Functional Connectivity Changes in Behavioral, Semantic, and Nonfluent Variants of Frontotemporal Dementia.

Frontotemporal dementia (FTD) affects behavior, language, and personality. This study aims to explore functional connectivity changes in three FTD variants: behavioral (bvFTD), semantic (svPPA), and nonfluent variant (nfvPPA). Seventy-six patients diagnosed with FTD by international criteria and thirty-two controls were investigated. Functional connectivity from resting functional magnetic resonance imaging (fMRI) was estimated for the whole brain. Two types of analysis were done: network basic statistic and topological measures by graph theory. Several hubs in the limbic system and basal ganglia were compromised in the behavioral variant apart from frontal networks. Nonfluent variants showed a major disconnection with respect to the behavioral variant in operculum and parietal inferior. The global efficiency had lower coefficients in nonfluent variants than behavioral variants and controls. Our results support an extensive disconnection among frontal, limbic, basal ganglia, and parietal hubs.

GRN and MAPT Mutations in 2 Frontotemporal Dementia Research Centers in Brazil.

BACKGROUND: Mutations in GRN (progranulin) and MAPT (microtubule-associated protein tau) are among the most frequent causes of monogenic frontotemporal dementia (FTD), but data on the frequency of these mutations in regions such as Latin America are still lacking. OBJECTIVE: We aimed to investigate the frequencies of GRN and MAPT mutations in FTD cohorts from 2 Brazilian dementia research centers, the University of Sao Paulo and the Federal University of Minas Gerais medical schools. METHODS: We included 76 probands diagnosed with behavioral-variant FTD (n=55), semantic-variant Primary Progressive Aphasia (PPA) (n=11), or nonfluent-variant PPA (n=10). Twenty-five percent of the cohort had at least 1 relative affected with FTD. RESULTS: Mutations in GRN were identified in 7 probands, and in MAPT, in 2 probands. We identified 3 novel GRN mutations (p.Q130X, p.317Afs*12, and p.K259Afs*23) in patients diagnosed with nonfluent-variant PPA or behavioral-variant FTD. Plasma progranulin levels were measured and a cutoff value of 70 ng/mL was found, with 100% sensitivity and specificity to detect null GRN mutations. CONCLUSIONS: The frequency of GRN mutations was 9.6% and that of MAPT mutations was 7.1%. Among familial cases of FTD, the frequency of GRN mutations was 31.5% and that of MAPT mutations was 10.5%.