- Anemia is a common blood condition characterized by a lack of healthy red blood cells in the body.
- A recent study examined how anemia may relate to dementia risk.
- The study results indicated that having anemia was associated with greater levels of blood biomarkers for Alzheimer’s disease and with an increased risk for dementia over time.
Anemia occurs when there is a low level of healthy red blood cells, and it has been linked to a number of chronic illnesses such as kidney failure, autoimmune diseases (rheumatoid arthritis and lupus), and inflammatory bowel disease like Crohn’s. Recently, scientists wanted to see if anemia had a link to dementia.
In a study published in JAMA Network Open, researchers examined data from over 2,200 adults and found that those with anemia had more biomarkers for Alzheimer’s disease.
In the long term, they observed that having anemia was associated with a higher risk of developing dementia. The participants who had the highest risk for dementia were those who had both anemia and higher levels of Alzheimer’s disease biomarkers.
To conduct this study, researchers used information from participants who were part of the Swedish National Study on Aging and Care in Kungsholmen. Participants were all at least sixty years old and did not have dementia at baseline. In all, researchers analyzed data from 2,282 participants.
To do this, they looked at blood hemoglobin levels and saw if they were below a certain level. Hemoglobin is a protein in red blood cells that helps supply the body with oxygen. They also had data on diagnoses of dementia and mild cognitive impairment and information on several covariates.
Among participants, 8.7% had baseline anemia. Participants with anemia were more likely to be male, have more chronic diseases, have a lower education level, and be older. Participants with anemia had higher levels of Alzheimer’s disease biomarkers. Two particular biomarkers were more elevated in men than in women.
There were 16 years of follow-up, and the average follow-up time was 9.3 years. Throughout the follow-up, 15.9% of participants developed dementia.
Overall, researchers found that anemia was associated with a higher risk of developing dementia. Participants with anemia had a 66% higher chance of developing dementia than participants who had normal hemoglobin levels.
They found that a higher risk for dementia remained true even after excluding participants who had mild cognitive impairment and who were diagnosed with dementia within six years of follow-up.
However, they found that anemia was not associated with higher dementia risk among participants who were carriers of APOE ε4, a gene that increases risk for Alzheimer’s disease.
The researchers also found the relationship between hemoglobin and higher dementia risk plateaued when hemoglobin levels reached a certain level, slightly above the definitions for anemia. When looking at sex, they found this nonlinear association was significant for men but not for women.
Finally, researchers found that the risk for dementia increased as levels of Alzheimer’s disease biomarkers increased and hemoglobin levels decreased. In contrast, participants who had low levels of the biomarkers and normal hemoglobin had the lowest risk for dementia.
One particular biomarker stood out: NfL. When combined with anemia, having an elevated level of this biomarker showed a risk for dementia that indicated an additive interaction. APOE-ε4 status also appeared to affect some results.
The researchers also found that anemia appeared to increase risk for dementia and be linked to higher Alzheimer’s disease blood biomarkers more in men than in women, though researchers encourage caution with sex-specific findings.
Courtney Kloske, PhD, Director, Scientific Engagement for the Alzheimer’s Association, who was not involved in the study, noted the following about the study’s findings:
“While previous research has linked anemia to an increased risk of dementia, this study adds new insight by examining that relationship with Alzheimer ’s-related blood biomarkers.”
“The research team found that people in the study with anemia, higher levels of pTau217, and a marker of brain cell death called neurofilament light chain (NfL) had an elevated dementia risk. The results also showed that study participants who did not have anemia and had lower levels of an Alzheimer ’s-related blood biomarker had the lowest dementia risk.”
— Courtney Kloske, PhD
This research provides valuable information, but also has a number of limitations. There is a risk for errors, such as in dementia diagnoses or in information that was self-reported by participants.
The hemoglobin levels of participants fell within a particular range, and over 90% of participants who had anemia still had normal-sized red blood cells. Thus, they had a limited ability to explore more extreme anemia cases or those with abnormally sized red blood cells. Researchers further note that they looked at Alzheimer’s disease biomarkers in the serum instead of in the plasma, and the biomarkers’ concentration tends to be lower in serum.
They also struggled with participants having missing data on hemoglobin levels and biomarkers, and these participants tended to have more comorbidities and be older than the participants they were able to include who had complete data. The authors note that these excluded participants were likely to be at a higher risk for dementia and anemia, and “their exclusion may have led to an underestimation of the associations.”
There was also only baseline data on blood biomarkers, so researchers couldn’t explore how hemoglobin related to the Alzheimer’s disease biomarkers in the long term.
Researchers were also limited because of the cohort they chose to use: individuals from a specific area of Sweden who were already enrolled in a long-term study. Most participants were also white. There should be caution when it comes to generalizing the results to other groups. Findings were also different between men and women, which is also an area that future research may be able to explore. Three of the study authors disclosed conflicts of interest.
Finally, it’s important to note that this research doesn’t establish a causal relationship.
Dung Trinh, MD, internist, of MemorialCare Medical Group and Chief Medical Officer of Healthy Brain Clinic in Irvine, CA, who was also not involved in the study, noted that “anemia may not just be a background health issue in older adults, but part of the biologic context that makes the brain more vulnerable to neurodegenerative disease. At the same time, this is an observational study, so it shows a strong association, not proof that anemia causes Alzheimer’s disease or dementia.”
The research suggests that addressing anemia could potentially help with dementia prevention. Martina Valletta, MD, PhD candidate at Karolinska Institutet, and first author of the study, explained the following to MNT:
“Our findings suggest that anemia is a relevant risk factor for dementia. Because anemia is relatively easy to detect with routine blood tests and, in many cases, treatable, it could represent a potentially modifiable target in dementia prevention strategies.”
“However, our study is observational, so we cannot conclude that treating anemia will directly prevent dementia. This remains an open question for future research,” Valletta said.
More broadly, it suggests the importance of evaluating anemia and not ignoring it.
“The main clinical implication is that anemia may deserve more attention in cognitive assessment, especially in older adults presenting with memory concerns. This study suggests low hemoglobin could be a meaningful risk marker that helps identify patients who may need closer monitoring or more complete evaluation.,” Trinh noted.
“It also raises the possibility that anemia could influence how clinicians interpret Alzheimer’s blood-based biomarkers in practice,” he added.
Why anemia alone is not a sign of dementia
“However, the findings do not mean that anemia is diagnostic of Alzheimer’s disease, nor do they prove that treating anemia will prevent dementia. For now, the practical takeaway is that anemia should not be dismissed as incidental in patients at risk for cognitive decline; it may be a clinically relevant signal that adds to the overall picture.”
— Dung Trinh, MD
