By: Grace Huff
A new paper led by Dimitry S. Davydow, MD, MPH, FACLP Vice Chair for Clinical Operations and Clinical Professor in the University of Florida Department of Psychiatry and Behavioral Sciences, sheds light on one of the biggest challenges in brain health: telling apart early dementia from psychiatric disorders. The study was published in JAMA Psychiatry.
Behavioral variant frontotemporal dementia (bvFTD) is one of the most common form of early-onset dementia, potentially appearing in people under 65. Its symptoms, changes in personality, mood, motivation, or behavior, frequently overlap with psychiatric disorders like depression or obsessive-compulsive disorder. Because of this, nearly half of patients are initially misdiagnosed, with some waiting more than six years before receiving the correct diagnosis.
Davydow and his team, which included collaborators from Johns Hopkins, UCSF, and the Norman Fixel Institute for Neurological Diseases at UF Health, conducted a systematic review of 12 studies involving nearly 2,300 patients. Their analysis found that neurofilament light chain (NfL), a protein measurable in cerebrospinal fluid (CSF) and blood, was consistently higher in patients with bvFTD compared to those with psychiatric disorders.
The findings are promising:
- CSF NfL levels showed promise in distinguishing bvFTD from psychiatric conditions, with sensitivities ranging from 63–96% and specificities from 81–100%.
- Blood NfL levels also performed reasonably well, with sensitivities of 65–100% and specificities of 69–96%.
- These results suggest that blood-based NfL tests, which are increasingly available in clinics, may become valuable aids to clinical evaluation to speed up diagnosis and reduce misdiagnosis.
“Too many patients with frontotemporal dementia and their families can face years of uncertainty when dementia symptoms are mistaken for psychiatric illnesses,” said Davydow. “Our review shows that neurofilament light chain is a promising biomarker that could help bring clarity to patients and their families sooner, but more real-world studies are needed before it can be fully integrated into clinical practice.”
The study also points to the next steps needed in this area: larger, real-world studies using standardized testing methods, age-adjusted diagnostic cutoffs, and correlation with brain pathology confirmed at autopsy. Together, these advances could transform how clinicians differentiate between neurodegenerative and psychiatric disorders, bringing clarity and support to patients during some of the most uncertain moments of their lives.