Cognitive function and all-cause mortality in maintenance hemodialysis patients

Abstract

Background: Cognitive impairment is common in hemodialysis patients and is associated with significant morbidity. Limited information exists about whether cognitive impairment is associated with survival and whether the type of cognitive impairment is important.

Study design: Longitudinal cohort.

Setting & participants: Cognitive function was assessed at baseline and yearly using a comprehensive battery of cognitive tests in 292 prevalent hemodialysis patients.

Predictor: Using principal component analysis, individual test results were reduced into 2 domain scores, representing memory and executive function. By definition, each score carried a mean of 0 and SD of 1.

Outcomes: Association of each score with all-cause mortality was assessed using Cox proportional hazards models adjusted for demographics and dialysis and cardiovascular (CV) risk factors.

Results: Mean age of participants was 63 years, 53% were men, 23% were African American, and 90% had at least a high school education. During a median follow-up of 2.1 (IQR, 1.1-3.7) years, 145 deaths occurred. Each 1-SD better executive function score was associated with a 35% lower hazard of mortality (HR, 0.65; 95% CI, 0.55-0.76). In models adjusting for demographics and dialysis-related factors, this relationship was partially attenuated but remained significant (HR, 0.81; 95% CI, 0.67-0.98), whereas adjustment for CV disease and heart failure resulted in further attenuation (HR, 0.87; 95% CI, 0.72-1.06). Use of time-dependent models showed a similar unadjusted association (HR, 0.62; 95% CI, 0.54-0.72), with the relationship remaining significant after adjustment for demographics and dialysis and CV risk factors (HR, 0.79; 95% CI, 0.66-0.94). Better memory was associated with lower mortality in univariate analysis (HR per 1 SD, 0.82; 95% CI, 0.69-0.96), but not when adjusting for demographics (HR, 1.00; 95% CI, 0.83-1.19).

Limitations: Patients with dementia were excluded from the full battery, perhaps underestimating the strength of the association.

Conclusions: Worse executive function and memory are associated with increased risk of mortality. For memory, this association is explained by patient demographics, whereas for executive function, this relationship may be explained in part by CV disease burden.

Keywords: Cognition; cardiovascular disease; cognitive impairment; end-stage renal disease (ESRD); executive function; hemodialysis; memory; mortality; neurocognitive testing.

Figure 1

Figures 1A and 1B Unadjusted and age adjusted mortality rates by quartiles of executive and memory function. * = significant trend p value

Figure 2

Figures 2A and 2B Kaplan-Meier plots by quartiles of executive and memory function. A global p-value is provided (log rank test) for each plot.