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1.  Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia 
Brain  2011;134(9):2456-2477.
Based on the recent literature and collective experience, an international consortium developed revised guidelines for the diagnosis of behavioural variant frontotemporal dementia. The validation process retrospectively reviewed clinical records and compared the sensitivity of proposed and earlier criteria in a multi-site sample of patients with pathologically verified frontotemporal lobar degeneration. According to the revised criteria, ‘possible’ behavioural variant frontotemporal dementia requires three of six clinically discriminating features (disinhibition, apathy/inertia, loss of sympathy/empathy, perseverative/compulsive behaviours, hyperorality and dysexecutive neuropsychological profile). ‘Probable’ behavioural variant frontotemporal dementia adds functional disability and characteristic neuroimaging, while behavioural variant frontotemporal dementia ‘with definite frontotemporal lobar degeneration’ requires histopathological confirmation or a pathogenic mutation. Sixteen brain banks contributed cases meeting histopathological criteria for frontotemporal lobar degeneration and a clinical diagnosis of behavioural variant frontotemporal dementia, Alzheimer’s disease, dementia with Lewy bodies or vascular dementia at presentation. Cases with predominant primary progressive aphasia or extra-pyramidal syndromes were excluded. In these autopsy-confirmed cases, an experienced neurologist or psychiatrist ascertained clinical features necessary for making a diagnosis according to previous and proposed criteria at presentation. Of 137 cases where features were available for both proposed and previously established criteria, 118 (86%) met ‘possible’ criteria, and 104 (76%) met criteria for ‘probable’ behavioural variant frontotemporal dementia. In contrast, 72 cases (53%) met previously established criteria for the syndrome (P < 0.001 for comparison with ‘possible’ and ‘probable’ criteria). Patients who failed to meet revised criteria were significantly older and most had atypical presentations with marked memory impairment. In conclusion, the revised criteria for behavioural variant frontotemporal dementia improve diagnostic accuracy compared with previously established criteria in a sample with known frontotemporal lobar degeneration. Greater sensitivity of the proposed criteria may reflect the optimized diagnostic features, less restrictive exclusion features and a flexible structure that accommodates different initial clinical presentations. Future studies will be needed to establish the reliability and specificity of these revised diagnostic guidelines.
doi:10.1093/brain/awr179
PMCID: PMC3170532  PMID: 21810890
behavioural variant frontotemporal dementia; diagnostic criteria; frontotemporal lobar degeneration; FTD; pathology
2.  Posterior cerebral atrophy in the absence of medial temporal lobe atrophy in pathologically-confirmed Alzheimer's disease 
Neurobiology of Aging  2012;33(3):627.e1-627.e12.
Medial temporal lobe atrophy (MTA) is a recognized marker of Alzheimer's disease (AD), however, it can be prominent in frontotemporal lobar degeneration (FTLD). There is an increasing awareness that posterior atrophy (PA) is important in AD and may aid the differentiation of AD from FTLD. Visual rating scales are a convenient way of assessing atrophy in a clinical setting. In this study, 2 visual rating scales measuring MTA and PA were used to compare atrophy patterns in 62 pathologically-confirmed AD and 40 FTLD patients. Anatomical correspondence of MTA and PA was assessed using manually-delineated regions of the hippocampus and posterior cingulate gyrus, respectively. Both MTA and PA scales showed good inter- and intrarater reliabilities (kappa > 0.8). MTA scores showed a good correspondence with manual hippocampal volumes. Thirty percent of the AD patients showed PA in the absence of MTA. Adding the PA to the MTA scale improved discrimination of AD from FTLD, and early-onset AD from normal aging. These results underline the importance of considering PA in AD diagnosis, particularly in younger patients where medial temporal atrophy may be less conspicuous.
doi:10.1016/j.neurobiolaging.2011.04.003
PMCID: PMC3657170  PMID: 21596458
Visual rating scales; Posterior atrophy; Medial temporal lobe atrophy; MRI; Dementia; Pathology; Manual volumes
3.  Visual assessment of posterior atrophy development of a MRI rating scale 
European Radiology  2011;21(12):2618-2625.
Objective
To develop a visual rating scale for posterior atrophy (PA) assessment and to analyse whether this scale aids in the discrimination between Alzheimer’s disease (AD) and other dementias.
Methods
Magnetic resonance imaging of 118 memory clinic patients were analysed for PA (range 0–3), medial temporal lobe atrophy (MTA) (range 0–4) and global cortical atrophy (range 0–3) by different raters. Weighted-kappas were calculated for inter- and intra-rater agreement. Relationships between PA and MTA with the MMSE and age were estimated with linear-regression analysis.
Results
Intra-rater agreement ranged between 0.93 and 0.95 and inter-rater agreement between 0.65 and 0.84. Mean PA scores were higher in AD compared to controls (1.6 ± 0.9 and 0.6 ± 0.7, p < 0.01), and other dementias (0.8 ± 0.8, p < 0.01). PA was not associated with age compared to MTA (B = 1.1 (0.8) versus B = 3.1 (0.7), p < 0.01)). PA and MTA were independently negatively associated with the MMSE (B = −1.6 (0.5), p < 0.01 versus B = −1.4 (0.5), p < 0.01).
Conclusion
This robust and reproducible scale for PA assessment conveys independent information in a clinical setting and may be useful in the discrimination of AD from other dementias.
doi:10.1007/s00330-011-2205-4
PMCID: PMC3217148  PMID: 21805370
Alzheimer; Dementia; MRI; Posterior atrophy
4.  The roots of social inappropriateness in frontotemporal dementia 
Abnormal social cognition in FTD
doi:10.1136/jnnp.2006.107805
PMCID: PMC2117824  PMID: 17056622
5.  Functional neural network analysis in frontotemporal dementia and Alzheimer's disease using EEG and graph theory 
BMC Neuroscience  2009;10:101.
Background
Although a large body of knowledge about both brain structure and function has been gathered over the last decades, we still have a poor understanding of their exact relationship. Graph theory provides a method to study the relation between network structure and function, and its application to neuroscientific data is an emerging research field. We investigated topological changes in large-scale functional brain networks in patients with Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) by means of graph theoretical analysis of resting-state EEG recordings. EEGs of 20 patients with mild to moderate AD, 15 FTLD patients, and 23 non-demented individuals were recorded in an eyes-closed resting-state. The synchronization likelihood (SL), a measure of functional connectivity, was calculated for each sensor pair in 0.5–4 Hz, 4–8 Hz, 8–10 Hz, 10–13 Hz, 13–30 Hz and 30–45 Hz frequency bands. The resulting connectivity matrices were converted to unweighted graphs, whose structure was characterized with several measures: mean clustering coefficient (local connectivity), characteristic path length (global connectivity) and degree correlation (network 'assortativity'). All results were normalized for network size and compared with random control networks.
Results
In AD, the clustering coefficient decreased in the lower alpha and beta bands (p < 0.001), and the characteristic path length decreased in the lower alpha and gamma bands (p < 0.05) compared to controls. In FTLD no significant differences with controls were found in these measures. The degree correlation decreased in both alpha bands in AD compared to controls (p < 0.05), but increased in the FTLD lower alpha band compared with controls (p < 0.01).
Conclusion
With decreasing local and global connectivity parameters, the large-scale functional brain network organization in AD deviates from the optimal 'small-world' network structure towards a more 'random' type. This is associated with less efficient information exchange between brain areas, supporting the disconnection hypothesis of AD. Surprisingly, FTLD patients show changes in the opposite direction, towards a (perhaps excessively) more 'ordered' network structure, possibly reflecting a different underlying pathophysiological process.
doi:10.1186/1471-2202-10-101
PMCID: PMC2736175  PMID: 19698093

Results 1-5 (5)