Research using brain imaging has found changes in the brain can be identified in people with frontotemporal dementia (FTD) 5-10 years before symptoms appear.  

In the study, published in The Lancet Neurology, researchers from UCL Institute of Neurology analysed data from 220 participants to identify whether neuroimaging and cognitive changes before symptom onset could be shown in FTD, as reflected in findings from studies of other genetic dementias.

The study was led by Dr Rohrer and Professor Rossor, as part of a consortium of research centres across Europe and Canada with expertise in familial FTD called the Genetic Frontotemporal dementia Initiative (GENFI).

By looking at all genetic subtypes together you see brain imaging changes first, somewhere around 10-15 years before predicted symptom onset, and then cognitive changes around five years before symptom onset. Dr Rohrer, Department of Neurodegenerative Diseases, UCL Institute of Neurology

FTD is highly heritable and the second most common form of young-onset dementia after Alzheimer’s disease. The disease is caused when nerve cells in the frontal and/or temporal lobes of the brain are affected by abnormal changes and eventually die. In about a third of patients the disease is caused by genetic mutations usually in one of three genes: GRN, MAPT or C9orf72.In the study participants were made up of 118 mutation carriers and 102 non-carriers (those at risk of carrying a mutation because a first-degree relative was a known symptomatic carrier).

The researchers calculated time to expected onset as the difference between age at assessment and mean age at onset within the family. Participants underwent a range of tests including standardised clinical assessments, MRI scans and neuropsychological battery. The researchers used linear mixed-effects models to examine whether the association of neuropsychology and imaging measures with time to expected onset of symptoms differed between mutation carriers and non-carriers.

The team found that examining changes in brain imaging could help define biomarkers that can track disease progression which is important for future therapeutic trials.

Looking at the individual genetic subgroups the researchers found different parts of the brain become affected first in each of the groups.

Although we call this disease FTD, it’s become clear in recent years that there are actually other parts of the brain that are important apart from the frontal and temporal lobes, such as the insula and cingulate. Interestingly, in the C9orf72 group we found the earliest change seemed to happen at least 25 years before predicted symptom onset, one hypothesis being that perhaps these could be developmental differences rather than degenerative changes. Dr Rohrer

There are now promising avenues for treatment of FTD however it is still not known when drugs should be started or how response to treatment should be measured. It is anticipated that eventually these markers will be utilised in future clinical trials of drugs in genetic FTD.

The value of studying gene carriers in familial disease has been established in Huntington’s disease and the rare cases of familial Alzheimer’s disease. The findings in FTD again show a long period of disease activity before symptoms start and a potential window of therapeutic opportunity. Professor Martin Rossor, Director of the NIHR Queen Square Dementia Biomedical Research Unit
GENFI investigates both people who have developed symptoms and also people who have a risk of developing symptoms in the future because they carry an abnormal genetic mutation. By studying these individuals who are destined to develop the disease later in life we can understand the development from the very earliest changes. The key objectives of GENFI are to develop markers which help identify the disease at its earliest stage as well as markers that allow the progression of the disease to be tracked Dr Rohrer

Further information