Numbers
- Commonest cause of dementia,
- Most cases are sporadic;
- 5% of cases are inherited
- Autosomal dominant trait mutations in the
- Amyloid precursor protein (chromosome 21),
- Presenilin 1 (chromosome 14),
- Presenilin 2 (chromosome 1) genes
- Risk of Alzheimer’s disease is increased in those with the apolipoprotein E allele E4 (present in 20% of population) is 15 times higher than those with two E3 alleles.
Clinical features
- Self-neglect
- Weight loss
- Especially when the patient is living alone.
- Paranoid ideation
- Common
- May be used by the patient as an explanation for symptoms of memory loss (e.g. misplacing items),
- Physical aggression
- Auditory and visual hallucinations are less common.
- Severity
- Mild AD is characterized by minor behavioral changes, loss of memory of recent events (e.g. conversations, events), misplace items, struggle to find the right word in conversation, confused or lose track of day/date, difficulty planning and making decisions, visuospatial impairment, and lose interest in people or activities.
- Moderate AD will need reminders about self-care, increasingly forgetful, not recognize people, place themselves/others at risk (e.g. miss medication, leave gas stove on), easily upset/angry/aggressive, night-day reversal, agitation, socially inappropriate, delusions/hallucinations.
- Severe AD is characterized by increasing dependence on others for nursing care, bed/wheelchair bound, weakness, unable to recognize familiar objects/people, incontinence, difficulty eating/swallowing and gradual loss of speech. Death is usually 8-10 years after symptom onset.
Investigation
- Pathological changes include widespread cerebral atrophy, particularly involving the cortex and hippocampus. In AD, FDG-PET can show hypometabolism in the temporoparietal regions and/or the posterior cingulum. On microscopy there are cortical plaques due to deposition of type A-Beta-amyloid protein and intraneuronal neurofibrillary tangles caused by abnormal aggregation of the tau protein (excessive phosphorylation). There is also reduced acetylcholine due to damage to ascending forebrain projection, hence acetylcholinesterase inhibitors (donepezil, galantamine, and rivastigmine) as options for managing mild to moderate Alzheimer’s disease. Memantine (a NMDA receptor antagonist) is reserved for patients with moderate—severe Alzheimer’s disease.
- Alzheimer disease radiological features
- Cerebral atrophy most strikingly in the mesial temporal structures,
- Temporal horns are usually widened due to the atrophy
- Atrophy in the parietal and frontal lobes.
- The occipital lobe is usually unaffected.
- From twitter Lea Alhiali and Essien 2023
- Notes
- Quantifies hippocampal volume loss
- It rates the amount of CSF around the hippocampus as a marker of volume loss
- CSF surrounds the hippocampus like a snake surrounding its prey—how far the snake has gone in getting its prey determines the MTA score
- MTA-1: Choroidal fissure opens, looks like the snake has started to slither in
- MTA-2: Temporal horn widens, looks like the snake has surround the hippocampus
- MTA-3: Moderate hippocampal atrophy, looks like the snake has begun to squeeze the hippocampus
- MTA-4: Severe hippocampal atrophy, looks like the snake has crushed the hippocampus
- Notes
- Quantifies entorhinal cortex volume loss
- Entorhinal cortex/parahippocampal gyrus & the adjacent fusiform gyrus look like two feet walking up the tentorium
- Volume loss here looks like the feet have slipped on a banana.
- ERICA-1
- Slight widening of the collateral sulcus, looks like the first foot has slipped forward a little & legs are little spread apart
- ERICA-2
- Entorhinal cortex volume loss lets CSF in between it & the tentorium (tentorial cleft sign). This looks like the foot has come off the floor
- ERICA-3
- Profound volume loss so the collateral sulcus is very wide—this looks like the legs have slipped so much they are doing the splits!
Medial temporal atrophy (MTA) score
Entorhinal cortex atrophy (ERICA) score
ERICA rates how far the feet have slipped
- Histopathology
- Senile plaques and neurofibrillary tangles, as well as neuronal loss
- Senile plaques are deposits of neuropil. They contain an Aβ peptide that is derived from a fragment of amyloid precursor protein (APP; a neuronal protein that is encoded on chromosome 21)
- Neurofibrillary tangles: Intracellular inclusion bodies, mainly containing tau protein
Differential diagnosis
- What are the main differentiating factors between Alzheimer and Lewy body dementia?
- In Alzheimer disease, cortical neuritic plaques and neurofibrillary tangles are seen; early impairment in short-term memory is evident. It is more prevalent in women.
- In Lewy body dementia, there is relatively preserved memory with impairments in executive functions; Parkinsonian and autonomic features are present. It is more prevalent in men.
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