Posterior Cortical Atrophy

Posterior cortical atrophy is a progressive neurodegenerative syndrome with early, prominent visuospatial and visuoperceptual dysfunction caused by degeneration of the parieto occipital and occipitotemporal cortex. Alzheimer disease pathology underlies about 80 to 90% of cases.

It is rare, with an unknown prevalence, and probably accounts for about 5% of early onset Alzheimer type dementia. Onset is usually between 50 and 65 years, earlier than typical Alzheimer disease, and women are slightly more affected.

Other causes. Corticobasal degeneration, Lewy body disease and prion disease account for most of the remainder.

Course. Progressive over 5 to 10 years. Memory and insight are relatively preserved early, and the delay in diagnosis is often 3 to 4 years, as patients first consult ophthalmologists.

Pathophysiology.

Neurofibrillary tangles and amyloid deposition concentrate in the occipital, parietal and posterior temporal cortex, disrupting dorsal (where) and ventral (what) visual streams.

The reason for this regional vulnerability is unknown.

• Difficulty reading, finding objects and judging distance despite normal eye tests; trouble with stairs, driving and dressing.
• Simultanagnosia (seeing parts but not the whole), optic ataxia, ocular apraxia and visual agnosia.
• Elements of Balint syndrome and Gerstmann syndrome (acalculia, agraphia, finger agnosia, left right confusion).
• Alexia, environmental disorientation, visual hallucinations in some.
• Memory, language and insight are relatively preserved early; anxiety and depression are common.

Red flags.

• Rapid decline over weeks to months (prion disease).
• Visual field loss, papilloedema or new focal signs (tumour, stroke).
• Seizures or myoclonus.

• Clinical diagnosis by consensus criteria: insidious onset, early visuospatial or perceptual deficits, and relative sparing of memory and insight.
• Ophthalmology review to exclude eye disease and cataract; visual field testing.
• Neuropsychology; MRI shows posterior atrophy, and FDG-PET or SPECT shows posterior hypometabolism.
• Amyloid PET or cerebrospinal fluid biomarkers to confirm Alzheimer pathology; EEG and diffusion MRI if prion disease is suspected.
• Blood tests for reversible dementia causes: B12, thyroid, calcium, HIV and syphilis serology.

Differential diagnosis. Typical Alzheimer disease, dementia with Lewy bodies, corticobasal syndrome, Creutzfeldt-Jakob disease (Heidenhain variant), occipital stroke, cataract and macular disease, and functional visual loss.

• Disease modifying treatment may be considered for early disease with confirmed amyloid pathology, through a specialist centre, but the evidence for atypical presentations is limited. Lecanemab 10 mg/kg intravenously over about 1 hour every 2 weeks. Maximum 10 mg/kg each infusion. Monitor with MRI before the 5th, 7th and 14th infusions for amyloid related imaging abnormalities, and for infusion reactions; test for APOE e4 before treatment. Avoid with anticoagulants, a history of large haemorrhage, multiple microhaemorrhages on MRI, and in pregnancy; no renal or hepatic adjustment. Availability and funding vary.
• Donepezil: 5 mg orally once daily at night for 4 to 6 weeks, then 10 mg once daily. Maximum 10 mg daily (23 mg daily in moderate to severe disease through a specialist). Monitor heart rate, weight, nausea, diarrhoea, sleep disturbance and syncope. Avoid in bradycardia, sick sinus syndrome, heart block and active peptic ulcer; use caution in asthma, chronic obstructive pulmonary disease and seizures; no renal adjustment; use caution in hepatic impairment.
• Memantine for moderate to severe disease: 5 mg orally once daily, increased by 5 mg weekly to 20 mg once daily. Maximum 20 mg daily. Monitor confusion, dizziness and blood pressure. Halve the dose (maximum 10 mg daily) when creatinine clearance is under 30 mL/min; avoid with epilepsy unless controlled.
• Treat depression and anxiety: sertraline 50 mg orally once daily, increased by 50 mg every 1 to 2 weeks as needed to 100 to 200 mg daily. Maximum 200 mg daily. Monitor mood and suicidal thoughts, sodium, bleeding and serotonin toxicity. Reduce dose (or use alternate days) in hepatic impairment; avoid with monoamine oxidase inhibitors.
• Occupational therapy, vision rehabilitation: good lighting, contrast, decluttering, large print or text-to-speech tools, labels, and home safety review.
• Driving cessation advice and a mobility plan; carer support and legal planning.

Monitoring. Review every 6 months; track cognition, function, mood and carer strain.

Referral and escalation. Memory clinic or cognitive neurology; low vision services; urgent review for rapid decline.

Special groups. Younger patients: employment, finances and family counselling; genetic counselling in familial cases.