Clinical syndromes associated with posterior atrophy: early age at onset AD spectrum

Abstract

Objective: Posterior cortical atrophy (PCA) and logopenic progressive aphasia (LPA) are clinical syndromes associated with posterior brain atrophy. We compared PCA and LPA to each other and to an age-matched group of patients with early age at onset of Alzheimer disease (EO-AD). We hypothesized that these 3 syndromes are part of a single clinical and biologic continuum.

Methods: Voxel-based morphometry (VBM) was used to assess atrophy in 14 PCA, 10 LPA, and 16 EO-AD patients compared to 65 healthy controls. Genetic analysis for APOE was conducted in 30 patients and 44 controls. Four patients came to autopsy. An additional 14 were studied with the beta-amyloid specific PET with tracer (11)C-labeled Pittsburgh Compound-B (PIB).

Results: VBM results demonstrated that, compared to controls, each patient group showed a large area of overlapping atrophy in bilateral parietal, occipital, precuneus, posterior cingulate, posterior temporal, and hippocampal regions. Surrounding this common area, group-specific atrophy was found in small, symptom-specific regions for each group: the right ventral-occipital and superior parietal regions in PCA, the left middle and superior temporal gyri in LPA, and the prefrontal cortex in EO-AD. APOE epsilon4 frequency was higher in all patient groups compared to controls. Four PCA, 5 LPA, and 8 EO-AD patients showed evidence of cortical amyloid at pathology (n = 3) or on PIB-PET (n = 14).

Conclusions: Logopenic progressive aphasia and posterior cortical atrophy showed largely overlapping anatomic and biologic features with early age at onset of Alzheimer disease, suggesting that these clinical syndromes represent the spectrum of clinical manifestation of the nontypical form of Alzheimer disease that presents at an early age.

Figure 1 Gray matter areas significantly atrophied in each patient group vs controls (A) Posterior cortical atrophy (PCA), (B) logopenic/phonological progressive aphasia (LPA), and (C) early age at onset AD (EO-AD). Regions of gray matter (GM) atrophy are shown on the 3-dimensional rendering of the Montreal Neurological Institute standard brain. Results are shown at a threshold of p < 0.05 corrected.

Figure 2 Common and specific areas of gray matter atrophy Gray matter (GM) atrophy common to all patients vs controls is shown in cyan, while GM regions specifically atrophied in each group compared with controls are indicated in blue for posterior cortical atrophy (PCA), green for logopenic/phonological progressive aphasia (LPA), and red for early age at onset AD (EO-AD). Results are superimposed on the 3-dimensional rendering of the Montreal Neurological Institute standard brain and on axial sections of the mean image of the scans used to obtain the template image. For display purposes, results are shown at a threshold of p < 0.05 corrected for common and of p < 0.001 uncorrected for specific areas.

Figure 3 Pattern of gray matter atrophy common to all autopsy-proven and PIB-positive patient groups vs controls Results are superimposed on the 3-dimensional rendering of the Montreal Neurological Institute standard brain and on coronal section of the mean image of the scans used to obtain the template image. Results are shown at a threshold of p < 0.001 uncorrected.