title: Neural correlates of cognitive impairment in posterior cortical atrophy.
abstract: 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.
authors.affiliation: Service de Médecine Nucléaire, GH Pitié-Salpêtrière, 47-83, boulevard de l'Hôpital, 75651 Paris Cedex 13, France. aurelie.kas@psl.aphp.fr
authors.forename: Aurélie
authors.initials: A
authors.lastname: Kas
authors.forename: Leonardo Cruz
authors.initials: LC
authors.lastname: de Souza
authors.forename: Dalila
authors.initials: D
authors.lastname: Samri
authors.forename: Paolo
authors.initials: P
authors.lastname: Bartolomeo
authors.forename: Lucette
authors.initials: L
authors.lastname: Lacomblez
authors.forename: Michel
authors.initials: M
authors.lastname: Kalafat
authors.forename: Raffaella
authors.initials: R
authors.lastname: Migliaccio
authors.forename: Michel
authors.initials: M
authors.lastname: Thiebaut de Schotten
authors.forename: Laurent
authors.initials: L
authors.lastname: Cohen
authors.forename: Bruno
authors.initials: B
authors.lastname: Dubois
authors.forename: Marie-Odile
authors.initials: MO
authors.lastname: Habert
authors.forename: Marie
authors.initials: M
authors.lastname: Sarazin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging; D001284:Atrophy / Q000150:complications / Q000000981:diagnostic imaging / Q000473:pathology; D001927:Brain Diseases / Q000150:complications* / Q000000981:diagnostic imaging; D001928:Brain Diseases, Metabolic; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000473:pathology*; D003072:Cognition Disorders / Q000000981:diagnostic imaging / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D025341:Principal Component Analysis; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D015899:Tomography, Emission-Computed, Single-Photon