Temporoparietal Hypometabolism in Frontotemporal Lobar Degeneration and Associated Imaging Diagnostic Errors

Department of Neurology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390-9129, USA.
Archives of neurology (Impact Factor: 7.42). 11/2010; 68(3):329-37. DOI: 10.1001/archneurol.2010.295
Source: PubMed


To evaluate the cause of diagnostic errors in the visual interpretation of positron emission tomographic scans with fludeoxyglucose F 18 (FDG-PET) in patients with frontotemporal lobar degeneration (FTLD) and patients with Alzheimer disease (AD).
Twelve trained raters unaware of clinical and autopsy information independently reviewed FDG-PET scans and provided their diagnostic impression and confidence of either FTLD or AD. Six of these raters also recorded whether metabolism appeared normal or abnormal in 5 predefined brain regions in each hemisphere-frontal cortex, anterior cingulate cortex, anterior temporal cortex, temporoparietal cortex, and posterior cingulate cortex. Results were compared with neuropathological diagnoses.
Academic medical centers.
Forty-five patients with pathologically confirmed FTLD (n=14) or AD (n=31).
Raters had a high degree of diagnostic accuracy in the interpretation of FDG-PET scans; however, raters consistently found some scans more difficult to interpret than others. Unanimity of diagnosis among the raters was more frequent in patients with AD (27 of 31 patients [87%]) than in patients with FTLD (7 of 14 patients [50%]) (P=.02). Disagreements in interpretation of scans in patients with FTLD largely occurred when there was temporoparietal hypometabolism, which was present in 7 of the 14 FTLD scans and 6 of the 7 scans lacking unanimity. Hypometabolism of anterior cingulate and anterior temporal regions had higher specificities and positive likelihood ratios for FTLD than temporoparietal hypometabolism had for AD.
Temporoparietal hypometabolism in FTLD is common and may cause inaccurate interpretation of FDG-PET scans. An interpretation paradigm that focuses on the absence of hypometabolism in regions typically affected in AD before considering FTLD is likely to misclassify a significant portion of FTLD scans. Anterior cingulate and/or anterior temporal hypometabolism indicates a high likelihood of FTLD, even when temporoparietal hypometabolism is present. Ultimately, the accurate interpretation of FDG-PET scans in patients with dementia cannot rest on the presence or absence of a single region of hypometabolism but rather must take into account the relative hypometabolism of all brain regions.

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    • "): (a) regional labeling of the supratentorial brain (region; 72 features), (b) selection of brain regions affected by AD or FTD based on the literature (selection; 28 features) [Foster et al., 2008; Fukuyama et al., 1994; Herholz et al., 2007; Ishii et al., 1996, 1998, 1997a, b, 2000; Johannsen et al., 2000; Minoshima et al., 1997; Santens et al., 2001; Scarmeas et al., 2004; Womack et al., 2011] "
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    ABSTRACT: Because hypoperfusion of brain tissue precedes atrophy in dementia, the detection of dementia may be advanced by the use of perfusion information. Such information can be obtained noninvasively with arterial spin labeling (ASL), a relatively new MR technique quantifying cerebral blood flow (CBF). Using ASL and structural MRI, we evaluated diagnostic classification in 32 prospectively included presenile early stage dementia patients and 32 healthy controls. Patients were suspected of Alzheimer's disease (AD) or frontotemporal dementia. Classification was based on CBF as perfusion marker, gray matter (GM) volume as atrophy marker, and their combination. These markers were each examined using six feature extraction methods: a voxel-wise method and a region of interest (ROI)-wise approach using five ROI-sets in the GM. These ROI-sets ranged in number from 72 brain regions to a single ROI for the entire supratentorial brain. Classification was performed with a linear support vector machine classifier. For validation of the classification method on the basis of GM features, a reference dataset from the AD Neuroimaging Initiative database was used consisting of AD patients and healthy controls. In our early stage dementia population, the voxelwise feature-extraction approach achieved more accurate results (area under the curve (AUC) range = 86 − 91%) than all other approaches (AUC = 57 − 84%). Used in isolation, CBF quantified with ASL was a good diagnostic marker for dementia. However, our findings indicated only little added diagnostic value when combining ASL with the structural MRI data (AUC = 91%), which did not significantly improve over accuracy of structural MRI atrophy marker by itself. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.
    Full-text · Article · Sep 2014 · Human Brain Mapping
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    • "Interestingly, a similar pattern of brain regional glucose metabolism has been recently described in FTD as well [44]. Obesity was reported as related to brain atrophy, cognitive deficit [45-47] and as a risk factor for other types of dementia [48]. "
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    Full-text · Article · Jun 2014 · Translational Neurodegeneration
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    • "Some studies report bilateral involvement of the temporoparietal junction (Saxe and Kanwisher, 2003), whereas others report selective involvement of the left (Samson et al., 2004) or the right (Saxe and Wexler, 2005; Perner et al., 2006; Aichhorn et al., 2009). The temporoparietal junction has been consistently identified as one element of the metabolic and structural brain alterations in Alzheimer's disease, in terms of either glucose metabolism (Friedland et al., 1983; Foster et al., 1984; Ibanez et al., 1998; Herholz et al., 2002; Matsuda et al., 2002; Nestor et al., 2003; Mosconi, 2005; Kawachi et al., 2006), brain perfusion (Varma et al., 2002) or cortical volume (Baron et al., 2001; Fox et al., 2001; Whitwell et al., 2008), but is less affected in behavioural variant FTD (Charpentier et al., 2000; Hu et al., 2010; Womack et al., 2011). Only half of our patients with Alzheimer's disease made errors compatible with a belief inference deficit, possibly because temporoparietal junction shrinkage only occurs in late-stage Alzheimer's disease (Frisoni et al., 2009). "
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    ABSTRACT: Theory of mind reasoning-the ability to understand someone else's mental states, such as beliefs, intentions and desires-is crucial in social interaction. It has been suggested that a theory of mind deficit may account for some of the abnormalities in interpersonal behaviour that characterize patients affected by behavioural variant frontotemporal dementia. However, there are conflicting reports as to whether understanding someone else's mind is a key difference between behavioural variant frontotemporal dementia and other neurodegenerative conditions such as Alzheimer's disease. Literature data on the relationship between theory of mind abilities and executive functions are also contradictory. These disparities may be due to underestimation of the fractionation within theory of mind components. A recent theoretical framework suggests that taking someone else's mental perspective requires two distinct processes: inferring someone else's belief and inhibiting one's own belief, with involvement of the temporoparietal and right frontal cortices, respectively. Therefore, we performed a neuropsychological and neuroimaging study to investigate the hypothesis whereby distinct cognitive deficits could impair theory of mind reasoning in patients with Alzheimer's disease and patients with behavioural variant frontotemporal dementia. We used a three-option false belief task to assess theory of mind components in 11 patients with behavioural variant frontotemporal dementia, 12 patients with Alzheimer's disease and 20 healthy elderly control subjects. The patients with behavioural variant frontotemporal dementia and those with Alzheimer's disease were matched for age, gender, education and global cognitive impairment. [(18)F]-fluorodeoxyglucose-positron emission tomography imaging was used to investigate neural correlates of theory of mind reasoning deficits. Performance in the three-option false belief task revealed differential impairments in the components of theory of mind reasoning; patients with Alzheimer's disease had a predominant deficit in inferring someone else's belief, whereas patients with behavioural variant frontotemporal dementia were selectively impaired in inhibiting their own mental perspective. Moreover, inhibiting one's own perspective was strongly correlated with inhibition in a Stroop task but not with other subprocesses of executive functions. This finding suggests that self-perspective inhibition may depend on cognitive processes that are not specific to the social domain. Last, the severity of the deficit in inferring someone else's beliefs correlated significantly over all subjects with hypometabolism in the left temporoparietal junction, whereas the severity of the deficit in self-perspective inhibition correlated significantly with hypometabolism in the right lateral prefrontal cortex. In conclusion, our findings provided clinical and imaging evidence to support differential deficits in two components of theory of mind reasoning (subserved by distinct brain regions) in patients with Alzheimer's disease and patients with behavioural variant frontotemporal dementia.
    Full-text · Article · Oct 2012 · Brain
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