Dementia and Alzheimer’s Flashcards
what is the definition of dementia
Dementia
Chronic progressive mental disorder that adversely affects higher cortical functions including memory, thinking, orientation, comprehension, calculation, learning capacity, language and judgment.
what is the definition of Alzheimer’s disease
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 behavior
what are the common symptoms of AD?
Cognitive
Memory loss
Failing intellect (inability to learn new skills)
Poor concentration
Language impairment
Disorientation/confusion
Non-cognitive
Depression
Delusion
Anxiety
Aggression
Sleep disturbances
Dis-inhibition
Disability
Difficulties with activities of daily living
Self-neglect
Incontinence and other physical disabilities
Symptoms of AD may be confused with:
-Vitamin deficiency
-Thyroid problems
-Infection
-Anxiety
-Brain Tumour
-Depression
-Diabetes
what is the pathology of AD?
Loosing brain tissues as it a neurogenerative disease
Ventricles are enlarged in Alzheimers
what are the proteins which are present in the brain when someone has AD?
Amyloid plaques and Neurofibrillary tangles
“scattered throughout the entire cortex……one found military foci that
were caused by the deposition of a peculiar substance” A. Alzheimer
*protein accumulation due to deposition)
what is the diagnosis of AD?
Symptoms & Memory assessment (Clinical criteria)
MRI and PET Scans for biomarkers (Neuropathological hallmarks)
Outcomes:
Memory tests can show problems in particular areas
CT and MRI scans may show brain shrinkage (atrophy)
PET scans may show areas of
Loss of function (fluoro deoxyglucose [FDG]PET)
Presence of AD biomarkers (PET with amyloid-binding radiotracer or chemical marker of cerebrospinal fluid [CSF] amyloid and tau proteins)
what is mini mental state exam?
and clock drawing test
Individuals’ ability to recall certain things
Quick but blunt to diagnose dementia
what does MRI show?
Highlights atrophy in hippocampus and mesiotemporal lobe (MT)
Can detect pre-symptomatic changes
Non-invasive
Reproducible and quantitative read out.
what does fluorodeoxyglucose(FDG)-positron emission tomography (PET)
show?
Highlights deficits in parietal lobe (P) and posterior cingulate gyrus (PCG).
Links metabolic state to synaptic activity.
Open to errors from other metabolic changes.
Useful tool in differentiating dementia’s (e.g. AD vs FTD).
what are the risk factors of AD?
40% cause-modifiable factors
60% - unknown
education
hearing loss
traumatic brain injury
hypertension
alcohol
obesity
smoking
depression
physcial activity etc
what are the genes associated with AD?
Psen 1, pesen 2, app – early onset (prink – guaranteed to develop AD)
Apoe + trem 2 – increases risk off – late onset
what are the 2 types of AD?
early onset
late onset
APP processing
APP- transmembrane protein
Normal healthy people – APP is cleaved by 2 diff enymes (alpha) – into segments
Develop AD- enzyme different which causes cleaves – beta – production of amyloid fragments – forming the plaques
what is the amyloid cascade hypothesis
initiated by
increase in amyloid B production
decreases amyloid B Degradation
increase Amyloid B accumulation
Amyloid B oligomerisation and deposition
Inflammatory response
Synapse loss
Oxidative stress
Ca2+ overload and neuronal death
what is the Current pharmacological options AD
Anti-amyloid monoclonal antibody [aducanumab]
Cholinergic signalling
Glutamatergic signalling
Cholinergic Synapse
Treating symptoms
Blocking ache -> eleveated levels of acetylcholine
Modulating neurotransmission
what are examples of Acetylcholinesterase Inhibitors
effects
side effects
Donepezil
Galantamine
Rivastigmine
Effects:
Enhance cholinergic transmission and improve cognitive functions
Therapeutic effectiveness decreases with increasing neuronal damage
Does not prevent progression of disease!
Benefit assessed by repeating the cognitive assessment after 3 months treatment.
Discontinue treatment if patient does not respond to therapy!
Only a subset of patients respond
High doses have side effects e.g., nausea, vomiting, diarrhoea
Glutamatergic transmission
AD- too much glutamate
Slow it down
NMDAR – dampen down the signalling from this receptor
N-methyl D-aspartate antagonism
moa
effects
interactions
Memantine- non-competitive antagonist at NMDA receptors.
Effects:
Improves cognitive functions
Effects evident at late stages of disease
Role in early stage of AD unclear…
Not certain if it prevents progression of disease…
Possible drug interactions e.g., antipsychotic (see non-cognitive changes and treatments!), anticoagulant (warfarin), analgesic and muscle relaxant.
what are the treatments for AD according to NICE guidelines
Donepezil, Galantamine and Rivastigmine recommended for managing:
mild
moderate Alzheimer’s disease
Memantine is now recommended as an option for managing:
moderate Alzheimer’s disease for people who cannot take AChE inhibitors
severe Alzheimer’s disease
In combination? Not currently recommended
what are Novel strategies for treating dementia
Modulating neurotransmission
Amyloid based therapies
Tau based therapies
Mitochondrial targeted therapy
Anti-inflammatory therapy
Drug repurposing
PHARMACOLOGICAL INTERVENTION
BEHAVIOUR That challenges
Antipsychotics
- Patients with mild-to moderate non-cognitive symptoms should not be prescribed antipsychotic drugs
- Patients with psychosis and/or agitated behaviour causing significant distress may be offered treatment with an antipsychotic
Sedatives
For challenging behaviour: violence, aggression, severe agitation: i.m. Lorazepam, Haloperidol or Olanzapine
EMOTIONAL disorders
Antidepressants
People with dementia who also have major depressive disorder should be offered antidepressant medication
Avoid certain TCA and MAOI as they have anticholinergic properties
Clinical trials/approvals
2022: lecanemab (Eisai)
2021: aducanumab (Biogen)
- CONTRAVERSIAL
Aducanumab is a monoclonal antibody that removes amyloid plaques.
The central controversy is whether the amyloid clearance protects
patients from cognitive and functional decline
