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Introduction: I-FP-CIT SPECT is increasingly used to differentiate between Alzheimer's dementia (AD) and dementia with Lewy bodies (DLB). The role of I-FP-CIT SPECT in frontotemporal dementia (FTD) is rather unclear, albeit nigrostriatal involvement may occur. The aim of this study was to evaluate its role in the differentiation of FTD, DLB, and AD., Methods: We analyzed 34 patients with clinical diagnosis of FTD (n = 13), DLB (n = 12), and AD (n = 9) undergoing combined F-FDG PET and I-FP-CIT SPECT. We performed a semiquantitative region of interest-based analysis to determine the binding potential values in caudate nucleus, putamen, and whole striatum including the caudate/putamen binding potential ratio and asymmetry indices. The receiver operating characteristic analyses and multinomial logistic regression were conducted to assess discrimination accuracy., Results: The putaminal binding potential separated DLB from AD with high accuracy (area under the receiver operating characteristic curve [AUC], 0.94). It also discriminated FTD from DLB with high accuracy (AUC, 0.92), whereas differentiation between FTD and AD was less accurate (AUC, 0.74). The binding potential ratio also provided high accuracy for differentiation of FTD and DLB (AUC, 0.91). Combination of these 2 parameters yielded slightly higher results for differentiation of FTD and DLB (AUC, 0.97). In a group including all patients, accuracy remained very high for DLB (AUC, 0.95), whereas values for FTD (AUC, 0.81) and AD (AUC, 0.80) were lower., Conclusions: Semiquantitative assessment of striatal dopamine transporter availability can differentiate between FTD and DLB as well as DLB and AD with high accuracy, whereas discrimination between AD and FTD is limited.

Several studies have demonstrated that fully automated pattern recognition methods applied to structural magnetic resonance imaging (MRI) aid in the diagnosis of dementia, but these conclusions are based on highly preselected samples that significantly differ from that seen in a dementia clinic. At a single dementia clinic, we evaluated the ability of a linear support vector machine trained with completely unrelated data to differentiate between Alzheimer's disease (AD), frontotemporal dementia (FTD), Lewy body dementia, and healthy aging based on 3D-T1 weighted MRI data sets. Furthermore, we predicted progression to AD in subjects with mild cognitive impairment (MCI) at baseline and automatically quantified white matter hyperintensities from FLAIR-images. Separating additionally recruited healthy elderly from those with dementia was accurate with an area under the curve (AUC) of 0.97 (according to Fig. 4). Multi-class separation of patients with either AD or FTD from other included groups was good on the training set (AUC >  0.9) but substantially less accurate (AUC = 0.76 for AD, AUC = 0.78 for FTD) on 134 cases from the local clinic. Longitudinal data from 28 cases with MCI at baseline and appropriate follow-up data were available. The computer tool discriminated progressive from stable MCI with AUC = 0.73, compared to AUC = 0.80 for the training set. A relatively low accuracy by clinicians (AUC = 0.81) illustrates the difficulties of predicting conversion in this heterogeneous cohort. This first application of a MRI-based pattern recognition method to a routine sample demonstrates feasibility, but also illustrates that automated multi-class differential diagnoses have to be the focus of future methodological developments and application studies.

Frontotemporal dementia (FTD) is a clinically and genetically heterogeneous disorder. Rare TREM2 variants have been recently identified in families affected by FTD-like phenotype. However, genetic studies of the role of rare TREM2 variants in FTD have generated conflicting results possibly because of difficulties on diagnostic accuracy. The aim of the present study was to investigate associations between rare TREM2 variants and specific FTD subtypes (FTD-S). The entire coding sequence of TREM2 was sequenced in FTD-S patients of Spanish (n = 539) and German (n = 63) origin. Genetic association was calculated using Fisher exact test. The minor allele frequency for controls was derived from in-house genotyping data and publicly available databases. Seven previously reported rare coding variants (p.A28V, p.W44X, p.R47H, p.R62H, p.T66M, p.T96K, and p.L211P) and 1 novel missense variant (p.A105T) were identified. The p.R47H variant was found in 4 patients with FTD-S. Two of these patients showed cerebrospinal fluid pattern of amyloid beta, tau, and phosphorylated-tau suggesting underlying Alzheimer's disease (AD) pathology. No association was found between p.R47H and FTD-S. A genetic association was found between p.T96K and FTD-S (p = 0.013, odds ratio = 4.23, 95% Confidence Interval [1.17-14.77]). All 6 p.T96K patients also carried the TREM2 variant p.L211P, suggesting linkage disequilibrium. The remaining TREM2 variants were found in 1 patient, respectively, and were absent in controls. The present findings provide evidence that p.T96K is associated with FTD-S and that p.L211P may contribute to its pathogenic effect. The data also suggest that p.R47H is associated with an FTD phenotype that is characterized by the presence of underlying AD pathology., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Behavioural variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD) dementia are characterised by progressive brain atrophy. Longitudinal MRI volumetry may help to characterise ongoing structural degeneration and support the differential diagnosis of dementia subtypes. Automated, observer-independent atlas-based MRI volumetry was applied to analyse 102 MRI data sets from 15 bvFTD, 14 AD, and 10 healthy elderly control participants with consecutive scans over at least 12 months. Anatomically defined targets were chosen a priori as brain structures of interest. Groups were compared regarding volumes at clinic presentation and annual change rates. Baseline volumes, especially of grey matter compartments, were significantly reduced in bvFTD and AD patients. Grey matter volumes of the caudate and the gyrus rectus were significantly smaller in bvFTD than AD. The bvFTD group could be separated from AD on the basis of caudate volume with high accuracy (79% cases correct). Annual volume decline was markedly larger in bvFTD and AD than controls, predominantly in white matter of temporal structures. Decline in grey matter volume of the lateral orbitofrontal gyrus separated bvFTD from AD and controls. Automated longitudinal MRI volumetry discriminates bvFTD from AD. In particular, greater reduction of orbitofrontal grey matter and temporal white matter structures after 12 months is indicative of bvFTD.

Mutations of the progranulin gene lead to progranulin haploinsufficiency and to frontotemporal lobar degeneration (FTD) with TDP-43 positive inclusions. It is assumed that unknown genetic, epigenetic and environmental factors are responsible for the observed marked degree of phenotypic variability among mutation carriers. This is the first published series of German FTD cases screened for progranulin mutations. Mean age at onset was 62 years, 19 patients (24%) had a positive family history of dementia, and 11 patients (14%) had a positive family history for probable FTD. Data on FTD subtypes are presented. Two mutations were identified (3%), one of which has been described previously. Clinically, both patients showed the frontal-behavioural variant type of FTD. Remarkably, a sibling of one case presented with progressive nonfluent aphasia, clinically distinct from the brother. We also performed quantitative PCR analyses to detect potential whole progranulin gene and exon deletions. Here, results were negative.

AbstractWe present the case of a 71-year-old woman with an 11-year history of slowly progressive decline of motor speech. Normal clinical investigations including routine magnetic resonance imaging (MRI) at 7, 8 and 10 years after the onset of speech dysfunction led to the suggestion of a psychogenic disorder. Extensive clinical, neuropsychological and neuroimaging investigations including 18 F-desoxyglucose-positron emission tomography (PET), quantitative MRI and MR spectroscopy were performed to look for subtle brain pathology. Quantitative assessment of 3D-MRI, F-desoxyglucose-PET and magnetic resonance spectroscopy all demonstrated clear evidence of multifocal frontotemporal brain pathology that had not been picked up on routine MRI investigations on previous admissions. This is the longest benign history of slowly progressive anarthria reported so far. It demonstrates a possible role of quantitative neuroimaging techniques in the diagnosis of complex neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]