Mild Hyponatremia is Associated with Impaired Cognition and Falls in Community-Dwelling Older Persons

To the Editor:

Hyponatremia is a common finding in older persons. Mild hyponatremia was once thought to be asymptomatic, but recent evidence suggests that mild hyponatremia is linked to attention deficits, gait disturbances, and risk of falls.1, 2 Published studies have examined hospitalized individuals with acute illnesses with the ensuing risk of Berkson's bias (a form of selection bias).3 No published study has included asymptomatic community-dwelling older persons or assessed cognition in hyponatremic subjects across multiple domains. It was hypothesized that mild hyponatremia (serum sodium 130–135 mmol/L) is associated with clinically subtle yet significant cognitive deficits, impaired balance, and propensity to fall in community-dwelling older persons. The relationship between mild hyponatremia and cognitive function, two surrogate markers of falls risk (functional reach (FR) and Timed Up and Go test (TUG)), and the incidence of falls was investigated.

Methods

Community-dwelling individuals (N = 3,282; mean age 66.8 ± 7.8, 51% female) were drawn from the Hunter Community Study, a population-based prospective cohort study established to assess factors important in the health and well-being of older Australians.4 Informed consent was obtained at enrollment, and the local ethics committee approved the study. Cognitive function was assessed using the Audio Recorded Cognitive Screening tool (ARCS), a short cognitive battery that probes most cognitive domains traditionally assessed using conventional neuropsychological tests.5 The overall ARCS score was calculated by summing the scaled scores for the critical domains and recalibrating that score to a population mean of 100 and a standard deviation of 15. A recent study of the Hunter Community Study cohort had previously demonstrated the ARCS to have excellent validity and reliability.5 Falls risk was assessed using FR and TUG, as previously described.6, 7 Health record linkage was performed through state government databases, and participants were considered to have had a fall if they self-reported, were admitted to hospital with a fall, or both.

All analyses were adjusted for age, sex, and diuretic usage, plus height in the case of FR. A multiple linear regression model was used to assess the effect of serum sodium on ARCS, FR and TUG. Multiple logistic regression was used to model the effect of serum sodium on the probability of a fall. Nonlinear effects of covariates were modeled using restricted cubic splines and robust covariance estimators to account for nonconstant variance. Assessment of statistical significance of model parameters was performed using partial sums of squares F-tests for linear regressions and Wald statistics for logistic regression.

Results and Discussion

Serum sodium measurement was available for 2,550 subjects (mean 140.6 ± 2.8 mmol/L), and 500 participants (15%) had a history of a fall. A nonlinear relationship was found between serum sodium and cognition scores. ARCS scores remained stable across the normal range of serum sodium (135–145 mmol/L) but dropped below this. The ARCS for subjects with a serum sodium level of 135 mmol/L was on average 4.67 units higher out of a standardized total of 100 (95% confidence interval (CI)=1.56–7.79, F = 6.3, P = .01) than for those with a sodium level of 130 mmol/L. Given that the ARCS is standardized to a score of 100 and a standard deviation of 15, this represents a 5% change in cognition, or a Z score of 0.33, which means a shift from the 50th to the 37th centile in terms of cognition.

After adjusting for age, sex, and diuretic use, hyponatremic subjects were still more likely to have suffered a fall (chi-square (χ²) =  8.16, P = .01). The effect of sodium was determined to be nonlinear on the log-odds scale, modelled using a statistically significant three-knot cubic spline (χ² =  6:16, P = .01); to explain the magnitude of this nonlinear effect, it was calculated that a 5-mmol/L drop in serum sodium from 135 to 130 mmol/L increased the risk of falling by 32% (odds ratio (OR) = 1.32, 95% CI = 1.04–1.64). To put this in context, a change in age of 13 years, from 60 to 73, increased the risk of falling by 27% (OR = 1.27, 95% CI = 1.01–1.59) (i.e., a 5-mmol/L drop in sodium had about the same effect on falls as aging 13 years). To express this in absolute terms rather than relative terms, the distribution of predicted probability for falls by serum sodium level was plotted (Figure 1). A statistically significant correlation was not found between hyponatremia and FR or TUG, although the surrogate markers chosen were crude and may not have detected subtle abnormalities in posture and gait that previous authors reported.8

Figure 1

Predicted probabilities for the logistic models of falls versus serum sodium, adjusted for age, sex, and diuretic use (bars on the blue line represent density of data, i.e., number of participants with that sodium value). The absolute risk graphed below is for a 66-year-old woman not taking diuretics.

Even mild degrees of hyponatremia can be associated with significant cognitive deficits and greater risk of falls in otherwise asymptomatic older persons.

Acknowledgments

Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper.

Author Contributions: All authors participated in study design, data collection, analysis, and manuscript preparation and submission.

Sponsor's Role: None.