S8) Dementia and Delirium Flashcards
What is dementia?
It is an umbrella term - best described as a set of symptoms
The result of the progressive destruction of neurons- a chronic, progressive syndrome of insidious onset
Symptoms will differ depending on where the damaged neurons are within the brain
Identify cognitive symptoms of dementia.
– Impaired memory (temporal lobe involvement)
– Impaired orientation (temporal lobe involvement)
– Impaired learning capacity ((temporal lobe involvement)
– Impaired judgement (frontal lobe involvement)
Identify non-cognitive symptoms of dementia.
– Behavioural symptoms
- Agitation
- Aggression (frontal lobe involvement)
- Wandering
- Sexual disinhibition (frontal lobe involvement)
– Depression and anxiety
– Psychotic features
- Visual and auditory hallucinations (hallucinations=false perceptions)
- Persecutory delusions (delusions=false beliefs)
– Sleep symptoms
- Insomnia
- Daytime drowsiness (decreased cortical activity)
Identify the different types of dementia in order of prevalence
- Alzheimer’s disease
- Vascular dementia
- Lewy body dementia
- Frontotemporal dementia
- Aids related dementia - uncommon
In Alzheimer’s disease, there is plaques and tangles.
Which protein is involved in the plaque formation and what is its normal role?
There’s this protein called Amyloid precursor protein (APP)
This helps to repair neurons following damage
In Alzheimer’s disease, there is plaques and tangles.
How are the plaques formed?
This is an extracellular process.
Protein called Amyloid precursor protein (APP) → this helps to repair neurons following damage
Being a protein, it is periodically replaced
Enzymes called alpha and gamma secretase normally chop it up for disposal (normally into soluble parts)
However, if Beta secretase gets involved, the resulting parts of APP are no longer soluble
These insoluble peptides accumulate outside the cell.: we get Beta amyloid plaques (not soluble .: can’t be disposed off - formation of plaque)
•It fills up the space between neurons + reduces signal transmission (leading to death)
What is the effect of the beta amyloid plaques seen in AD?
Plaques can also induce an inflammatory response → Causing neuronal death
If plaques deposit around blood vessels:
– Amyloid angiopathy can occur
– Weakened blood vessels can bleed
Note: usually we get a definite diagnosis of AD post-mortem to find the plaques
In Alzheimer’s disease, there is plaques and tangles.
Which protein is involved in the tangle formation and what is its normal role?
Tau proteins
play a role in stabilising microtubules within the neuronal cytoskeleton
• Microtubules help to mobilise nutrients around the neuron
How do we get the formation of tangles in AD?
This is an intracellular event
→ Beta amyloid plaques (outside the neuron) induce pathological processes within the neuron
→ Results in hyperphosphorylation of Tau proteins
→ Causes a change in the shape of Tau proteins
→ No longer able to support cytoskeleton
→ Neuron death
→ Also aggregate together into tangles - neurofibrillary tangles
What are the macroscopic changes seen in AD?
→ Global cortical atrophy
→ Sulcal widening
→ Enlarged ventricles (primarily lateral and third affected)
What are the microscopic changes seen in AD?
→ Plaques
• Composed of amyloid beta
→ Tangles
• Hyperphosphorylated tau protein
It is believed that plaques and tangles kill neurons.
Since neurogenesis is limited in the CNS, any neurones that die are unlikely to be replaced
* Predominant neurons affected: o Cholinergic (treatments target this)
o Noradrenergic o Serotonergic
o Those expressing somatostatin
What is the correlation of acetylcholine and AD?
Acetylcholine (ACh), a neurotransmitter essential for processing memory and learning, is decreased in both concentration and function in patients with Alzheimer’s disease.
This deficit and other presynaptic cholinergic deficits, including loss of cholinergic neurons and decreased acetylcholinesterase activity, underscore the cholinergic hypothesis of Alzheimer’s disease.
This is important to be aware of as certain Alzheimer’s medications target this problem e.g. acetylcholinesterase inhibitors - inhibits the breakdown of AcH .: enhances the levels of AcH at the synapse.
What are the two types of AD?
- Sporadic
- Familial
Identify features of sporadic type of AD.
– 90-95% of AD is this type
– Causes are poorly understood
• Genetic and environmental (in other words, we don’t know)
– Prevalence increases with age
• 50% of 85 year olds
Identify features of familial type of AD.
– 5-10% of AD
– Early onset dementia
– PSEN 1/2 genes - mutated- implicated
– Mutation of gamma secretase - resulting in formation of beta amyloid plaques
– Trisomy 21 (Down’s syndrome) - more likely to produce beta amyloid plaques
– Disease may present as early as 40 years old
Identify symptoms of AD.
Related to severity of disease
- Initially symptoms hard to detect
- Short term memory (hippocampus) often first to show
- Motor and language skills affected
- Long term memory loss
- Disorientation
- Immobilisation is often linked to cause of death
- Pneumonia
How can we diagnose AD?
– CT scan – showing macroscopic changes (can also rule out other intracranial pathology)
– Brain biopsy (postmortem) is only definitive method
Diagnosis by exclusion:
- Exclude organic causes of cognitive decline
o Hypothyroidism
o Hypercalcaemia
o B12 deficiency
o Normal pressure hydrocephalus
→ Abnormal gait
→ Incontinence
→ Confusion
- Exclude delirium
- Look for features of progressive cognitive decline, impairment of activities of daily living in a patient with a normal conscious level (cf. delirium where conscious level is diminished with acute cognitive decline)
How can we assess mental health?
Mental State Examination (MMSE - 30 points) can be used to classify the severity of cognitive impairment in Alzheimer’s disease
– mild Alzheimer’s disease: MMSE 21 to 26
– moderate Alzheimer’s disease: MMSE 10 to 20
– moderately severe Alzheimer’s disease: MMSE 10 to 14
– severe Alzheimer’s disease: MMSE less than 10
What treatment is available for AD?
– No cure
– Acetylcholinesterase inhibitors - due to deficient AcH Associated with AD - inhibits the enzyme that breaks down Act the synaptic cleft.
– Memantine (for advanced cases)
• Glutamate receptor antagonist. - glutamate is an excitatory neurotransmitter - v high levels of this is said to make AD worse .: we give an antagonist.
Describe features of Lewy body dementia.
– Dementia like features early
– Parkinsonian features later
– Occurs 50-85 years old
– More rapid progression
Essentially the same disease as Parkinson’s. If movement disorder followed by dementia then we call this Parkinson’s disease. If dementia precedes movement disorder we call it dementia with Lewy bodies
– often misdiagnosed as it has similar presentation to AD and Parkinson’s disease.
What is the protein involved in Lewy body dementia?
Alpha synuclein
What is Lewy body dementia caused by? (pathology)
Caused by misfolding of a protein (in the neuron) called alpha-synuclein
These misfolded proteins aggregate into Lewy bodies. - forms spherical intracytoplasmic inclusions
What are the main sites of deposition of the misfolded protein in Lewy body dementia?
Main sites of deposition are the:
– Cortex (dementia type symptoms) - similar to Alzheimer’s disease symptoms
– Substantia Nigra (parkinsonian features)
– Temporal lobe
– Frontal lobe
– Cingulate gyrus (found just above the corpus callosum)
Note: Can label alpha synuclein in the brain using advanced imaging techniques
How does a person with Lewy body dementia present?
o Fluctuating cognition and alertness
o Vivid visual hallucinations
o Parkinsonian features
→ May cause repeated falls
o Do not give antipsychotics (dopamine antagonists) as can cause neuroleptic malignant syndrome, a psychiatric emergency
→ Fever
→ Encephalopathy (confusion)
→ Vital signs instability (tachycardia, tachypnoea (v.sensitive sign), fluctuating BP)
→ Elevated creatine phosphokinase
→ Rigidity (caused by dopamine antagonism)
In a person with Lewy body dementia, why should we not give antipsychotics?
These are dopamine antagonists - as can cause neuroleptic malignant syndrome, a psychiatric emergency
→ Fever
→ Encephalopathy (confusion)
→ Vital signs instability (tachycardia, tachypnoea (v.sensitive sign), fluctuating BP)
→ Elevated creatine phosphokinase
→ Rigidity (caused by dopamine antagonism)
What are the symptoms seen in Lewy body dementia?
Cognitive symptoms (early)
- Very distressing hallucinations (often small people and furry animals)
- Depression
- REM sleep disorders
• Sleep walking/talking
Parkinson’s symptoms (later)
- Bradykinesia
- Resting tremor
- Stiffness
What is the treatment for Lewy body dementia?
– symptom based
– levodopa (dopamine analogue) - precursor to dopamine - helps with the Parkinsonian symptoms
What is frontotemporal dementia?
Over the past decade or two, it has become apparent that FTLD is an umbrella term for a heterogeneous group of diseases that can be characterized based on the type of glial and neuronal proteinaceous inclusions or underlying genetic mutation
2nd most common cause of early onset dementia
Affects the frontal and temporal lobe atrophy
Broadly similar disease process to Alzheimer disease
Often younger patients
What causes frontotemporal dementia?
Aggregated proteins (inclusion bodies)
• Tau protein hyperphosphorylation (Pick’s disease) - they are called Pick’s bodies (not tangles) in this dementia
What symptoms do you see in frontotemporal lobe dementia?
Symptoms are related to loss of function of these areas
- *Frontal lobe**
- Behavioral and emotional changes
- Disinhibition (hostility)
- Inappropriate social behaviour
- Loss of motivation without depression (caused by damage to anterior cingulate cortex)
- Repetitive/ritualistic behaviours
- Non fluent (Broca type) aphasia
- *Temporal lobe**
- Language impairment (progressive aphasia)
What investigation can you do to diagnose frontotemporal dementia? What will you find?
MRI scan
- Unilateral (or bilateral) frontal/temporal atrophy
- Ventricle enlargement
What is vascular dementia?
– 2nd most common cause of dementia
– it is a heterogenous dementia
– can affect multiple sites in brain
– Presentation related to area of brain affected
– Risk factors are usual suspects
Describe the presentation of vascular dementia.
Stepwise, maybe with focal neurological features
What are the risk factors for vascular dementia?
o Previous stroke / MI etc
o Hypertension
o Hypercholesterolaemia
o Diabetes
o Smoking
What causes vascular dementia?
Cognitive impairment caused by cerebrovascular disease
Caused by multiple infarcts and ischaemia
• Atherosclerosis/emboli/hypertension and vasculitis
(multiple small strokes)
What is the treatment for vascular dementia?
Treatments target risk factors
e.g. reducing blood pressure, thinning blood - anticoagulants? antiplatelets?
Describe features of HIV and AIDs dementia.
Not particularly common as HIV and AIDs is not common
– Individuals are living much longer - As patients with HIV infection live longer thanks to modern treatments, their chance of developing AIDs
associated dementia is increasing
– Occurs when CD4+ count falls below threshold
– Damage caused by virus itself (not opportunistic infections)
– Viral proteins cause injury/inflammation → Result is neuron damage
– AIDS dementia complex can affect behaviour, memory, thinking, and movement
What is the pathology of AIDs dementia?
– Cause poorly understood:
: entry of HIV infection macrophages into the brain is thought to lead to indirect damage of the neurons.
What is the presentation of AIDs dementia?
– Insidious onset but rapid progression once established
– Clinical features (related to global damage but also some manifestations of cerebellar involvement)
o Cognitive impairment
o Psychomotor retardation (slow thoughts and movements, also seen in depression)
o Tremor
o Ataxia
o Dysarthria
o Incontinence
How can we generally manage dementia?
Using the biopsychosocial model
Use of drugs:
o Acetylcholinesterase inhibitors (e.g. donepezil, rivastigmine, galantamine)
-Modest efficacy for mild to moderate Alzheimer’s disease
o NMDA antagonists (e.g. memantine)
-Useful for treating agitation
-NMDA antagonist
Psychological:
Few psychological treatments are available for dementia due to its progressive nature
Social:
– Mainstay of management
– Key themes:
o Explain the diagnosis sensitively
o Talk about problems that will arise and how they will be managed
o Give results of any special investigations (e.g. scans)
o Driving – often a difficult topic to deal with as patients frequently desperate to retain their independence
o Finances
– Will – Power of attorney
o Day care and respite care (mainly to allow carers to rest and provide supportive environment for patients)
o Residential/nursing home placement
What is delirium?
Delirium (sometimes called ‘Acute confusional state’) is an acute, fluctuating syndrome of disturbed consciousness, attention, cognition and perception.
Often reversible, due to organic cause
- *Associated with a variety of insults to the brain which may cause**
- *neuronal damage and inflammation**
What is the relationship between dementia and delirium?
Dementia can predispose to episodes of delirium but is not the only reason behind delirium.
How does delirium present?
– Presents suddenly
– Rapid onset of confusion
– Clouded consciousness (may be drowsy)
– Fluctuating course
– Maybe transient visual hallucinations
– Often exaggerated emotional responses (e.g. aggression)
Categorised as:
• Hyperactive
– Agitated/aggressive
– Delusions
– Restless
• Hypoactive
– Withdrawn
– Drowsy
– Quiet
– Consequently more likely to be missed / confused with
something else
or can be a mixture of both …
→ Mood may rapidly fluctuate
→ Persecutory delusions (narrative of elusion often not coherent)
→ Symptoms worse at start and end of day
• Maybe related to changes in endogenous cortisol levels
What are some causes of delirium?
Drugs e.g. opioid - co-codamol, e.g. steroids → psychosis
Epilepsy/ Electrolyte imbalance
Liver failure/ low oxygen (MI, PE)
Infection e.g. UTI
Retention (urinary/ faecal - constipation)
Intracranial
Uraemia
Metabolism
Multifarious (use a surgical sieve approach)
o Nutritional
Vitamin deficiencies
o Intracranial
Strokes, TIAs, epilepsy, infection etc.
o Extracranial infections
UTI, pneumonia
o Iatrogenic
Infections
Drugs
o Alcohol
Intoxication
Withdrawal (including delirium tremens, caused by changes in GABA and NMDA receptors induced by long term alcohol consumption)
o Endocrine
Thyroid
Pancreas
o Metabolic
Hypoxia
Renal (e.g. electrolyte disturbances)
Hepatic
What would the history be like for a person with suspected delirium?
– Not explained by previous neurological condition
– Conversely, can be attributed to a known risk factor
How can you treat delirium?
– Find and treat the underlying cause
– Minimise/treat precipitating factors (e.g. correct electrolyte imbalance)
– Encourage normal day/night cycle
– Allow wandering if safe (don’t want to upset/ aggravate them)
– Involve family/loved ones
– For challenging behaviours – distraction techniques
– Medications last resort
• Haloperidol/newer antipsychotics
What is the prognosis of delirium?
– Increases risk of dementia
– Associated with mortality
– These patients often have lengthy hospital stays and have a high risk of readmission
Fill in this table: delirium vs dementia
What is the natural history of dementia? Why do people with dementia die?
It is a chronic progressive disorder - slow progression until death
involves neurodegeneration - damage and death of neuron
Dementia deaths can arise rom:
– immobility - huge factor
– lose ability to speak and swallow .: can die from aspiration pneumonia
– UTI
– general malaise (unable to swallow and therefore malnourished)
