Older adults with anemia have significantly higher levels of blood biomarkers for Alzheimer’s disease and a significantly increased risk for the disease itself, particularly when anemia is combined with the presence of the biomarkers, Swedish study data show.
The findings “suggest that anemia may interact with neuropathologic processes, potentially accelerating dementia development,” write Martina Valletta, MD, from Karolinska Institutet and Stockholm University in Sweden, and co-authors in JAMA Network Open.
Their analysis included data for 2282 dementia-free participants (median age, 72 years, 62% women) of the population-based Swedish National Study on Aging and Care in Kungsholmen. Of these, 8.7% had anemia at baseline.
The researchers report that participants with anemia had significantly higher baseline levels of the Alzheimer’s disease blood biomarkers phosphorylated tau 217 (p-tau217; 0.2 vs 0.1 pg/mL), neurofilament light chain (NfL; 36.6 vs 17.0 pg/mL), and glial fibrillary acidic protein (GFAP; 187.8 vs 117.4 pg/mL) relative to individuals with normal hemoglobin levels.
During a mean follow-up of 9.3 years, 362 (15.9%) participants developed dementia, with the incidence significantly higher among those with versus without anemia, at 4.4 and 1.7 cases per 100 person–years, respectively.
After adjustment for multiple potential confounding factors, like age, sex, education level, chronic kidney disease, heart disease, cerebrovascular disease, cancer, weight, iron and vitamin supplementation, and interleukin-6 level, the difference between the two groups corresponded to a significant 1.7-fold higher risk for developing dementia during follow-up among the participants with anemia relative to those with normal hemoglobin levels.
Valletta and colleagues note that the relationship between baseline hemoglobin levels and incident dementia was nonlinear. Specifically, below hemoglobin levels of approximately 14 g/dL dementia risk was inversely associated with hemoglobin level. Above this cutoff, the association plateaued.
In addition, the team found that co-occurrence of low hemoglobin and elevated Alzheimer’s disease blood biomarkers further amplified dementia risk.
For example, compared with participants without anemia and with low NfL, the risk for dementia was a non-significant 1.1-fold higher among those with anemia only, a significant 2.2-fold higher among those with high NfL only, and a significant 3.6-fold higher among participants with both anemia and high NfL.
Elevated dementia risk also occurred when anemia was combined with high p-tau217 or GFAP levels, but no additive interaction was detected for these biomarkers.
In general, the risk associations were stronger in men than women and among participants not carrying APOE ε4 compared with carriers.
The researchers say there are several potential interpretations for their findings, including the possibility that “anemia may reduce brain resilience, thereby lowering the threshold at which neuropathology manifests clinically as dementia.”
They conclude that the study data “suggest anemia is a clinically relevant factor in the context of dementia risk stratification and is possibly a modifiable target in dementia prevention strategies.”
“Future studies should further investigate this possibility and formally assess whether—and which—blood biomarkers mediate the relationship between anemia and dementia development.”
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