Send Orders for Reprints to reprints@benthamscience.net Current Alzheimer Research, 2014, 11, 941-954 941 Brain Perfusion SPECT with Brodmann Areas Analysis in Differentiating Frontotemporal Dementia Subtypes Varvara Valotassiou 1,* , John Papatriantafyllou 2 , Nikolaos Sifakis 3 , Chara Tzavara 1 , Ioannis Tsougos 1 , Dimitrios Psimadas 1 , Eftychia Kapsalaki 4 , Ioannis Fezoulidis 4 , George Hadjigeorgiou 5 and Panagiotis Georgoulias 1 1 Department of Nuclear Medicine, University Hospital of Larissa, School of Medicine, University of Thessaly, Larissa, Greece; 2 Memory & Cognitive Disorders Clinic, Department of Neurology, “G.Gennimatas” Hospital, Athens, Greece; 3 Department of Nuclear Medicine, “Alexandra” University Hospital, Athens, Greece; 4 Department of Radiology, Uni- versity Hospital of Larissa, School of Medicine, University of Thessaly, Larissa, Greece; 5 Department of Neurology, University Hospital of Larissa, School of Medicine, University of Thessaly, Larissa, Greece Abstract: Despite the known validity of clinical diagnostic criteria, significant overlap of clinical symptoms between Frontotemporal dementia (FTD) subtypes exists in several cases, resulting in great uncertainty of the diagnostic bounda- ries. We evaluated the perfusion between FTD subtypes using brain perfusion 99m Tc-HMPAO SPECT with Brodmann ar- eas (BA) mapping. NeuroGam TM software was applied on single photon emission computed tomographic (SPECT) stud- ies for the semi-quantitative evaluation of perfusion in BA and the comparison with the software’s normal database. We studied 91 consecutive FTD patients: 21 with behavioural variants (bvFTD), 39 with language variants (lvFTD) [12 with progressive non-fluent aphasia (PNFA), 27 with semantic dementia (SD)], and 31 patients with progressive supranuclear palsy (PSP)/corticobasal degeneration (CBD). Stepwise logistic regression analyses showed that the BA 28L and 32R could independently differentiate bvFTD from lvFTD, while the BA 8R and 25R could discriminate bvFTD from SD and PNFA, respectively. Additionally, BA 7R and 32R were found to discriminate bvFTD from CBD/PSP. The only BA that could differentiate SD from PNFA was 6L. BA 6R and 20L were found to independently differentiate CBD/PSP from lvFTD. Moreover, BA 20L and 22R could discriminate CBD/PSP from PNFA, while BA 6R, 20L and 45R were found to independently discriminate CBD/PSP from SD. Brain perfusion SPECT with BA mapping can be a useful additional tool in differentiating FTD variants by improving the definition of brain areas that are specifically implicated, resulting in a more accurate differential diagnosis in atypical or uncertain forms of FTD. Keywords: Brain perfusion imaging, brodmann areas, frontotemporal dementia, SPECT. INTRODUCTION Frontotemporal dementia (FTD) represents a common cause of dementia in subjects younger than 65 years old. The age at onset is typically 45–65 years, with a mean in the 50s [1]. It is characterized by a progressive decline in behaviour or language and is associated with degeneration of the fron- tal and anterior temporal lobes [2]. FTD is a clinically het- erogeneous syndrome which encompasses distinct clinical variants [3]. Unlike FTD, which is a clinical term, fronto- tempolar lobar degeneration (FTLD) is a pathological term that was designated to encompass the underlying molecular pathologies [3, 4]. The most common phenotypes are the behavioural variant (bvFTD), and the language variants (lvFTD) semantic dementia (SD) and progressive non-fluent aphasia (PNFA). PNFA and SD are often incorporated under the broad term primary progressive aphasia (PPA) [3]. In addition, other phenotypes, such as progressive supranuclear *Address correspondence to this author at the Department of Nuclear Medi- cine, University Hospital of Larissa, 41110 Mezourlo Larissa, Greece; Tel: +30 241 350 2916; Fax: +30 241 350 1863; E-mails: valotasiou@med.uth.gr or vvalotasiou@gmail.com palsy (PSP) and corticobasal degeneration (CBD), are part of the clinical manifestation within the FTLD spectrum [1, 5]. These different phenotypes reflect the clinical heterogeneity of FTD and the underlying clinico-pathological spectrum of FTLD. The current classification of FTLD neuropathology is based on the major biochemical abnormality identified at post-mortem, i.e. the major protein accumulation: microtu- bule-associated tau, TAR DNA-binding protein of 43 kD (TDP-43), and fused in sarcoma (FUS). Abnormal phos- phorylation, ubiquitination, and proteolytic cleavage are the common pathologic signature of tau and TDP-43 accumu- lated in diseased brains [4, 5]. At present, FTD classification relies upon clinical symp- toms at disease presentation. Although each FTD variant is associated with characteristic behavioural and/or linguistic features, the fact that they harbour different underlying pathological processes, results in mismatch between clinical pictures and pathology and make the present classification largely unsatisfactory and the diagnostic work up of these patients a highly challenging task [6] in several cases. This suggests the need of an additional alternative explanation to describe FTLD discrete clinical presentations. 17- /14 $58.00+.00 © 2014 Bentham Science Publishers