Haemoglobin levels in routine blood tests linked to long-term dementia risk

A blood test that millions of people already receive during ordinary health check-ups may offer an early glimpse of their risk of developing dementia years or even decades later, according to new research being presented at the 39th ECNP Congress in Munich and published in the Journal of Alzheimer’s Disease. The study, one of the largest of its kind, followed more than three hundred thousand adults for up to fifteen years and found that people whose haemoglobin levels sat at either extreme of the normal distribution were more likely to receive a dementia diagnosis during follow-up than those whose levels fell in the middle ranges. Because haemoglobin is measured routinely in standard blood panels across the world, the finding raises the tantalising possibility that a familiar, inexpensive laboratory value already sitting in medical records could serve as a simple flag for long-term brain health risk.

The research drew on an exceptionally robust data source: the Korean National Health Insurance Service. In 2004 and 2005, 316,542 adults aged 40 and over took part in a national health screening programme during which their haemoglobin concentrations were measured. The researchers then linked these baseline measurements to national health insurance records and tracked whether participants went on to receive a new diagnosis of dementia through to the end of 2019, a follow-up period extending as long as fifteen years. Rather than treating haemoglobin as a continuous variable alone, the team divided the cohort into five equal groups, or quintiles, ranging from the twenty percent of participants with the lowest haemoglobin levels to the twenty percent with the highest. This design allowed them to compare dementia outcomes across the full spectrum of haemoglobin values observed in a general population.

The results revealed a pattern that was striking in its symmetry at the extremes. People in the lowest quintile of haemoglobin had a sixteen percent higher risk of all-cause dementia compared with the group that showed the lowest dementia rate, while those in the highest quintile carried a seven percent higher risk. In other words, both unusually low and unusually high haemoglobin were associated with elevated risk, with the strongest signal coming from the low end of the distribution. The association was not uniform across dementia subtypes, however, and this nuance is one of the study’s most technically interesting features. For Alzheimer’s disease, the increased risk was concentrated almost entirely among participants with the lowest haemoglobin levels, who showed a fourteen percent higher risk than the reference group.

Vascular dementia, the form of the disease caused by reduced blood flow to the brain, told a different and more complicated story. Participants in the lowest haemoglobin quintile had a nineteen percent higher risk of vascular dementia, while those in the highest quintile had an eighteen percent greater risk. Yet the relationship across all five haemoglobin groups did not follow a simple linear or dose-response pattern, suggesting that whatever mechanisms connect high haemoglobin to vascular dementia may operate differently from those connecting low haemoglobin to the disease. The researchers also observed that the association was clearer and more consistent in women than in men, a sex difference that may reflect biological factors such as iron stores, menstrual blood loss, hormonal influences on erythropoiesis, or differences in baseline haemoglobin distributions between the sexes, though the study design cannot pin down the precise explanation.

Understanding why haemoglobin might matter for the brain requires a brief return to basic physiology. Haemoglobin is the iron-containing protein packed inside red blood cells, and its job is to bind oxygen in the lungs and release it to tissues throughout the body, including the brain. The brain is extraordinarily metabolically demanding, consuming roughly a fifth of the body’s oxygen supply, so any sustained compromise in oxygen-carrying capacity is a plausible threat to neural health. Low haemoglobin is the laboratory hallmark of anaemia, a condition with many possible causes including iron deficiency, chronic disease, kidney dysfunction and nutritional gaps. Chronically reduced oxygen delivery to brain tissue has been implicated in white matter damage, cognitive decline and cerebrovascular injury in previous research, providing a biologically coherent pathway linking anaemia to dementia risk.

High haemoglobin, by contrast, is often a marker of very different processes. Elevated levels can reflect cigarette smoking, dehydration that concentrates the blood, chronic lung or heart disease that triggers compensatory red cell production, or other underlying medical conditions. Some of these factors, particularly smoking and cardiopulmonary disease, are themselves well-established contributors to cerebrovascular damage and dementia. This is why the study’s lead author, Dr Hyun Soo Kim, assistant professor at Dong-A University College of Medicine in Busan, South Korea, is careful to frame haemoglobin as a signal rather than a cause. The findings, he explained, do not show that haemoglobin itself causes dementia, but suggest that abnormal haemoglobin levels may be a visible marker of wider physical vulnerability relevant to brain health.

Dr Kim emphasised the broader context in which the work should be read. Dementia is one of the fastest-growing health challenges in ageing societies, and there are not many treatments and no cure. Identifying simple, accessible markers of future risk could help researchers and clinicians better understand how whole-body health relates to brain health over time. In a statement accompanying the research, he added that a blood test most people already get at a routine check-up may say something about their brain health many years later, noting that in this large Korean cohort people with unusually low haemoglobin, and to a smaller degree those with unusually high haemoglobin, were more likely to develop dementia. He stressed that this does not prove haemoglobin causes dementia, but supports the idea that general physical health, including the body’s ability to carry oxygen, matters for long-term brain health.

Like all observational research, the study comes with important caveats that the authors themselves are careful to spell out. Observational designs can identify associations but cannot prove causation, and reverse causation is a particular concern in dementia research. Early, undiagnosed neurodegenerative processes may begin silently years before any diagnosis is made, and these processes can affect nutrition, frailty, weight loss and appetite in ways that could produce anaemia or otherwise lower haemoglobin. In such a scenario, low haemoglobin would be a consequence of preclinical disease rather than a contributor to it, inflating the apparent association. Confounding by lifestyle factors, socioeconomic status and coexisting illness is also possible, even in a cohort as large as this one, and the Korean population studied may not generalise fully to other ethnic and demographic groups.

Perhaps the most important practical message from the researchers is what the findings do not mean for individual patients. Dr Kim was explicit on this point: the results should not be interpreted as advice to take iron supplements, to raise haemoglobin levels, or to lower high haemoglobin levels in order to prevent dementia. There is no evidence from this study that manipulating haemoglobin would change anyone’s dementia risk, and indiscriminate iron supplementation carries its own health risks. Instead, he advised that an abnormal haemoglobin result should simply be discussed with a doctor, because it may point to underlying health issues that deserve attention in their own right. The value of the finding lies in awareness and follow-up, not in self-treatment.

Independent experts have responded with measured interest. Dr Lindsey Sinclair of the University of Southampton, who was not involved in the work, noted that there is a growing body of evidence that physical health and brain health are intertwined, and that changes supporting better brain health, whether medical or lifestyle changes, are increasingly recognised as important in mid-life to reduce the risk of later dementia. She observed that while the study shows a possible link between haemoglobin levels and dementia risk, more work is required to understand whether this link is present in people from a wider range of backgrounds, and what can best be done to reduce dementia risk in people with the lowest and highest levels of haemoglobin. Her comments capture the consensus view: haemoglobin is a promising and remarkably accessible candidate marker, but it is a starting point for further research rather than a finished clinical tool. For now, the study adds weight to an increasingly persuasive argument that the health of the brain cannot be separated from the health of the body, and that clues about future cognitive decline may already be sitting, unnoticed, in the routine blood results of ordinary check-ups around the world.

Subject of Research: Association between routine haemoglobin blood test levels and long-term dementia risk

Article Title: Routine blood test may suggest future dementia risk

Article References: Routine blood test may suggest future dementia risk. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: dementia, haemoglobin, blood test, Alzheimer's disease, vascular dementia, anaemia, observational study, ECNP Congress, brain health, Korean cohort, risk markers, ageing