S9 L1 Dementia, delirium and toxic insult Flashcards
Define dementia?
Progressive condition
Deterioration in cognition resulting in behavioural problems and impairment in the activities of daily living
Extensive affecting multiple domains of intellectual functioning
What are the different types of dementia?
- Alzheimer’s → most common (50-70%)
- Vascular → (25%)
- Lewy Body (15%)
- Frontotemporal
- AIDS-dementia complex
What is the pathophysiology of Alzheimer’s disease?
1- Global atrophy of brain lobes → Mostly frontal, parietal and temporal lobes 2- Macroscopic feature → Global cortical atrophy → Sulcus widening → Enlarged 3rd and 4th ventricles 3- Microscopic → Plaques - composed of amyloid beta → Tangles - hyperphosphorylated tau - Two hypothesis 1. The amyloid hypothesis 2. The tau theory
What is the amyloid hypothesis?
- Excess of interneuronal amyloid (Abeta) peptides, due to overproduction or diminished clearance of beta-amyloid
- Formation of dense amyloid oligomers, which are deposited as diffuse plaques
- Inflammatory process through microglial activation, cytokine formation, and activation of the complement cascade
- Formation of neuritic plaques, causing synpatic and neuritic injury and cell death
What is the tau theory?
Abnormal aggregation of tau protein, a microtubule-associated protein that stabilises microtubules in the cell
- Tau accumulates into interneuronal masses → neurofibrillary tangles and dystrophic neurites
- Abundance of tangles is roughly proportional to the severity of clinical disease and cognitive decline
What are the main neurones that are affected in AD?
- Cholinergic
- Noradrenergic
- Serotonergic
- Those expressing somatostatin
What are the risk factors for AD?
- Head injury
- ↑serum cholesterol and homocysteine levels pose a risk for development of AD
- Lifestyle factors
→ Smoking
→ Midlife obesity
→ Diet high in saturated fats
What is the history of someone with AD?
- Risk factors
- Memory loss → recent memory first (recall memory from long time ago)
- Disorientation to time and place → misplacing items/ getting lost
- Nominal dysphasia → proper names and low-frequency words decline first
- Apathy → emotional disturbances, ‘lack of care’
- Decline in activities of daily living
- Personality/mood changes
What is the pathophysiology of vascular dementia?
Cognitive impairment caused by cerebrovascular disease (multiple small strokes)
Common end point of many vascular pathologies intracranially
→ Infarction
→ Leukaraiosis → white matter disease - subcortical leukoencephalopathy - lack of blood supply due to deposition in the brain
→ Haemorrhage
→ Alzheimer’s disease → although not classified as a vascular pathology, AD has a strong vascular risk factor spectrum
What is the history of someone with vascular dementia?
- History of stroke
- Difficulty solving problems
- Apathy
- Disinhibition
- Slowed processing of information
- Poor attention
- Retrieval memory deficit
- Risk factors similar to IHD (idiopathic heart disease)
What is the pathology of Lewy body dementia?
- Accumulation of Lewy bodies in vulnerable sites of CNS
→ Substantia Nigra
→ Temporal lobe
→ Frontal lobe
→ Cingulate gyrus - Lewy bodies are composed of the proteins alpha-synuclein, a cytoplasmic protein and associated with synaptic vesicles
- Other proteins include neurofilament and ubiquitin
- The distribution and density of Lewy bodies are thought to be correlated with clinical symptoms
- Co-existing AD pathology is common
How can you tell if a patient PD or Lewy body disease?
Movement disorder followed by dementia call it PD
Dementia precede movement disorder we call it Lewy Bodies
What is the history of someone with Lewy body dementia?
- Risk factors → old age
- Cognitive fluctuations → fine for long periods of time, then deteriorate, then improve
- Hallucinations, typically visual and complex, up to 80% of patients
- Motor symptoms → Parkinsonian features present in >85% of patients
- Vivid dreams are accompanied by loss of associated atonia of REM sleep, ‘acting out’ dream
- Depression
- Repeated falls/syncope
- Urinary incontinence
- Constipation
What is the pathophysiology of someone with frontotemporal dementia?
- Focal neurodegeneration of the frontal or temporal lobes of the brain
- Dutch epidemiological study reported a positive family history in 43% of cases
- Definitive diagnosis depends on pathological examination of brain tissue and identification of patterns of neuronal injury and characteristic intra-neuronal and glial cell inclusion
→ FTD-tau
→ FTD-U (ubiquitin)
What is the classification of FTD?
Classification:
- Apathetic (not interested in anything)
- Disinhibited
- Stereotypic
Can be overlapping
Behavioural FTD v Primary Progressive aphasia
What is the history of FTD?
- Coarsening of personality, social behaviour and habits
- Progressive loss if language fluency or comprehension
- Development of memory impairment, disorientation or apraxias
- Progressive self-neglect and abandonment of work, activities and social contacts
- Age of onset at peak in mid-50s
- FHx- big impact
- Altered eating habits
What is the pathophysiology of AIDs dementia complex?
- Patient with HIV infection live long thanks to modern treatments, their chance of developing AIDs associated dementia is increasing
- HIV infected macrophages enter the brain, causing indirect damage to neurones
- Insidious onset, but rapid progression once established
What are the clinical features of AID-dementia complex?
Related to global damage but also some manifestations of cerebellar involvement:
- Cognitive impairment
- Psychomotor retardation (slow thoughts and movements, also seen in depression)
- Tremor
- Ataxia
- Dysarthria
- Incontinence
What are the 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)
What are the 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 (delusion= false beliefs) - Sleep symptoms
→ Insomnia
→ Daytime drowsiness (decreased cortical activity)
How is dementia diagnosed?
Diagnosed by exclusion - Exclude organic causes of cognitive decline → Hypothyroidism → Hypercalcaemia → B12 deficiency → Normal pressure hydrocephalus →→Abnormal gait →→Incontinence →→Confusion - Exclude delirium - Look for feature of progressive cognitive decline, impairment of activities of daily living in a patient with normal conscious levels
What investigations would you perform for suspected dementia?
- Mini mental state exam- questionaire used to score dementia patients
- Dementia screen (checking for things that can mimic dementia)
→ FBC → anaemia
→ U&E → deranged sodium, calcium and glucose
→ TSH → hyper/hypothyroidism
→ Serum Vitamin B12 - Urine drug screen
- CT head
- MRI brain
- ECG in vascular dementia
- Routine syphilis testing is not necessary but should be done if a risk is identified in the history
What is a mini mental state examination?
- Orientation
- Registration
- Attention and calculation
- Recall
- Language
- Copying
What is the management for dementia?
Bio-psycho-social model
Biological
- Drugs
→ Acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine), modest efficacy for mild to moderate AD
→ NMDA antagonists (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
→ Explain the diagnosis sensitivity
→ Talk about the problems that will arise and how they will be managed
→ Give the results of any special investigations
→ Driving - often difficult topic- patient want to retain independence
→ Finances - will, power of attorney
→ Day care and respite care (mainly to allow carers to rest and provide supportive environment for patients)
→ Residential/nursing home placement
What is delirium?
Acute confused state
An acute, fluctuating syndrome of disturbed consciousness, attention, cognition and perception
Often reversible
Associated with a variety of insults to the brain which may cause neuronal damage and inflammation
What are the different type of delirium?
Hyperactive
Hypoactive
Mixed
What is hyperactive delirium?
Restless
Agitated
Aggressive
What is hypoactive delirium?
Withdrawn
Quiet
Sleepy
Consequently more likely to be missed/ confused with something else
What can causes delirium?
THINK DELIRIUM
T- trauma
H- hypoxia
I- increasing age/ frailty
N- neck of femur fracture
K- smoker or alcohol withdrawal
D- drugs- new started/ stopped, side effects of drug interactions
E- environment- confusing for patient if moved around a lot
L- lack of sleep, reverse sleep-wake cycle
I- imbalanced electrolytes (Na+, Ca2+, glucose, liver function)
R- retention (urinary or constipation)
I- Infection/sepsis
U- uncontrolled pain
M- medial conditions (dementia, PD)
What are the features of delirium?
- Rapid onset of confusion
- Clouded consciousness (may be drowsy)
- Fluctuating course
- Maybe transient visual hallucinations
- Often exaggerated emotional response (e.g. aggression)
What is another method for determining the causes of delirium?
Multifarious - surgical sieve approach
- Nutritional → vitamin deficiencies
- Intra cranial → strokes, TIAs, epilepsy, infection
- Extracranial infections → UTI, pneumonia
- Iatrogenic → infections, drugs
- Alcohol → intoxication, withdrawal
- Endocrine → thyroid, pancreas
- Metabolic → hypoxia, renal, hepatic
What is the management process for delirium?
Find and treat the underlying cause
- Minimise/treat precipitating factors
- Encourage normal day/night cycle
- Allow wandering if safe
- Consider DOLS (deprivation of liberty)
- Involve family/love ones
- For challenging behaviour- distraction techniques, medication last resort
What is the prognosis of patients with deilirum?
Prognosis
→ ↑risk of dementia
→ associated with mortality
→ patient often have lengthy hospital stays and have a high risk of re-admission
→ ↑risk of institutionalisation on discharge
