Semantic Variant Primary Progressive Aphasia

Semantic variant primary progressive aphasia (semantic dementia) is a neurodegenerative syndrome with progressive loss of word meaning and object knowledge, caused by degeneration of the anterior temporal lobes, usually more on the left. Speech remains fluent, and repetition and grammar are preserved.

It accounts for about 20 to 25% of frontotemporal dementia. The prevalence is about 1 to 2 in every 100,000 people. Onset is usually between 55 and 65 years, with a slight male predominance and few family cases.

Pathology. TDP-43 type C in most (about 80%), and Alzheimer disease or tau in a minority.

Course. Slow progression over 8 to 12 years. Behavioural change and right temporal involvement develop in time.

Pathophysiology.

Degeneration of the anterior temporal lobe, which acts as a hub of semantic knowledge, disrupts conceptual representation across modalities.

Right sided atrophy produces prosopagnosia and behavioural change.

• Loss of word meaning: poor naming and comprehension of single words ("what is a...?"), with fluent, empty speech.
• Surface dyslexia and dysgraphia (regularising irregular words), and loss of object and face knowledge.
• Preserved repetition, grammar and fluency; preserved episodic memory and visuospatial skills early.
• Behavioural change: rigidity, compulsions, food fads, sweet craving, emotional blunting and loss of empathy; right sided disease gives prosopagnosia and more behavioural change.

Red flags.

• Rapid progression, seizures or focal signs (tumour, encephalitis, herpes simplex encephalitis).
• Severe behavioural disinhibition or risk to self or others.
• Motor neurone disease signs or parkinsonism.

• Clinical diagnosis by consensus criteria: impaired confrontation naming and single word comprehension, with at least 3 of impaired object knowledge, surface dyslexia, intact repetition and spared speech production.
• MRI shows asymmetric anterior temporal lobe atrophy (a "knife edge" appearance); FDG-PET shows anterior temporal hypometabolism.
• Neuropsychology and speech and language assessment, including semantic testing.
• Amyloid biomarkers to exclude Alzheimer disease; genetic testing is rarely needed.
• Exclude herpes simplex encephalitis sequelae, stroke and tumour.

Differential diagnosis. Alzheimer disease, logopenic and nonfluent variants of primary progressive aphasia, behavioural variant frontotemporal dementia, herpes simplex encephalitis sequelae, temporal tumour and depression.

• No disease modifying treatment exists; care is supportive and focuses on communication and behaviour.
• Speech and language therapy: maintain a personal vocabulary of everyday words, relearn and use pictures, and train family communication.
• Cholinesterase inhibitors and memantine do not help and may worsen behaviour; they are avoided.
• Compulsions, food fads and behaviour: 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; no renal adjustment; avoid with monoamine oxidase inhibitors.
• Structured routine, activity planning and environmental adjustments; dietary advice to limit weight gain and diabetes.
• Carer education and support, respite, financial and legal planning, and driving review.
• Advance care planning early, when the person can still take part.

Monitoring. Review every 6 months; track language, behaviour, weight and carer strain.

Referral and escalation. Cognitive neurology, speech and language therapy and old age psychiatry; palliative care in advanced disease.

Special groups. Younger patients: employment and family support. Carers: respite and psychological help.