20B. Alzheimer disease
Alzheimer disease (AD) is the most common neurodegenerative disease and the cause of 2/3 of all cases of dementia. It’s characterised by progressive loss of neurons, initially cholinergic ones but later others as well, as well as accumulation of intracellular neurofibrillary tangles and extracellular amyloid plaques.
Risk factors
- Old age
- Family history
- Head trauma
- Vascular risk factors
- APOE e4 genotype
- Down syndrome
Protective factors
- Higher education
- Good diet
- Exercise
- Statins
Pathomechanism
Transmembranous APP is cleaved into Aβ peptides, which aggregate and form amyloid plaques extracellularly, which may have a neurotoxic effect. Hyperphosphorylated tau protein in the cells form neurofibrillary tau tangles, which may have a neurotoxic effect.
These changes begin in the limbic structures and spread from there, eventually reaching the cortex. These changes can be staged according to the Braak staging.
Clinical features
Patients initially have impairment of memory and learning. Later, impairment of executive function, perceptual motor ability and language occurs. The symptoms progress slowly and it’s difficult to determine the onset.
Diagnosis and evaluation
First, the diagnosis of dementia must be established, with tests like MMSE or the clock-drawing test. Typical clinical features and a typical clinical course is usually enough for diagnosis, but in all cases of dementia, neuroimaging and screening tests for reversible causes should be made (see topic 11B).
We can perform amyloid PET scan, which shows the amyloid plaques in the brain. We can also measure amyloid plaques or phosphorylated tau tangles in the CSF.
Only an autopsy can truly confirm whether the condition was Alzheimer or not.
Treatment
Pharmacological treatment improves the symptoms of Alzheimer; no pharmacological treatment is available to slow the progression of the disease. However, these drugs also cause significant side effects in elderly. Non-pharmacological interventions are more important in case of AD.
Treatment options include cholinesterase inhibitors and memantine. These slightly improve cognitive functions, but have significant side effects.
A drug called aducanumab (Aduhelm®) was recently approved by the FDA in the treatment of AD, but there is no evidence that it actually helps. I wrote more about it in pharmacology.