Dementia Flashcards
What is the DSM-5 definition of dementia?
Evidence of significant cognitive decline from prior level of performance in ≥1 cognitive domains
→ Concern of the individual, a knowledgeable informant or the clinician that there has been significant decline in cognitive function
→ A substantial impairment in cognitive performance preferably documented by standardised neuropsychological testing, or in its absence other quantified clinical assessments
Cognitive deficits interfere w independence in everyday activities
Cognitive deficits do not occur exclusively in the context of delirium
Cognitive defects are not better explained by another mental disorder
What is the DSM-5 definition of Minor Neurocognitive Disorder?
Evidence of modest cognitive decline from prior level of performance in one or more cognitive domains
→ Concern of the individual, a knowledgeable informant, or the clinician that there has been mild decline in cognitive function
→ A modest impairment in cognitive performance preferably documented by standardised
Cognitive deficits interfere w independence in everyday activities
Cognitive deficits do not occur exclusively in the context of delirium
Cognitive defects are not better explained by another mental disorder
What are the modifiable risk factors for dementia?
- Hypertension
- Diabetes
- Binge drinking
- Smoking
- Limited physical activities
- Obesity
- Hearing loss
- Depression
What are the non-modifiable risk factors for dementia?
- Age (>65yo – 5-10%, >85yo – 50%)
- Female
- Ethnicity (Black, Hispanic)
- Genetics (Alzheimer’s: APOE4 gene)
What is the pathophysiology of Alzheimer’s?
When amyloid precursor protein is broken down by beta and gamma secretase (2 separate enzymes), other molecules are generated - Aβ is the main culprit
Aβ tends to misfold and become sticky, sticking together to form soluble oligomers (multiple copies of Aβ stuck together) - can further aggregate to form insoluble fibrils that deposit in the brain as plaques
→ Some of these plaques stop brain from forming or retrieving memories by interfering w neurons
Microglia - release cytokines that can damage neurons when they encounter plaques, and also start to remove synapses by phagocytosis
→ As synapses malfunction and the neurons die, abnormal patterns of activity emerge
→ Brain eventually cannot process and store information properly
Neurodegeneration - neuronal death and damage (triggered by Aβ and tau)
Tau is a protein component of tangles
→ Stabilise the microtubules that carry signals along the axon
→ In Alzheimer’s, modified tau proteins dissociate from the microtubules, resulting in the microtubules adopting an abnormal shape and moving from the apexes to the cell body
→ Modified tau proteins can be soluble or insoluble
→ Lack of tau in microtubules eventually cause microtubules to disintegrate, destroying neurons
→ Misfolded tau proteins can travel across synapses into healthy neurons and cause normal tau proteins to misfold, spreading pathology across the brain - direction of spread correlates with the symptoms of Alzheimer’s observed
What are the non-pharmacological management options?
- Cognitively stimulating activities
- General Health: Physical exercise, Healthy diet such as Mediterranean diet, Adequate sleep, Proper personal hygiene
- Social interactions with others
- Safety, including inside the home (e.g. using kitchen appliances) and outside (e.g. driving)
- Medical and advanced care directives (e.g. designation of power of attorney)
- Long-term health care planning (e.g. for living arrangements in late stage of dementia)
- Financial planning (allocation of assets)
- Effective communication (e.g. for expressing needs and desires, such as visual aids)
- Psychological health (e.g. participating in personally meaningful activities, such as playing music)
What are the pharmacological management options for dementia?
- Acetylcholinesterase Inhibitors (Donepezil, galantamine, rivastigmine)
- Memantine
What is the MOA of the acetylcholinesterase inhibitors?
Inhibit acetylcholinesterase enzyme – inc amount of acetylcholine at the synaptic cleft for cholinergic neurotransmission
What are the differences between the AchEis?
Rivastigmine: PO or transdermal patches
* Shorter half-life than galantamine
* Primarily metabolised by kidneys
Galantamine: only PO tab
* May also act on nicotinic receptors in brain
* Metabolised by CYP450s (2D6, 3A
What are the SEs of the AchEis?
- Cholinergic hyperactivation: N/V/D
- Less common: muscle cramp, bradycardia, loss of appetite, inc gastric juice secretion
What is the MOA of memantine?
Non-competitive NMDA receptor antagonist – blocks NMDA receptor mediated excitotoxicity
What are the SEs of memantine?
hallucination, confusion, dizziness, headaches
How should dementia be managed pharmacologically?
- Mild to moderate: Acetylcholinesterase Inhibitors
- Moderate to severe: Memantine
- If patient has established diagnosis of Alzheimer’s disease, but already on acetylcholinesterase inhibitor, add on memantine (consider if moderate, just add on if already severe)
- Reduce polypharmacy where possible
- Review medications that may contribute to cognitive impairment
- Assist caregiver on medication management issues – e.g. simplify regimen, arrange for refills
- Evaluate risk vs benefit of existing medications – e.g. anti-thrombotics
What is the definition of BPSD?
- Refers to the spectrum of non-cognitive and non-neurological symptoms of dementia e.g. agitation, aggression, psychosis, depression and apathy
- Often an attempt by the patient to communicate – therefore, understanding why the behaviour or symptom is occurring is the key to management
- Depression and anxiety can be among the first symptoms of dementia, while agitation and aggression more commonly occur later, especially as the person’s ability to communicate and influence their environment changes
What are the pharmacologic treatment options for BPSD?
SSRI, Antipsychotics
