(PM3B) Dementia & Alzheimer's Flashcards
What are the types of dementia?
(1) Alzheimer’s disease – 62%
(2) Mixed dementia – 10%
(3) Vascular dementia – 17%
(4) Rarer causes of dementia – 5%
(5) Dementia with Lewy bodies – 4%
(6) Frontotemporal dementia – 2%
What is dementia?
Chronic progressive mental disorder that adversely affects higher cortical functions
Including:
- memory
- thinking
- orientation
- comprehension
- calculation
- learning capacity
- language
- judgment
What is Alzheimer’s disease?
Most common form of dementia
Degenerative cerebral disease with characteristic neuropathological and neurochemical features
Onset and development is slowly but steadily over several years
Progressive deterioration in cognition, function and behaviour
What are the major categories of symptoms of Alzheimer’s disease?
(1) Cognitive
(2) Non-cognitive
(3) Disability
What are some cognitive symptoms of Alzheimer’s disease?
(1) Memory loss
(2) Disorientation/ confusion
(3) Poor concentration
(4) Failing intellect
(5) Language impairment
What are some non-cognitive symptoms of Alzheimer’s disease?
(1) Depression
(2) Anxiety
(3) Delusion
(4) Aggression
(5) Sleep disturbances
(6) Dis-inhibition – inability to suppress inappropriate behaviour
What are some disabling symptoms of Alzheimer’s disease?
(1) Difficulties with daily living
(2) Self-neglect
(3) Incontinence
What may the symptoms of Alzheimer’s disease be confused with?
(1) Diabetes
(2) Thyroid problems
(3) Vitamin deficiency
(4) Infection
(5) Anxiety
(6) Brain tumour
(7) Depression
With regard to dementia, what are plaques and tangles?
Alzheimer’s disease
1) Amyloid plaques (Aß
(2) Neurofibrillary tangles (Tau)
How does the brain tissue of a patient with Alzheimer’s disease compare to the brain tissue of a healthy patient?
(1) Enlargement of the ventricles – loss of tissue
(2) Hippocampus is degenerated
(3) Grooves of cerebral cortex are much more defined
What is the significance of the weight of an orange with regard to dementia?
Approximately the mass of the brain lost in a patient with dementia
What molecule composes amyloid plaques?
Aß – amyloid beta
What molecule composes neurofibrillary tangles?
Tau
What are the significant toxic peptides in dementia or Alzheimer’s disease?
(1) Tau
(2) Amyloid beta – Aß
How is Alzheimer’s disease diagnosed?
(1) Symptom + memory assessment
(2) MRI + PET scans for biomarkers
Why are memory tests used to diagnose Alzheimer’s disease?
Show problems in particular areas
Why are CT and MRI scans used to diagnose Alzheimer’s disease?
Can show brain shrinkage (atrophy)
What questionnaire is often used for diagnosis of Alzheimer’s disease?
Mini Mental State Exam (score /30)
What is the clock drawing test?
A test for Alzheimer’s disease diagnosis
Points are lost for incorrect drawing of a clock
Describe the common level of amyloid beta (Aß) levels in a patient first diagnosed with dementia.
Almost at its maximum
What is the purpose of using an MRI in dementia or Alzheimer’s disease diagnosis?
(1) Highlights atrophy in hippocampus
(2) Can detect pre-symptomatic changes
(3) Non-invasive
(4) Reproducible
What is the purpose of using an FDG scan in dementia or Alzheimer’s disease diagnosis?
(1) Highlights deficits in parietal lobe
(2) Links metabolic state to synaptic activity
(3) Useful in differentiating between types of dementia
What is the predominant risk factor for dementia?
(1) Age
What are some of the risk factors for dementia?
(1) Age – >65yrs old
(2) History of stroke
(3) Head injury
(4) Vascular diseases
(5) Diabetes
(6) Smoking
(7) Drinking
(8) ApoE4 genotype
(9) ApoJ genotype
(10) TREM2 status
What is dementia pugilistica?
Punch drunk
Head injuries in sport
Subsequent development of dementia
What are some of the biomarkers that increase following a traumatic head injury?
(1) Hyperphosphorylated Tau
(2) Amyloid plaque deposition
Name 3 early onset genes for Alzheimer’s disease.
(1) APP
(2) PSI
(3) PSII
What is the amyloid cascade hypothesis?
(1) Amyloid beta accumulation
(2) Amyloid beta oligomerisation (clump) + deposition
(3) Inflammatory response – from glial cells?
(4) Synapse loss
(5) Oxidative stress
(6) Ca2+ overload
(7) Neuronal death
What treatment strategies are available for dementia?
No disease modifying therapy exists
Management of symptoms
Focus on cholinergic + glutamatergic signalling
What are the two major types of cholinergic receptor?
(1) Muscarinic – M1-M4
(2) Nicotinic – nAChR
Which molecule breaks down acetylcholine in the synaptic cleft?
Acetylcholinesterase
What are some acetylcholinesterase inhibitors?
(1) Donepezil
(2) Galantamine
(3) Rivastigmine
What is the purpose of acetylcholinesterase inhibitors?
To limit the breakdown of neurotransmitter acetylcholine
What are some of the effects of acetylcholinesterase inhibitors?
(1) Enhance cholinergic transmission - improve cognitive function
(2) Therapeutic effectiveness decreases with disease progression
(3) Does NOT affect disease progression
(4) Cognitive assessment repeated to assess benefit
(5) Poor response = discontinue treatment
What are some key issues acetylcholinesterase inhibitors in the treatment of dementia?
(1) Do not affect disease progression
(2) Effect decreases as disease progresses
(3) Only a subset of patients respond well
(4) Side-effects at high dose
What is anticholinergic burden (ACB)?
Score given to anticholinergic drugs (1-3)
1 = least severe
3 = most severe
What is a drug with an ACB score of 1?
Warfarin
What is a drug with an ACB score of 2?
Cyclobenzaprine
What is a drug with an ACB score of 3?
Diphenhydramine
What is glutamatergic transmission?
Neurotransmitter glutamate
What are some of the receptors for glutamate?
(1) MGluR5
(2) NMDAR
(3) AMPAR
(4) KainateR
What role does an astrocyte have in glutamatergic transmission?
Deals with excess glutamate
Recycles + repackages
(1) Takes in glutamate via GLT1
(2) Converts to glutamine
(3) Re-enters presynaptic membrane via GlnT
Name an antagonist of NMDA receptors.
Memantine
What are some of the potential effects of antagonism of NMDA receptors?
(1) Improves cognitive function
(2) Effects evident at late stages of disease
What are some of the possible drug interactions of NMDA receptors antagonists?
(1) Antipsychotics
(2) Anticoagulants
(3) Analgesics
(4) Muscle relaxants
What are the current NICE guidelines for management of mild-moderate Alzheimer’s disease?
(1) Donepezil
(2) Galantamine
(3) Rivastigmine
What are the current NICE guidelines for the management of severe Alzheimer’s disease, or those who cannot take acetylcholinesterase inhibitors?
Memantine
Is a combination of an acetylcholinesterase inhibitor and a glutamatergic inhibitor recommended for the treatment of Alzheimer’s disease?
Not currently
What are some potential areas for future development of drugs to treat Alzheimer’s disease?
(1) Modulation of neurotransmission
(2) Amyloid-based therapies
(3) Tau-based therapies
(4) Oxidative stress reduction
(5) Mitochondrial-targeted therapies
(6) Modulation of calcium homeostasis
(7) Anti-inflammatory therapy
What is aducanumab?
Monoclonal antibody
Anti-amyloid antibody
What is the neuroAD system?
Neuronix
Combines transcranial stimulation + cognitive training
What are behavioural and psychological symptoms of dementia?
Experienced by ~90% of patients
Potentially treatable
(1) Marked agitation
(2) Ideation
(3) Anxiety
(4) Hallucinations
(5) Misperceptions
(6) Aggressive behaviour
(7) Depression
When are antipsychotics recommended for patients with dementia?
Mild-moderate non-cognitive symptoms should NOT be given antipsychotics
Patients with psychosis/ agitated behaviour
When are sedatives recommended for patients with dementia?
For challenging behaviour
Violence/ aggression/ severe agitation
e.g. lorazepam/ haloperidol/ olanzapine
When are antidepressants recommended for patients with dementia?
Emotional disorders
Dementia + major depressive disorder
AVOID TCA + MAOI due to anticholinergic properties
