Dementia Flashcards
1
Q
Definition of dementia
A
A group of chronic, progressive, degenerative organic brain disorders all with a common characteristic: Continuous deterioration in cognitive function leading to a gradual decrease in intellectual capacity.
2
Q
Clinical features of dementia
A
- Impaired memory and poor cognitive function
- Impaired thinking
- Disturbed behaviour
- Lack of insight
- Lack of spontaneity
- Poverty of speech
- Low mood
3
Q
What are features of impaired memory and poor cognitive function?
A
- Forgetfulness
- Poor attention
- Disorientation in time and place
- Agnosia (not recognising objects, people or themselves)
- Dysphasia (not remembering names of things)
- Dyspraxia (not understanding commands)
4
Q
What are features of impaired thinking?
A
- Slow
- Impoverished
- Incoherent
- Rigid
5
Q
What are features of disturbed behaviour?
A
- Disorganised
- Inappropriate
- Distracted
- Restless
- Antisocial
6
Q
What are the risk factors of someone developing dementia?
A
- Older age
- Poor cognitive performance
- Low BMI or overweight
- Slow physical performance
- Not eating vegetables
- Lack of alcohol consumption
- Diabetes
- Depression and bipolar
- apoE4
- MRI showing white matter disease
- Ventricular enlargement
- Carotid artery thickening
- History of bypass surgery
7
Q
What is the survival rate of dementia?
A
5-8 years from diagnosis
8
Q
What are the 6 types of dementia?
A
- Alzheimer’s disease
- Lewy Body dementia
- Vascular dementia
- Frontotemporal dementia
- Mixed
-Other e.g. Parkinson’s/ Huntington’s related dementia, Brain injury, HIV infection
9
Q
What is the most common type of dementia?
A
Alzheimer’s disease 50-60% of cases
10
Q
Symptoms of the early stages of Alzheimer’s disease (1-3 years)
A
- Language difficulties
- Depression
- Losing direction when out and about
- Recent memory impairment and forgetting names
- Increased number of accidents whilst driving
- Impaired activity of daily living
11
Q
Symptoms of mid stage Alzheimer’s disease (2-7 years)
A
- Aphasia (not recognising objects, people, themselves)
- Amnesia
- Inability to bathe, eat, toilet or dress without assistance
- Inability to calculate solutions and problem solve
- Behavioural and psychiatric changes
12
Q
Symptoms of late stage Alzheimer’s disease (years 7+)
A
- Seizures
- Short and long term memory loss
- Double incontinence
- Mutism or nonsensical speech
- Complete dependence on others
- Rigid posture
13
Q
Onset and progression of Alzheimer’s disease?
A
Gradual onset and continual decline
14
Q
Onset and progression of Vascular dementia?
A
Sudden onset followed by a step wise progression
Onset is usually around late 60s-70s
15
Q
What are the focal neurological signs of vascular dementia? (not present in AD)
A
- Gait disturbance (Shuffling gait)
- Weakness of extremities
- Extensor plantar response
- Pseudobulbar palsy
- Exaggeration of deep tension reflexes
16
Q
Onset and progression in Lewy body dementia?
A
Progressive cognitive decline, especially in attention and visuospatial ability
17
Q
What are the key features of Vascular dementia?
A
- Emergence of emotional and personality changes, followed by memory impairment
- Apraxia
- Agnosia
- Dysarthria
- Dizziness
18
Q
What is apraxia?
A
The inability to perform voluntary motor tasks or movements even though the person has the physical ability to do so.
19
Q
What is agnosia?
A
The inability to recognise and identify objects, people or sounds despite their senses being otherwise functional.
20
Q
What is dysarthria?
A
Difficulty speaking due to weakness in the muscles involved.
21
Q
What is aphasia?
A
Inability to communicate effectively with others due to damage to the brain.
22
Q
What are the key features of Lewy body dementia?
A
- Persistent and well-formed visual hallucinations (sometimes auditory)
- Early gait disturbances
- Parkinson’s type features
23
Q
What is gait disturbance?
A
Disruption to the ability to walk.
24
Q
Aetiology of Alzheimer’s disease
A
- Increasing age
- Family history
- Down syndrome
- ApoE4
- Low IQ
- Previous head injury
- Cerebrovascular disease
- Depression
- Diabetes Mellitus
- Obesity
25
Aetiology of Vascular dementia
- Family history
- Male
- Hypertension
- History of stroke or TIAs
- Diabetes Mellitus
- Smoking
- AF
26
Aetiology of Lewy body dementia
- Family history
- No known environmental risk factors
- Closely related to Parkinson's disease
27
Onset and progression of Frontotemporal dementia
Insidious onset with slow progression
28
Aetiology of Frontotemporal dementia
PRIMARILY UNKNOWN
- Mutations in progranulin (GRN)
- TAU -linked to chromosome 17
- TDP-43 and C90RF72 genes
29
Key features of Frontotemporal dementia
- Early loss of insight
- Early signs of disinhibition
- Distractibility and impulsivity
- Progressive decrease in speech output
- Echolalia
- Perseveration
- Depression
- Apathy
- Emotional blunting
30
What is perseveration (in speech)?
Can be:
the repetition of words, phrases or sounds.
Can also be:
Being stuck on a topic on conversation, inability to change the subject.
31
What is the importance of early diagnosis of dementia?
- Patient's personal affairs can be put in order while they still have insight
- The patient and their family are able to plan for the future
- Early access to support groups
- Access to treatment that may slow the progression of the disease.
32
What are the clinical screening tools used in the diagnosis of dementia? (4)
- Mini mental state examination (MMSE)
- Abbreviated mental test score (AMTS)
- Alzheimer's disease assessment scale- cognitive subscale (ADAS-cog)
- Addenbrooke's cognitive examination 3 (ACE3 or mini ACE)
33
What investigations can be done in primary care to establish the cause of dementia and potential differential diagnosis?
- FBC
- U and Es
- LFT's
-CRP
- Calcium and phosphate
- Thyroid function
- Vitamin B12 and folate
- Urine dipstick
- Blood glucose
- Temperature
34
What investigations can be done in secondary care to establish the cause of dementia and potential differential diagnosis?
- MRI and CT scan
- Urinalysis
- HIV status
- Neuropsychological assessment
- EEG
35
What is the Mini-Mental State Examination and what does it involve?
- Used to assess cognitive function and decline
- It tests memory, attention, calculation, orientation, language, the ability to follow commands
- Primarily to aid in the diagnosis of dementia
It takes less than 10-15 minutes to perform and involves 8 questions.
Gives a score between 0 and 30 ( the higher the score the better the patients cognitive function)
36
What are the possible agents used to prevent dementia?
- NSAIDs (started early)
- Antihypertensives
- Beer
- Oestrogen
- Fish
- Lithium
- Statins
- Vitamins B, C, E, folic acid
37
What medications are commonly used at the onset of Alzheimer's disease? (3)
Donepezil, Galantamine, Rivastigmine
(AChEi's)
38
What is the dosage of Donepezil in Alzheimer's disease?
5-10mg OD ON
39
What is the dosage of Galantamine in Alzheimer's disease?
4-12mg BD
40
What is the dosage of Rivastigmine in Alzheimer's disease?
1.5-6mg BD
41
If AChEI's are effective in Alzheimer's disease, what effects can they have?
- The progression of the disease can be delayed for several months or years
--This reduces carer burden
--This delays the need for transfer to a dementia-care home or hospital
42
Which AChEi is licenced for both Alzheimer's disease and Parkinson's disease?
Rivastigmine
43
What are the common side effects of AChEi's?
- Nausea, vomiting, diarrhoea, sleep disturbance, abnormal dreams, headache, incontinence, fatigue, agitation
-Bradycardia (dangerous in certain heart diseases or if taking heart-slowing drugs such as beta-blockers, CCB's ,digoxin)
44
How to minimise nausea when taking AChEi's?
Take doses after food.
45
How to combat rashes caused by rivastigmine patches?
- If the rash is mild, an emollient cream can be used.
- If severe the prescriber should be informed.
- Rotation of the application site
46
How to minimise sleep disturbance and nightmares caused by donepezil?
Take the dose in the morning.
47
What is Memantine licenced for?
Moderate to severe dementia in Alzheimer's disease.
48
What is the usual dosing of memantine in Alzheimer's disease?
Initially 5mg OD for one week then is increased by 5mg per week until 20mg OD is reached.
Monotherapy is recommended.
49
What are the common side effects of memantine?
Headache, constipation, dizziness, hypertension, dyspnoea
50
What medications are offered to patients with Lewy Body dementia? (Unlicenced use)
Donepezil or Rivastigmine
51
When is Galantamine considered for a patient with Lewy Body dementia?
When donepezil and rivastigmine are not tolerated.
52
What drugs should not be offered in frontotemporal dementia?
AChEi's or Memantine
53
When can AChEi's or Memantine be considered for patients with Vascular dementia?
When they have suspected comorbid Alzheimer's disease, Parkinson's disease dementia or Lewy body dementia.
54
What are the NICE guidelines for first line AChEi in Alzheimer' disease?
- Use the least expensive one first
55
What are the behavioural symptoms of dementia?
- Physical aggression
- Screaming
- Wandering
- Culturally inappropriate behaviour
- Sexual disinhibition
- Swearing
56
What are the psychological symptoms of dementia?
- Anxiety
- Depression
- Hallucinations
- Delusions
57
What are the 5 typical delusions patients with dementia can have?
- People are stealing their things
- Spouse or other care giver is an imposter
- Abandonment
- Misidentification
- Convinced their spouse is unfaithful
58
What are the major adverse outcomes of antipsychotics in dementia?
- They double the risk of death
- Over-sedation and dehydration
- Infection risk is tripled
- Stroke risk is tripled
- Falls and fractures are doubled
59
What are the adverse effects of antipsychotics?
- Sedation
- Parkinsonism
- Gait disturbance
- Dehydration
- Falls
- Chest infections
- Confusion
- Movement problems ( tremor, rigidity)
- Agitation/restlessness
- Dry mouth
- Blurred vision
- Constipation
60
What is Risperidone used for in dementia?
To treat/manage the behavioural and psychiatric symptoms of dementia.
61
When is Risperidone appropriate in dementia? (4)
- Persistent aggression
- Moderate to severe Alzheimer's dementia.
- Unresponsive to non-drug approaches
- There is a risk of harm to themself or others.
62
What is the dosage of Risperidone in Alzheimer's disease?
Initialy 0.25mg BD then can be increased by 0.25 BD every other day.
The optimum dose for most patients is 0.5mg BD but some patients need 1mg BD.
Maximum 6 weeks.
63
Why are benzodiazepines not used for behavioural and psychiatric symptoms of dementia?
They increase the patients fall risk 8 fold.
64
What is the first line treatment for the behavioural and psychiatric symptoms of dementia?
-Non-drug psychosocial interventions
- Treatment of non-dementia cause e.g. pain, infections, depression
65
What are the pathological findings for Alzheimer's disease?
- Atrophy in the cerebral cortex and hippocampus
- Extracellular beta-amyloid plaques
- Functional losses in cholinergic, GABAergic and monoaminergic transmitter systems
- Intra-neuronal neurofibrillary tangles made mainly of tau protein
66
APP cleavage pathways:
Formed from amyloid precursor protein (APP) and the action of secretases:
-----10% of APP is cleaved by beta-secretase into soluble APP beta (sAPP beta) and C-terminal fragment beta (CTF beta). CTF is then cleaved by gama secretase into A beta 40 (80-90%) and A beta 42 (10-20%).
-----90% of APP is cleaved by alpha secretase into soluble APP alpha and C-terminal fragment alpha (CTF alpha).
67
How is beta amyloid produced?
Beta secretase cleavage pathway.
(Cleavage of APP)
68
What are the plaques in Alzheimer's disease made of?
Beta amyloid
(A beta 40, A beta 42)
69
Is A beta 40 or A beta 42 more abundant?
A beta 40
70
Is A beta 40 or A beta 42 more insoluble?
A beta 42
71
How do beta amyloid plaques cause neuronal cell death? (2)
1. They have direct cytotoxic effects
2. They cause an inflammatory response (microglial activation + cytokine release)
72
How are neurofibrillary tangles formed?
1- Tau becomes hyperphosphorylated
2- This aggregates to form paired helical filaments
3- Microtubules are depolymerised
73
What happens to the amount of ACh in the brain during Alzheimer's disease?
Decreased
74
What causes early onset Alzheimer's (genetics)?
- Trisomy 21
- Mutations in APP
- Mutations in Presenilin 1 and Presenilin 2
- Mutations in Tau
75
What causes late onset Alzheimer's (genetics)?
- ApoE4 mutations
76
What are the two classes of drugs used to treat Alzheimer's disease?
Anticholinesterases and NMDA antagonist
77
How do Acetylcholinesterase inhibitors work in Alzheimer's?
They inhibit acetylcholinesterase from breaking down acetylcholine, enhancing the action of acetylcholine.
78
What are the downsides to acetylcholinesterase inhibitors in the treatment of Alzheimer's?
- They rely on the patient having some in tact cholinergic neurones to synthesise acetylcholine
- The side effects can be limiting
79
What two enzymes does galantamine inhibit?
Acetylcholinesterase and butyrylcholinesterase (BuChE)
80
How does memantine work in Alzheimer's disease?
It is a non-competitive NMDA antagonist.
It reduces neuronal excitation.
81
Do acetylcholinesterase's need to cross the BBB?
Yes
