Alzheimer and frontotemporal pathology in subsets of primary progressive aphasia

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.Results-The 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.Interpretation-Subtyping 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.The relation of disease markers to dementia phenotypes has been investigated most productively in Alzheimer's disease (AD). In most AD cases, neurofibrillary tangles (NFTs) This report includes 23 consecutive, unselected autopsies on patients with the clinical syndrome of PPA. One goal was to explore factors that could predict AD versus FTLD pathology. Another was to determine whether AD pathology in the aphasic dementia of PPA had a different distribution than in the amnestic dementia of DAT. following account of her problem: "I have to force myself to tell people about understand me. Words come out wrong the way." Patient 4 was the only one classified as semantic based on the constellation of preserved fluency and syntax but abnormal language comprehension. Patients with intact syntax and comprehension but frequent word-finding pauses and variable fluency were classified as logopenic. Patients with agrammatism and also comprehension deficits of comparable magnitude, or whose language output was too limited for specific characterization, were designated as "mixed" in Table 1. Demographic data were analyzed using independent samples t tests. Fisher's exact test was used to examine group differences in categoric data.© Patients and Methods PatientsAll specime...

Frontotemporal Dementia: Implications for Understanding Alzheimer Disease

“…They include most cases of PNFA, 45% of cases of bvFTD and some cases of SD (Piguet et al 2011a). Most cases of LPA are characterized by focal Alzheimer disease pathology (Ab plaques and tau tangles), as are some cases of SD and PNFA (Mesulam et al 2008;Rabinovici et al 2008). Focal Alzheimer disease pathology accounts for 25% of autopsy cases of PPA.…”

L'aphasie (primaire) progressive: un diagnostic simple ou complexe

“…La variante logopénique occupe une place spéciale [33,34]. Elle est classée dans les APP fluentes pour la plupart des auteurs.…”

Avaliação fonoaudiológica da deglutição na demência frontotemporal

“…Achados neuropatológicos apontam a doença Alzheimer como a causa mais comum da APP-L, porém há relato de uma pequena parcela, cerca de um terço dos casos, que são decorrentes da degeneração frontotemporal (Mesulam et al, 2008).…”

“…Estudos como os de Gorno-Tempini et al, (2004e 2008, já relatavam a disfunção cognitiva na APP-L. Outros estudos também observaram alterações de memória de trabalho verbal, habilidades visuo-construcionais, atenção dividida e flexibilidade cognitiva (Wicklund et al, 2007.…”

“…A demência semântica e a afasia progressiva não-fluente (também denominada agramática) são caracterizadas pelo comprometimento progressivo da linguagem e são consideradas subtipos da afasia progressiva primária (APP). Outro subtipo da APP, a afasia logopênica, ocorre em menor proporção em decorrência da DLFT (Mesulam et al, 2008).…”