New longitudinal data suggest anaemia is not just a comorbidity in older adults but may amplify underlying neurodegenerative processes.
Anaemia in later life may be doing more than signalling frailty but could also be interacting with core Alzheimer disease pathways and accelerating progression to dementia.
That’s the finding of a large population-based cohort study tracking more than 2200 older adults over almost a decade. The full report has been published in JAMA Network Open.
“Overall, our findings expand previous knowledge of the anaemia-dementia association by suggesting an interplay between anaemia and neuropathology – as measured by blood biomarkers – in dementia development,” the researchers wrote.
Researchers analysing data from the Swedish National Study on Ageing and Care in Kungsholmen reported that anaemia was associated with significantly higher levels of blood biomarkers reflecting Alzheimer pathology, neurodegeneration and glial activation, alongside a 66% increased risk of incident dementia.
The risk escalated markedly when low haemoglobin coexisted with elevated biomarkers, pointing to a potential biological interplay that may lower the brain’s resilience to neuropathology.
The study followed dementia-free adults aged 60 years and older for a mean of 9.3 years.
At baseline, individuals with anaemia showed higher circulating concentrations of phosphorylated tau 217 (p-tau217), neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP), with the strongest elevations seen in NfL and p-tau217.
These markers have been increasingly recognised as sensitive indicators of early Alzheimer-related changes and neuroaxonal injury, detectable years before clinical diagnosis.
Over follow-up, 15.9% of participants developed dementia, the researchers reported. Incidence rates were notably higher in those with anaemia, and multivariable analyses confirmed a robust association even after adjustment for comorbidities, inflammation, nutritional factors and supplement use.
A nonlinear relationship emerged, with dementia risk rising as haemoglobin declined up to around 14 g/dL before plateauing.
The researchers said the most striking finding for clinicians may be the combined effect of anaemia and biomarker elevation.
Participants with both anaemia and high NfL levels had more than a threefold increase in dementia risk compared with those with normal haemoglobin and low biomarker levels. Similar patterns were observed for p-tau217 and GFAP, although the additive interaction was most pronounced with NfL.
These findings lend weight to the hypothesis that chronic cerebral hypoxia and related oxidative stress in anaemia may exacerbate neuronal vulnerability.
Alternatively, elevated biomarkers may represent downstream mediators linking low haemoglobin to neurodegeneration. Either pathway suggests that anaemia is not merely a bystander but could be modifying the trajectory from subclinical pathology to overt cognitive decline.
Sex differences were observed, with stronger associations between anaemia, biomarkers and dementia risk in males, though interaction effects were not consistently significant.
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The reasons remained unclear but may relate to differing aetiologies and physiological tolerance of low haemoglobin across sexes, the researchers wrote.
“While females tend to have lower haemoglobin levels and higher anaemia prevalence early in life, often due to reproductive factors, anaemia in males is less common, occurs later, and is frequently driven by chronic diseases, inflammation, or nutritional deficiencies,” they wrote.
“Females’ generally lower baseline haemoglobin levels might confer greater tolerance to anaemia, buffering its impact on brain health.
“This study’s findings should be interpreted cautiously, as sex interactions were not always significant and prior studies have not directly examined sex-specific associations between haemoglobin, AD biomarkers, and dementia risk.”
The implications were twofold for clinicians, they said. Haemoglobin may have added value in dementia risk stratification when interpreted alongside emerging blood-based biomarkers; and anaemia could represent a modifiable target in prevention strategies, particularly if future research confirms causal pathways.
The researchers cautioned that most anaemia cases in the cohort were normocytic and that biomarker data were only available at baseline, limiting insights into temporal dynamics.
However, they said their study provided some of the strongest evidence to date linking haematological status with molecular markers of Alzheimer disease and long-term cognitive outcomes.
