2 Neuroscience2.13 Neurodegeneration
2.13.9 Metabolic cognitive syndromes
2 min read
Written by Resident Doctor Committee · Published
New in the 2027 syllabus
The College added this topic for exams from January 2027.
Look for treatable causes
Metabolic disease can cause cognitive decline, behavioural change or delirium. The brain's energy supply is disrupted, toxic substances build up, or a nutrient is lacking.
The time course helps. Acute confusion that fluctuates suggests a different process from a dementia syndrome that worsens slowly.
Causes can be mixed. Finding a metabolic abnormality does not rule out a neurodegenerative disorder alongside it.
Cause | Mechanism or clue |
|---|---|
Hypothyroidism | Less thyroid hormone signalling, with slowed thinking |
Vitamin B12 deficiency | Neurological problems, sometimes without anaemia |
Thiamine deficiency | Brain energy metabolism is impaired; part of the Wernicke-Korsakoff spectrum |
Hepatic or renal failure | Substances build up that affect brain function |
Wilson disease | Copper builds up and damages the liver and brain |
Wilson disease
Wilson disease is an autosomal recessive disorder caused by pathogenic (disease-causing) variants in the ATP7B gene. The liver cannot properly excrete copper into bile or load it into caeruloplasmin, the protein that carries most copper in the blood. Copper then builds up.
How it presents
liver disease
psychiatric symptoms: personality change, depression or psychosis
neurological signs: tremor, dystonia, dysarthria (slurred speech) and parkinsonism
cognitive problems, which often affect executive function.
Kayser-Fleischer rings are copper deposits in the cornea. They need proper ophthalmological assessment. Their absence does not exclude the disease.
Diagnosis
Combine the clinical findings with copper studies, and sometimes genetic or liver investigations. No single caeruloplasmin result is enough on its own.
Total serum copper can be low even when the tissues hold too much copper. This is because much of the copper in the blood normally travels bound to caeruloplasmin.
Management
Treatment, under specialist supervision, lowers the body's copper load and stops more building up. Recognising the disease early can change the course of the illness.
Once the diagnosis is confirmed, assess the family. Relatives who seem well may also need investigation.