Logopenic Variant Primary Progressive Aphasia

Logopenic variant primary progressive aphasia is a neurodegenerative syndrome with impaired single word retrieval and impaired repetition of sentences and phrases, caused by left temporoparietal degeneration. Alzheimer disease pathology is present in about 80 to 90% of cases.

It accounts for about 30% of primary progressive aphasia. The prevalence is not well known, and onset is usually between 55 and 70 years. Both sexes are affected.

Pathology. Alzheimer disease (amyloid and tau) in most; frontotemporal lobar degeneration with GRN variants in a few.

Course. Progressive over 8 to 10 years, with memory impairment and other cognitive deficits developing; the course is generally similar to early onset Alzheimer disease.

Pathophysiology.

Atrophy of the left posterior superior temporal and inferior parietal cortex disrupts the phonological loop, which supports short term verbal storage.

Neurofibrillary tangles and amyloid plaques concentrate in these regions.

• Slow speech with frequent word finding pauses; impaired repetition of long sentences.
• Phonological errors (sound substitutions) in speech, with preserved grammar, motor speech and single word comprehension.
• Difficulty with digit span and verbal short term memory.
• Later memory loss, anxiety, mood change and reduced calculation.

Red flags.

• Sudden onset (stroke) or rapid decline over weeks (prion disease, tumour).
• Seizures, headache or focal signs.
• Prominent behavioural change or motor neurone disease features.

• Clinical diagnosis by consensus criteria: impaired single word retrieval in speech and naming, with impaired repetition of sentences and phrases, and at least 3 of phonological errors, spared single word comprehension, spared motor speech and absence of frank agrammatism.
• Speech and language assessment; neuropsychology.
• MRI shows left posterior temporal and inferior parietal atrophy; FDG-PET shows left temporoparietal hypometabolism.
• Amyloid PET or cerebrospinal fluid (amyloid and tau) or plasma biomarkers to confirm Alzheimer pathology.
• Blood tests to exclude reversible causes; genetic testing for early onset with family history.

Differential diagnosis. Alzheimer disease with amnestic onset, nonfluent and semantic variants, stroke, tumour, Creutzfeldt-Jakob disease, depression and functional language disorder.

• Speech and language therapy: word retrieval strategies, repetition tasks, written aids and training for family partners.
• 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.
• 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.
• Lecanemab 10 mg/kg intravenously over about 1 hour every 2 weeks may be considered in early disease with confirmed amyloid pathology, through a specialist centre. Maximum 10 mg/kg each infusion. Monitor with MRI before the 5th, 7th and 14th infusions for amyloid related imaging abnormalities; test for APOE e4 before treatment. Avoid with anticoagulants, a history of large haemorrhage and multiple microhaemorrhages. Availability and funding vary, and evidence is limited for atypical presentations.
• 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.
• Carer support, advance care planning, driving review and legal planning.

Monitoring. Review every 6 months; track language, memory, function and carer strain.

Referral and escalation. Memory clinic or cognitive neurology; speech and language therapy; old age psychiatry.

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