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.

Memory impairment at initial clinical presentation in posterior cortical atrophy

“…However, the results support the conclusion that memory impairment can be detected at initial presentation with a simple screening instrument, and with a relatively short average symptom duration compared to other studies (for example, [6,10]). Despite differences in the predominant clinical symptoms in PCA and EOAD, the concomitant and significant memory impairment early in the clinical course may reflect the common underlying AD pathology.…”

Posterior Cortical Atrophy

“…Data from functional imaging studies using single photon emission computed tomography (SPECT) and fluorodeoxyglucose positron emission tomography (FDG-PET) are largely consistent with structural changes in parieto-occipital areas (see Figure 2) 20,[47][48][49][50]51 . In addition to posterior regions, FDG-PET has revealed specific areas of hypometabolism in the frontal eye fields bilaterally which may occur secondary to loss of input from occipitoparietal regions and underpin ocular apraxia in PCA 20,52 .…”

“…Age at onset tends to be much earlier in PCA than in typical amnestic AD, with most studies reporting PCA symptom onset in patients' mid 50s and early 60s 17,19 although some studies have reported a wider age spread (45-74 years 20 , 40-86 years 21 ). In terms of gender distribution, some studies have reported no difference in the prevalence based on gender 15,17,19 , whereas others have reported an over-representation among women 18,[20][21][22][23][24] .…”

“…The most frequently cited neuropsychological deficits in PCA are visuospatial and visuoperceptual impairments, alexia and features of Balint's syndrome (simultanagnosia, oculomotor apraxia, optic ataxia, environmental agnosia) and Gerstmann's syndrome (acalculia, agraphia, finger agnosia, left/right disorientation) 15,17,[19][20][21][25][26][27][28][29][30][31] . Working memory deficits and limb apraxia have also been emphasised 20 .…”

Posterior kortikal atrofi

“…Menn og kvinner rammes antakelig like ofte (3,4), selv om det i enkelte artikler antydes hyppigere forekomst hos kvinner (5,6). Gjennomsnittlig tid mellom debutsymptomer og rett diagnose er omtrent fire år.…”