Alzheimer’s Research & Therapy | January 12, 2024

Benussi A, Premi E, Grassi M, Alberici A, Cantoni V, Gazzina S, Archetti S, Gasparotti R, Fumagalli GG, Bouzigues A, Russell LL, Samra K, Cash DM, Bocchetta M, Todd EG, Convery RS, Swift I, Sogorb-Esteve A, Heller C, van Swieten JC, Jiskoot LC, Seelaar H, Sanchez-Valle R, Moreno F, Laforce RJ, Graff C, Synofzik M, Galimberti D, Rowe JB, Masellis M, Tartaglia MC, Finger E, Vandenberghe R, Mendonça A, Tiraboschi P, Butler CR, Santana I, Gerhard A, Le Ber I, Pasquier F, Ducharme S, Levin J, Sorbi S, Otto M, Padovani A, Rohrer JD, Borroni B; Genetic Frontotemporal dementia Initiative (GENFI).

Alzheimers Res Ther. 2024

https://doi.org/10.1186/s13195-024-01383-1

Abstract

Background

The Genetic Frontotemporal Initiative Staging Group has proposed clinical criteria for the diagnosis of prodromal frontotemporal dementia (FTD), termed mild cognitive and/or behavioral and/or motor impairment (MCBMI). The objective of the study was to validate the proposed research criteria for MCBMI-FTD in a cohort of genetically confirmed FTD cases against healthy controls.

Methods

A total of 398 participants were enrolled, 117 of whom were carriers of an FTD pathogenic variant with mild clinical symptoms, while 281 were non-carrier family members (healthy controls (HC)). A subgroup of patients underwent blood neurofilament light (NfL) levels and anterior cingulate atrophy assessment.

Results

The core clinical criteria correctly classified MCBMI vs HC with an AUC of 0.79 (p < 0.001), while the addition of either blood NfL or anterior cingulate atrophy significantly increased the AUC to 0.84 and 0.82, respectively (p < 0.001). The addition of both markers further increased the AUC to 0.90 (p < 0.001).

Conclusions

The proposed MCBMI criteria showed very good classification accuracy for identifying the prodromal stage of FTD.