What is the definition and epidemiology of Delirium?
Delirium is an acute and transient state of disturbed consciousness. It is an emergency and is associated with poor outcomes. It is very common, affecting up to:
- 20% of inpatients
- ~50% of post-operative patients
- 70% of elderly ITU patients
It is more common in patients who are elderly and those with a decreased cognitive reserve notably those with dementia.
What is the aetiology of delirium?
Delirium is a sign that something is physically wrong and is often caused by multiple pre-disposing and precipitating factors notably polypharmacy and infection. Causes of delirium can be broken down into:
- Substance-related
- Alcohol
- Prescribed medications
- Psychotropic medications
- Use of more than one drug
- Physiological causes
- Septicaemia
- Infection even as minor as a UTI can tip a patient into delirium
- Trauma e.g. head injury
- Metabolic causes such as liver failure, renal failure, electrolyte imbalance
- Hypoxia
- Endocrine e.g. hypoglycaemia
- Neurological causes
- Post-ictal
- Head injury
- Space-occupying lesion
- Encephalitis
- Pain
- Constipation
- Dehydration
- Sleep deprivation
What are the clinical features of delirium?
The clouding of consciousness is of sudden onset (hours-days) which is important, as dementia and depression have a more gradual onset. Furthermore, delirium symptoms fluctuate throughout the day and often get worse at night. Clinical features include:
- Disorientation with poor attention and short-term memory
- Mood changes may be prominent
- Illusions and hallucinations are common. Hallucinations are often visual.
- Delusions may also be present, and are often persecutory. The delusions are not as thought out as those in schizophrenia
Sleep is commonly disturbed, with insomnia or reversal of sleep-wake cycle.
Behavioural change usually takes one of two forms:
- Hyperactivity, aggression, agitation.
- Wandering, climbing into other patients’ beds, pulling out catheters
- Easy to spot
- Hypoactivity, lethargy, stupor, drowsiness, withdrawal.
- Quiet delirium e.g. silently lying in bed
- Easily missed
Describe the investigations for delirium
It is essential to identify and treat the underlying cause. Mainstay investigations include:
- Physical examination
- Collateral history - especially asking the onset, is the patient usually forgetful etc. as dementia is the main differential.
- Check the drug chart for recently added drugs.
- Blood tests are essential, including FBC, E&Es, G, Ca2+
- Other tests such as MSU, ECG, CXR and septic screen
- Consider LFTs, blood cultures, CT head, CSF and EEG.
Describe the management for delirium
- It is important to treat the cause of the delirium, but also manage aggravating factors such as pain, constipation and dehydration.
- The mainstay of the treatment is non-pharmacological behavioural management. In many cases behavioural management is sufficient whilst the cause of delirium is being investigated. Work with nursing staff to ensure:
- Frequent reorientation e.g. with clocks, calendars and verbal reminders
- Good lighting - adequate lighting during the day as gloomy conditions can increase hallucinations and illusions; at night ensure dark but enough light to recognise where they are.
- Address sensory problems such as with spectacles and hearing aids
- Minimise change by avoid moving the patient excessively and avoid changing staff. Establish a routine.
- Move patient to a side room so address over-stimulation.
- Medications:
- Antipsychotics are usually the first-line though should be limited to cases with severe agitation and for psychotic symptoms. Atypical antipsychotics are often prescribed instead of haloperidol. Antipsychotics should be avoided for delirium tremens (delirium associated with alcohol withdrawal).
- A nocturnal dose of benzodiazepines used to be used, but should really not because of risk of falls in the elderly.
Describe the features of frontal lobe syndrome
Frontal lobe syndrome is due to damage to the frontal lobe which is critical for personality, judgment and prefrontal inhibition of impulsive behaviours.
The syndrome consists of dysfunctions with the following domains:
- Executive dysfunction leading to poor judgement, poor reasoning and problem-solving, poor planning and decision making.
- Social behaviour and personality change: loss of social awareness, disinhibition, impulsivity, emotional lability, repetitive or compulsive behaviours
- Apathy: lack of motivation and initiative, decline in self-care
Depending on the part of the loves most affected, people tend to be either apathetic or disinhibited, impulsive, aggressive and socially inappropriate.
Define dementia and it’s epidemiology
Dementia is the decline in cognitive function enough to interfere with daily life.
Dementia is very common affecting 1 in 14 of those over the age of 65.
List the causes of dementia in order of prevalence
The causes of dementia in order of prevalence are:
- Alzheimer’s disease accounts for 65% of dementia cases - cortical atrophy in frontal, parietal and temporal areas caused by beta-amyloid plaques and neurofibrillary tangles.
- Dementia with Lewy bodies accounts for 15% of dementia in the UK. Affected neurones form Lewy bodies instead of tangles.
- Vascular dementia accounts for at least 10%, but possibly more with a mixed disease with Alzheimer’s. Caused by widespread small vessel disease within the brain (diabetes or hypertension), or due to mini-strokes.
- Other progressive intracranial pathology (e.g. brain tumour, MS, Pick’s disease, MND)
- Alcohol and drugs
- Rare infections and deficiencies (e.g. HIV-AIDS, syphilis, B vitamin deficiency)
What are the clinical features of vascular dementia?
As Alzheimer’s dementia can often co-occur with vascular dementia, it can be difficult to separate the two. Vascular dementia patients have risk factors of stroke including: obesity, age, hypertension and cigarette smoking, diabetes.
Patients present with problems with executive function such as problem solving, and signs of frontal cognitive syndrome (apathy, disinhibition, slowed processing of information, poor attention).
Patients tend to have better recall and fewer intrusions than those suffering from Alzheimer’s, though also suffer from memory impairment.
If dementia is caused my mini-strokes, impairment progresses in a stepwise way, with every mini-stroke.
How would you investigate someone with suspected dementia?
Bedside/GP cognitive testing will show cognitive impairments. The pattern of which can help differentiate the dementias, alongside a good history. Cognition can be assessed with:
- Mini Mental State Examination (MMSE) which as a sensitivity and specificity for dementia of around 80% when a cut-off score of 23 is chosen, but NICE says <24. The MoCA and clock test are valuable and brief alternatives.
Assess daily functioning by asking about activities of daily living such as bathing, dressing, and continence, doing housework, preparing meals, shopping etc. The Bristol Activities of Daily Living Scalecan be used for this.
To help identify reversible causes of dementia and exclude other causes of symptoms, blood tests are performed in primary care:
- FBC - to rule out anaemia
- Metabolic panel - to exclude sodium, calcium and glucose levels causing the dementia
- Serum TSH - exclude hypothyroidism
- Serum B12 - as B12 deficiency can cause dementia.
- LFTs
In secondary care CT or MRI are useful, and can show characteristic changes for the different dementias. Other tests include:
- Urinalysis
- Syphilis serology
- HIV status
- Chest radiography
- Neuropsychological assessment
- Genetic testing, EEG, PET and CSF measurement of amyloid and tau can also be done if the centre has the resources.
Describe the management of suspected dementia in primary care
- Risk assessment and arrange for admission of they are severely disturbed and admission is necessary for the health and safety of themselves or others.
- Refer to specialist psychiatry or neurological services (with urgency depending on clinical dementia) if they are likely to have a genetic cause, have rapid cognitive decline, have learning difficulties, or are younger than 65.
- Refer all other people with suspected dementia to a memory assessment service such as a memory clinic or community mental health team for further specialist assessment and management.
- Discuss DVLA regulations on driving and cognitive impairments.
- Treat any modifiable risk factors such as excessive alcohol intake, diabetes, hypertension, obesity and smoking.
- [Kanay] Social needs and occupational therapy assessment.
Arrange follow-ups and monitor physical and mental health functional ability, as well as response to, and adverse effects from, dementia treatments and the progression of dementia.
What is the epidemiology of Alzheimer’s disease?
Alzheimer’s is the most common cause of neurodegenerative dementia.
Around 60% of dementia is accountable to Alzheimer’s disease
The rate of Alzheimer’s disease doubles every 5 years in the elderly. Onset tends to be around age 65. Earlier than this is called early-onset Alzheimer’s disease.
What are the risk factors for Alzheimer’s Disease?
Risk factors include:
- Age is the main risk factor. It is marginally more common in women.
- Genetics: family history and ApoE4. Familial Alzheimer’s is caused by mutations in presenilin 1 and 2 genes and APP gene.
- Vascular risk factors such as cerebrovascular disease and diabetes
- Low IQ and educational attainment
- Head injury
- Down’s syndrome
Describe the neuropathology associated with Alzheimer’s disease
The neuropathology of Alzheimer’s Dementia involves:
- Extracellular plaques also called Senile plaques (composed of Aβ) - lumps of protein sitting in the parenchyma of the brain.
- Neurofibrillary tangles (due to hyperphosphorylated tau) - tangles are much better correlated to clinical picture of dementia.
- Cerebral amyloid angiopathy (CAA) (Aβ) - same protein in the blood vessels.
- Neuronal loss (cerebral atrophy)
- Cholinergic loss: cholinergic pathways are most commonly affected in AD.
Alzheimer’s disease typically involves initial memory deficits secondary to dysfunction of medial temporal lobe structures (entorhinal cortex and hippocampus). Although pathology starts at the medial temporal lobe, it is a global disease. For reasons we do not know, the primary motor and sensory cortices are unaffected.
What are the clinical features of Alzheimer’s disease?
The first symptom is usually memory impairment with gradual onset and continuing decline. Starts as episodic memory loss particularly for recent events, with relative sparing of memory for remote events.
Language is also affected early on (aphasia) with difficulty finding words or naming objects, and impairments in the ability to construct fluent and informative sentences. As disease progresses: apraxia (difficulty planning movements), agnosia (inability to interpret sensations and recognise patterns such as faces), anosmia and disturbance in executive functioning.
Other features of depression include:
- Depression (though link is complex and not as straight forward and strong as the link by PD)
- Psychosis - delusions and hallucinations occur in a significant minority of patients at some stage in the illness.
- Behavioural problems - sleep-wake cycle flipping, sun-downing, aggression, changes in sexual behaviour
- Personality change
Describe the specific management of Alzhimer’s disease
Non-pharmacological management options should be offered to all patients, NICE recommends:
- ‘A range of activities to promote wellbeing that are tailored to the person’s preference’.
- Group cognitive stimulation therapy for patients with mild and moderate dementia
- Other options to consider include group reminiscence therapy (recalling and processing life’s events; used to support elderly patients with AD) and cognitive rehabilitation.
Pharmacological management - NICE updated it’s dementia guidelines in 2018:
- The three acetylcholinesterase inhibitors (donepezil, galantamine and rivastigmine) as options for managing mild to moderate Alzheimer’s disease
- Memantine (an NMDA receptor antagonist) is in simple terms the ‘second-line’ treatment for Alzheimer’s, NICE recommend it is used in the following situation reserved for patients with:
- Moderate Alzheimer’s who are intolerant of, or have a contraindication to, acetylcholinesterase inhibitors
- As an add-on drug to acetylcholinesterase inhibitors for patients with moderate or severe Alzheimer’s
- Monotherapy in severe Alzheimer’s
In managing non-cognitive symptoms, NICE does not recommend antidepressants for mild to moderate depression in patients with dementia. Antipsychotics should only be used for patients at risk of harming themselves or others, or when the agitation, hallucinations or delusions are causing them severe distress
What is with all the names of Lewy Body Dementia/Dementia with Lew Bodies/Parkinson’s disease dementia???
Lewy body dementia is an umbrella term that includes:
- Parkinson’s disease dementia - dementia symptoms occurring at least one year after the onset of Parkinsonism
- Dementia with Lewy Bodies - dementia symptoms preceding or concurrently with parkinsonism. However not all patients will develop parkinsonism.
Dementia with Lewy bodies is closely related to Parkinson’s disease, and both are characterized as ‘synucleinopathies’, reflecting the abnormal aggregation of α-synuclein protein present in Lewy bodies.
Describe the neuropathology of Lewy Body dementias
Lewy bodies are hyaline (smooth) circular inclusions in the neuronal cell bodies composing of α-synuclein protein. In Lewy body dementias, these are found in the cerebral cortex. The neuronal inclusions also contain ubiquitin
- In Parkinson’s disease, these are also seen in the substantia nigra, and their biochemical composition is the same in both diseases. The main pathology of PD is degeneration of the dopaminergic neurones of the substantia nigra pars compacta, though other dopaminergic pathways are free of pathology.
- There is also a significant neuropathological overlapwith Alzheimer’s disease, with dementia with Lewy bodies often exhibitingabundant senile plaquesand widespread reductions in choline acetyltransferase in the neocortex; however, neurofibrillary tangles are rare.
What are the clinical features of Lewy body dementias?
- Progressive cognitive decline especially in visuospatial ability and attention. There is often pronounced day to day fluctuations in cognition and attention.
- Recurrent visual hallucinations which are well formed and detailed. Often involving animals or people.
- Motor features of parkinsonism (tremor, bradykinesia and rigidity). See Parkinson’s Disease
Parkinson’s disease is strongly associated with depression.
How is Lewy body dementia diagnosed?
Largely a clinical diagnoses though SPECT (single-photon emission computer tomography) can also be used.
What drugs are used to treat Lewy body dementia?
Both acetylcholinesterase inhibitors (e.g. donepezil, rivastigmine) and memantine can be used as they are in Alzheimer’s.
What drugs are used in the management of Parkinsonism?
Managing the primary (movement) symptoms of Parkinson’s disease is accomplished by using drugs to increase the amount of dopamine available in the brain. The first-line treatment for treating motor symptoms is levodopa (dopamine precursor) which is usually combined with a dopamine decarboxylase inhibitor such as carbidopa (which prevents metabolism of levodopa to dopamine in the periphery, as the drug doesn’t cross the BBB).
Dopamine receptor antagonists such as bromocriptine and cabergoline can also be used. They have a longer duration of action than L-DOPA (which is cleared away very quickly and has to be given 4 times daily) - hence has a smoother and more sustained response. Actions are also independent of presynaptic dopaminergic neurons. The incidence of dyskinesias is lower. But there are side-effects as it’sless tolerated/effective that L-DOPA.
Other drugs that work to increase dopamine include:
- Monoamine Oxidase B (MOA-B) inhibitors such as selegiline
- Amantadine (mechanism not dully understood)
- Catechol-O-Methyl Transferase (COMT) inhibitors such as entacapone and tolcapone. Used in conjunction of levodopa in patients with well established PD.
What are the psychiatric side-effects of Parkinson’s drugs?
- Drugs that increase dopamine release in the brain can cause psychotic symptoms such as visual hallucinations due to increased dopamine in the mesolimbic pathway.
- They can also cause impulse control disorders (especially dopamine receptor antagonists such as bromocriptine and cabergoline) such as gambling, or OCD-like syndrome, binge-eating.
What MMSE score suggests dementia
Mini Mental State Examination (MMSE)which as a sensitivity and specificity for dementia of around 80% when a cut-off score of 23 is chosen. However, NICE says:
- Mild dementia is a score of 20-24
- Moderate dementia is a score of 10-20
- Severe dementia is a score of <10.
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In Practise16
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Psychopharmacology44
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Affective Disorders and Self-Harm29
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Schizophrenia18
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Anxiety and Obsessions22
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Child and Adolescent Psychiatry20
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Neuropsychiatry29
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Substance Misuse22
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Reactions to Stress17
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Eating Disorders12
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Problems following Childbirth18
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Personality Disorders14
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Psychopathology15
