Advanced MRI Detects Early Frontotemporal Dementia

A multinational investigation spearheaded by investigators at Karolinska Institutet shows that subtle neuronal alterations can be identified early in hereditary frontotemporal dementia (FTD) through cutting‑edge magnetic‑resonance imaging. The findings appear in Molecular Psychiatry.

Frontotemporal dementia is a neurodegenerative condition most common before 65 years of age and notoriously difficult to diagnose early. Initial symptoms are often behavioural and can mimic primary psychiatric illness, while later manifestations resemble Alzheimer’s or Parkinson’s disease. Roughly one third of cases carry a known genetic mutation, making mutation carriers a valuable cohort for research.

The research team, in partnership with a global consortium, examined brain microstructure in over 700 participants, including both mutation carriers and control subjects.

They employed a novel diffusion‑weighted MRI technique that gauges how water molecules move within gray‑matter tissue – greater spread reflects microstructural damage before overt cortical thinning or brain atrophy becomes apparent.

Compared to the standard method of measuring cortical thickness, the new approach proved more sensitive. In carriers of the C9orf72 mutation, detectable change occurred before any clinical sign emerged; MAPT mutation carriers showed alterations at mild symptomatic stages, while GRN mutation carriers developed changes only in more advanced phases.

“Our data demonstrate that microstructural alterations can precede visible atrophy and are tightly linked to disease progression,” says corresponding author Elena Rodriguez‑Vieitez, neurobiology researcher at Karolinska Institutet.

“This method could help identify at‑risk individuals and evaluate novel therapies during trials.”

The investigators also performed longitudinal follow‑ups, finding that higher initial diffusion correlated with accelerated decline in behaviour and cognition across all three genetic groups.

“These results suggest that microstructural measurements might become a key tool for risk screening and disease monitoring in future clinical studies,” notes lead author Caroline Graff, professor and senior investigator.