Dementia and Alzheimer’s (spring) Flashcards
define dementia
Chronic progressive mental disorder that adversely affects higher cortical functions including memory, thinking, orientation, comprehension, calculation, learning capacity, language and 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 behavior
common symptoms of Alzheimer’s disease
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
Diagnosis of Alzheimer’s disease
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)
- SPECT and PET scans may show areas of: Loss of function (fluoro deoxyglucose [FDG]PET), and Presence of AD biomarkers (PET with amyloid-binding radiotracer or chemical marker of cerebrospinal fluid [CSF] amyloid and tau proteins)
what do different scores on the Mini Mental State Exam mean?
Scored out of 30
- ≥27 = Normal
- 19-24 = Mild cognitive impairment
- 10–18 = Moderate impairment
- ≤9 = Severe impairment
what does an MRI scan show in Alzheimer’s disease?
advantages of MRI scan?
Highlights atrophy in hippocampus and mesiotemporal lobe (MT)
Can detect pre-symptomatic changes
Non-invasive
Reproducible and quantitative read out.
what does an FDG scan show in Alzheimer’s disease?
advantages of FDG scan?
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).
Risk factors for Alzheirmer’s
- Age >65
- ApoE4 genotype
- ApoJ genotype
- TREM2 status
- History of stroke (hypoxic episodes)
- Head injury
- Vascular diseases
- Diabetes
- Smoking
- Drinking
- Education
Traumatic brain injury biomarkers
what are early-onset inherited cases of Alzheimer’s caused by?
rare mutations in 3 genes: PSEN 1, PSEN 2, APP
in Alzheimer’s what is scattered throughout the cortex?
Amyloid plaques and Neurofibrillary tangles
describe the amyloid cascade hypothesis leading to Alzheimer’s
Increased Aβ production & Decreased Aβ degradation leading to…
- ↑Amyloid β accumulation
- Amyloid β oligomerisation and deposition
- Inflammatory response (Glial cells)
- Synapse loss
- Oxidative stress
- Ca2+ overload and neuronal death
Treatment strategies for dementia
No disease modifying therapy exists for dementia.
Current treatment strategies center around neurotransmitter modulation as a symptomatic approach. In particular, cholinergic and glutamatergic signalling.
- Acetylcholinesterase Inhibitors
- N-methyl D-aspartate antagonism
examples Acetylcholinesterase Inhibitors for dementia
what effects does it have?
how are benefits assessed?
success rate?
side effects?
Acetylcholinesterase Inhibitors: 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
give an example of an N-methyl D-aspartate antagonism
effects?
Possible drug 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.
