Dementia and Neurodegenerative diseases Flashcards
Define dementia?
Can be defined as an acquired global impairment of intellect, reason and personality without impairment of consciousness.
(Emotional lability and memory are common problems implying involvement of cerebral cortex and limbic system.)
What disorders can cause dementia?
A variety:
- neurodegenerative (Alzheimers, diffuse Lewy body disease, frontotemporal lobar degeneration, Huntington disease)
- cerebrovascular disease eg multi infarct dementia
- infections eg CJD, HIV
- intracranial SOLs; neoplasms or chronic subdural haematoma
- hydrocephalus
- drugs and toxins; barbiturates, digoxin, anticholinergic agents, alcohol, heavy metals
- metabolic disorders; hypothyroidism, hypoparathyroidism, uraemia, hepatic failure
- vitamin deficiencies eg B1 Wernicke-Korsakoff syndrome, B2, B12
- paraneoplastic syndromes eg limbic en encephalitis
What are the the most common causes of dementia in the the West?
- Alzheimers disease (70%)
- Lewy body dementia
- Vascular dementia
Frontotemporal lobar degeneration
Alzheimers epidemiology?
70% of Uk dementia cases.
Affects 5% of people over 65 and 15% of those over 80.
“Silent epidemic” with ageing population.
Most Alzheimers cases are sporadic cases.
But what genes may be implicated in inherited Alzheimers?
Inherited autosomal dominant cases may have:
- amyloid precursor protein APP gene on chr21,
- PSEN1 gene on chr14,
- PSEN2 gene on chr1,
- e4e4 genotype in ApoE gene on chr19 (early onset)
What molecule may have a primary role in Alzheimers pathogenesis?
ABeta protein amyloid
ABeta protein is derived from abnormal cleavage of a normal protein encoded by APP on chr21 (hence more cases in Down’s syndrome as more APP gene).
What does ABeta protein amyloid do in the Alzheimer brain?
What else happens?
Amyloid plaques:
Mostly ABeta protein, develop an amyloid core and reactive astrocytes and microglia at periphery.
Amyloid angiopathy:
ABeta amyloid deposited in arteriole wall predispose vessels to rupture and haemorrhage.
Neurofibrillary tau tangles:
Thickened fibrils within neuronal cytoplasm made of hyperphosphorylated and cross linked tau (a microtubule associated protein). Found in hippocampus, cortex, subcortical grey, brainstem nuclei.
Synaptic and neuronal loss:
Synaptic degeneration in limbic system and then in cortex, cognitive impairement and reduce cholinergic neurotransmitter. Anticholinesterase inhibitors increase ACh and improve cognition in early stages.
Onset of Alzheimer’s?
Usually insidious onset, steady progression over years.
Short term memory loss first then personality, language, visuspacial skills, apraxia and agnosia.
Average course is 8 - 10 years.
Ix for dementia?
No clinical test.
Hx
MMSE (out of 30, 18-24 mild/moderate)
AMTS (quick 10 or 11 questions)
exclude rare:
FBC, LFT, TFT, B12
CT if young
MRI will show atrophy of mesial temporal lobe structures, including hippocampi, progressing eventually to generalized cerebral atrophy
MRI + score = diagnosis
Management of Alzheimers?
No specific management
Treat any associated depression or anxiety
Increasing ACh availability with AChEi
Memantine ([NMDA receptor antagonist) is used in moderate or severe Alzheimer’s or where cholinesterase inhibitors are not tolerated.
Community care and may eventually need residential home.
Name some AChEi used in Alzheimers?
Acetylcholinesterase inhibitors: - donepezil, - rivastigmine and - galantamine Increase cholinergic transmission by inhibiting cholinesterase at the synaptic cleft.
Memantine ([NMDA receptor antagonist) is used in moderate or severe Alzheimer’s or where cholinesterase inhibitors are not tolerated.
What is Lewy body dementia?
Protein involved?
2nd most common dementia after Alzheimer’s.
Protein deposits, called Lewy bodies, develop in nerve cells in the brain regions involved in thinking, memory and movement (motor control).
alpha-synuclein
You get:
Visual hallucinations, changes in alertness and attention.
You also get symptoms of Parkinson’s ie rigidity, bradykinesia and tremors.
What characterises presentation of Lewy body dementia?
Characterized by fluctuating cognition with pronounced variation in attention and alertness.
You get:
Visual hallucinations, changes in alertness and attention.
(can look like recurrent episodes of delirium)
You also get symptoms of Parkinson’s ie rigidity, bradykinesia and tremors.
Depression and sleep disorder
(dont use neuroleptic drugs)
How is Lewy body dementia different to Parkinsons?
Lewy body dementia get dementia 1st and Parkinsonism later. It is ‘dopamine sensitive’ meaning L-dopa etc trigger hallucinations, agitation and confusion.
Parkinson disease yo get Parkinsonism 1st (Tremor, Rigidity, Akinesia, Postural instability) and dementia later on. Treatment is with L-Dopa.
What happens in Vascular dementia?
aka multiinfarct dementia
Stepwise progression of decline
May have multiple TIAs and / or arteriopathy.
