Conditions Flashcards
(28 cards)
What is the most common cause of dementia in the UK?
Alzheimer’s disease
What are the characteristic histological features of Alzheimer’s dementia?
-Amyloid plaques (clumps of beta amyloid)
-Neurofibrillary tangles (bundles of filaments within neurons, mostly made from tau protein)
The accumulation of these leads to a reduction in information transmission, and eventually to the death of brain cells, with abnormal depositions remaining post-mortem)
What is the pathology of Alzheimer’s disease?
Accumulation of beta-amyloid peptide, a degradation product of amyloid precursor protein, results in:
-Progressive neuronal damage
-Neurofibrillary tangles
-Increased numbers of amyloid plaques
-Loss of the neurotransmitter acetylcholine
Vascular effects are also important - 95% of AD patients show evidence of vascular dementia
What is the clinical presentation of Alzheimer’s disease?
Progressive, Persistent and global cognitive impairment.
-Visuospatial skill
-Memory
-Verbal abilities
-Executive function
-Anosognosia (lack of insight into the problem caused by the disease)
In later stages there may be:
-Irritability
-Mood disturbance (depression or psychosis)
-Behavioural change (aggression, wandering, disinhibition)
-Psychosis (hallucinations or delusions)
-Agnosia (not recognising self in the mirror)
What are the risk factors for Alzheimer’s disease?
-1st degree relative with AD
-Down’s syndrome (AD inevitable, often <40 years)
-Homozygosity for apolipoprotein E (ApoE) E4 allele
-PICALM, CL1 and CLU variants
-Vascular risk factors (high BP, diabetes, dyslipidaemia, high homocysteine, AF)
-Decreased physical/cognitive activity
-Depression
-Loneliness
-Smoking
What three pharmacological treatment types may be used in the management of Alzheimer’s disease?
- Acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine)
- Antiglutamatergic treatment (Memantine - NMDA antagonist)
- Antipsychotics (Haloperidol, Risperidone)
When and why are acetylcholinesterase inhibitors used in the treatment of Alzheimer’s?
Should not be used in mild disease and should be discontinued if there is no worthwhile effect on symptoms.
Used to increase CNS acetylcholine by inhibiting the protein causing its breakdown.
Types are donepezil, rivastigmine and galantamine
When might memantine by indicated for treatment of Alzheimer’s?
For people with moderate disease who are contraindicated acetylcholinesterase inhibitors
OR
In severe disease
What are the side effects of memantine?
Confusion
Headaches
Hallucinations
Tiredness
When might antipsychotics be indicated for treatment of Alzheimer’s? Which are licensed for use in this condition?
In severe, non-cognitive symptoms eg psychosis or extreme agitation
Haloperidol and risperidone.
What are the risk of acetylcholinesterase inhibitors?
Cholinergic effects may exacerbate peptic ulcer disease and heart block. Always ask about symptoms and do an ECG first.
What are the risks of antipsychotic use in alzheimer’s?
Possible increased risk of stroke/TIA. Assess risk and cerebrovascular risk factors. Avoid in mild-to-moderate disease.
What are the preventative interventions for development of Alzheimer’s disease?
The condition progresses slowly over years. Changes in CSF beta-amyloid can be seen 25 years before onset of symptoms and deposition can be detected 15 years before onset. CSF tau protein and brain atrophy can also be detected 15 years before.
Prevention is therefore most effective before any of this starts and involves looking after cardiovascular health (eg BP regulation), attaining higher educational level before the illness to increase cognitive reserve, use of statins and antioxidants.
What non-pharmacological interventions can be used in Alzheimer’s disease?
Aim is to promote cognition, independence and wellbeing in mild to moderate disease.
-Cognitive stimulation therapy - activities and discussions in groups
-Group reminiscence therapy
-Cognitive rehabilitation or occupational therapy to support functional ability.
What is the pathophysiology of Parkinson’s disease?
The basal ganglia are a group of structures situated in the middle of the brain. They are responsible for coordinating habitual movements such as walking or looking around, controlling voluntary movements and learning specific movement patterns. Part of the basal ganglia called the substantia nigra produces a neurotransmitter called dopamine. Dopamine is essential for the correct functioning of the basal ganglia. In Parkinson’s disease, there is a gradual but progressive fall in the production of dopamine, leading to disorders of movement. The symptoms are characteristically asymmetrical, with one side affected more than the other.
What is the classic triad of parkinsonism?
- Resting unilateral tremor: The tremor in Parkinson’s has a frequency of 4-6 Hz, meaning it occurs 4-6 times a second. This is described as a “pill rolling tremor” because it looks like they are rolling a pill between their fingertips and thumb. It is more pronounced when resting and improves on voluntary movement. The tremor is worsened if the patient is distracted. Asking them to do a task with the other hand, such as miming the motion of painting a fence, can exaggerate the tremor.
- Rigidity: Rigidity is a resistance to passive movement of a joint. If you take their hand and passively flex and extend their arm at the elbow, you will feel a tension in their arm that gives way to movement in small increments (like little jerks). This is what leads to the cogwheel description.
- Bradykinesia: Bradykinesia describes how their movements get slower and smaller. This presents in a number of ways:
-Their handwriting gets smaller and smaller (this is a classic presenting complaint in exams)
-They can only take small steps when walking (“shuffling gait”)
-They have difficulty initiating movement (e.g. from standing still to walking)
-They have difficulty in turning around when standing, having to take lots of little steps and often freeze at obstacles or doors due to poor simultaneous motor and cognitive function.
-They have reduced facial movements and facial expressions (hypomimia)
What features other than the classic triad of parkinsonism may be present in Parkinson’s disease?
There are a number of other features that often affect patients with Parkinson’s disease:
-Depression and psychosis
-Sleep disturbance and insomnia
-Loss of the sense of smell (anosmia)
-Postural instability
-Cognitive impairment and memory problems including dementia
-Autonomic dysfunction: Postural hypotension, constipation, urinary frequency/urgency, dribbling of saliva
What are the main features that differentiate a Parkinson’s tremor from benign essential tremor?
Parkinson’s Tremor
-Asymmetrical
-4-6 hertz
-Worse at rest
-Improves with intentional movement
-Other Parkinson’s features
-No change with alcohol
Benign Essential Tremor
-Symmetrical
-5-8 hertz
-Improves at rest
-Worse with intentional movement
-No other Parkinson’s features
-Improves with alcohol
What are the ‘Parkinson’s plus’ syndromes?
-Progressive supranuclear palsy
-Multiple system atrophy
-Cortico-basal degeneration
-Lewy-body dementia
What is multiple system atrophy?
This is a rare condition where the neurones of multiple systems in the brain degenerate. It affects the basal ganglia as well as multiple other areas. The degeneration of the basal ganglia lead to a Parkinson’s presentation. The degeneration in other areas lead to autonomic dysfunction (causing postural hypotension, constipation, abnormal sweating and sexual dysfunction) and cerebellar dysfunction (causing ataxia). Rigidity > tremor.
How is Parkinson’s disease diagnosed?
Parkinson’s disease is diagnosed clinically based on symptoms and examination. The diagnosis should be made by a specialist with experience in diagnosing Parkinson’s. Diagnosis is based on the core features. Cerebellar and frontotemporal disease should be excluded. Clinical response to dopaminergic therapy is supportive
What are the main pharmacological treatments for Parkinson’s disease?
- Levodopa: This is synthetic dopamine given orally to boost their own dopamine levels. This is given with…
- Peripheral decarboxylase inhibitors: Carbidopa and benserazide.
- Dopamine Agonists: These mimic dopamine in the basal ganglia and stimulate the dopamine receptors. They are less effective than levodopa in reducing symptoms. They are usually used to delay the use of levodopa and are then used in combination with levodopa to reduce the dose of levodopa that is required to control symptoms. One notable side effect with prolonged use of ergot-derived dopamine agonists (Bromocryptine, Pergolide, Carbergoline) is pulmonary fibrosis. Ropinirole and pramipexole may be preferred.
- Monoamine Oxidase-B Inhibitors: block the enzymes that break down neurotransmitters to help increase the circulating dopamine. Similarly to dopamine agonists, they are usually used to delay the use of levodopa and then in combination with levodopa to reduce the required dose. Eg Selegiline, Rasagiline
- COMT Inhibitors: The main example of this is entacapone. These are inhibitors of catechol-o-methyltransferase (COMT). The COMT enzyme metabolises levodopa in both the body and brain. Entacapone is taken with levodopa (and a decarboxylase inhibitor) to slow breakdown of the levodopa in the brain. It extends the effective duration of the levodopa.
What are the issues with Levodopa treatment?
Levodopa is the most effective treatment for symptoms but becomes less effective over time, requiring larger and more frequent dosing with worsening SEs and response fluctuations. It is often reserved for when other treatments are not managing to control symptoms.
The main side effect of dopamine is when the dose is too high patients develop dyskinesias. Theses are abnormal movements associated with excessive motor activity. Examples are:
-Dystonia: This is where excessive muscle contraction leads to abnormal postures or exaggerated movements.
-Chorea: These are abnormal involuntary movements that can be jerking and random.
-Athetosis: These are involuntary twisting or writhing movements usually in the fingers, hands or feet.
Other side effects include psychosis, visual hallucinations, nausea and vomiting.
The medication should not be withdrawn suddenly as this risks acute akinesia and neuroleptic malignant syndrome.
What are the non-pharmacological management options for Parkinson’s disease?
-Deep brain stimulation (may help those who are partly dopamine-responsive)
-Surgical ablation of overactive basal ganglia circuits (eg subthalamic nuclei)
