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Posterior Cortical Atrophy


Quick Start: Posterior Cortical Atrophy

Definition and etiology

  • Posterior cortical atrophy (PCA) is a clinical syndrome characterized by progressive visual and visuospatial dysfunction.

  • Most patients present between the ages of 50 and 65 years (mean age 59 years), although some present in their 70s and 80s.

  • Underlying Alzheimer’s disease pathology is most common. Other common pathologies include Lewy body disease and corticobasal degeneration.

Prevalence

  • Posterior cortical atrophy is rare, making up about 5% of patients in a specialty cognitive clinic.

Cognitive and behavioral symptoms

  • Common visuospatial and perceptual deficits include: neglecting or not perceiving space (often on the left), difficulty perceiving objects and faces (prosopagnosia), difficulty reading, and Balint syndrome (ocular motor apraxia, optic ataxia, and simultanagnosia).

  • Common nonvisuospatial deficits include: apraxia and Gerstmann syndrome (acalculia, left-right disorientation, finger agnosia, and agraphia).

  • The following should all be relatively spared at onset: episodic memory, speech and nonvisual language, executive function, behavior, personality, and insight.

Diagnostic criteria Core features of the posterior cortical atrophy clinico-radiological syndrome

  • Clinical features:

    • All 3 must be present: insidious onset, gradual progression, prominent early disturbance of visual ± other posterior cognitive functions.

  • Cognitive features:

    • At least 3 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, apperceptive prosopagnosia, agraphia, homonymous visual field defect, finger agnosia.

    • All of the following must be relatively spared: anterograde memory, speech and nonvisual language, executive functions, behavior and personality.

  • Neuroimaging: Predominant occipito-parietal or occipito-temporal atrophy/hypometabolism/hypoperfusion on MRI/FDG-PET/SPECT

  • Exclusion criteria: Evidence of: a brain tumor or other mass lesion sufficient to explain the symptoms, significant vascular disease including focal stroke sufficient to explain the symptoms, afferent visual cause (e.g., optic nerve, chiasm, or tract), or other identifiable causes for cognitive impairment (e.g., renal failure)

Treatment

  • Most patients will benefit from cholinesterase inhibitors and all patients will benefit from nonpharmacological treatment approaches.

Top differential diagnoses

  • Underlying Alzheimer’s disease pathology is most common. Other common pathologies include Lewy body disease, corticobasal degeneration, and rarely, prion disease. Cerebrovascular disease may also produce similar symptoms.

A 62-year-old woman was referred for difficulty reading. She made several trips to her optometrist for new glasses over the last year without improvement. The optometrist could find no cause for her reading difficulty, although he documented a partial left lateral hemianopsia. The optometrist recommended she see her ophthalmologist who, upon finding no ocular problems, referred her to a general neurologist. After ruling out a strokes and mass lesions, the general neurologist referred her to us.

Her chief complaint was, “No one can get my eyeglass prescription right.” In addition to difficulty reading, we learned that she had scraped the left side of her car backing out of her garage. Her examination showed that although she was impaired in reading paragraphs she had no difficulty reading single words, and she performed normally on tests of memory for visually or auditorily presented words. She was able to write sentences without difficulty. She was normal on tests of word fluency to letters and categories. Her naming of line drawings was impaired, but it was clear that it was owing to difficulties perceiving and comprehending the drawings, because when she was given a semantic cue (such as, “It’s an ocean animal”) she was usually able to say the correct name. She experienced difficulty finding the numbers on the Trailmaking Test Part A, resulting in an impaired, slow performance. She showed a similar impairment on the Trailmaking Test Part B. Subtracting serial 7s from 100 was also impaired. The elementary neurological examination showed the previously noted partial left lateral hemianopsia, which seemed to diminish with a stronger stimulus, making us wonder if it were actually left-sided neglect. Her magnetic resonance imaging (MRI) scan showed prominent atrophy in right greater than left occipital and parietal cortices.

A diagnosis of the posterior cortical atrophy syndrome was made. We counseled her about not driving and provided her and her family with a home safety tips and recommendations handout for individuals with dementia and visual dysfunction. She was interested in both standard and experimental pharmacological treatments. After starting her on a cholinesterase inhibitor we screened her for a clinical trial, which included both amyloid and tau positron emission tomography (PET) scans. These revealed that although she had amyloid plaques throughout the brain, she had tau concentrated posteriorly in bilateral occipital and parietal cortices.

Visual problems are common in many dementias, including Alzheimer’s disease, dementia with Lewy bodies, corticobasal syndrome, and vascular dementia. Some patients with progressive visual problems severe enough to compromise function do not meet criteria for any neurodegenerative diseases. These patients are best characterized as having posterior cortical atrophy (sometimes abbreviated as PCA).

Prevalence, Definition, and Pathology

Posterior cortical atrophy is not a disease. It is a clinical syndrome that patients may manifest, with varying underlying neurodegenerative disease etiologies. Alzheimer’s disease (see Chapter 4 ) is by far the most common underlying pathology for posterior cortical atrophy, which is why other terms for this disorder include the “visual variant of Alzheimer’s disease” and “biparietal Alzheimer’s disease.” In fact, one study showed that 14% of patients diagnosed with Alzheimer’s disease had prominent visuospatial problems, suggesting that posterior cortical atrophy may be one end of a continuum of Alzheimer’s signs and symptoms ( ). Other common pathologies underlying posterior cortical atrophy include Lewy body disease (see Chapter 8 ), corticobasal degeneration (see Chapter 13 ), and rarely, prion disease (see Chapter 16 ). Interestingly, according to the criteria, cerebrovascular disease (see Chapter 7 ) sufficient to cause the syndrome of posterior cortical atrophy is exclusionary, but the phenomenology and nonpharmacological treatment approaches outlined below would be equally relevant.

Most individuals with posterior cortical atrophy are young, presenting between 50 and 65 years of age, although some patients present in their 70s and 80s. In one study the mean age of onset was approximately 59 years, with almost 83% presenting before age 65 years ( ). Posterior cortical atrophy is rare, making up about 5% of patients in a specialty cognitive clinic and up to 13% of cases of early-onset Alzheimer’s disease ( ).

Criteria

Posterior cortical atrophy is described using a three-level classification framework. Level 1 establishes the clinical syndrome, based upon clinical, cognitive, and neuroimaging data ( Box 11.1 ). Level 2 establishes whether the presentation is “pure” or whether the patient meets the criteria for posterior cortical atrophy plus another neurodegenerative disease syndrome ( Box 11.2 ). Level 3 adds biomarker evidence of the underlying pathology (or pathologies) ( Box 11.3 ).

Box 11.1
Core Features of the Posterior Cortical Atrophy Clinico-Radiological Syndrome (Level 1)
Modified from Crutch, S. J., Schott, J. M., Rabinovici, G. D., et al. 2017. Consensus classification of posterior cortical atrophy. Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, 13(8), 870–884.
Clinical, cognitive, and neuroimaging features are rank ordered by frequency at first assessment as rated by online survey participants. FDG-PET , 18F-labeled fluorodeoxyglucose positron emission tomography; MRI , magnetic resonance imaging; SPECT , single-photon emission computed tomography.

Clinical features (all three must be present):

  • Insidious onset

  • Gradual progression

  • Prominent early disturbance of visual ± other posterior cognitive functions

Cognitive features:

  • At least three 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 occipito-parietal or occipito-temporal 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)

Box 11.2
Classification of Posterior Cortical Atrophy-Pure and Posterior Cortical Atrophy-Plus (Level 2)
Modified from Crutch, S. J., Schott, J. M., Rabinovici, G. D., et al. 2017. Consensus classification of posterior cortical atrophy. Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, 13(8), 870–884.

Posterior cortical atrophy-pure:

  • Individuals must fulfill the criteria for the core clinico-radiological posterior cortical atrophy syndrome (level 1), and not fulfill core clinical criteria for any other neurodegenerative syndrome.

Posterior cortical atrophy-plus:

  • Individuals must fulfill the criteria for the core clinico-radiological posterior cortical atrophy syndrome (level 1) and also fulfill core clinical criteria for at least one other neurodegenerative syndrome, such as:

Box 11.3
Diagnostic Criteria for Posterior Cortical Atrophy Disease-Level Descriptions (Level 3)
Modified from Crutch, S. J., Schott, J. M., Rabinovici, G. D., et al. 2017. Consensus classification of posterior cortical atrophy. Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, 13(8), 870–884.

Posterior cortical atrophy-Alzheimer’s disease:

  • Fulfillment of the posterior cortical atrophy syndrome (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 cerebrospinal fluid

    • Increased tracer retention on amyloid positron emission tomography (PET)

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

  • If autopsy confirmation of Alzheimer’s disease is available, the term definite posterior cortical atrophy-Alzheimer’s disease would be appropriate.

Posterior cortical atrophy-Lewy body disease:

  • Molecular biomarkers for Lewy body disease are currently unavailable; therefore an in vivo diagnosis of posterior cortical atrophy-Lewy body disease cannot be assigned at present.

  • For individuals who are both:

    • classified as posterior cortical atrophy-plus by virtue of fulfilling dementia with Lewy bodies clinical criteria (see Chapter 8 ) and

    • shown to be Alzheimer’s disease-biomarker negative, the term probable posterior cortical atrophy-Lewy body disease may be appropriate.

  • If autopsy confirmation of Lewy body disease is available, the term definite posterior cortical atrophy-Lewy body disease would be appropriate.

  • Other disease-level classifications may also be appropriate for individuals with mixed or multiple pathologies (e.g., posterior cortical atrophy-Alzheimer’s/Lewy body diseases).

Posterior cortical atrophy-corticobasal degeneration:

  • Molecular biomarkers for corticobasal degeneration are currently unavailable; therefore an in vivo diagnosis of posterior cortical atrophy-corticobasal degeneration cannot be assigned at present.

  • For individuals who are both:

    • classified as posterior cortical atrophy-plus by virtue of fulfilling corticobasal syndrome criteria (see Chapter 13 ) and

    • shown to be Alzheimer’s disease-biomarker negative, the term probable posterior cortical atrophy-corticobasal degeneration may be appropriate.

  • If autopsy confirmation of corticobasal degeneration is available, the term definite posterior cortical atrophy-corticobasal degeneration would be appropriate.

  • Other disease-level classifications may also be appropriate for individuals with mixed or multiple pathologies (e.g., posterior cortical atrophy-Alzheimer’s disease/corticobasal degeneration).

Posterior cortical atrophy-prion disease:

  • There are a number of promising biomarkers for prion disease; pending this process, an in vivo diagnosis of posterior cortical atrophy-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 posterior cortical atrophy-prion would be appropriate.

Common Signs, Symptoms, and Stages

There are two types of symptoms and signs that are commonly seen in posterior cortical atrophy. The first are visuospatial and perceptual deficits, including neglecting or not perceiving space (often on the left), difficulty perceiving objects and faces (prosopagnosia), difficulty reading, and Balint syndrome (ocular motor apraxia, optic ataxia, and simultanagnosia; see later). The second are nonvisuospatial deficits that arise with posterior cortical dysfunction including apraxia (see Chapter 13 ) and Gerstmann syndrome (acalculia, left-right disorientation, finger agnosia, and agraphia; see below). Importantly, the following should all be relatively spared at onset: episodic memory, speech and nonvisual language, executive function, behavior, personality, and insight. As with most neurodegenerative disorders, as the disease progresses many of these initially spared functions will become impaired.

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