Brain inflammation linked to uncommon type of ‘early-onset’ dementia

“Inflammation in the brain ‘linked to several forms of dementia'”, reported ITV News.

The headline stems from research into a rare type of dementia called frontotemporal dementia. This type of dementia mostly affects adults who are 45 to 65 years of age and involves the front sections of the brain. It causes symptoms such as behaviour and personality change, rather than the memory loss of Alzheimer’s disease. People with frontotemporal dementia can have variable symptoms and disease findings.

Recent research has shown that in Alzheimer’s disease, areas of inflammation in the brain (neuroinflammation) are positioned around areas of abnormal clumps of proteins (protein clusters) that are typical of the disease. This new research into frontotemporal dementia aimed to see if inflammation may be also linked with the protein build-up or other features seen in the condition.

The researchers used PET brain scans, which produce 3-dimensional images of the brain, to identify areas of inflammation and where proteins were clustered abnormally. They scanned 31 patients with frontotemporal dementia and 31 healthy people for a comparison group.

The results showed that people with frontotemporal dementia had areas of inflammation and protein clusters in specific areas of their brain which are linked to the disease. This was not the case for the people in the control group.

The researchers say that if neuroinflammation is part of the process of developing frontotemporal dementia, future research could look for ways to target inflammation in the hope of finding a treatment.

At present, there is no cure for frontotemporal dementia, although there are treatments to help manage the disease.

The researchers who carried out the study were from the University of Cambridge and The Walton Centre in the UK, and the Istituto di Bioimmagini e Fisiologia Molecolare in Italy. The study was funded by the National Institute of Health Research, Wellcome Trust, Cambridge Centre for Parkinson-plus, Medical Research Council, Association of British Neurologists and the Patrick Berthoud Charitable Trust, and the Lundbeck Foundation. It was published in the peer-reviewed journal Brain and is free to read online.

The reports by The Times and ITV News appear to be accurate and balanced.

This was cross-sectional research where a small group of patients with frontotemporal dementia and healthy controls received brain scans and the findings were compared. This is useful for early-stage research when doctors are trying to better understand what causes disease. However, these one-off assessments cannot provide the whole answer, for example, the initial stages of the disease before people developed symptoms.

Researchers scanned the brains of 31 people with 3 types of frontotemporal dementia.

10 people had symptoms predominantly affecting their behaviour (behavioural variant), 11 mainly had problems understanding language (semantic variant) and 10 had problems with speech (non-fluent variant).

The researchers looked for two things:

• C-PK-11195, a molecule which binds to the brain’s immune cells (microglia) when they are triggered, and is used as a marker for inflammation
• F-AV-1451, a molecule which binds to tau and similar proteins linked to dementia, used as a marker for protein clusters

They also scanned the brains of 14 healthy volunteers in a similar way.

They used computer models to analyse similarities and differences between people with and without frontotemporal dementia, and with different types of the condition. They wanted to see whether areas of inflammation or protein clusters in the brain could predict whether someone had frontotemporal dementia, and which type.

They also examined the brains of 12 people who had died of frontotemporal dementia, to see whether they got the same results.

The researchers found that both the C-PK-11195 marker for inflammation and F-AV-1451 marker for protein clusters, were more common in the front (frontal) and sides (temporal) of the brain in people with frontotemporal dementia than the healthy comparison group.

Among people with frontotemporal dementia, there were also differences by symptom type. For example, people with the semantic variant showed more of the marker for protein clusters in the temporal regions of the brain than those with other types.

The results showed that areas of the brain with the most markers for inflammation also had the most markers for protein clusters. This suggests that inflammation and protein clusters are closely linked.

The results from autopsy brain samples showed that microglia (brain immune cells) were more common in areas with protein clusters, which also suggests a link between inflammation and protein clusters.

The researchers said: “Together, these observations suggest that neuroinflammation and protein aggregation [clustering] co-occur in symptomatic stages.” They added: “A causal role for neuroinflammation in neurodegeneration [damage to brain cells] would inform future drug targets and potential clinical trials in frontotemporal dementia.”

This research adds more to what we know about the disease processes in frontotemporal dementias and the differences seen between types. This may help researchers to investigate drugs or other treatments that could potentially help people with these conditions in future.

However, these one-off brain scans do not show that inflammation in the brain is the cause of frontotemporal dementia. The findings just show that inflammation seems to be present alongside protein clusters in people who have already developed the condition. We don’t have earlier scans to compare with when they were healthy, or follow-up scans to see how the disease may progress. This type of early-stage research is valuable for finding out more about the disease process but does not answer all the questions.

The study is also fairly small, with only a few people in each sub-group of types of frontotemporal dementia. That means it may not be possible to apply these findings to all people with this type of dementia. Future studies may confirm the results in other groups of people with these dementia types.

Much more research will be needed before we will know whether these findings have the potential to help the development of treatments for frontotemporal or any other type of dementia.

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