During the study period, 7580 people aged ≥ 70 years visited the NCGG Memory Disorder Outpatient Center. Of them, 2961 met the inclusion criteria: 10 had moderate or more severe hyponatremia (SNa < 130 mEq/L), 75 had mild hyponatremia (SNa 130–135 mEq/L), 2872 had normonatremia (SNa 136–145 mEq/L), and 4 had hypernatremia (SNa > 145 mEq/L). Thus, 75 participants with mild hyponatremia and 2872 with normonatremia were included in this study.
The characteristics of hyponatremia and normonatremia are summarized for all participants in Table 1. The mild hyponatremia group was significantly older (median [interquartile range], 81.0 [76.0–84.0] vs 79.0 [75.0–83.0] years), had fewer women (46.7% vs 64.3%), had a lower Barthel Index score (100 [85.0–100.0] vs 100[95.0–100.0]), had a more history of cardiac disease (20.0% vs 11.7%), had more hearing problems (65.3% vs 52.1%), had higher diuretic use (9.3% vs 3.7%), and had higher potassium (4.4 [4.1–4.6] vs 4.1[3.9–4.4] mEq/L) compared with the normonatremia group. As shown in Table 2, the mild hyponatremia group also had more cases of sarcopenia, slower WS, shorter OLS time, and higher GDS-15 score.
Table 1
Participant characteristics
| n | Mild hyponatremia group | n | Normonatremia group | p |
Age, years | 75 | 81.0 (76.0–84.0) | 2872 | 79.0 (75.0–83.0) | 0.01 |
Female, n (%) | 75 | 35 (46.7) | 2872 | 1846 (64.3) | 0.002 |
Education, years | 73 | 9.0 (8.0–12.0) | 2813 | 9.0 (9.0–12.0) | 0.5 |
Barthel Index | 75 | 100.0 (85.0-100.0) | 2872 | 100.0 (95.0-100.0) | 0.004 |
Heavy drinker*, n (%) | 74 | 2 (2.7) | 2840 | 55 (1.9) | 0.6 |
Body mass index, kg/m2 | 74 | 21.4 (19.4–23.6) | 2861 | 21.9 (19.8–24.2) | 0.3 |
History of cardiac disease, n (%) | 75 | 15 (20) | 2872 | 335 (11.7) | 0.03 |
History of diabetes, n (%) | 75 | 8 (10.7) | 2872 | 205 (7.1) | 0.2 |
History of liver disease, n (%) | 75 | 1 (1.3) | 2872 | 62 (2.2) | 0.6 |
History of cancer, n (%) | 75 | 9 (12) | 2872 | 233 (8.1) | 0.2 |
Joint pain, n (%) | 75 | 28 (37.3) | 2838 | 1161 (48.7) | 0.5 |
Visual impairment, n (%) | 75 | 39 (52.0) | 2836 | 1588 (56.0) | 0.5 |
Hearing impairment, n (%) | 75 | 49 (65.3) | 2837 | 1804 (52.1) | 0.02 |
Diuretics use, n (%) | 75 | 7 (9.3) | 2872 | 107 (3.7) | 0.01 |
CNS active drug use**, n (%) | 75 | 28 (37.3) | 2872 | 1117 (38.9) | 0.8 |
Inactivity, n (%): | 74 | 21 (28.4) | 2824 | 945 (33.5) | 0.4 |
Systolic BP, mmHg | 70 | 149.0 (127.0-161.3) | 2790 | 149.0 (134.0-166.0) | 0.2 |
BNP, pg/mL | 42 | 32.1 (18.6–70.0) | 1503 | 31.6 (16.1–58.3) | 0.3 |
eGFR, mL/min/1.73 m2 | 75 | 69.6 (57.5–85.2) | 2872 | 69.0 (56.0-73.5) | 0.4 |
CRP, mg/dL | 75 | 0.06 (0.03–0.2) | 2872 | 0.05 (0.03–0.1) | 0.1 |
Hemoglobin, mg/dL | 75 | 13.2 (12.1–14.1) | 2872 | 13.4 (12.5–14.3) | 0.08 |
TSH, µlU/ml | 75 | 1.6 (0.9–2.1) | 2872 | 1.5 (1.0-2.2) | 0.9 |
Potassium, mEq/L | 75 | 4.4 (4.1–4.6) | 2872 | 4.1 (3.9–4.4) | < 0.001 |
Values are median (interquartile range) or number (percentage). Differences were assessed using the Kruskal–Wallis test for continuous variables or the Chi-squared test for categorical variables. Abbreviations: BNP, brain natriuretic peptide; BP, blood pressure, CNS, central nervous system; CRP, C-reactive protein; eGFR, estimated glomerular filtration rate; TSH, thyroid stimulating hormone. *> 60 g/day of alcohol, **antiepileptic, antipsychotic, antidepressant and benzodiazepine drugs. |
Table 2
Difference in physical and cognitive function between the groups
| n | Mild hyponatremia group | n | Normonatremia group | p |
Sarcopenia, n (%) | 41 | 25 (61.0) | 1816 | 793 (43.7) | 0.03 |
SMI, kg/m2 | 48 | 6.3 (6.0–7.0) | 2324 | 6.3 (5.7–7.1) | 0.6 |
Physical function tests | | | | | |
Grip strength, kg | 37 | 18.6 (14.1–25.2) | 1702 | 20.1 (15.7–25.5) | 0.2 |
Walking speed, m/s | 15 | 0.8 (0.5–0.9) | 631 | 1.0 (0.8–1.2) | < 0.001 |
One-leg standing time, s | 45 | 5.8 (2.6–13.3) | 2259 | 9.0 (3.9–23.2) | 0.02 |
Neuropsychological tests | | | | | |
MMSE | 75 | 20.0 (17.0–25.0) | 2862 | 21.0 (17.0–25.0) | 0.7 |
FAB | 41 | 9.0 (7.0–12.0) | 1699 | 10.0 (8.0–12.0) | 0.6 |
Digit Span forward | 44 | 5.0 (5.0–6.0) | 1741 | 5.0 (5.0–6.0) | 0.6 |
Digit Span backward | 44 | 3.0 (3.0–4.0) | 1728 | 3.0 (3.0–4.0) | 0.9 |
Category fluency | 73 | 8.0 (5.5–10.0) | 2853 | 8.0 (6.0–10.0) | 0.3 |
Logical memory Ⅱ | 44 | 3.0 (3.0-12.5) | 1743 | 3.0 (3.0–11.0) | 0.2 |
GDS-15 | 72 | 5.0 (2.0–8.0) | 2820 | 4.0 (2.0–6.0) | 0.02 |
Values are median (interquartile range) or number (percentage). Differences were assessed using the Kruskal–Wallis test for continuous variables or the Chi-squared test for categorical variables. Abbreviations: FAB, Frontal Assessment Battery; GDS-15, 15-item Geriatric Depression Scale; MMSE, Mini–Mental state examination; SMI, skeletal muscle mass index. |
ANCOVA showed that mild hyponatremia had a significant effect on SMI (F [1, 2199) = 6.2, p = 0.01) GS (F [1, 1627] = 7.1, p = 0.008) WS (F [1, 605] = 14.3, p < 0.001), OLS time (F [1, 2154] = 4.0, p = 0.049), and GDS-15 score (F [1, 2689] = 5.0, p = 0.003) after controlling for covariates (Table 3).
Table 3
ANCOVA results for the comparison of skeletal mass index, physical function, and psychological tests between the groups
| | Mild hyponatremia group | | Normonatremia group | | | |
| n | Adjusted mean ± SD | n | Adjusted mean ± SD | F | p | η2 |
Skeletal muscle mass index, kg/m2 | 43 | 6.5 ± 0.1 | 2178 | 6.7 ± 0.09 | 6.2 | 0.01a | 0.003 |
Grip strength, kg | 33 | 19.4 ± 1.3 | 1616 | 21.9 ± 1.0 | 7.1 | 0.008a | 0.004 |
Walking speed, m/s | 15 | 0.6 ± 0.09 | 612 | 0.9 ± 0.07 | 14.3 | < 0.001a | 0.03 |
One-leg standing test, s | 42 | 4.9 ± 3.5 | 2134 | 10.0 ± 2.7 | 4.0 | 0.049a | 0.002 |
Mini–Mental State Examination | 67 | 21.4 ± 0.8 | 2655 | 20.9 ± 0.6 | 1.0 | 0.3b | < 0.001 |
Frontal Assessment Battery | 39 | 9.7 ± 0.7 | 1610 | 9.4 ± 0.5 | 0.5 | 0.5b | < 0.001 |
Digit Span forward | 42 | 5.4 ± 0.2 | 1647 | 5.3 ± 0.1 | 0.6 | 0.4b | < 0.001 |
Digit Span backward | 42 | 3.3 ± 0.2 | 1633 | 3.2 ± 0.2 | 0.9 | 0.3b | 0.001 |
Verbal fluency | 66 | 2.9 ± 0.3 | 2651 | 2.7 ± 0.3 | 0.6 | 0.4b | < 0.001 |
Logical memory II | 42 | 10.9 ± 3.6 | 1650 | 8.5 ± 2.7 | 0.8 | 0.4b | 0.001 |
15-item Geriatric Depression Scale | 66 | 4.9 ± 0.5 | 2644 | 4.1 ± 0.4 | 5.0 | 0.03b | 0.002 |
η2, the effect size |
aCovariates adjusted for were age, sex, years of education, alcohol consumption, Barthel Index, body mass index, history of heart disease, diabetes, liver disease, cancer, and joint pain, visual impairment, hearing impairment, diuretics use, central nervous system active drug use, inactivity, hypotension, estimated glomerular filtration rate < 60, C-reactive protein, and Mini–Mental State Examination. |
bCovariates adjusted for in modela excluded the Mini–Mental State Examination. |
The results of multiple logistic regression using each cutoff score are shown in Table 4. After entering all variables selected from previous studies(10) into multivariable models 2 and 3, the elderly with mild hyponatremia were significantly more likely to have weaker muscle strength as indicated by GS (odds ratio [OR]: 2.3, 95% confidence interval [CI]: 1.0–5.2; p = 0.048), poor physical performance as indicated by slower WS (OR: 7.6, 95% CI: 1.6–37.1; p = 0.01), impaired postural balance (OR: 2.1, 95% CI: 1.1–4.1, p = 0.03), and severe depressive mood (OR: 2.6, 95% CI: 1.2–5.7, p = 0.001). However, mild hyponatremia was not significantly associated with sarcopenia (OR:1.9, 95% CI: 0.9–4.0, p = 0.09) or lower SMI (OR: 1.7, 95% CI: 0.8–3.4, p = 0.1). There was no overfitting, and goodness of fit (Hosmer-Lemeshow test) indicated that each logistic model fit well.
Table 4
Results of logistic regression analysis for predicting sarcopenia, skeletal muscle mass, and physical and cognitive functions
Dependent variables | Model 1 | | | Model 2 | | |
| n | OR (95% CI) | p | n | OR (95% CI) | p |
Sarcopenia | 1857 | 1.9 (1.0-3.5) | 0.06 | 1762 | 1.9 (0.9-4.0) | 0.09 |
Low skeletal muscle mass indexa | 2372 | 1.8 (1.0-3.2) | 0.05 | 2221 | 1.7 (0.8–3.4) | 0.1 |
Low muscle strengthb | 1739 | 2.6 (1.2–5.8) | 0.02 | 1649 | 2.3 (1.0-5.2) | 0.048 |
Poor physical performance; Walking speed < 1 m/s | 646 | 6.1 (1.3–28.6) | 0.02 | 627 | 7.6 (1.6–37.1) | 0.01 |
Impaired postural balance; One-leg standing test ≤ 5 s | 2186 | 1.9 (1.0-3.6) | 0.06 | 2059 | 2.1 (1.1–4.1) | 0.03 |
Dependent variables | Model 1 | | | Model 3 | | |
| n | OR (95% CI) | p | n | OR (95% CI) | p |
Cognitive disturbance; MMSE < 24 | 2879 | 0.9 (0.5–1.5) | 0.6 | 2722 | 0.9 (0.5–1.6) | 0.9 |
Executive dysfunction; FAB < 12 | 1719 | 0.8 (0.4–1.6) | 0.5 | 1649 | 0.6 (0.3–1.3) | 0.3 |
Poor walking memory; Digit Span forward < 6 | 1759 | 0.8 (0.4–1.6) | 0.5 | 1689 | 0.9 (0.5–1.9) | 0.8 |
Poor walking memory; Digit Span backward < 4 | 1746 | 0.8 (0.4–1.6) | 0.6 | 1675 | 0.8 (0.4–1.6) | 0.6 |
Poor attention; the category fluency subtest of the HDS-R < 6 | 1759 | 0.8 (0.8–0.9) | 0.5 | 2717 | 0.7 (0.4–1.3) | 0.2 |
Memory disorderc | 1762 | 0.6 (0.3–1.1) | 0.09 | 1691 | 0.6 (0.3–1.1) | 0.1 |
Severe depression; GDS-15 ≥ 10 | 2856 | 2.7 (1.3–5.4) | 0.005 | 2707 | 2.6 (1.2–5.7) | 0.001 |
aLow skeletal muscle mass was defined as skeletal muscle mass index < 7.0 kg/m2 in men and < 5.7 kg/m2 in women |
bReduced grip strength was defined as < 28 kg for men and < 18 kg for women |
cRaw WMS-R II score ≤ 8/9 for > 16 years of education, ≤ 4/5 for 8–15 years of education, ≤ 2/3 for 0–7 years of education |
Model 1. Adjusted for age and sex |
Model 2. In binary logistic regression analysis, all variables were entered into the multivariable model (age, sex, years of education, alcohol consumption, Barthel Index, body mass index > 25, body mass index < 18.5, history of heart disease, diabetes, liver disease, cancer, and joint pain, visual impairment, hearing impairment, diuretics use, central nervous system active drugs, inactivity, hypotension, estimated glomerular filtration rate < 60, C-reactive protein; and MMSE ) using |
Model 3. In binary logistic regression analysis, all variables in Model 2 were entered into a multivariable model excluding the MMSE using |
Abbreviations: CI, confidence interval; FAB, Frontal Assessment Battery; GDS-15, 15-item Geriatric Depression Scale; HDS-R, Hasegawa Dementia Rating Scale-Revised; MMSE, Mini–Mental State Examination; OR, odds ratio; WMS-R, Wechsler Memory Scale-Revised |