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Original ArticlesAcid/Base and Electrolyte Disorders
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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 and Michel Chonchol
CJASN March 2018, 13 (3) 366-374; DOI: https://doi.org/10.2215/CJN.07400717
Kristen L. Nowak
1Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado;
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Kristine Yaffe
2Departments of Psychiatry, Neurology, and Epidemiology, University of California San Francisco, San Francisco, California;
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Eric S. Orwoll
3Bone and Mineral Unit, Oregon Health and Science University, Portland, Oregon;
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Joachim H. Ix
4Divisions of Nephrology and Preventative Medicine, University of California San Diego, San Diego, California;
5Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, California;
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Zhiying You
1Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado;
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Elizabeth Barrett-Connor
6Division of Epidemiology, Department of Family Medicine and Public Health, University of California San Diego, La Jolla, California; and
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Andrew R. Hoffman
7Division of Endocrinology, Gerontology and Metabolism, Stanford University, Stanford, California
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Michel Chonchol
1Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado;
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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

    VariableTertile 1 (126–140 mmol/L) (n=1814)Tertile 2 (141–142 mmol/L) (n=1818)Tertile 3 (143–153 mmol/L) (n=1803)
    Age, yr74±674±674±6
    Race (% white)a899292
    Education
     High school or less232427
     Some college242322
     College181818
     Some graduate school111111
     Graduate school252423
    Smokinga
     Never smoker363838
     Current smoker533
     Former smoker595959
    Alcohol intake, ≥12 drinks in past 12 moa686463
    BMI category
     Underweight0.20.10.1
     Normal weight282726
     Overweight515052
     Obese212322
    Physical activity score146±70147±67148±68
    CKD-EPI eGFR, ml/min per 1.73 m276±1675±1575±15
    Serum glucose, mg/dla109±29105±23103±18
    CVD242423
    Diabetesa14109
    Hypertensiona484042
    Stroke656
    COPD111011
    Excellent or good health status858486
    SF-12 MCS score55.6±7.155.7±6.855.4±6.9
    Thiazide diuretic usea171110
    3MS score93±693±693±6
    Trails B, time, sa138±62133±57134±58
    Serum sodium, mmol/La139±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)

    ModelTertile 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)
    Unadjusted1.26 (1.04 to 1.52)Ref1.10 (0.90 to 1.33)1.19 (1.02 to 1.37)
    Model 11.31 (1.07 to 1.61)Ref1.11 (0.90 to 1.36)1.24 (1.06 to 1.45)
    Model 21.32 (1.08 to 1.62)Ref1.11 (0.90 to 1.37)1.25 (1.07 to 1.47)
    Model 31.30 (1.05 to 1.59)Ref1.10 (0.90 to 1.36)1.24 (1.05 to 1.45)
    Model 41.30 (1.06 to 1.61)Ref1.09 (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

    VariableTertile 1 (126–140 mmol/L) (n=1175)Tertile 2 (141–142 mmol/L) (n=1214)Tertile 3 (143–153 mmol/L) (n=1222)
    Age, yr72±572±573±5
    Race (% white)a929395
    Education
     High school or less181921
     Some college232322
     College191920
     Some graduate school121312
     Graduate school282626
    Smoking
     Never smoker383940
     Current smoker423
     Former smoker583958
    Alcohol, ≥12 drinks in past 12 mo716868
    BMI category
     Underweight0.20.10.1
     Normal weight282624
     Overweight505155
     Obese212321
    Physical activity score155±69153±66152±66
    CKD-EPI eGFR, ml/min per 1.73 m277±1476±1476±14
    Serum glucose, mg/dla107±28105±22103±18
    CVD202020
    Diabetesa1197
    Hypertensiona443840
    Stroke444
    COPD91010
    Excellent or good health status899189
    SF-12 MCS score56.1±6.656.2±6.256.2±5.9
    Thiazide diuretic usea141110
    3MS score95±495±495±3
    Trails B time, s116±39115±38115±36
    Serum sodium, mmol/La139±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.

    • View popup
    Table 4.

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

    VariableTertile 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)
    Unadjusted1.36 (1.06 to 1.75)Ref1.30 (1.02 to 1.67)1.01 (0.83 to 1.24)
    Model 11.37 (1.06 to 1.77)Ref1.32 (1.03 to 1.70)0.99 (0.81 to 1.22)
    Model 21.38 (1.07 to 1.78)Ref1.33 (1.03 to 1.71)1.00 (0.82 to 1.22)
    Model 31.37 (1.06 to 1.77)Ref1.33 (1.03 to 1.71)0.99 (0.81 to 1.21)
    Model 41.37 (1.06 to 1.77)Ref1.32 (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.

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Clinical Journal of the American Society of Nephrology: 13 (3)
Clinical Journal of the American Society of Nephrology
Vol. 13, Issue 3
March 07, 2018
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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
CJASN Mar 2018, 13 (3) 366-374; DOI: 10.2215/CJN.07400717

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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
CJASN Mar 2018, 13 (3) 366-374; DOI: 10.2215/CJN.07400717
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