Millions of people worldwide living with dementia may have developed the condition partly through a process driven by the immune system, according to a major new research review. The study, published in the Journal of Psychiatric Research, analysed inflammatory markers in people diagnosed with four types of dementia and found that each appeared to trigger its own distinct pattern of immune activity, independent of other illnesses known to cause inflammation.
The research examined Alzheimer’s disease, vascular dementia, dementia with Lewy bodies, and fronto-temporal dementia. Researchers at Adelaide University reviewed 41 eligible studies drawn from nearly 80,000 references, covering almost 4,000 participants in total. What made this review different from earlier work was its deliberate exclusion of people with conditions such as arthritis, diabetes, and depression, which are themselves associated with raised inflammation, making it harder to isolate whether the immune response was being driven by the dementia itself.
Alzheimer’s disease had the most robust findings. People with Alzheimer’s showed higher levels of several inflammatory markers, including IL17A, IL1alpha, IL10, and G-CSF, compared to healthy controls. These markers are linked to immune activity that can disrupt the blood-brain barrier, potentially allowing immune cells to enter the brain and contribute to the neurodegeneration associated with dementia.
The findings also offered tentative support for what researchers call the inflammatory-mediated neurodegeneration hypothesis. This theory proposes that mental illnesses such as depression, anxiety, and PTSD may trigger a chronic inflammatory response that, over time, damages the brain in ways that lead to dementia. Of particular interest was the finding that IL17A, elevated in Alzheimer’s patients, has also been found at higher levels in people with depression in a related earlier study by the same team.
Vascular dementia, dementia with Lewy bodies, and fronto-temporal dementia each showed different inflammatory patterns, suggesting these conditions involve separate immune pathways rather than a shared one. But findings for these three types were based on very few studies and small participant numbers, and the authors were clear that replication is needed before firm conclusions can be drawn.
A key strength of the review was its broader scope. Rather than focusing only on cytokines, which are signalling proteins, it included immune cells such as lymphocytes and monocytes as well as the molecules they produce. This gave a more complete picture of the inflammatory environment associated with each dementia subtype. Most of the 82 markers examined were only studied in the context of one type of dementia, highlighting how much research remains to be done.
The authors noted that most existing studies relied on blood samples rather than cerebrospinal fluid or brain imaging. Blood may not always accurately reflect what is happening inside the brain, and future research using central nervous system measures would help clarify whether the inflammation observed is truly neuroinflammatory or reflects a wider systemic response.
Whether inflammation is a cause or a consequence of dementia remains unanswered, and the team called for prospective longitudinal research tracking people with mental illness over time. If confirmed, early treatment of conditions like depression could one day reduce dementia risk.