Silvia Morbelli1, Michela Ferrara2, Francesco Fiz3, Barbara Dessi2, Dario Arnaldi2, Agnese Picco2, Irene Bossert3, Ambra Buschiazzo3, Jennifer Accardo2, Lorena Picori3, Nicola Girtler2,4, Paola Mandich5, Marco Pagani6,7, Gianmario Sambuceti3, Flavio Nobili2. 1. Nuclear Medicine Unit, Department of Health Science (DISSAL), University of Genoa and IRCCS AOU San Martino-IST, Largo R. Benzi 10, 16132, Genoa, Italy. Silviadaniela.morbelli@hsanmartino.it. 2. Clinical Neurology, Department of Neuroscience (DINOGMI), University of Genoa and IRCCS AOU San Martino-IST, Genoa, Italy. 3. Nuclear Medicine Unit, Department of Health Science (DISSAL), University of Genoa and IRCCS AOU San Martino-IST, Largo R. Benzi 10, 16132, Genoa, Italy. 4. Clinical Psychology, Department of Neuroscience (DINOGMI), University of Genoa and IRCCS AOU San Martino-IST, Genoa, Italy. 5. Medical Genetics, Department of Neuroscience (DINOGMI), University of Genoa and IRCCS AOU San Martino-IST, Genoa, Italy. 6. Institute of Cognitive Sciences and Technologies, CNR, Rome, Italy. 7. Department of Nuclear Medicine, Karolinska Hospital, Stockholm, Sweden.
Abstract
PURPOSE: 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. METHODS: 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-). RESULTS: 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. CONCLUSION: 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.
PURPOSE: 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. METHODS: 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 bvFTDpatients were divided into two subgroups: those with predominant disinhibition (bvFTD+) and those with apathy (bvFTD-). RESULTS: 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. CONCLUSION: 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.
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