Brain atrophy in primary progressive aphasia involves the cholinergic basal forebrain and Ayala's nucleus.

Primary progressive aphasia (PPA) is characterized by left hemispheric frontotemporal cortical atrophy. Evidence from anatomical studies suggests that the nucleus subputaminalis (NSP), a subnucleus of the cholinergic basal forebrain, may be involved in the pathological process of PPA. Therefore, we studied the pattern of cortical and basal forebrain atrophy in 10 patients with a clinical diagnosis of PPA and 18 healthy age-matched controls using high-resolution magnetic resonance imaging (MRI). We determined the cholinergic basal forebrain nuclei according to Mesulam's nomenclature and the NSP in MRI reference space based on histological sections and the MRI scan of a post-mortem brain in cranio. Using voxel-based analysis, we found left hemispheric cortical atrophy in PPA patients compared with controls, including prefrontal, lateral temporal and medial temporal lobe areas. We detected cholinergic basal forebrain atrophy in left predominant localizations of Ch4p, Ch4am, Ch4al, Ch3 and NSP. For the first time, we have described the pattern of basal forebrain atrophy in PPA and confirmed the involvement of NSP that had been predicted based on theoretical considerations. Our findings may enhance understanding of the role of cholinergic degeneration for the regional specificity of the cortical destruction leading to the syndrome of PPA.

Loss of word-meaning with spared object semantics in a case of mixed primary progressive aphasia.

This article provides a detailed assessment of patient HT with a history of progressive language deterioration of approximately 6years presenting now as a fluent jargon aphasic with severe impairment of both speech production and comprehension. Neuropsychological testing of non-verbal cognitive functions showed no impairment, leading to the assumption of primary progressive aphasia (PPA). Contrary to the clinical criteria of the known PPA-subtypes there was nearly parallel decline of word comprehension and motor speech. HT also showed a significant dissociation between verbal and non-verbal semantic abilities resulting in severely impaired word comprehension with object semantics relatively spared. MRI scanning revealed pronounced focal atrophy of the left anterior temporal lobe and the left perisylvian region with relatively spared right temporal involvement. The clinical diagnostic criteria for PPA-subtypes do not seem to apply to the language features shown by our patient. The similarities and distinctions to semantic dementia and progressive non-fluent aphasia (PNFA) as subtypes of PPA will be discussed. The distinction between PNFA and SD may represent an oversimplification of the clinical presentations of PPA. It is also suggested that a mixed version of primary progressive aphasia should be taken into consideration as accepted clinical subtype.