Dementia Flashcards
Define Dementia
Umbrella term.
Chronic progressive mental disorder that adversely affects higher cortical functions including memory, thinking, orientation, comprehension, calculation, learning capacity, language and judgement.
Define 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
Approximately how many people suffer with dementia in the UK?
820,000
What are the cognitive symptoms?
Memory loss Failing intellect (inability to learn new skills) Poor concentration Language impairment Disorientation/confusion
What are the non-cognitive symptoms?
Depression Delusion Anxiety Aggression Sleep disturbances Disinhibition
What are disability symptoms?
Difficulties with activities of daily living
Self-neglect
Incontinence and other physical disabilities
What could the symptoms of AD be mistaken for?
- Vitamin deficiency
- Thyroid problems
- Infection
- Anxiety
- Brain Tumour
- Depression
Describe plaques and tangles
Amyloid plaques and Neurofibrillary tangles each have different proteins underlying each. They are characteristic of dementia when they undergo a conformational change and become toxic
What techniques are used for the diagnosis of dementia
- symptoms and memory assessment
2. MRI and PET scans for biomarkers
What are the outcomes of using Memory tests and MRI and PET scans?
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)
Presence of AD biomarkers (PET with amyloid-binding radiotracer or chemical marker of cerebrospinal fluid [CSF] amyloid and tau proteins)
Describe the scoring system of the mini mental state exam?
Scored out of 30 ≥27 = Normal 19-24 = Mild cognitive impairment 10–18 = Moderate impairment ≤9 = Severe impairment
What does an MRI scan highlight in pathology?
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 highlight?
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 for dementia? In order of highest effect
Age >65 ApoE genotype - if have one copy of the APOE 4 makes them 3 times as likely and if have two copies makes them more than 8 times more likely. TREM2 status History of stroke (hypoxic episodes) Parkinson’s disease Head injury Vascular diseases Diabetes Smoking Drinking Education
What is dementia pugilistica?
Dementia Pugilistica is a form of dementia that poses a serious long-term threat to individuals involved in contact-heavy sports, or who have sustained multiple concussions throughout their lives.
otherwise known as “punch-drunk syndrome” or “boxer’s dementia,” is a form of dementia that originates with repeated concussions or other traumatic blows to the head.
What is the Amyloid cascade hypothesis? Describe the cascade
The amyloid cascade hypothesis, which posits that the deposition of the amyloid-β peptide in the brain is a central event in Alzheimer’s disease pathology.
1. Increased amyloid-β production OR decreased amyloid-β degradation Leads to: 2. Increase in amyloid-β accumulation 3. amyloid-β oligomenisation and deposition 4. Inflammatory response 5. Synapse loss 6. Oxidative stress 7. Ca2+ overload ad neuronal death
What are the current treatment strategies for Dementia?
No disease modifying therapy exists for dementia.
Current treatment strategies centre around neurotransmitter modulation as a symptomatic approach.
In particular, cholinergic and glutamatergic signalling.
Modulating neurotransmission: What do Acetylcholinesterase inhibitors do? and give examples
Enhance cholinergic transmission and improve cognitive functions
Therapeutic effectiveness decreases with increasing neuronal damage
Does not prevent progression of disease!
Examples:
Donepezil
Galantamine
Rivastigmine
How do we know if Acetylcholinesterase inhibitors are working?
Benefit assessed by repeating the cognitive assessment after 3 months treatment.
Discontinue treatment if patient does not respond to therapy!
What are the effects of N-methyl D-aspartate antagonism? give an example
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…
e.g. Memantine- Non-competitive antagonist at NMDA receptors
What are the possible drug interactions when using N-methyl D-aspartate antagonists?
Possible drug interactions e.g., antipsychotic (see non-cognitive changes and treatments!), anticoagulant (warfarin), analgesic and muscle relaxant
Which drugs does NICE recommend to use for mild or moderate Alzheimer disease?
Donepezil, Galantamine and Rivastigmine
What is Memantine now recommneded as an option for by NICE?
moderate Alzheimer’s disease for people who cannot take AChE inhibitors
severe Alzheimer’s disease
In combination? Not currently recommended
What are some novel strategies for treating dementia?
Modulating neurotransmission Amyloid based strategies Tau based therapies Modulating intracellular signalling cascades Oxidative stress reduction Mitochondrial targeted therapy Modulation of cellular calcium homeostasis Anti-inflammatory therapy
