Association of Anemia with Cognitive Function and Dementia Among Older Adults: The Role of Inflammation

Background: The association of anemia with cognitive function and dementia remains unclear.

Objective: We aimed to investigate the association of anemia with cognitive function and dementia risk and to explore the role of inflammation in these associations.

Methods: Within the UK Biobank, 207,203 dementia-free participants aged 60+ were followed for up to 16 years. Hemoglobin (HGB) and C-creative protein (CRP) were measured from blood samples taken at baseline. Anemia was defined as HGB <13 g/dL for males and <12 g/dL for females. Inflammation was categorized as low or high according to the median CRP level (1.50 mg/L). A subset of 18,211 participants underwent cognitive assessments (including global and domain-specific cognitive). Data were analyzed using linear mixed-effects model, Cox regression, and Laplace regression.

Results: Anemia was associated with faster declines in global cognition (β= -0.08, 95% confidence interval [CI]: -0.14, -0.01) and processing speed (β= -0.10, 95% CI: -0.19, -0.01). During the follow-up of 9.76 years (interquartile range 7.55 to 11.39), 6,272 developed dementia. The hazard ratio of dementia was 1.57 (95% CI: 1.38, 1.78) for people with anemia, and anemia accelerated dementia onset by 1.53 (95% CI: 1.08, 1.97) years. The risk of dementia tended to be higher in people with both anemia and high CRP (1.89, 95% CI: 1.60, 2.22). There was a statistically significant interaction between anemia and CRP on dementia risk (p-interaction = 0.032).

Conclusions: Anemia is associated with cognitive decline (specifically for processing speed) and increased risk of dementia, especially in people with high inflammation.