Imaging correlates of posterior cortical atrophy
Introduction
Posterior cortical atrophy (PCA) is a rare, slowly progressive, dementia characterized by the development of early higher order visuospatial and visual perceptual deficits, often accompanied, or followed by features of Balint's syndrome, Gerstmann syndrome, and transcortical sensory aphasia [4], [17], [54]. These early clinical features differ from those of typical Alzheimer's disease (AD) in which memory impairment is an early feature, although as both diseases progress there is considerable overlap. In addition, the most frequent pathological findings of PCA are neurofibrillary tangles (NFT) and neuritic plaques characteristic of typical AD [48], although distributed differently, leading some authors to suggest that PCA is simply an atypical presentation of AD [19]. These differences and similarities beg the question of whether PCA is a distinct entity from typical AD.
Visual assessments of MRI have been reported in cases of PCA and have typically shown a pattern of bilateral posterior cerebral atrophy, predominantly affecting the occipital, parietal, and the temporal lobes [1], [4], [21], [24], [32], [39], [41], [43]. However, a number of recent automated image analysis techniques have been applied to study patterns of cerebral atrophy on MRI. One such technique that has been used extensively in various neurodegenerative disorders [9], [45] is voxel-based morphometry (VBM). This technique uses unbiased statistics to assess patterns of cerebral atrophy throughout the whole brain in groups of subjects. A number of VBM studies have demonstrated atrophy of the hippocampus and medial temporal lobe regions, the posterior cingulate gyrus, precuneus, temporoparietal neocortex and prefrontal cortex in typical AD [3], [10], [30], [44], [52].
Proton MR spectroscopy (1H MRS) is a technique that provides information regarding the neurochemistry of the brain, and has been useful in differentiating the common degenerative dementias [14], [29]. The neuronal integrity marker N-acetyl aspartate (NAA) level is decreased, and the glial activity marker myo-inositol (mI) level is elevated in brain regions affected by the neurodegenerative pathologies in typical AD and frontotemporal lobar degeneration [14], [28].
Neither VBM nor 1H MRS has been applied to study the characteristics of PCA, or to compare features of PCA and typical AD. Therefore, the primary aim of this study was to assess the patterns of cerebral atrophy and 1H MRS findings in a large group of PCA patients, and then to compare this to the patterns identified in patients with typical AD and control subjects. Based on the pattern of pathological involvement, we hypothesize that the patterns of atrophy on MRI would differ between patients with PCA and typical AD, yet the pattern of single voxel 1H MRS acquired from the posterior cingulate would be similar.
Section snippets
Subjects
The Mayo Clinic medical records database was used to identify all cases with a clinical diagnosis of PCA and at least one volumetric MRI that had been evaluated between January 1st 1995 and December 31st 2005. Seventy cases were identified with a clinical diagnosis of PCA, of which 47 cases had at least one volumetric MRI.
The medical records of each of these 47 cases were reviewed by one behavioral neurologist (KAJ) to ensure that they fulfilled a set of rigorous clinical criteria. In order to
Clinical
The demographics of all subjects are shown in Table 1. In each group of 38 subjects, 22 were female and the majority of subjects were right handed. The typical AD and PCA groups only differed in terms of their STMS performance (Wilcoxon rank-sum; p = 0.02).
The clinical features of the patients with PCA are shown in Table 2. The most frequent sign or symptom documented in the PCA cohort was visuospatial deficits. Episodic memory loss occurred in 17 cases (45%), however, in over 70% of these the
Discussion
This study investigated the patterns of atrophy on MRI, and 1H MRS neurochemistry, in a group of PCA patients, and compared the findings to typical AD and healthy controls.
The clinical features of these 38 PCA patients were typical of other described cases and case series of PCA [4], [19], [39], [43], [48]. In all our patients the clinical features were characterized by predominant visuospatial, visuoperceptual deficits, and visual agnosia, as well as problems with reading and writing and
Disclosures
The authors have reported no conflicts of interest.
Acknowledgments
This study was supported by the NIH Roadmap Multidisciplinary Clinical Research Career Development Award Grant (K12/NICHD)-HD49078, by grants P50 AG16574, U01 AG06786 and R01 AG11378 from the National Institute on Aging, Bethesda, MD, NIRG-03-4842 from the Alzheimer's Association, and the generous support of the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program of the Mayo Foundation, USA.
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