Associations of Hyponatremia with Cognition Function and All-Cause Mortality: Post Hoc Analysis of the Systolic BP Intervention Trial

Key Points:center dot Incident hyponatremia is associated with probable dementia.center dot Incident hyponatremia does not seem to be associated with mild cognitive impairment or death.Background Acute neurologic effects of severe hyponatremia are well-known. However, the long-term association of hyponatremia with cognitive impairment is unclear.Methods In this post hoc analysis of the Systolic Blood Pressure Intervention Trial, we examined whether incident hyponatremia is a risk factor of mild cognitive impairment (MCI) or probable dementia (PD). In those with baseline serum sodium level >= 130 mmol/L, we defined incident hyponatremia in the first 6 months as a Systolic Blood Pressure Intervention Trial safety alert for serum sodium level <130 mmol/L from randomization to the 6-month visit. In multivariate Cox regression models adjusted for baseline cognitive function and other variables, we related incident hyponatremia in the first 6 months with subsequent MCI or PD in 8540 participants with cognitive outcomes data and with all-cause mortality (ACM) in 9135 participants with mortality data.Results Incident hyponatremia in the first 6 months was noted in 116 participants (1.4%). Older age, female sex, non-Black race, lower body mass index, and randomization to intensive systolic BP control were associated with incident hyponatremia. Compared with those without hyponatremia, those with incident hyponatremia had higher risk of PD (2.1 versus 0.9 events/100 person-years; hazard ratio [HR], 3.08; 95% confidence interval [CI], 1.48 to 6.41) but not MCI (3.1 versus 3.6 events/100 person-years; HR, 0.95; 95% CI, 0.54 to 1.68) and the composite of MCI/PD (5.0 versus 4.2 events/100 person-years; HR, 1.28; 95% CI, 0.82 to 2.0). There were no significant differences in ACM (HR, 1.84; 95% CI, 0.90 to 3.73).Conclusions Biologic plausibility for the association of incident hyponatremia with PD but not MCI or death is unclear. The association of incident hyponatremia with PD could reflect a chance finding or noncausal biologic association or causal relationship.