Dementia Flashcards
Dementia is a term used to describe
a group of related chronic, organic, brain disorders. They all share a common characteristic of deterioration of cognitive function leading to gradual decrease in intellectual capacity
Dementia is a term used to describe
a group of related chronic, organic, brain disorders
Cognitive decline is
a significant decline from what was normal for an individual in any of the following
- consciousness
- memory
- concentration + attention
- insight
- self awareness
- general knowledge
- intellectual performance
- orientation
- judgement
What are the types of dementia?
Dementia of Alzheimer's Type Early onset Dementia of Alzheimer's Type Late onset Vascular Dementia Lewy body/ Parkinson's Disease Dementia Others - Pick's Disease, Huntington's Chorea
Neuropathology of AD
- Generalised atrophy, especially frontal, parietal and temporal lobes
- Widespread deposition of neurofibrillary tangle and amyloid plaques
- Depletion of NT levels, especially ACh
- Loss of brain volume - upto 15% enlargement of sulci and ventricles
- Dramatic loss of central neurones
Neuropathology of AD; NFTs and Amyloid plaques
NFTS:
- remains of defective neurones
- normal part of ageing, greater number in AD
- number on post mortem correlates with duration and severity of AD
Neuritic/ Senile plaques:
- Clumps of dying nerve axons and dendrites
- appear where neurone loss is most severe
Wha is the neurotransmitter hypothesis
Cholinergic systems are critical for normal memory and other cognitive functions.
A selective loss of cholinergic cells from the basal forebrain.
Depletion of neurones in this area results in memory and cognitive decline.
By the time mild symptoms are detectable, there is already a significant loss of ACh
Post mortem shows there are reduced levels of synaptosomal ACh and low levels of acetylcholesterase and acetyltransferase.
What is the inflammatory hypothesis.
-
What is the inflammatory hypothesis.
- individuals on long term anti inflammatory drugs have lower incidence of AD
- Insult to brain results in neuronal damage and debris deposition
- Cascade process is set up leading to neuronal death and starts inflammatory response
- Anti inflammatory prevent further propagation of process
What is the oxidative hypothesis?
- AD is due to free radical mediated cell damage
- Oxidative stress leads to tissue inflamation
Progression and Staging of AD:
1st stage is between:
2nd stage is between:
3rd stage is between:
What happens in each stage?
1st: first three years; recent memory impairment, ADL impairment, forgetting names, losing direction when out, depression, language difficulties
2nd: 2nd and 10th year; amnesia, aphasia, calculation/ problem solving difficulties, personality, behavioural and psychiatric changes, inability to perform ADL
3rd: 8th and 12th year; short and long term memory loss, muted or nonsensical speech, rigid posture, complete dependence on others
Vascular dementia occurs when neuronal death is brought about by
hypoxia or other damage secondary to stroke.
It presents with sudden onset and follows step wise progression
No association between choline acetyltransferase and degree of cognitive decline
Frequent Hx of hypertension, stroke
Damage can be focal
Assessment tools used to differentiate
Lewy Body Dementia is progressive dementia distinguished from AD by
fluctuating course and presence of psychotic symptoms.
Lewy Body Dementia is progressive dementia distinguished from AD by
fluctuating course and presence of psychotic symptoms.
characterised from parkinsons symptoms and extreme sensitivity to EPSE from antipsychotics.
like AD, widespread reduction in choline acetyltransferase.
Also reduction in Dopamine
Lewy bodies are detectable intracellular masses found on post mortem
Senile plaques may be found but not NFTs
Lewy bodies are found in non demented patients but in different brain region to demented PD patients.
Diagnosis of AD can only be made when:
other general medical conditions have been excluded,
other psychiatric disorders have been excludes and
other neurological conditions and reversible causes have been excluded
Criteria for diagnosis of probable AD:
- onset between 40-90 years
- absence of systemic or neurological disorders
- objective testing e.g. MMSE
- decline in two or more cognitive areas
- progressive worsening of memory + other cognitive functions
- no disturbance of consciousness
What is the MMSE?
Mini Mental State Examination
- Clinical screening tool that tests memory, attention and calculation
- quick to perform, widely used and understood
- fairly crude, considered insensitive to change but sensitive to effects of cholinesterase inhibitors
- each questions tests different aspect of cognition
What does MMSE test?
- orientation
- registration
- reading and writing
- recall and STM
- concentration and attention
- constructional ability
- learning, naming objects and repeating words
- three stage command
What are the MMSE scores?
mild: 21-26
moderate: 10-20
moderately severe: 10-14
severe: less than ten
What is the class of drugs prescribed for dementia? How do they work? What do they improve?
AChE- inhibitor
inhibit breakdown by cholinesterase
improve cholinergic transmission, possible slowing down neuronal degeneration
AChEIs most commonly prescribed?
Donepazile
Rivastigmine
Galantamine
AChEIs most commonly prescribed?
Donepezil
Rivastigmine
Galantamine
What drugs act on AChE in brain?
Donepezil
Rivastigme
Rivastigme inhibits
AChE and BuchE
Which drugs are selective inhibitors of AchE?
Donepezil and Galantamine
Which drugs are selective inhibitors of AchE?
Donepezil and Galantamine
Galantamine acts on
both AchE (inhibits) and Nicotinic receptors (excites to indirectly release Ach)
Predictable side effects of AChEIs?
Nausea/ Vomiting Diarrhoea Sweating Dizziness Insomnia
ACheEiS can exacerbate
Peptic Ulcer Disease
Asthma
COPD
Which drug is not a substrate for hepatic metabolism?
Rivastigmine
Which drugs are metabolised by CYP 3A4 and 2D6?
Donepezil and Galatamine
What is Memantine? What class of drugs?
non competitive NMDA receptor antagonist
Patients intolerant or have a contraindication to AChEI are prescribed
memantine
Patients with moderate or severe AD are prescribed
memantine
What is Memantine? What class of drugs? What does it target?
non competitive NMDA receptor antagonist
targets glutamate
Memantine works by blocking
the pathological activation of glutamate receptors without blocking physiological) activation (memory function
Side effects of memantine?
Hallucinations Confusion Dizziness Headache Vomiting
How are behavioural symptoms of dementia treated? What is the problem with using this class of drugs?
Antipsychotics
Little evidence that it is efficient
Has side effects of falls due to sedation/ hypotensive effects, EPSE (even with some SGAs), concerns over cardiac side effects e.g stroke
What would be the most suitable antipsychotic in terms of a patient who is at high risk of CVD?
Quetiapine
