An international study led by researchers at Karolinska Institutet in Sweden demonstrates that it is possible to detect subtle changes in the brain and identify early signs of hereditary frontotemporal dementia using advanced brain imaging techniques. The study has recently been published in Molecular Psychiatry.

Frontotemporal dementia, or FTD, is a neurodegenerative disease that often affects people in middle age and is a common cause of dementia before the age of 65. The disease is particularly difficult to diagnose in its early stages, as the earliest symptoms are behavioural changes and may resemble primary psychiatric disease and symptoms later on can resemble conditions such as Alzheimer’s disease and Parkinson’s disease. In about a third of cases, frontotemporal dementia is hereditary, making families with known mutations an important resource for research.

New type of MRI technique

In the current study, researchers from Karolinska Institutet, together with an international research network, examined the brain’s microstructure in over 700 individuals – both carriers of FTD mutations and control subjects. The researchers used a new type of MRI technique that measures how water molecules spread within the grey matter of the brain, where greater diffusion indicates microstructural damage to brain tissue. In this way, the technique can reveal early damage in the cerebral cortex before the brain begins to shrink, known as brain atrophy, or cognitive problems arise.

The results revealed that the new method is more sensitive than the established imaging technique that measures the thickness of the cerebral cortex. Among individuals with a mutation in the C9orf72 gene, the researchers could detect changes in the brain even before any clinical symptoms appeared. For mutations in the MAPT gene, changes were observed at mild symptom stages, whereas for carriers of GRN mutations, alterations emerged only at more advanced stages.

Identifying individuals at risk

“Our findings show that changes in the brain’s microstructure can be detected before visible brain atrophy, and these changes are closely linked to how the disease develops,” explains corresponding author Elena Rodriguez-Vieitez, researcher at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet. “This could be valuable for identifying individuals at risk and for evaluating new therapies in clinical trials.”

The researchers also followed the participants over time and showed that a greater spread of water molecules in brain tissue at the start of the study was linked to a faster decline in behaviour and cognitive ability. This was true for all three mutation types.

“Our results suggest that measurements of the brain’s microstructure could become an important tool for identifying individuals at risk of frontotemporal dementia and for monitoring disease progression in clinical trials,” says Caroline Graff, professor at the same department and last author of the study.

The study is part of the international research collaboration GENFI (GENetic Frontotemporal dementia Initiative) and has been funded by, among others, the Swedish Research Council, Schörling Foundation, Alzheimerfonden, Hjärnfonden, Demensfonden, Neuroförbundet and Region Stockholm. The researchers report no conflicts of interest.