Alzheimer's disease Flashcards
Symptom of dementia?
impaired memory, poor cognition
disturbed behaviour- restless, inappropriate
lack of insight
poor speech
low mood
forgetfulness
poor attention
disorientation of space/time
Agnosia- can’t recognise objects, people, themselves
dysphasia- can’t name things
What is agnosia?
Agnosia- can’t recognise objects, people, themselves
What are the risk factors for dementia?
Older age
poor cognitive function
low BMI/underweight
Diabetes - poor glucose control
Alcohol consumption\lack of exercise
lack of veg
depression, BPD
ApoE4 variant gene
Ventricular enlargement
carotid artery thickening
History of bypass surgery
family history
learning disabilities and down syndrome
parkinsons disease
black minority groups
What are the 4 types of dementia?
Alzheimer’s disease (50-60%)
Vascular (20-25%)
Lewy body (15-20%)
Frontotemporal lobar degeneration (7%)
Discuss the progression of symptoms during Alzheimer’s disease?
Early stages: years 1-3
language difficulties
depression
losing direction when out
memory impairment, forgetting names
incidents when driving
impaired activity of daily living e.g. dressing, eating
Mild stages: years 2-7
aphasia
amnesia- memory loss
inability to bath, eat, toilet, dress without assistance
inability to calculate solutions and problem solve
behavioural and psychiatric changes
Late stages: years 7+
seizures
memory loss- short and long term
incontinence
mutism
complete dependence
rigid posture
What are the risk factors for AD?
Demographic:
Age
Family history
Down syndrome
Genetic
ApoE4 gene
Down syndrome
Environmental/medical
Low IQ
Head injury
cerebrovascular disease
depression
Diabetes
obesity
What is AD?
Memory impairment with gradual onset and continual decline
What is vascular dementia?
Sudden onset with step-wise progressive decline
Onset is around 60-70 years
Caused by infarct- often history of HTN, stroke, TIAs
Symptoms/features of vascular dementia?
Emergence of emotional and personality changes
apraxia
agnosia
dysarthria
dizziness
gait disturbances
weakness of extremities
extensor plantar response- stroking the sole produces extension (dorsiflexion) of the big toe, often with extension and abduction (“fanning”) of the other toes
pseudobulbar palsy- inability to control muscles of the face
exaggeration of deep tension reflexes
What are the risks of vascular dementia?
Family history
male
HTN
History of TIA/Stroke
DM
Smoker
AF
What is Lewy body dementia?
Progressive cognitive decline especially in aeration and visuospatial ability caused by abnormal deposits of a protein called alpha-synuclein in the brain
What are the symptoms of Lewy body dementia?
Repeated falls
hallucinations
early gait disturbances
Parkinsons type features
decreased consciousness
psychotic features
delusions
depression
REM sleep issues
Is closely related to parkinsons
often family history
What is front-temporal dementia?
Is the most common form of pre-senile dementia with an onset of 45-75 years old.
The frontal lobe is responsible for behaviour and personality changes.
The temporal Lobeo is responsible for language disorder.
- has an insidious onset, slow progression
has a strong genetic link
What are the symptoms of frontotemporal dementia?
decreased speech output
echolalia- repeating words or phrases
depression
apathy
emotional blunting
What genes are thought to be associated with development of frontotemporal dementia?
Mutation in progranulin (GRN)
TAU- linked to chromosome 17
TDP-43 & C90RF72 genes
What investigations for diagnosing dementia may be done?
Primary care
abc
u&e
LFTs
CRP
calcium and phosphate
thyroid function
Vit B12 and folate
urine dipstick
blood glucose
temperature
Secondary care
MRI, CT scan
HIV status
Neuropsychological assessment
EEG
assessments e.g.
Mini-mental state examination- most common. Tests memory, attention, calculation, language, ability to follow directions etc via 8 questions
Abbreviated mental state score
AD assessment
Adenbrookes’s cognitive exam 3
What do the scores of the Mini-mental state exam mean?
27-30: normal cognitive funxtion
25-27- mild cognitive impairment
21-26= mild AD
10-20- moderate AD
10-14- Moderately-severe AD
<10- severe
What re the limitations of using a mini mental state exam?
- Less sensitive in early stages of dementia
- Less effective in those of a higher intellect- prior schooling and intellect play an issue e.g. if never learnt the info or had poor maths/spelling before
- in non-caucasians where English is not the first language
- low socio-economic background
What is the 1st line treatment at onset of dementia?
Acetylcholine esterase inhibitors:
- These don’t cure, but slow the progression of the condition.
- Are licensed for mild-moderate AD (rivastigmine is also licensed for PD):
- Donepezil:
70-80% of patients are given this first as it is least expensive
5mg ON- may feel dizzy as can cause bradycardia
increase to 10mg ON- need 4 weeks before dose can be increased
Galantamine:
4mg BD at start, increased to 12mg BD usually
need 4 weeks before dose increase
Rivastigmine:
1.5mg BD oral start or 4.6mg/24 hours patch OD
- Maintenance = 6mg BD oral or 9.5mg/24 hr patch
- 2 weeks before oral dose increase and 4 weeks for patches
What are the 3 outcomes of acetylcholine esterase inhibitors when used in AD?
1/3: Show improvement of condition for 6 months to 2 years before it declines
1/3: no-decline- halts progressions for 6-12 months
1/3: no response and continue to decline
When can rivastigmine be used where galantamine and donepezil isn’t?
Parkinson-disease associated dementia
What are the potential adverse effects of AchEis inhibitors?
Cause cholinergic side effects:
N+V
Diarrhoea
Apetite loss
Sleep disturbance
Headache
Fatigue
- can cause bradycardia- caution in cardiac diseases or if patient is on HR lowering drugs e.g. B-blockers, CCBs, digoxin
What kinds of drugs do you not want to be co-prescribed with acetylcholine esterase inhibitors?
Medicines that cause increased anticholinergic burden as these will be counterproductive to the acetylcholine inhibitors (cancel out the effects)
e.g.
antihistamines
TCAs
APs e.g. quetiapine
Drugs used in urinary incompetence e.g. solifenacin, oxybutynin
hyoscine
pain meds e.g. morphone
asthma and COPD meds
What counselling points are important for patients on the acetylcholine esterase inhibitors?
- The meds will take time to work
- The aim is to hold current level of functioning for longer and only 1/3 see an improvement
- Best if taken regularly:
Donepezil- longes t1/2 of 70 hours and so 1 missed dose won’t cause much
Rivastigmine Short t1/2 (1 hour)- need to take regularly - if cause nausea, take after food
- seek advice if bradycardia occurs
- if rivastigmine patch causes rash, can use emollient creams if mild. if severe, report. Remember to rotate patch sites.
Which AchEi can cause sleep disturbances and what can be done?
Donepezil can cause sleep distrubances/nightmares= give dose in the morning instead
What medications can be added at later stages of AD, where acetylcholine esterase inhibitors are insufficient?
- Memantine is licensed for moderate-severe AD
is a NMDA receptor antagonist on glutamate neurones = neuroprotective
usual start dose 5mg OD for 1 week, then increase by 5mg per week until at 20mg- there is a starter pack to help
S/Es: headache, constipation, sissiness, HTN, dyspnea
caution in epilepsy or seizures
Do you add memantine to the AchEi or swap them?
There is no extra benefit of using them in combination but can be done by a specialist.
What are the unlicensed use of treatments for dementia that isn’t AD?
Unlicensed:
- Donepezil or rivastigmine in mild-mod lewy body dementia
- only offer memantine or AchEis in vascular dementia if have suspected co-morbid AD, PD dementia or dementia with leeway bodies
- Do NOT offer AchEIs or memantine in frontotemporal dementia
What are the behavioural and psychological symptoms of dementia?
Behavioural:
physical agression
Screaming
wandering
inappropriate behaviour
sexual disinhibition
Psychological:
anxiety
depression
hallucinations
delusions
What is the first-line option for BPSD symptoms?
Non-drug intervention
- modify behaviour of carer
- may resolve themselves
- music therapy, massage, reminiscence therapy
Identify which symptoms cause the most concern ‘ABC’ approach:
Antecedents: what happened before the aggression/upset behaviour
Behaviour: what behaviour occured
Consequence: what happened after
BPSD can be caused by the patient being in pain which they don’t often report. What may be used to identify pain?
The abbey pain scale. Look for:
- vocalisation- crying, groaning
- facial expression- frown
- body language- rosking
- behaviour- not eating, confusion
- physiological- temp, pulse, BP
- physical- tears in skin, arthritis, pressure sores
What is the usual pharmacological management for BPSD symptoms?
Anti-psychotics
- However, they have a double risk of death in dementia patients as they can cause over-sedation and dehydration which can lead to infection and strokes.
The stroke risk increases by 3-fold and the fracture/fall risk by 2-fold
What are the side effects associated with the anti-psychotics used to treat BPSDs ?
sedation
parkinsonism
gait disturbance
falls
dehydration
chest infection
confusion
movement problems- tremor, rigidity
agitation, restlessness, akathisia
anti-cholinergic SEs
What drug can be used for short-term treatment of BPSDs?
Risperidone
- Can be used for short-term (6 weeks) for persistent aggression in moderate-severe AD (not licensed for other types of dementia)
Start dose:
250mcg BD and increase by 250mcg on alternate days where needed.
Optimum dose in most 500mcg BD but some may need 1mg BD
- Review regularly
- Max prescription dose is 6 weeks
Why would you not want a patient with AD to be using oxybutynin for urinary incontinence?
Oxybutynin is an anti-muscarinic drug (anti-cholinergic) and so will counteract the cholinergic effects of the acetylcholine esterase inhibitors used for treatment of AD (galantamine, donepezil, rivastigmine) this is good for stopping urinary incompetence BUT oxybutynin can cross bbb and will also cancel out the positive effects on cognition that these drugs have.
Instead, a drug such as Mirabegron may be more preferable. Mirabegron is a beta-3-adrenergic receptor agonist as it doesn’t have anti-cholinergic effects and so reduces any cholinergic burden and doesn’t react with the acetylcholin esterase inhibitors.
What drug is recommended for urinary incompetence in AD?
Mirabegron- a beta-3-adrenergic receptor agonist
- it doesn’t have anti-cholinergic effects and so reduces any cholinergic burden and doesn’t react with the acetylcholine esterase inhibitors.
Dose: 50mg OD
