Posterior cortical atrophy: clinical, neuroimaging, and neuropathological features

ABSTRACT

Introduction

Posterior Cortical Atrophy (PCA) is a neurodegenerative disorder characterized by impairment of higher-order visual processing in the setting of progressive atrophy of the parietal and occipital lobes. The underlying pathology is variable but most commonly Alzheimer’s disease. The majority of individuals develop symptoms before 65 years of age; however, delayed diagnosis is common due to misattribution of symptoms to ocular rather than cortical pathology.

Areas covered

The purpose of this review is to provide readers with an in-depth analysis of Posterior Cortical Atrophy syndrome, including clinical, imaging, pathological, and genetic features, management, and treatments.

Expert opinion

Most patients present initially with a relatively pure visuoperceptual-visuospatial syndrome, though other cognitive domains become affected over time. Structural neuroimaging demonstrates parieto-occipital or temporo-occipital predominant atrophy. Cerebrospinal fluid Alzheimer’s disease biomarkers, or amyloid/tau PET imaging can help evaluate for underlying Alzheimer’s disease, which is the most common underlying neuropathology. The cornerstone of management is focused on nonpharmacologic measures. Early etiologic diagnosis is important with the arrival of disease-modifying therapies, especially for Alzheimer’s disease.

KEYWORDS:

• Alzheimer’s disease
• early onset Alzheimer’s
• posterior cortical atrophy
• Lewy body disease
• visual agnosia

Article highlights

• The diagnosis of posterior cortical atrophy is frequently delayed or misdiagnosed.

• The disorder is characterized by insidious onset and gradual progression of prominent early visuoperceptual or visuospatial disturbance with variable involvement of other posterior cortical functions.

• Structural imaging and advanced imaging techniques such as FDG-PET, Amyloid, and Tau PET can aid in the diagnosis of underlying pathology.

• Underlying pathology is most frequently: Alzheimer’s disease with less frequent pathological causes including Lewy Body Disease, Corticobasal Degeneration, prion disease, or frontotemporal lobar degeneration with TDP-43 Type A inclusions.

• The cornerstone of management is focused on nonpharmacologic measures. Treatment with emerging disease modifying amyloid and other therapies may provide meaningful benefit; however, further study is warranted.

• Further research into genetic, neurodevelopmental, and environmental risk factors is required.

Acknowledgments

We would like to thank Dr Renaud La Joie and Ashley DuBord for their assistance with imaging and figure generation.

Declaration of interest

G Rabinovici receives research support from NIH, Alzheimer’s Association, American College of Radiology, Rainwater Charitable Foundation, Avid Radiopharmaceuticals, GE Healthcare, Genentech, Life Molecular Imaging. He has served on scientific advisory boards for Alector, Eli Lilly, Genentech, Roche, and Merck. He serves on a DSMB for Johnson & Johnson. He is an Associate Editor for JAMA Neurology. He receives funding from NIH/NIA P30-AG062422, NIH/NIA R35 AG072362, Alzheimer’s Association ZEN-21-848,216, Rainwater Charitable Foundation. J Best receives research support from a NIH research training grant – T32 AG 23481-17. M Chapleau received research support from the Fonds de recherche du Québec - Santé (FRQS). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work is supported with grant funding support from NIH/NIA P30-AG062422, NIH/NIA R35 AG072362, Alzheimer’s Association ZEN-21-848216, Rainwater Charitable Foundation.