Cognition and anatomy in three variants of primary progressive aphasia

Abstract

We performed a comprehensive cognitive, neuroimaging, and genetic study of 31 patients with primary progressive aphasia (PPA), a decline in language functions that remains isolated for at least 2 years. Detailed speech and language evaluation was used to identify three different clinical variants: nonfluent progressive aphasia (NFPA; n = 11), semantic dementia (SD; n = 10), and a third variant termed logopenic progressive aphasia (LPA; n = 10). Voxel-based morphometry (VBM) on MRIs showed that, when all 31 PPA patients were analyzed together, the left perisylvian region and the anterior temporal lobes were atrophied. However, when each clinical variant was considered separately, distinctive patterns emerged: (1) NFPA, characterized by apraxia of speech and deficits in processing complex syntax, was associated with left inferior frontal and insular atrophy; (2) SD, characterized by fluent speech and semantic memory deficits, was associated with anterior temporal damage; and (3) LPA, characterized by slow speech and impaired syntactic comprehension and naming, showed atrophy in the left posterior temporal cortex and inferior parietal lobule. Apolipoprotein E ε4 haplotype frequency was 20% in NFPA, 0% in SD, and 67% in LPA. Cognitive, genetic, and anatomical features indicate that different PPA clinical variants may correspond to different underlying pathological processes.Isolated speech and language difficulties are often the first symptoms of focal forms of neurodegenerative diseases, particularly frontotemporal lobar degeneration (FTLD) and corticobasal degeneration (CBD). 1,2 Alzheimer's disease (AD) patients also have been shown to present with atypical focal cognitive manifestations, including fluent and nonfluent progressive aphasia. 3-7 When speech and language deficits remain the only complaint for at least 2 years, the term primary progressive aphasia (PPA) has been applied. 8Pathologically, the most frequent finding in PPA is an FTLD-type of damage such as dementia lacking distinctive pathology (DLDH) 9-11 or Pick's disease. 12,13 Cases with AD, 3 Creutzfeldt-Jakob disease, 1,4 and FTLD with motor neuron disease (FTLD-MND) pathology also have been reported 15 (for review, see Mesulam, 16 Grossman, 17 and Black 18 ). Kertesz first included CBD in the FTLD/Pick's spectrum of diseases and recently reported four PPA cases with pathologically proven CBD. 12,19 Address correspondence to Dr Gorno-Tempini, UCSF Memory and Aging Center, 350 Parnassus Avenue, Suite 706, Box 1207. San Francisco, CA 94143. E-mail: marilu@itsa.ucsf.edu. NIH Public Access Author ManuscriptAnn Neurol. Author manuscript; available in PMC 2008 May 1. Published in final edited form as:Ann Neurol. 2004 March ; 55(3): 335-346. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptDifferent clinical presentations of PPA have been reported, but large studies that investigate both cognitive and neuroimaging findings in the same group of patients are still lacking. Here, we consider the clinical variants that have be...

Anatomical and functional alterations in semantic dementia: A voxel-based MRI and PET study

“…The findings of our MRI study highlight, as expected, significant GM reduction in the left temporal neocortex (temporal pole, and inferior, middle and superior temporal gyri), and at a lesser degree, in the right temporal neocortex, in accordance with previous quantitative volumetric [7,22,39] and VBM [4,25,26,29,49] studies. This pattern of results is in agreement with the severe semantic memory deficits in our group of SD patients.…”

“…The GM reduction was also found to concern at a lesser degree the left fusiform gyrus, consistently with previous studies in SD [22,26,49], as well as in the amygdala, parahippocampal gyrus and hippocampus, predominantly on the left hemisphere. Left amygdala atrophy in SD has recently been shown in VBM [4,25] and in volumetric [39,78] MRI studies, and seems to be more pronounced than in Alzheimer"s disease.…”

“…Left-sided predominant atrophy is more frequent than right predominant or symmetrical involvement (e.g., [7,26,29]). Visual inspection of MRI brain scans has suggested that the hippocampal complex is preserved in SD, which might fit with normal day-to-day memory, or near normal performance on episodic memory tests in some patients [27,28,57,58].…”

“…In sum, only a few studies have applied the VBM procedure in SD [4,25,26,29,48,49,64]. Moreover, two of these studies investigated a small group of patients ([48] N = 4;…”

Odour identification in frontotemporal lobar degeneration

“…FTLD is both pathologically and clinically heterogeneous [2][3][4][5][6]. Diseases in the FTLD spectrum involve cortical areas that have been implicated in olfactory processing in functional imaging studies of healthy subjects [7][8][9][10][11][12][13][14] and in human lesion studies [15][16][17][18].…”