DEMENTIA Flashcards
signs and symptoms of dementia
- loss of cognitive ability
- changes not associated with normal ageing
- generally associated with progressive neurodegeneration
- finding it hard to follow conversations
- repeating yourself
stages of dementia - mild
- increasingly noticeable memory loss, cognitive impairment
- has ability to cover this up
- may be normal ageing in older people
stages of dementia - moderate
- memory lapses and confusion becomes more obvious
- personality and mental ability changes, some physical problems may develop
- repeated reminders for everyday functions - eat. toilet etc.
stages of dementia - severe
- memory and personality deteriorate further
- impaired ability to communicate
- become dependent on others
multiple causes of dementia
- Alzheimer’s disease
- Parkinson’s disease
- dementia with Lewy bodies
- vascular dementia
- frontotemporal dementia (FTD)
- mixed dementia
diagnosing tests for dementia
- mini-mental state examination (MMSE)
- memory impairment screen (MIS)
- eight-item informant interview to differentiate ageing and dementia (AD8)
Alzheimer’s disease diagnosis
- progressive decline in cognitive ability
- regular visits to GP and memory clinics
- no definitive diagnostic test
- postmortem associated with plaques (amyloid) and neurofibrillary tangles (Tau)
vascular dementia diagnosis
- CT or MRI scans
- reduced blood flow to brain
- able to rule out other conditions that may have similar symptoms
dementia with Lewy bodies diagnosis
- SPECT scan - more sensitive than CT and MRI
- neuronal deposits of a-synuclein
- CT or MRI scans to rule out other conditions that may have similar symptoms
frontotemporal dementia (FTD) diagnosis
- usually affects people 45-64 years old
- CT or MRI scans to identify damage to frontal and temporal lobes
- tauopathy
plaques around neurons are…
extracellular
(amyloid beta protein)
tangles within neurons are…
intracellular
(Tau protein)
suggested roles of amyloid
- angiogenesis (vascular plug)
- antimicrobial peptide
- tumour suppression
- LTP (learning and memory)
- regulates hyperexcitability
- neurogenesis/survival
suggested roles of Tau
- iron homeostasis
- promotes myelination
- permits hyperexcitability
- motor control
- sleep-wake cycle
- neurogenesis/synaptogenesis
- axon transport
- insulin signalling
- transcription/protects DNA
what goes wrong
APP cleaved B secretase followed by Y secretase = AB = toxicity
incorrect cleavage of amyloid precursor protein (APP) by secretases
hyperphosphorylation of Tau
- usually not highly phosphorylated and does not aggregate
- tauopathies linked to many diseases
- FTD is a tauopathy
first-line treatment for mild to moderate Alzheimer’s disease
AchE inhibitors:
donepezil
rivastigmine
galantamine
dosage for AchE inhibitors in AD
- donepezil
- 5mg daily at bedtime
- increased to 10mg after 1 month if no side effects
side effects of AchE inhibitors
diarrhoea
muscle cramps
fatigue
nausea
vomiting
insomnia
first-line treatment for severe Alzheimer’s disease
non-competitive NMDA antagonist:
- memantine
- can be given in moderate AD if AchE inhibitors are not tolerated
dosage for non-competitive NMDA antagonist in AD
- memantine
- 5mg once daily
- increased weekly to max 20mg
side effects of non-competitive NMDA antagonist
dizziness
headache
constipation
somnolence
hypertension
evidence for memantine
- medium affinity for NMDA affinity
- voltage-dependent channel blocker
- prolonged low levels stimulation via increased glutamate in AD, memantine blocks NMDA receptor
- transient high levels of glutamate i.e. synaptic transmission - memantine block relieved
- high affinity channel blockers
