Alzheimer’s disease (AD)

 

 

Alzheimer’s disease – most common from of dementia occurring in patients over 45 years of age.

In dementia there is a progressive irreversible loss of intellectual function.

Prognosis – 10 years

Dementia is common affecting 5% of people aged over 65 years and 20% of those over 80.

 

 

Aetiology of Alzheimer’s disease

 

AD is primary

 

Genetic component, 15% of cases are familial mostly the autosomal dominant and early onset groups. Late onset probably is less familial.

 

History of head injury or Down’s also increases risk.

 

 

Clinical features

 

Delayed recall

Gradual impairment of memory

Memories for recent events are lost first

Inability to learn new things

Inability to perform purposeful acts or manipulate objects (apraxia)

Insidious - progressive loss intellect and memory

Personality changes

Language function declines

Disorientation

Depression in early stages, later loss of insight

Occasional aggression

Made worse by coexisting illness

 

 

Pathophysiology

 

General loss of neurones, atrophy of cerebral cortex and hippocampus.

 

Microscopically there are extracellular deposits of abnormal amyloid; amyloid deposition may also damage the walls of blood vessels in the brain.

 

Within the cytoplasm of abnormal neurones are pathological structures called neurofibrillary tangles.

 

Reduction in production of acetylcholine may partly account for memory disturbance, also disturbances of 5HT, glutamate and substance P.

 

 

Other causes of dementia

 

The second most common cause of dementia has a vascular aetiology and is usually called multi-infarct dementia.

 

Third most common is Lewy body dementia.

Lewy body are collections of abnormal protein found inside neurones.

 

Other forms of dementia are Creutzfeldt – Jakob, Pick’s, Huntington’s and Parkinson’s disease.

 

 

Pharmacology in dementia

 

Initial cognitive impairment is caused by decline in levels of acetylcholine in cerebral cortex and basal forebrain.

 

Acetylcholinesterase inhibitors such as Donepezil (Aricept) improve symptoms, the do not delay, stop or cure Alzheimer’s dementia.

 

Memantine is a NMDA receptor antagonist, blocks the effects of pathologically raised levels of glutamate.