Role of Anemia in Dementia Risk Among Veterans With Incident CKD

RATIONALE & OBJECTIVE: While some evidence exists of increased dementia risk from anemia, it is unclear if this association persists among adults with CKD. Anemia may be a key marker for dementia among adults with CKD. We therefore evaluated if 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] <60 mL/min/1.73 m 2) 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.

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

OUTCOMES: 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, mean age was 72 years, 97% were male, and mean eGFR was 51 mL/min per 1.73 m 2. Over a median 4.1 years of follow-up, 92,306 (15%) veterans developed dementia before kidney failure or death. Compared to veterans with CKD without anemia, multivariable-adjusted models showed a 16% (95% confidence interval [CI] 14% to 17%) significantly higher risk of dementia for those with mild anemia and a 27% (95% CI 23% to 31%) higher risk with moderate/severe anemia. Combined risk of kidney failure or death was higher at 39% (95% CI 37% to 40%) and 115% (95% CI 112% to 119%) for mild and moderate/severe anemia, respectively, compared to no anemia.

LIMITATIONS: Residual confounding from the observational study design. Findings may not be generalizable to the broader U.S.

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