With the prospect of disease-modifying drugs that will target the physiopathological process of Alzheimer's disease, it is now crucial to increase the understanding of the atypical focal presentations of Alzheimer's disease, such as posterior cortical atrophy. This study aimed to (i) characterize the brain perfusion profile in posterior cortical atrophy using regions of interest and a voxel-based approach; (ii) study the influence of the disease duration on the clinical and imaging profiles; and (iii) explore the correlations between brain perfusion and cognitive deficits. Thirty-nine patients with posterior cortical atrophy underwent a specific battery of neuropsychological tests, mainly targeting visuospatial functions, and a brain perfusion scintigraphy with 99mTc-ethyl cysteinate dimer. The imaging analysis included a comparison with a group of 24 patients with Alzheimer's disease, matched for age, disease duration and Mini-Mental State Examination, and 24 healthy controls. The single-photon emission computed tomography profile in patients with posterior cortical atrophy was characterized by extensive and severe hypoperfusion in the occipital, parietal, posterior temporal cortices and in a smaller cortical area corresponding to the frontal eye fields (Brodmann areas 6/8). Compared with patients with Alzheimer's disease, the group with posterior cortical atrophy showed more severe occipitoparietal hypoperfusion and higher perfusion in the frontal, anterior cingulate and mesiotemporal regions. When considering the disease duration, the functional changes began and remained centred on the posterior lobes, even in the late stage. Correlation analyses of brain perfusion and neuropsychological scores in posterior cortical atrophy highlighted the prominent role of left inferior parietal damage in acalculia, Gerstmann's syndrome, left-right indistinction and limb apraxia, whereas damage to the bilateral dorsal occipitoparietal regions appeared to be involved in Bálint's syndrome. Our findings provide new insight into the natural history of functional changes according to disease duration and highlight the role of parietal and occipital cortices in the cognitive syndromes that characterize the posterior cortical atrophy.

Within primary progressive aphasia the logopenic variant remains less understood than the two other main variants, namely semantic and non-fluent progressive aphasia. This may be because of the relatively small number of explored patients and because of the lack of investigations with a comprehensive three-level characterization of cognitive, brain localization and biological aspects. The aim of the present study was to decipher the logopenic variant through a multimodal approach with a large cohort of 19 patients (age 66.5 ± 8.7 years, symptom duration 3.2 ± 0.6 years) using detailed cognitive and linguistic assessments, magnetic resonance imaging and perfusion single-photon emission computed tomography as well as cerebrospinal fluid biomarkers screening for Alzheimer pathology. The linguistic assessment unveiled that language dysfunction is not limited to the typical feature of word finding and verbal working memory impairments but that it extends into the language system affecting to some degree syntactic production, phonological encoding and semantic representations. Perfusion tomography revealed damage of the temporal-parietal junction with a peak of significance in the superior temporal gyrus (Brodmann area 42), and of some less significant prefrontal areas (Brodmann areas 8, 9 and 46), whereas hippocampal cortices were unaffected. Magnetic resonance imaging, which was visually assessed in a larger group of 54 patients with logopenic, non-fluent, semantic variants as well as with posterior cortical atrophy, confirmed that the logopenic variant demonstrates predominant atrophy of left temporal-parietal junction, but that this atrophy pattern has a relatively poor sensitivity and specificity for clinical diagnosis. Finally, the biomarker study revealed that two-thirds of the logopenic patients demonstrated a profile indicative of Alzheimer pathology whereas one-third had a non-Alzheimer profile. Splitting the two groups showed that logopenic aphasia due to probable Alzheimer pathology is a more aggressive variant characterized by more extensive language/cognitive disorders affecting, in addition to lexical processes and verbal working memory, also phoneme sequencing, semantic processing and ideomotor praxis. Concordantly, logopenic aphasia due to probable Alzheimer pathology demonstrated more extensive brain hypoperfusion involving larger regions throughout the inferior parietal, the posterior-superior and the middle temporal cortex. These findings allow for unfolding logopenic aphasia into two subvariants differing by disease severity, lesion nature and lesion distribution, which has important implications for diagnosis, patient management and for potential future trials with anti-Alzheimer drugs. The present data therefore provide novel insight into the cognition and brain damage of logopenic patients while unveiling the existence of distinct diseases constituting a 'logopenic aphasia complex'.