight	50	51	55
Obese	21	23	21
Physical activity score	155±69	153±66	152±66
CKD-EPI eGFR, ml/min per 1.73 m²	77±14	76±14	76±14
Serum glucose, mg/dl^a	107±28	105±22	103±18
CVD	20	20	20
Diabetes^a	11	9	7
Hypertension^a	44	38	40
Stroke	4	4	4
COPD	9	10	10
Excellent or good health status	89	91	89
SF-12 MCS score	56.1±6.6	56.2±6.2	56.2±5.9
Thiazide diuretic use^a	14	11	10
3MS score	95±4	95±4	95±3
Trails B time, s	116±39	115±38	115±36
Serum sodium, mmol/L^a	139±2; 139 (138, 140)	142±1; 142 (141, 142)	144±1; 144 (143, 145)

Data are mean±SD, median (interquartile range), or %. Serum glucose is missing in n=81, thiazide diuretic use is missing for n=150, and change in Trails B time is missing for n=28. P values are comparisons across tertiles made using a chi-squared test for categoric data and ANOVA for continuous variables. BMI, body-mass index; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; CVD, cardiovascular disease; COPD, chronic obstructive pulmonary disease; SF-12 MCS score, Medical Outcomes Study 12-Item Short Form Mental Health Composite Score (health-related quality of life); 3MS, modified Mini-Mental Status examination; Trails B, Trail Making Test Part B.
↵a P<0.05 across tertiles by chi-squared test for categoric data and ANOVA for continuous variables.

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Table 4.

Associations (odds ratio [95% confidence interval]) between tertiles of serum sodium levels with cognitive decline by logistic regression models (longitudinal analysis)

Variable	Tertile 1 (126–140 mmol/L) (n=1175)	Tertile 2 (141–142 mmol/L) (n=1214)	Tertile 3 (143–153 mmol/L) (n=1222)	Continuous (per 5 mmol/L lower serum sodium)
Unadjusted	1.36 (1.06 to 1.75)	Ref	1.30 (1.02 to 1.67)	1.01 (0.83 to 1.24)
Model 1	1.37 (1.06 to 1.77)	Ref	1.32 (1.03 to 1.70)	0.99 (0.81 to 1.22)
Model 2	1.38 (1.07 to 1.78)	Ref	1.33 (1.03 to 1.71)	1.00 (0.82 to 1.22)
Model 3	1.37 (1.06 to 1.77)	Ref	1.33 (1.03 to 1.71)	0.99 (0.81 to 1.21)
Model 4	1.37 (1.06 to 1.77)	Ref	1.32 (1.03 to 1.71)	0.97 (0.79 to 1.19)

The incidence of cognitive decline was 14% (n=159), 10% (n=125), and 13.0% (n=159) for tertile 1, tertile 2, and tertile 3. Model 1: adjusted for age, race/ethnicity, and education. Model 2: adjusted for model 1, smoking, alcohol intake, body-mass index category, and physical activity. Model 3: model 2+eGFR (Chronic Kidney Disease Epidemiology Collaboration equation), and history of cardiovascular disease, diabetes, hypertension, stroke, and chronic obstructive pulmonary disease. Model 4: model 3+quality of life and serum glucose level. Serum glucose is missing in n=81.