Flashcards in Dementia Deck (58):
What is Alzheimer's disease?
- neurodegenerative disease leading the patient to a state of depersonalisation and complete dependence
- best known cause of dementia, about 2/3 of cases
Risk factors for Alzheimer's?
- genetic inheritance
- lifestyle and general health
- environmental factors
Two main types of symptoms of Alzheimer's?
1. cognitive deficits
2. non-cognitive impairments
- depression, psychosis, agitation, apathy, insomnia, sexual disinhibition
- 90% of people will develop these symptoms at some point in their lives
- associated with increased caregiver burden, higher costs of care etc.
What is BPSD?
Behavioural and Psychological Symptoms of Dementia (the non-cognitive impairments)
What are the two abnormal proteins that build in the brain in Alzheimer's?
- B-amyloid plaques
- Tau tangles
What is the Amyloid Cascade hypothesis?
- APP cut by alpha secretase which releases useful proteins (neurogenic and neurotrophic)
- when APP is cut by beta secretase, releases amyloid which deposit and turn into plaques - leading to neurodegeneration
What happens to amyloid beta that causes damage?
- Oligomers form protofibrils and annular aggregates
These then form amyloid fibrils which lead to plaques
Place of cholinesterase inhibtors in Alzheimer's?
useful for patients with mild to moderate disease
inhibit breakdown of acetylcholine so increase amount of neurotransmitter in the brain
don't slow disease progression but can help to improve function
What are the three cholinesterase inhibs used in Alzheimer's?
What are three novel approaches in treating Alzheimer's?
1. Secretase modulators (decrease amyloid beta production)
2. Anti-aggregants (prevent amyloid beta aggregation)
3. Immunotherapies (clear amyloid beta depositions)
What are the difficulties in trialling Alzheimer's treatment in terms of biomarkers?
Amyloid beta is almost completely accumulated by the time the patient is clinically significant, so difficult to intervene before the plaque buildup
What is a current focus of alzheimer's research?
Understanding how Aβ oligomers target synapses
Effect of resveratrol on amyloid beta oligomers?
Reduces oligomers, far less binding and attack of neurones
disrupts binding of amyloid beta to neurones
What are the spectrum of symptoms that describe dementia?
- loss of concentration
- orientation problems
- memory problems
- mood and behaviour changes
- impaired decision making and judgement
- later: speech/swallowing difficulties, incontinence and mobility issues
What occurs at mild dementia?
prominent memory loss. Core activities of daily living (ADL) maintained but higher level functions impaired
What happens at moderate dementia?
worsening cognition. Core ADL now affected. Challenging behaviours may become more prominent
What happens at severe dementia?
apathy and dependency prominent. Many patients receiving 24 hour care
Characteristics of vascular dementia?
- decline can be gradual or sudden (e.g. stroke)
- memory may be better preserved
- physical symptoms include slurred speech, dizziness, inability to recognise objects, difficulty performing motor tasks
- emotional liability
Characteristics of Alzheimer's disease?
- memory impairment is the most prominent feature early on
- difficulty finding words, disorientation, memory loss, problems performing activities of daily living
Characteristics of Lewy Body dementia?
- cognitive slowing is an important feature
- degeneration of motor function
- confusion, attention deficit, executive function etc, not memory problems
Three key features:
- fluctuating cognition
- recurrent visual hallucinations
- spontaneous Parkinsonianism
How is dementia diagnosed?
- accurate and comprehensive history
- routine haemotology and biochemistry, thyroid, b12, folate
- mid-stream urine, X-ray, ECG
- opportunistic screening, e.g. hospital admission, NHS health checks
- MRI scans can be used to exclude space occupying lesions
ICD-10 criteria for dementia diagnosis?
- Memory loss must be present
- Plus decline in one other domain of cognition (e.g. judging, reasoning, planning) such as that it interferes with activities of daily living (ADLs)
- Some change in social behaviour (e.g. irritable, apathy, lability)
- Decline lasting at least 6 months
NICE guidance on diagnosing dementia?
diagnosis should be supported by a referral to a specialist service such as a memory clinic, who perform a range of tests including those for cognition
Dementia tests: Mini mental state examination
Listen carefully. I am going to say three words. You say them back after I stop. Ready? Here they are... apple [pause], penny [pause], table [pause]. Now repeat those words back to me.'
[Repeat up to 5 times, but score only the first trial.]
Dementia tests: 7 minute screen
Benton Temporal Orientation Test: identify the correct day, month, year, date, time of day. Answers adjusted for how close they are to the correct answer.
Count backwards from 20-1
[Correct – 0 points] [one error – 2 points] [ >1 error – 4 points]
General principles of treating dementia?
- Treatment is not curative
- Multiple drug and non-drug treatments may be needed to control the illness
- Treatment should be guided by a holistic view of the patient and their carer(s)
- try to facilitate community living
- always try to involve in decisions
- speak to patients about lasting power of attorney
Holistic treatment factors to consider for dementia?
- Identify and accommodate specific cultural, dietary, spiritual, age related and gender issues
- Consider learning disability, communication difficulties, sensory impairment
- Identify and address problems with nutrition and self-care
- Ensure co-morbidities managed appropriately
What are the two main types of drugs licensed for dementia treatment?
- Acetylcholinesterase (AChE) inhibitors are the main drug treatment
- Memantine is a NMDA antagonist and is the only other drug licensed
Which AChE inhibitors are the most effective?
None - no major differences in efficacy
When are AChE inhibitors cautioned?
Sick sinus syndrome or cardiac conduction conditions (e.g. sinoatrial block)
Those at risk of ulcers
History of asthma/COPD
Renal/hepatic impairment, more specific advice for memantine
Side effects of AChE inhibitors?
GI: N&V, anorexia, ulceration, upset
CNS: Alertness and agitation, hallucinations, dizziness, insomnia, seizures
GUS: Urinary incontinence
Cardiac: Bradycardia, sinoatrial/atrioventricular block
Side effects of memantine?
headache, dizziness, constipation, hypertension, somnolence
Non-pharmacological treatments for dementia?
- Lifestyle interventions
- Familiarity and routine
- Enhancing visibility
- Consider holistic needs
- Treat comorbidities
- Cognitive stimulation
- Challenging behaviours
Lifestyle interventions for dementia?
stop smoking, weight reduction, reduce alcohol, 5-a-day, proper exercise, sugar/salt/fat management
Familiarity and routine to implement for dementia?
- Keep a diary or use reminder charts
- Remember rooms are designed to look like by-gone eras
How to enhance visibility in dementia?
Use colour and size to make things stand out, e.g. telephones, toilets and doorways
Orientation boards containing date, weather symbols and time
How can you treat challenging behaviours in dementia?
Animal therapy, massage, music, multisensory stimulation
When are AChE recommended according to NICE for dementia?
mild to moderate Alzheimer's
When are NMDA antagonists recommended for dementia according to NICE?
- moderate Alzheimer's when AChE not possible
- severe Alzheimer's
When can combination therapy in Alzheimer's be considered?
Considered if moderate disease
Offered if severe disease
Treatment options for vascular dementia?
DO NOT use AChE inhibitors or memantine for treatment of VD, except if co-morbid AD
Risk factor control is central - treating hypertension (though not much evidence statins/anticlotting reduces disease progression
Treatment options for Lewy Body dementia?
Offer donepezil or rivastigmine to those with mild-moderate DLB, galantamine in reserve. Consider these in severe DLB. Offer memantine if AChE not tolerated/contraindicatred
Response rate of Alzheimer's patients to AChE inhibitors?
1/3 show no response at all
1/3 show transient improvements then decline
1/3 show steady state functioning before declining
In those who do not respond, switching is useful in 50%of patients
How to increase doses of dementia drugs?
Galantamine after 1 month
Rivastigmine after 2 weeks
Memantine after 1 week
Counselling points for rivastigmine?
- change site of patch daily, avoid previous sites for 14 days
- give away from food (galantamine also)
NICE guidance on stopping dementia drugs?
do not stop due to disease severity alone - effects are lost rapidly and difficult to recover
Difficulties in giving medication to dementia patients?
- swallowing ability
- covert administration
- remembering and understanding the need for tablets
What formulations of dementia medicines are available?
Tablets - donepezil, rivastigmine, galantamine (also capsules), memantine
Soluble tablets - donepezil
Liquid - rivastigmine, galantamine, memantine
Patch - rivastigmine
Drugs to avoid in dementia?
Anticholinergics (Hyoscine hydrobromide (NOT butylbromide), Procyclidine, Oxybutynin, Promethazine, Orphenadrine)
Alpha blockers (Prazosin, tamsulosin)
Sedating antihistamines (Chlorphenamine, cyclizine, promethazine)
Examples of BPSD?
agitation (Verbal / physical, Antisocial behaviours, Sexual arousal/aggression, Self harm, Apathy / withdrawal), wandering, aggression, abnormal vocalisations, mood changes and psychosis
First line treatment for BPSD?
watchful waiting, central goal of preventing harm and suffering
How to rule out other causes of BPSD?
Physical problems – infection, pain, constipation, dehydration, malnourishment?
Activity related – washing, dressing?
Iatrogenic – side effects of medication, inappropriate care?
Noise and other environmental factors such as lighting
Non-drug methods for treating/dealing with BPSD?
Talking down and distraction
Aromatherapy, music therapy
Psychoeducation for carers – understanding individual patients
Pharmacological treatments for BPSD?
a trial of paracetamol might be worthwhile
- Use pharmacotherapy only if severe distress or an immediate risk of harm to the person with dementia or others
- Drug treatments include Antipsychotics, AChE inhibitors and memantine. Some evidence for AChE inhibitors of modest positive effects, NICE recommends use in DLB and in AD when other non-pharmacological treatments are not effective or inappropriate, and when antipsychotics are also inappropriate or ineffective. Less evidence for memantine . Antidepressants. Use SSRIs in some cases, evidence is weak
Only licensed UK treatment is risperidone
covert administration may be required
Why avoid older antipsychotics in BPSD?
Parkinson’s symptoms, EPSE, falls and drowsiness, cognitive blunting
Why try to avoid antipsychotic use in BPSD when possible?
Increased risk of stroke and mortality with all antipsychotics now limit use - Possible mechanism due to orthostatic hypotension and tachycardia
Most evidence for risperidone/olanzapine in BPSD, but also greatest harm risk