Mattia Losa , Sara Garbarino , Alessio Cirone , Lucia Argenti , Lorenzo Lombardo , Francesco Calizzano , Nicola Girtler , Andrea Brugnolo , Pietro Mattioli , Matteo Bauckneht , Stefano Raffa , Gianmario Sambuceti , Antonio Canosa , Stefano Caneva , Michele Piana , Giulia Bozzo , Luca Roccatagliata , Gianluca Serafini , Antonio Uccelli , Fabio Gotta , Matteo Pardini
{"title":"Clinical and metabolic profiles in behavioural frontotemporal dementia: Impact of age at onset","authors":"Mattia Losa , Sara Garbarino , Alessio Cirone , Lucia Argenti , Lorenzo Lombardo , Francesco Calizzano , Nicola Girtler , Andrea Brugnolo , Pietro Mattioli , Matteo Bauckneht , Stefano Raffa , Gianmario Sambuceti , Antonio Canosa , Stefano Caneva , Michele Piana , Giulia Bozzo , Luca Roccatagliata , Gianluca Serafini , Antonio Uccelli , Fabio Gotta , Matteo Pardini","doi":"10.1016/j.cortex.2025.01.011","DOIUrl":null,"url":null,"abstract":"<div><h3>Aim</h3><div>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.</div></div><div><h3>Materials and methods</h3><div>We retrospectively studied consecutive patients diagnosed with prodromal or overt bvFTD with [<sup>18</sup>F]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 [<sup>18</sup>F]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.</div></div><div><h3>Results</h3><div>101 bvFTD (62 prodromal bvFTD) were enrolled (EO-bvFTD: <em>n</em> = 36, prodromal <em>n</em> = 21; LO-bvFTD: <em>n</em> = 36, prodromal: <em>n</em> = 22; vLO-bvFTD: <em>n</em> = 29, prodromal: <em>n</em> = 19). Greater verbal memory deficit was evident in LO-bvFTD and vLO-bvFTD compared to EO-bvFTD (immediate recall: <em>p</em> = .018; <em>p</em> = .024; delayed recall: both <em>p</em> = .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.</div></div><div><h3>Discussion</h3><div>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.</div></div>","PeriodicalId":10758,"journal":{"name":"Cortex","volume":"185 ","pages":"Pages 84-95"},"PeriodicalIF":3.2000,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cortex","FirstCategoryId":"102","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0010945225000280","RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BEHAVIORAL SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
CORTEX is an international journal devoted to the study of cognition and of the relationship between the nervous system and mental processes, particularly as these are reflected in the behaviour of patients with acquired brain lesions, normal volunteers, children with typical and atypical development, and in the activation of brain regions and systems as recorded by functional neuroimaging techniques. It was founded in 1964 by Ennio De Renzi.