Role of Anemia in Dementia Risk Among Veterans With Incident CKD

Abstract

Rationale & objective: Although some evidence exists of increased dementia risk from anemia, it is unclear whether this association persists among adults with CKD. Anemia may be a key marker for dementia among adults with CKD, so we evaluated whether anemia is associated with an increased risk of dementia among adults with CKD.

Study design: Retrospective cohort study.

Setting & participants: The study included 620,095 veterans aged≥45 years with incident stage 3 CKD (estimated glomerular filtration rate [eGFR]<60mL/min/1.73m²) between January 2005 and December 2016 in the US Veterans Health Administration system and followed through December 31, 2018, for incident dementia, kidney failure, or death.

Exposure: Anemia was assessed based on the average of hemoglobin levels (g/L) during the 2 years before the date of incident CKD and categorized as normal, mild, or moderate/severe anemia (≥12.0, 11.0-11.9,<11.0g/dL, respectively, for women, and≥13.0, 11.0-12.9,<11.0g/dL for men).

Outcome: Dementia and the composite outcome of kidney failure or death.

Analytical approach: Adjusted cause-specific hazard ratios were estimated for each outcome.

Results: At the time of incident CKD, the mean age of the participants was 72 years, 97% were male, and their mean eGFR was 51mL/min per 1.73m². Over a median 4.1 years of follow-up, 92,306 veterans (15%) developed dementia before kidney failure or death. Compared with the veterans with CKD without anemia, the multivariable-adjusted models showed a 16% (95% CI, 14%-17%) significantly higher risk of dementia for those with mild anemia and a 27% (95% CI, 23%-31%) higher risk with moderate/severe anemia. Combined risk of kidney failure or death was higher at 39% (95% CI, 37%-40%) and 115% (95% CI, 112%-119%) for mild and moderate/severe anemia, respectively, compared with no anemia.

Limitations: Residual confounding from the observational study design. Findings may not be generalizable to the broader US population.

Conclusions: Anemia was significantly associated with an increased risk of dementia among veterans with incident CKD, underscoring the role of anemia as a predictor of dementia risk.

Plain-language summary: Adults with chronic kidney disease (CKD) often have anemia. Prior studies among adults in the general population suggest anemia is a risk factor for dementia, though it is unclear whether this association persists among adults with CKD. In this large study of veterans in the United States, we studied the association between anemia and the risk of 2 important outcomes in this population: (1) dementia and (2) kidney failure or death. We found that anemia was associated with a greater risk of dementia as well as risk of kidney failure or death. The study findings therefore emphasize the role of anemia as a key predictor of dementia risk among adults with CKD.

Keywords: Anemia; ESKD; chronic kidney disease; dementia; kidney failure.

Figure 1.

Association between anemia at baseline and outcome in select baseline subgroups. Hazard ratios are stratified by levels of subgroups for age, sex, race/ethnicity, diabetes status, urinary albumin-to-creatinine ratio (UACR), transfusion status, availability of transferrin saturation (TSAT) measurement (yes/no), and TSAT (<20% / ≥20%) (among those with available TSAT), adjusting for all covariates included in the adjusted models shown in Table 2, provided it is not the stratifying variable. The rhombus symbol indicates the hazard ratios (HR) for mild anemia versus no anemia and the circle symbol indicates the HRs for moderate/severe versus no anemia. Abbreviations: P(int) = p value for the interaction test.