Clinical Accuracy of Serum Neurofilament Light to Differentiate Frontotemporal Dementia from Primary Psychiatric Disorders is Age-Dependent.

BACKGROUND: Symptoms of behavioral variant frontotemporal dementia (bvFTD) overlap with primary psychiatric disorders (PPD) making diagnosis challenging. Serum neurofilament light (sNfL) is a candidate biomarker to distinguish bvFTD from PPD, but large-scale studies in PPD are lacking. OBJECTIVE: Determine factors that influence sNfL from a large database of PPD patients, and test its diagnostic accuracy. DESIGN, SETTINGS, SUBJECTS, MEASUREMENTS: Clinical data of people aged 40-81 were obtained from healthy subjects (n = 69), and patients with PPD (n = 848) or bvFTD (n = 82). sNfL was measured using Simoa technology on an HD-X instrument. Data were analyzed using general linear models, and Receiver Operating Characteristic (ROC) curve analyses to determine global and age-specific sNfL cutoffs to distinguish bvFTD from PPD, using the Youden Index. RESULTS: sNfL increased with age, while sex, BMI and diabetes status were modestly associated with sNfL. sNfL was slightly higher in PPD than healthy subjects (14.1 versus 11.7 pg/mL), when controlling for covariates. sNfL was markedly lower in PPD than bvFTD (14.1 versus 44.1 pg/mL). sNfL could differentiate PPD from bvFTD with an AUC = 0.868, but the effect was driven by the younger subjects between age 40-60 years at a cutoff of 16.0 pg/mL. No valid cutoff was detected over age 60, however, values of sNfL above 38.5 pg/mL, or below 13.9 pg/mL, provided 90% diagnostic certainty of bvFTD or PPD, respectively. CONCLUSION: PPD have mildly elevated sNfL compared to healthy subjects but much lower than bvFTD. Results support the use of sNfL as a biomarker to differentiate PPD from bvFTD at age 60 or below, but accuracy decreases in older ages.

Cortical function in Alzheimer's disease and frontotemporal dementia.

OBJECTIVES: Alzheimer's disease (AD) and the behavioral variant of frontotemporal dementia (bvFTD) are the most common causes of dementia; however, their overlapping clinical syndromes and involved brain regions make a differential diagnosis difficult. We aimed to identify the differences in the cognition and motor cortex excitability between AD and bvFTD patients. METHODS: Twenty-seven AD patients and 30 bvFTD patients were included in the study. Each participant received a neurological evaluation. Cognitive event-related potentials (P300) were recorded during an auditory oddball task. Next, the excitability of the motor cortex, including the resting, facilitated motor threshold (RMT and FMT) and cortical silent period (CSP), were assessed during transcranial magnetic stimulation (TMS). RESULTS: The bvFTD patients exhibited significantly longer P300 latencies compared with AD patients. There was a significant negative correlation between cognition and P300 latency in the bvFTD group. The AD patients showed significantly reduced RMT and FMT values compared to the bvFTD group; however, no significant correlation was found between AD severity and the excitability of the motor cortex. CONCLUSIONS: Cognition and motor cortical functions are different between AD and bvFTD patients. Noninvasive electrophysiological examinations have the potential to identify unique pathophysiological features that can be used to differentially diagnose AD and bvFTD patients.