delirium and cognition Flashcards
What is cognition
The mental processes involved in making sense of and learning about the world around us, including:
* Memory
* Attention
* Perception
* Knowledge
* Problem solving
* Judgement
* Language
When might young adults without health problems experience cognitive impairment?
- Acute illness * Post-surgery * Sleep deprivation * Extreme exercise * Alcohol * Drugs * Depression
Does cognition decline with age?
“Crystallised” cognitive abilities are well-preserved
* Cumulative skills and memories from cognitive
processing that occurred in the past
* E.g. preserved on tests of general knowledge,
vocabulary, reading comprehension, maths,
science
“Fluid” cognitive abilities
* Processing new information to quickly solve
problems * Linear decline from age of 20
What is delirium?
“Acute brain failure”
Usually caused by systemic illness
Also referred to as “acute confusional state”
Key features of delirium?
Key features
* Acute onset
* Impairment of attention and awareness
* Fluctuating (hr(s) to hr)
* Often worse in evening
Delirium clinical features?
- Impaired awareness, attention and concentration
- Disorientated – person, time, place
- Memory may be preserved
- Hallucinations, especially visual
- Delusions – often complex and distressing
- Mood – often anxious, low, labile
Behaviour
* Hyperactive – agitation, pacing, aggression
* Hypoactive – reduced movement, appetite, withdrawn, sleepy (more dangerous)
* Mixed – fluctuates between hypo- and hyper-active
delirium is important because…
What three groups are more likely to develop delirium?
> 20% of hospital inpatients
* Up to half of elderly inpatients
* High prevalence in ITU patients
delirium is important because…
What risks increase after delirium?
- If hospitalized, two-fold increased mortality risk year afterwards
- Increased risk of dementia in the years following a delirium
- Worse outcomes for longer period of delirium
Who is at greater risk of delirium?
- Higher risk in older people and young children
- Multiple medical problems/frailty
- Polypharmacy
- Pre-existing cognitive impairment (dementia)
- Sensory impairment
List some common causes of delirium?
Systemic infection
post-surgery
pain
consiptaion
medication (sedatives/analgesics/polypharm)
MI
Hepatic/renal failure
CVA
Heart failure
Alcohol withdrawal, Drug intox/withdraw
Neuro inf. (meningitis/encephalitis)
Vitamin deficiencies (B12/folate)
Trauma/ head injury
Hypo or Electrolyte abnormality (esp. low Na)
Tumours/raised intracranial pressure
Epilepsy: post-ictal or status epilepticus
What can help prevent delirium?
Is this easy in hospital setting?
Early detection and treatment of any infection
* Orientation
* Preventing dehydration and constipation
* Maximise healthy sleep patterns
* Encourage mobility where possible
* Manage pain well
* Ensure good nutrition (includes looking after dentures)
How is delirium managed?
Is this easy in hospital setting?
Treat underlying cause
* Calm, quiet environment
* Regular reorientation
* Consistent routine
* Promote healthy sleep pattern * Appropriate lighting
* Medications for aggression are sometimes needed
* Follow-up in multidisciplinary clinic
What is dementia?
Dementia is an umbrella term for impaired cognition cause by a group of progressive, neurodegenerative brain disorders
* Impairment in memory, thinking and behaviour that interferes with a person’s normal activities of daily living
* Many different types of dementia
* Each with specific patterns of symptoms and cause
Why is dementia important?
There are currently about 850 000 people in UK with dementia,
set to rise to 1.6 million by 2040 * Financial cost of dementia in the UK is £34.7 billion per annum
* Prevalence increases with increasing age
* One in 100 people aged 65-69yrs
* One in 25 people aged 70-79yrs
* One in 6 people over 80yrs
* 70% of people living in care homes have dementia
What is young-onset dementia?
Dementia under 65y
What is dementia with onset late in life?
Dementia over 65y
Why is dementia important?
- Dementia is one of the main causes of disability later in life ahead of cancer, cardiovascular disease and stroke.
- UK spends much less on dementia than on these other
conditions.
Delirium v Dementia…
Onset rapid v gradual?
Alertness and attention?
Hallucinations?
Dementia is gradual, delirium is rapid onset and action needs to be taken quickly
Delirium has an impact on attention alertness, dementia usually does not.
Most types of dementia do not include hallucinations (there are exceptions)
Name 4 subtypes of dementia
Which two are often comorbid?
Alzheimers disease and Vascular dementia (often comorbid)
Lewy body disorders
FTD
Subtypes of Lewy-body disorders…
——– with —- —–
and
———’s disease dementia
Dementia with Lewy bodies
Parkinson’s disease dementia
Pathology of dementia: Which proteins can be misfiled?
Amyloid
Tau
Synuclein
Which proteins are misfolded in Alzheimers?
Amyloid and tau
Which protein is misfolded in Parkinson’s disease dementia?
Synuclein
What is the difference b/ween Alzheimers and dementia?
Alzheimers is the name of an underlying disease with particular molecular mechanism, dementia would be the clinical presentation
Which protein misfolding causes FTD
Tau
What diseases can Tau misfolding causes?
Alzheimers and FTD
What disease can synuclein misfolding causes?
FTD
What disease can amyloid misfolding causes?
Alzheimers
What disease can amyloid misfolding causes?
Alzheimers
Hos is dementia assessed?
No single diagnostic test
* Good clinical history of paramount importance (including
collateral)
* Physical examination, focus on neurological
* Basic blood tests
* FBC, U&Es, LFTs, Thyroid, Ca, Glucose, B12 and folate, ESR
* Neuroimaging
* CT, MRI, advanced imaging
* Cognitive testing
* Lumbar puncture in some cases, especially young onset
what is Alzheimers disease?
Most common form of dementia (62%)
* German Neurologist, Alois Alzheimer, early 1900s
* Survival from diagnosis 4-20 years
What is happening in the brains of people with Alzheimer’s disease
Amyloid plaques (Extracellular deposits)
* Insoluble protein
* Neurofibrillary tangles (Intracellular)
* Tau = normal intracellular protein, binds to microtubules and
supports axonal transport and maintenance of cytoskeleton * Abnormal phosphorylation
* Paired helixes * Neurofibrillary tangles
* Reduced cholinergic activity in cortex
What happens in Alzheimers brains at a molecular level?
The amyloid cascade hypothesis
beta-Amyloid is cleaved from a transmembrane protein called amyloid precursor protein (APP). APP is usually broken down into non-beta-amyloid peptides by what has been called the alpha-secretase pathway. The amyloid cascade hypothesis suggests that there is more breakdown of APP by other pathways (called beta- and gamma-secretase pathways), leading to overproduction of beta-amyloid. beta-Amyloid is i
What are the clinical features of Alzheimer’s disease?
Amnesia
Impairment of short- term memory
Later impairment of long-term memory
Disorientation
Loss of motor skills (apraxia)
Disturbances in recognition of objects and faces (agnosia)
Disturbances of speech (nominal dysphasia)
Difficulty in performing complex tasks
Planning, organization, sequencing, abstraction
Behavioural and psychological disturbances
Are there genetic links to Alzheimers?
Complicated, generally different for young and late onset
Young onset Alz D genetics?
Young onset clusters within families (rare) – mutations in amyloid precursor protein gene (APP) and two presenilin genes (PSEN-1 and PSEN-2)
Late onset Alz d genetics?
Late onset is more complex - small but growing number of risk genes (not mutations)
Apolipoprotein ε4 (APOE ε4) largest known risk factor
what Investigations in Alzheimer’s disease?
Most important factor in diagnosis is history
Cognitive testing helpful
CT/MRI: Global cortical atrophy, hippocampal atrophy
Lumbar puncture: beta-Amyloid ratios in csf, other measures
Amyloid PET (Positron emission tomography)
what is vascular dementia?
caused by cerebrovascular disease
who is at risk of vascular dementia?
Age
Vascular risk factors
(e.g. hypertension, hypercholesterolaemia, smoking, physical inactivity, diabetes)
Alzheimer’s disease and vascular dementia often co-exist
Share many risk factors
Dementia develops in 15-30% of people in 3 months after stroke (not fully understood)
Clinical features of vascular dementia
Diverse presentation
Classically stepwise progression
(Rarely seen, gradual decline also possible)
Abrupt onset/decline may be associated with CVA (cerebral vascular accident/abnorm)
Focal neurology may be present
Patchy cognitive impairment
Slowing of gait and falls
what is common to Dementia with Lewy bodies and Parkinson’s disease dementia
Both conditions are caused by Lewy bodies
Intracellular inclusions
a-synuclein
Subcortical Lewy bodies in Parkinson’s disease
Cortical Lewy bodies in Dementia with Lewy bodies (DLB)
Many people with Parkinson’s disease develop dementia
Increases with length of years lived with condition
Does everyone with CLB (dementia Lewy bodies) develop movement diorsders?
DLB diagnosed if cognitive symptoms onset before or about same time as movement symptoms (as opposed to Parkinsons movement first)
Not everyone with DLB develops movement symptoms, but most do
If cognitive symptoms present concurrently with movement symptoms, is Dementia with Lewy bodies more or less likely diagnosis than Parkinson’s?
DLB
DLB is diagnosed if cognitive symptoms onset before or about same time as movement symptoms (as opposed to Parkinsons movement first)
What is “DLB”
Dementia with Lewy bodies
what are the core features of dementia with Lewy bodies
One of more of cardinal motor features of Parkinson’s disease
Visual hallucinations
Marked fluctuations in cognition and alertness
REM sleep behaviour disorder
Also note:
High sensitivity to antipsychotic medication
Risk of falls
DLB can be difficult to differentiate from delirium – the speed of onset and presence of parkinsonism can be helpful
can you prescribe antipsychotics to DLB pt?
not recommended due to high sensitivity to antipsychotic medication
what is REM sleep behaviour disorder?
thrashing in sleep
what is REM sleep behaviour disorder?
thrashing in sleep
a sleep disorder in which you physically act out vivid, often unpleasant dreams with vocal sounds and sudden, often violent arm and leg movements during REM sleep — sometimes called dream-enacting behavior.
Investigations in dementia with Lewy bodies?
MRI/CT often normal, may show atrophy
SPECT imaging using a ligand for the dopamine transporter protein has high sensitivity and specificity
Investigations in dementia with Lewy bodies?
MRI/CT often normal, may show atrophy
SPECT imaging using a ligand for the dopamine transporter protein has high sensitivity and specificity
What is SPECT?
SPECT = single photon emission computed tomography – relies on a radiolabelled ligand attaching to the target protein after being injected peripherally (e.g. in SPECT scan for DLB, the radiolabelled ligand is injected into a vein in the arm, and the scan is taken several hours later)
What does this image show?
This image shows MRI (top row) and FP-CIT SPECT (bottom row) scans in Alzheimer’s disease (AD), dementia with Lewy bodies (DLB) and normal control (NC). The MRI scan in Alzheimer’s disease shows marked global and hippocampal atrophy, which is not the case in the DLB and NC scans. The FPCIT SPECT scan shows normal upate of the dopamine trasporter protein ligand across both the caudate and putamen (“comma” in AD and NC, and severely reduced uptake in DLB, limited to the caudate.
Image from: McKeith, I.G. et al (2017) ”Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB consortium” Neurology 89: 88-100 (creative commons licence)
what is notable in this image?
FTD - atrophy
What is frontotemporal dementia (FTD)?
Diverse group of conditions that are collectively a common cause of young onset dementia
Selective progressive atrophy involving the frontal or temporal lobes or both
Also referred to as frontotemporal lobar degeneration (FTLD)
complex range of underlying mechanisms
what three main pathologies cause FTD/FTLD? (molecular)
Three major pathogenic proteins responsible for different types of FTD
Phosphorylated tau
Transactive response DNA-binding protein 43 (TDP-43)
Fused in sarcoma protein (FUS) protein
What is pick’s disease?
Pick’s disease is a type of FTD caused by Tau
what disease is caused by problems with these proteins?
Phosphorylated tau
Transactive response DNA-binding protein 43 (TDP-43)
Fused in sarcoma protein (FUS) protein
FTD/FTLD
FTD population prevalence of _______ per 100 000 under ____ years in European and US epidemiological studies?
Population prevalence of 4-15 per 100 000 under 65 years in European and US epidemiological studies
Typical FTD onset
50s/60s, but can be younger and not well supported socially financially. Takes a while to diagnose as unexpected
FTD pathology always genetic or not?
Often genetic, although many cases sporadic
What are the clinical features of FTD?
Noticable behavioural disinhibition
Behavioural variant (frontal lobe)
Affects personality/behaviour
Relative preservation of memory
Often misdiagnosed as psychiatric condition or personality disorder
Language variant (temporal lobe)
Affects language
Different subtypes affect language differently
Investigations in frontotemporal dementia
MRI/CT: Frontal and/or temporal lobe atrophy
Amyloid-PET negative
Perfusion studies (FDG-PET): Reduced perfusion in frontal/temporal lobes
Lumbar puncture:
Normal Alzheimer’s disease biomarkers
Elevated neurofilament light
Genetics: Testing may identify specific mutation
Behavioural and psychological symptoms of dementia
Multiple brain processes are disrupted in dementia
Cognitive impairment is a central feature
Dementia also results in a range of neuropsychiatric symptoms
What is BPSD?
“behavioural and psychological symptoms of dementia”
range of dementia associated neuropsychiatric symptoms-
Referred to as BPSD
Includes symptoms of disturbed:
Perception
Thought content
Mood
Behaviour
What is good support for ppl with dementia?
Person-centred
Services designed to meet needs of people living with dementia
Many people with mild dementia do not need dementia-specific services
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