Posterior Cortical Atrophy

Abstract

Posterior cortical atrophy (PCA) is a relatively rare neurodegenerative syndrome marked by prominent disturbance in visuoperceptual and visuospatial functioning. Its prevalence and incidence rates are unknown (Crutch SJ, Lehmann M, Schott JM, Rabinovici GD, Rossor MN, Fox NC, Lancet Neurol. 11:170-178, 2012). There has been increased awareness of this condition among the general public, with the diagnosis made by British author Sir Terry Pratchett (1948–2015). He was quite open about his journey with the disease, making several documentaries and appearing on a number of radio programs. He was initially misdiagnosed, which is typical with the challenges of making this diagnosis. This condition was also written about by American neurologist/author Dr. Oliver Sacks in his 2010 book, The Mind’s Eye, in which he describes this condition in one of his case reports.

In clinical settings, presenting complaints from patients with differential diagnosis of PCA often involve disturbance in activities of daily living, such as difficulties recognizing familiar routes, reading maps, or locating and organizing objects in the environment. They may report recent history of fender benders or more serious car accidents. Reading may have become challenging because of its visuospatial component, but verbal comprehension likely remains intact. In a recent study, patients with PCA were found to be more severely impaired in everyday skills and self-care (majority associated with visuoperceptual and visuospatial impairments) than their Alzheimer’s disease (AD) counterparts, while more AD patients showed high levels of impairment in stereotypic and motor behaviors, but they maintained motivation to keep in contact with friends or family (Shakespeare TJ, Yong KX, Foxe D, Hodges J, Crutch SJ. Journal of Alzheimer’s Disease 43:381–384, 2015).

Appendix 1 [6]

Core Features of the PCA Clinico-radiological Syndrome (Classification Level 1)

Clinical, cognitive, and neuroimaging features are rank ordered in terms of (decreasing) frequency at first assessment, as rated by online survey participants.

Clinical Features

• Insidious onset

• Gradual progression

• Prominent early disturbance of visual +/− other posterior cognitive functions

Cognitive Features

At least three of the following must be present as early or presenting features +/– evidence of their impact on activities of daily living:

• Space perception deficit

• Simultanagnosia

• Object perception deficit

• Constructional dyspraxia

• Environmental agnosia

• Oculomotor apraxia

• Dressing apraxia

• Optic ataxia

• Alexia

• Left/right disorientation

• Acalculia

• Limb apraxia (not limb-kinetic)

• Apperceptive prosopagnosia

• Agraphia

• Homonymous visual field defect

• Finger agnosia

All of the following must be evident:

• Relatively spared anterograde memory function

• Relatively spared speech and nonvisual language functions

• Relatively spared executive functions

• Relatively spared behavior and personality

Neuroimaging

• Predominant occipitoparietal or occipitotemporal atrophy/hypometabolism/hypoperfusion on MRI/FDG-PET/SPECT

Exclusion Criteria

• Evidence of a brain tumor or other mass lesion sufficient to explain the symptoms

• Evidence of significant vascular disease including focal stroke sufficient to explain the symptoms

• Evidence of afferent visual cause (e.g., optic nerve, chiasm, or tract)

• Evidence of other identifiable causes for cognitive impairment (e.g., renal failure)

Classification of PCA-Pure and PCA-Plus (Classification Level 2)

PCA-Pure

Individuals must fulfill the criteria for the core clinico-radiological PCA syndrome (level 1) and not fulfill core clinical criteria for any other neurodegenerative syndrome.

PCA-Plus

Individuals must fulfill the criteria for the core clinico-radiological PCA syndrome (level 1) and also fulfill core clinical criteria for at least one other neurodegenerative syndrome, such as dementia with Lewy bodies (DLB).

Following the diagnostic criteria proposed by the DLB consortium [19], individuals must exhibit two or more core features of DLBs (list A) or one or more core features (list A) and one or more suggestive features (list B):

• A. Core features

Fluctuating cognition with pronounced variations in attention and alertness

• Recurrent visual hallucinations that are typically well formed and detailed

• Spontaneous features of parkinsonism

• B. Suggestive features

• Rapid eye movement (REM) sleep behavior disorder

• Severe neuroleptic sensitivity

Low dopamine transporter uptake in basal ganglia demonstrated by SPECT or PET imaging

Corticobasal Syndrome (CBS)

Following the modified CBS criteria proposed by [20], a diagnosis of probable CBS requires asymmetric presentation of two of the following:

• (a) Limb rigidity or akinesia

• (b) Limb dystonia

• (c) Limb myoclonus

plus two of the following:

• (d) Orobuccal or limb apraxia

• (e) Cortical sensory deficit

• (f) Alien limb phenomena (more than simple levitation)

Possible corticobasal syndrome may be symmetric and requires presentation of one of a–c plus one of d–f.

Diagnostic Criteria for Disease-Level Descriptions (Classification Level 3)

PCA-AD

Following International Working Group (IWG2) [21], the classification of PCA-AD (and, by extension, of IWG2’s broader category of “atypical AD”) requires fulfillment of the PCA syndrome (classification level 1) plus in vivo evidence of Alzheimer’s pathology (at least one of the following):

• Decreased Aβ_1–42 together with increased T-tau and/or P-tau in CSF

• Increased tracer retention on amyloid PET

• Alzheimer’s disease autosomal-dominant mutation present (in PSEN1, PSEN2, or APP)

• If autopsy confirmation of AD is available, the term definite PCA-AD would be appropriate.

PCA-LBD

Molecular biomarkers for LBD are currently unavailable; therefore, an in vivo diagnosis of PCA-LBD cannot be assigned at present. For individuals who are both classified as PCA-mixed by virtue of fulfilling DLB clinical criteria and shown to be AD-biomarker negative, the term probable PCA-LBD may be appropriate. If autopsy confirmation of LBD is available, the term definite PCA-LBD would be appropriate. Other disease-level classifications may also be appropriate for individuals with mixed or multiple pathologies (e.g., PCA-AD/LBD).

PCA-CBD

Molecular biomarkers for CBD are currently unavailable; therefore, an in vivo diagnosis of PCA-CBD cannot be assigned at present. For individuals who are both classified as PCA-mixed by virtue of fulfilling CBS criteria and shown to be AD-biomarker negative, the term probable PCA-CBD may be appropriate. If autopsy confirmation of CBD is available, the term definite PCA-CBD would be appropriate.

PCA-Prion

There are a number of promising biomarkers for prion disease (e.g., [22,23,24]), but these have yet to be incorporated into diagnostic criteria. Pending this process, an in vivo diagnosis of PCA-prion may be feasible. If autopsy confirmation of prion disease is available or a known genetic form of prion disease has been determined, the term definite PCA-prion would be appropriate.

From: Crutch SJ, Schott JM, Rabinovici GD, et al. Consensus classification of posterior cortical atrophy [6].