Distinct clinical and metabolic deficits in PCA and AD are not related to amyloid distribution

Abstract

Background/objective: Patients with posterior cortical atrophy (PCA) often have Alzheimer disease (AD) at autopsy, yet are cognitively and anatomically distinct from patients with clinical AD. We sought to compare the distribution of β-amyloid and glucose metabolism in PCA and AD in vivo using Pittsburgh compound B (PiB) and FDG-PET.

Methods: Patients with PCA (n = 12, age 57.5 ± 7.4, Mini-Mental State Examination [MMSE] 22.2 ± 5.1), AD (n = 14, age 58.8 ± 9.6, MMSE 23.8 ± 6.7), and cognitively normal controls (NC, n = 30, age 73.6 ± 6.4) underwent PiB and FDG-PET. Group differences in PiB distribution volume ratios (DVR, cerebellar reference) and FDG uptake (pons-averaged) were assessed on a voxel-wise basis and by comparing binding in regions of interest (ROIs).

Results: Compared to NC, both patients with AD and patients with PCA showed diffuse PiB uptake throughout frontal, temporoparietal, and occipital cortex (p < 0.0001). There were no regional differences in PiB binding between PCA and AD even after correcting for atrophy. FDG patterns in PCA and AD were distinct: while both groups showed hypometabolism compared to NC in temporoparietal cortex and precuneus/posterior cingulate, patients with PCA further showed hypometabolism in inferior occipitotemporal cortex compared to both NC and patients with AD (p < 0.05). Patients with AD did not show areas of relative hypometabolism compared to PCA.

Conclusions: Fibrillar amyloid deposition in PCA is diffuse and similar to AD, while glucose hypometabolism extends more posteriorly into occipital cortex. Further studies are needed to determine the mechanisms of selective network degeneration in focal variants of AD.

Figure 1. Patterns of Pittsburgh compound B (PiB) and FDG binding in Alzheimer disease (AD) and posterior cortical atrophy (PCA) compared to normal controls (NC) and to each other

T-score maps are rendered on the ch2 template brain. All results are presented at a threshold of p < 0.001, uncorrected for multiple comparisons.

Figure 2. Box plots representing pre-atrophy and post-atrophy Pittsburgh compound B (PiB) and FDG uptake for the lateral occipitotemporal region and occipital percentage (ratio of occipital to global cortical PiB/FDG)

*Less than Alzheimer disease (AD) and posterior cortical atrophy (PCA), p < 0.05. **Greater than AD and PCA, p < 0.05. †Less than normal controls (NC), p < 0.05. ‡Less than AD and NC, p < 0.05.