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ABSTRACT: Objective
To identify predictors of Alzheimer's disease (AD) versus frontotemporal lobar degeneration pathology in primary progressive aphasia (PPA), and determine whether the AD pathology is atypically distributed to fit the aphasic phenotype.Methods
Neuropsychological and neuropathological analyses of 23 consecutive PPA autopsies. All had qualitative determination of neurofibrillary tangle (NFT) density. Additional quantitation was done in four of the PPA/AD cases and four AD cases with the typical amnestic dementia of the Alzheimer type.ResultsThe sample contained mostly logopenic, agrammatic, and mixed forms of PPA. All six agrammatics had frontotemporal lobar degeneration (five of six with tauopathy). Seven of the 11 logopenics had AD. In logopenics, lower memory scores increased the probability of AD, but there were exceptions. The PPA/AD group showed predominance of entorhinal NFT typical of the amnestic dementia of the Alzheimer type. In the small subgroup examined quantitatively, neocortical NFTs were more numerous in the left hemisphere of PPA/AD. However, the asymmetry was low and inconsistent. Neuritic plaques did not display consistent asymmetry. Apolipoprotein E4, a major risk factor for typical AD, did not predict AD pathology in PPA.InterpretationSubtyping PPA helps to predict AD versus frontotemporal lobar degeneration pathology at the group level. However, our results and the literature also indicate that no clinical predictor is completely reliable in individual patients. The inconsistent concordance of NFT distribution with the asymmetric atrophy and the nonamnestic phenotype also raises the possibility that the AD markers encountered at autopsy in PPA may not always reflect the nature of the initiating neurodegenerative process. Ann Neurol 2008
Annals of Neurology 05/2008; 63(6):709 - 719. · 11.09 Impact Factor
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Annals of Neurology 10/2004; 56(5):750 - 750. · 11.09 Impact Factor
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Annals of Neurology 06/2003; 54(S5):S11 - S14. · 11.09 Impact Factor
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Sreepadma P. Sonty BA,
M.-Marsel Mesulam MD,
Cynthia K. Thompson PhD,
Nancy A. Johnson PhD, Sandra Weintraub PhD,
Todd B. Parrish PhD,
Darren R. Gitelman MD,
Sreepadma P. Sonty,
M.‐Marsel Mesulam,
Cynthia K. Thompson,
Nancy A. Johnson,
Sandra Weintraub,
Todd B. Parrish,
Darren R. Gitelman
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ABSTRACT: Primary Progressive Aphasia (PPA) is a behaviorally focal dementia syndrome with deterioration of language functions but relative preservation of other cognitive domains for at least the first two years of disease. In this study, PPA patients with impaired word finding but intact comprehension of conversational speech and their matched control subjects were examined using voxel-based morphometry (VBM) and functional magnetic resonance imaging (fMRI). fMRI compared signal changes during phonological and semantic language tasks with those during a control task (matching letters). PPA patients showed longer reaction times and reduced accuracy versus controls on the language tasks, but no performance differences on the control task. VBM demonstrated reduced gray matter in left superior temporal and inferior parietal regions in the PPA group. However, these patients showed a normal pattern of activation within the classical language regions. In addition, PPA patients showed activations, not seen in normals, in fusiform gyrus, precentral gyrus, and intra-parietal sulcus. These activations were found to correlate negatively with measures of naming and task performance. The additional activations in PPA may therefore represent a compensatory spread of language-related neural activity or a failure to suppress activity in areas normally inhibited during language tasks. Ann Neurol 2003;53:000–000
Annals of Neurology 12/2002; 53(1):35 - 49. · 11.09 Impact Factor
