Hippocampal Sclerosis of Ageing

Hippocampal sclerosis of ageing is neuronal loss and gliosis in the CA1 region and subiculum of the hippocampus that is out of proportion to Alzheimer pathology. It is a frequent cause of amnestic dementia in the very old.

It is found at autopsy in a notable minority of people over 85, and it is commonly accompanied by TDP-43 deposition.

Pathophysiology. Most cases show TDP-43 pathology (like limbic predominant age related TDP-43 encephalopathy), and many have Alzheimer, vascular or Lewy changes. Vascular insufficiency and chronic hypoperfusion have been proposed contributors. Hippocampal sclerosis from epilepsy or hypoxia is a different disorder.

Slowly progressive amnestic cognitive impairment, which can mimic Alzheimer disease, with a later onset and often slower decline. Language and executive function are initially spared. Seizures are uncommon.

Definite diagnosis is by neuropathology. During life, MRI shows hippocampal atrophy (especially of the head and CA1) out of proportion to cortical atrophy, with amyloid biomarkers negative or showing a low load. Exclude Alzheimer disease, vascular dementia, depression, and metabolic and drug causes.

Differential diagnosis.

• Alzheimer disease.
• Limbic predominant age related TDP-43 encephalopathy and primary age related tauopathy.
• Temporal lobe epilepsy and limbic encephalitis.

There is no disease modifying treatment. Manage vascular risk factors, hearing and vision, mood and sleep; offer exercise and cognitive engagement. Cholinesterase inhibitors may be tried but benefit is uncertain. Provide carer support and advance planning.

Monitoring. Cognition and function every 6 to 12 months.