Consensus classification of posterior cortical atrophy

Abstract

Introduction: A classification framework for posterior cortical atrophy (PCA) is proposed to improve the uniformity of definition of the syndrome in a variety of research settings.

Methods: Consensus statements about PCA were developed through a detailed literature review, the formation of an international multidisciplinary working party which convened on four occasions, and a Web-based quantitative survey regarding symptom frequency and the conceptualization of PCA.

Results: A three-level classification framework for PCA is described comprising both syndrome- and disease-level descriptions. Classification level 1 (PCA) defines the core clinical, cognitive, and neuroimaging features and exclusion criteria of the clinico-radiological syndrome. Classification level 2 (PCA-pure, PCA-plus) establishes whether, in addition to the core PCA syndrome, the core features of any other neurodegenerative syndromes are present. Classification level 3 (PCA attributable to AD [PCA-AD], Lewy body disease [PCA-LBD], corticobasal degeneration [PCA-CBD], prion disease [PCA-prion]) provides a more formal determination of the underlying cause of the PCA syndrome, based on available pathophysiological biomarker evidence. The issue of additional syndrome-level descriptors is discussed in relation to the challenges of defining stages of syndrome severity and characterizing phenotypic heterogeneity within the PCA spectrum.

Discussion: There was strong agreement regarding the definition of the core clinico-radiological syndrome, meaning that the current consensus statement should be regarded as a refinement, development, and extension of previous single-center PCA criteria rather than any wholesale alteration or redescription of the syndrome. The framework and terminology may facilitate the interpretation of research data across studies, be applicable across a broad range of research scenarios (e.g., behavioral interventions, pharmacological trials), and provide a foundation for future collaborative work.

Keywords: Alzheimer's disease; Biomarker; Clinico-radiological syndrome; Pathophysiology; Posterior cortical atrophy.

Fig. 1

Single-participant axial images for one control participant and one patient with PCA showing cerebral blood flow (ASL), glucose metabolism (FDG-PET), atrophy (structural magnetic resonance imaging), and amyloid deposition (florbetapir-PET). For clinical purposes, ¹⁸F-florbetapir images should be read on a gray scale. Abbreviations: ASL, arterial spin labeling; CBF, cerebral blood flow; FDG-PET, ¹⁸F-labeled fluorodeoxyglucose positron emission tomography; PCA, posterior cortical atrophy; SUVR, standard uptake value ratio. For tau deposition data see Ossenkoppele et al [2]. Adapted from Lehmann et al., 2016, Figure 1.

Fig. 2

Mean and standard error ratings of clinical presentation features, symptoms, and signs in PCA, as rated by experts in the online survey. Abbreviation: PCA, posterior cortical atrophy.

Fig. 3

Diagnostic process and PCA classification. Key diagnostic questions at each level are shown in boxes. Syndrome-level descriptions (classification levels 1 and 2) are lightly shaded and disease-level descriptions (classification level 3) are darkly shaded. Among the disease-level classifications, PCA-AD and PCA-prion (solid ovals) are distinguished from PCA-LBD and PCA-CBD (dashed ovals) owing to the current availability of in vivo pathophysiological biomarkers. Other disease-level classifications may be appropriate (e.g., a patient with PCA plus visual hallucinations may have LBD-variant of AD) or anticipated (e.g., PCA attributable to GRN mutations). The thickness of lines connecting classification levels 2 and 3 is intended to reflect the status of AD as the most common cause of PCA. Abbreviations: AD, Alzheimer’s disease; CBD, corticobasal degeneration; LBD, Lewy body disease; PCA, posterior cortical atrophy; tbc, to be confirmed.

Fig. 4

Case study of a PCA patient presenting with “nonvisual” symptoms. Abbreviation: PCA, posterior cortical atrophy.

Fig. 5

Longitudinal clinical, neuropsychological, and neuroimaging profile of an individual with pathologically proven PCA-AD showing example timelines for the provisional stages of prodromal PCA, PCA, and advanced PCA. Serial MR images (top row) show a sagittal view of the patient’s right hemisphere for all nine visits. Repeat scans were fluid-registered to the baseline image, and color-coded voxel-compression maps were produced (bottom row). The scale shows the percentage volume change per voxel (−20% to 20%) with green and blue representing contraction and yellow and red representing expansion. See Kennedy et al. [43] for a more detailed case description. Abbreviations: AD, Alzheimer’s disease; MR, magnetic resonance; PCA, posterior cortical atrophy.