Clinical and metabolic profiles in behavioural frontotemporal dementia: Impact of age at onset

Aim: Frontotemporal dementia (FTD) is a heterogeneous neurodegenerative disorder, with considerable variability of age-at-onset. We explored clinical and metabolic differences between early- and late-onset behavioural FTD (bvFTD), assuming that they might represent different disease phenotypes. Materials and methods: We retrospectively studied consecutive patients diagnosed with prodromal or overt bvFTD with [18F]FDG PET scan, neuropsychological assessment (NPS), and Neuropsychiatric Inventory (NPI) available at baseline. Patients were divided into three groups based on age-at-onset: early onset-bvFTD (EO-bvFTD, age<70), late onset-bvFTD (LO-bvFTD, age 70–75) and very late onset-bvFTD (vLO-bvFTD, age>75). NPS and NPI were compared between groups and in the subset of prodromal patients, to study different syndromic phenotypes. Voxel-based analysis compared brain [18F]FDG PET of EO-bvFTD, LO-bvFTD and vLO-bvFTD independently, with respect to healthy controls, to explore metabolic differences. An inter-regional metabolic covariance analysis was performed in frontal lobe subregions, to explore differences in brain connectivity. Moreover, we supported our result using a correlation-based approach on clinical and metabolic variables. Results: 101 bvFTD (62 prodromal bvFTD) were enrolled (EO-bvFTD: n = 36, prodromal n = 21; LO-bvFTD: n = 36, prodromal: n = 22; vLO-bvFTD: n = 29, prodromal: n = 19). Greater verbal memory deficit was evident in LO-bvFTD and vLO-bvFTD compared to EO-bvFTD (immediate recall: p = .018; p = .024; delayed recall: both p = .001, respectively), with similar results in the subset of prodromal patients. EO-bvFTD and LO-bvFTD had a higher behavioural severity than vLO-bvFTD. LO-bvFTD and vLO-bvFTD showed more widespread relative hypometabolism, with a greater involvement of posterior, subcortical and temporo-limbic regions compared with EO-bvFTD. Moreover, vLO-bvFTD showed a different pattern of intrafrontal metabolic covariance compared to EO-bvFTD and LO-bvFTD. Discussion: The cognitive–behavioural profile of bvFTD differs between early- and late-onset, already from the prodromal stage of the disease. Both metabolic pattern and functional connectivity vary based on age-at-onset. Understanding these differences could contribute to improve diagnostic accuracy and understanding the underling pathological heterogeneity.