Distinct Antemortem Profiles in Patients With Pathologically Defined Frontotemporal Dementia

Department of Neurology, 2 Gibson, University of Pennsylvania School of Medicine, 3400 Spruce St, Philadelphia, PA 19104-4283, USA.
JAMA Neurology (Impact Factor: 7.42). 12/2007; 64(11):1601-9. DOI: 10.1001/archneur.64.11.1601
Source: PubMed


Clinical-pathologic studies are crucial to understanding brain-behavior relations and improving diagnostic accuracy in neurodegenerative diseases.
To establish clinical, neuropsychological, and imaging features of clinically diagnosed patients with frontotemporal dementia (FTD) that help discriminate between pathologically determined tau-positive FTD, tau-negative FTD, and frontal-variant Alzheimer disease.
Retrospective clinical-pathologic survey.
Academic medical center. Patients Sixty-one participants with the clinical diagnosis of a frontotemporal spectrum disorder who underwent a neuropsychological evaluation and had an autopsy-confirmed disease.
Neuropsychological performance and high-resolution structural magnetic resonance imaging (MRI).
Distinguishing features of patients with tau-positive FTD include visual perceptual-spatial difficulty and an extrapyramidal disorder significantly more often than other patients, significant cortical atrophy in the frontal and parietal regions as evidenced on MRI, and the burden of pathology is greatest in the frontal and parietal regions. Patients with tau-negative FTD are distinguished by their greater difficulties with social, language, and verbally mediated executive functions, significant cortical atrophy in the frontal and temporal regions as evidenced on MRI, and significant frontal and temporal pathology. Patients with Alzheimer disease at autopsy have significantly impaired delayed recall during episodic memory testing; atrophy that involves temporal areas, including the hippocampus, as evidenced on MRI; and widely distributed pathology including the medial temporal structures. A discriminant function analysis grouped patients on the basis of clinical and neuropsychological features with 87.5% accuracy.
Clinical, neuropsychological, and imaging profiles can contribute to accurate antemortem diagnosis in FTD.

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    • "In contrast, patients with AD pathology showed a decline between first and second recall, consistent with impaired learning or rapid forgetting as has been described previously in the literature [29] [30]. Our findings are consistent with neuropsychological studies showing that patients with AD perform more poorly on delayed recall than patients without AD diagnosed by neuropathologic finding [2] [4] [5] [7] [10]. They are also consistent with the power of delayed recall as well as cued recall tests to distinguish cerebrospinal fluid profiles consistent with AD [31]. "
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    ABSTRACT: We compared the sensitivity and specificity of two delayed recall scores from the Modified Mini-Mental State (3MS) test with consensus clinical diagnosis to differentiate cognitive impairment due to Alzheimer's disease (AD) versus non-AD pathologies. At a memory disorders clinic, 117 cognitively impaired patients were administered a baseline 3MS test and received a contemporaneous consensus clinical diagnosis. Their brains were examined after death about 5 years later. Using logistic regression with forward selection to predict pathologically defined AD versus non-AD, 10-min delayed recall entered first (p = 0.001), followed by clinical diagnosis (p = 0.02); 1-min delayed recall did not enter. 10-min delayed recall scores ≤4 (score range = 0-9) were 87% sensitive and 47% specific in predicting AD pathology; consensus clinical diagnosis was 82% sensitive and 45% specific. For the 57 patients whose initial Mini-Mental State Examination scores were ≥19 (the median), 3MS 10-min delayed recall scores ≤4 showed some loss of sensitivity (80%) but a substantial gain in specificity (77%). In conclusion, 10-min delayed recall score on the brief 3MS test distinguished between AD versus non-AD pathology about 5 years before death at least as well as consensus clinical diagnosis that requires much more comprehensive information and complex deliberation.
    Journal of Alzheimer's disease: JAD 11/2013; 39(3):575-582. DOI:10.3233/JAD-130524 · 4.15 Impact Factor
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    • "For that, we might argue that FTD patients with CSF AD-like pattern are instead cases with atypical and focal AD pathology [11]. The percentage of patients reclassified by CSF analysis (21%) is indeed in line with several previous pathological series [19] [37]. Alternatively, we cannot even exclude that CSF and neuroimaging AD-like changes may herald and co-occur in patients with FTLD [23]. "
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    ABSTRACT: Background: Differential diagnosis between frontotemporal dementia (FTD) and Alzheimer's disease (AD) is often challenging. Autopsy series have identified AD pathology in a consistent percentage of patients clinically diagnosed with frontotemporal dementia (FTD). It has been demonstrated that the levels of tau and Aβ42 in cerebrospinal fluid (CSF) are a reliable marker for AD. Objective: To evaluate the presence of a CSF AD-like pattern in patients with FTD, and the related brain changes, to assess whether these patients had features resembling an AD pattern of hypoperfusion. Methods: Clinically-diagnosed non-monogenic FTD patients underwent an extensive neuropsychological assessment, 99mTc-ECD SPECT, and CSF analysis (tau and Aβ42 levels). FTD AD-like and FTD non-AD-like patterns were identified, and neuropsychological and neuroimaging features compared. Results: CSF AD-like pattern was reported in 9 cases out of 43 (21%). FTD AD-like and non-AD-like patients did not differ in demographic characteristics, cognitive deficits, or behavioral changes. Both groups had greater hypoperfusion in frontotemporal lobes as compared to age-matched controls. When FTD AD-like patients were compared to the FTD non-AD-like group, the former had greater hypoperfusion in brain areas typically affected by AD, namely precuneus, temporal, and parietal areas. Conclusions: CSF AD-like profile in FTD is associated with brain abnormalities typically found in classical AD, confirming the usefulness of CSF testing. Detecting an ongoing AD pathological process in FTD has several implications for defining distinctive treatment approaches, guiding genetic screening, and helping in patient selection in future clinical trials in both FTLD and AD therapeutics.
    Journal of Alzheimer's disease: JAD 04/2013; 36(1). DOI:10.3233/JAD-121969 · 4.15 Impact Factor
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    • "Revised criteria for the clinical diagnosis of bvFTD have recently been validated against pathologically verified FLTD (Rascovsky et al. 2011), which may improve diagnostic accuracy. Particularly compelling are retrospective studies that have shown a double dissociation in which mildly to moderately demented patients with autopsy-confirmed FTLD are more impaired than those with autopsy-confirmed AD on tests sensitive to frontal lobe dysfunction (e.g., word generation tasks), but less impaired on tests of memory and visuospatial abilities sensitive to dysfunction of medial temporal and parietal association cortices (e.g., Rascovsky et al. 2002; Grossman et al. 2007). In one study, Rascovsky and colleagues (2002) used multivariate analysis of covariance to show that FTLD patients performed significantly worse than AD patients on word generation tasks that are sensitive to frontal lobe dysfunction (particularly letter fluency), but significantly better on tests of memory (i.e., Mattis Dementia Rating Scale [DRS] Memory subscale) and visuospatial abilities (i.e., WAIS Block Design and Clock Drawing tests), which are sensitive to dysfunction of medial temporal and parietal association cortices , respectively. "
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    ABSTRACT: Neuropsychological assessment has featured prominently over the past 30 years in the characterization of dementia associated with Alzheimer disease (AD). Clinical neuropsychological methods have identified the earliest, most definitive cognitive and behavioral symptoms of illness, contributing to the identification, staging, and tracking of disease. With increasing public awareness of dementia, disease detection has moved to earlier stages of illness, at a time when deficits are both behaviorally and pathologically selective. For reasons that are not well understood, early AD pathology frequently targets large-scale neuroanatomical networks for episodic memory before other networks that subserve language, attention, executive functions, and visuospatial abilities. This chapter reviews the pathognomonic neuropsychological features of AD dementia and how these differ from "normal," age-related cognitive decline and from other neurodegenerative diseases that cause dementia, including cortical Lewy body disease, frontotemporal lobar degeneration, and cerebrovascular disease.
    Cold Spring Harbor Perspectives in Medicine 04/2012; 2(4):a006171. DOI:10.1101/cshperspect.a006171 · 9.47 Impact Factor
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