Mapping brain morphological and functional conversion patterns in predementia late-onset bvFTD

  • Silvia MorbelliEmail author
  • Michela Ferrara
  • Francesco Fiz
  • Barbara Dessi
  • Dario Arnaldi
  • Agnese Picco
  • Irene Bossert
  • Ambra Buschiazzo
  • Jennifer Accardo
  • Lorena Picori
  • Nicola Girtler
  • Paola Mandich
  • Marco Pagani
  • Gianmario Sambuceti
  • Flavio Nobili
Original Article



The diagnosis of behavioural variant frontotemporal dementia (bvFTD) is challenging during the predementia stage when symptoms are subtle and confounding. Morphological and functional neuroimaging can be particularly helpful during this stage but few data are available.


We retrospectively selected 25 patients with late-onset probable bvFTD. Brain structural MRI and FDG PET were performed during the predementia stage (mean MMSE score 27.1 ± 2.5) on average 2 years before. The findings with the two imaging modalities were compared (SPM8) with those in a group of 20 healthy subjects. The bvFTD patients were divided into two subgroups: those with predominant disinhibition (bvFTD+) and those with apathy (bvFTD−).


Hypometabolism exceeded grey matter (GM) density reduction in terms of both extension and statistical significance in all comparisons. In the whole bvFTD group, hypometabolism involved the bilateral medial, inferior and superior lateral frontal cortex, anterior cingulate, left temporal and right parietal cortices and the caudate nuclei. GM density reduction was limited to the right frontal cortex and the left medial temporal lobe. In bvFTD+ patients hypometabolism was found in the bilateral medial and basal frontal cortex, while GM reduction involved the left anterior cingulate and left inferior frontal cortices, and the right insula. In bvFTD− patients, atrophy and mainly hypometabolism involved the lateral frontal cortex and the inferior parietal lobule.


These findings suggest that hypometabolism is more extensive than, and thus probably precedes, atrophy in predementia late-onset bvFTD, underscoring different topographic involvement in disinhibited and apathetic presentations. If confirmed in a larger series, these results should prompt biomarker operationalization in bvFTD, especially for patient selection in therapeutic clinical trials.


Frontotemporal dementia Brain PET Mild cognitive impairment 


Compliance with ethical standards

Conflicts of interest

This study received no sponsorship. Dr. Morbelli received honoraria to teach amyloid PET reading on behalf of Eli-Lilly & Co. in 2014 – 2015. Dr. Nobili received honoraria to teach amyloid PET reading on behalf of Eli-Lilly & Co. in 2014 – 2015. He received speaker honoraria from G.E. Healthcare in 2015. The other authors have nothing to disclose.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. The study protocol was approved by the local Ethics Committee.

Informed consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Silvia Morbelli
    • 1
    Email author
  • Michela Ferrara
    • 2
  • Francesco Fiz
    • 1
  • Barbara Dessi
    • 2
  • Dario Arnaldi
    • 2
  • Agnese Picco
    • 2
  • Irene Bossert
    • 1
  • Ambra Buschiazzo
    • 1
  • Jennifer Accardo
    • 2
  • Lorena Picori
    • 1
  • Nicola Girtler
    • 2
    • 3
  • Paola Mandich
    • 4
  • Marco Pagani
    • 5
    • 6
  • Gianmario Sambuceti
    • 1
  • Flavio Nobili
    • 2
  1. 1.Nuclear Medicine Unit, Department of Health Science (DISSAL)University of Genoa and IRCCS AOU San Martino-ISTGenoaItaly
  2. 2.Clinical Neurology, Department of Neuroscience (DINOGMI)University of Genoa and IRCCS AOU San Martino-ISTGenoaItaly
  3. 3.Clinical Psychology, Department of Neuroscience (DINOGMI)University of Genoa and IRCCS AOU San Martino-ISTGenoaItaly
  4. 4.Medical Genetics, Department of Neuroscience (DINOGMI)University of Genoa and IRCCS AOU San Martino-ISTGenoaItaly
  5. 5.Institute of Cognitive Sciences and Technologies, CNRRomeItaly
  6. 6.Department of Nuclear MedicineKarolinska HospitalStockholmSweden

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