Quantitative validation of a visual rating scale for frontal atrophy: associations with clinical status, APOE e4, CSF biomarkers and cognition.

Objectives: To validate a visual rating scale of frontal atrophy with quantitative imaging and study its association with clinical status, APOE ε4, CSF biomarkers, and cognition.

Methods: The AddNeuroMed and ADNI cohorts were combined giving a total of 329 healthy controls, 421 mild cognitive impairment patients, and 286 Alzheimer's disease (AD) patients. Thirty-four patients with frontotemporal dementia (FTD) were also included. Frontal atrophy was assessed with the frontal sub-scale of the global cortical atrophy scale (GCA-F) on T1-weighted images. Automated imaging markers of cortical volume, thickness, and surface area were evaluated. Manual tracing was also performed.

Results: The GCA-F scale reliably reflects frontal atrophy, with orbitofrontal, dorsolateral, and motor cortices being the regions contributing most to the GCA-F ratings. GCA-F primarily reflects reductions in cortical volume and thickness, although it was able to detect reductions in surface area too. The scale showed significant associations with clinical status and cognition.

Conclusion: The GCA-F scale may have implications for clinical practice as supportive diagnostic tool for disorders demonstrating predominant frontal atrophy such as FTD and the executive presentation of AD. We believe that GCA-F is feasible for use in clinical routine for the radiological assessment of dementia and other disorders.

Key Points: • The GCA-F visual rating scale reliably reflects frontal brain atrophy. • Orbitofrontal, dorsolateral, and motor cortices are the most contributing regions. • GCA-F shows significant associations with clinical status and cognition. • GCA-F may be supportive diagnostic tool for disorders demonstrating predominant frontal atrophy. • GCA-F may be feasible for use in radiological routine.