[12] Dementia Flashcards
What is dementia?
Dementia is a syndrome of generalised decline of memory, intellect, and personality, without impairment of conscious, leading to functional impairment
What are the irreversible causes of dementia?
- Alzheimer’s disease
- Fronto-temporal dementia
- Lewy body dementia
- Vascular dementia
- Pick’s disease
- Parkinson’s disease with dementia
- Huntington’s disease
- HIV
- Encephalitis
- Syphilis
- CJD
- Alcohol
- Barbituates
- Benzodiazepines
- Multi-infarct dementia
- CVD
- Traumatic head injury
What neurotransmisser is deficient in Alzheimer’s disease?
Acetylcholine
What causes the deficiency in acetylcholine in Alzheimer’s disease?
There is a degeneration of cholinergic neurons in the nucleus basalis of Meynert, leading to a deficiency in acetylcholine
What microscopic changes occur in Alzheimer’s disease?
Formation of intracellular neurofibrally tangles, and extracellular formation of ß-amyloid plaques
What macroscopic changes occur in Alzheimer’s disease?
- Cortical atrophy (commonly hippocampal)
- Widened sulci
- Enlarged ventricles
What genes play a role in early onset Alzheimer’s disease?
- Presenillin 1
- Presenillin 2
- Amyloid precursor protein
What gene contributes to late onset Alzheimer’s?
ApoE-4
What gene is thought to be protective from Alzheimer’s disease?
ApoE-2
What causes vascular dementia?
It occurs as a result of cerebrovascular disease, either due to stroke, multi-infarcts (multiple smaller, unrecognised strokes), or chronic changes (arteriosclerosis) in the small vessels
What causes Lewy-Body dementia?
There is abnormal deposition of Lewy body within the neurones of the brainstem, substantia nigra, and neocortex.
What is Lewy body?
A protein
What are Lewy bodies associated with outside the brainstem?
Profound cholinergic loss (more so than Alzheimer’s)
What are Lewy bodies associated with within the brainstem?
Dopaminergic loss and Parkinsonian-like symptoms
What is the pathological process in fronto-temporal dementia?
There is specific degeneration (atrophy) of the frontal and temporal lobes of the brain
What is Pick’s disease?
A type of fronto-temporal dementia, where Pick’s bodies (protein tangles) are seen histologically
What are the reversible causes of dementia?
- Normal pressure hydrocephalus
- Intracranial tumours
- Chronic subdural haematoma
- B12, folic acid, thiamine, or nicotinic acid deficiency
- Cushing’s syndrome
- Hypothyroidism
What can dementias be divided on the basis of?
Cortical, subcortical, or mixed dysfunction
Give two cortical dementias
- Alzheimer’s
- Fronto-temporal dementia
Give a subcortical dementia
Lewy Body dementia
Give a mixed dementia
Vascular dementia
What is the importance of the differentiation between cortical and subcortical dementias?
Cortical and subcortical dementias have different presentations, which could aid diagnosis
How do cortical and subcortical dementias differ in terms of memory loss?
It is severe in cortical, moderate in subcortical
How do cortical and subcortical dementias differ in terms of mood?
It is normal in cortical, low in subcortical
How do cortical and subcortical dementias differ in terms of speech and language?
You get early aphasia in cortical, can get dysarthria in subcortical
How do cortical and subcortical dementias differ in terms of personality?
Patients are indifferent in cortical, apathetic in subcortical
How do cortical and subcortical dementias differ in terms of coordination?
Normal in cortical, impaired in subcortical
How do cortical and subcortical dementias differ in terms of praxis?
Apraxia in cortical, normal in subcortical
How do cortical and subcortical dementias differ in terms of motor speed?
Normal in cortical, slow in subcortical
What are the risk factors for dementia?
- Advancing age
- Family history
- Down’s syndrome
- Low IQ
- Cerebrovascular disease, or vascular risk factors
What are the ICD-10 criteria for the presentation of dementia?
Evidence of a decline in memory, which is most evident in learning new information, although in more severe cases, the recall of previously learnt information may also be affected, and a decline in other cognitive abilities, characterised by the deterioration in judgement and thinking, such as planning and organizing, and in the general processing of information.
For these things to be evident, there must be a preserved awareness of the environment for long enough to demonstrate them.
There should be a decline in emotional control or motivation, or a change in social behaviour, manifested either as emotional lability, irritability, apathy, and coarsening of social behaviour.
For a confident diagnosis, these things should have been present for 6 months.
What are the symptoms of Alzheimer’s disease?
- Memory loss
- Impairment of cognitive and executive functions
- Non-cognitive symptoms
How does the memory loss in Alzheimer’s initially present?
There is initially an inability to recall new information, memory lapses, and forgetting the names of people/places
What happens to memory with progression of Alzheimer’s?
Long-term memory declines
What feature closely related to memory impairment is present with late Alzheimer’s?
Disorientation to time and place
Give 4 executive functions that will be impaired in Alzheimer’s
- Problem solving
- Abstract thinking
- Reasoning
- Decision making
What symptoms might appear due to cognitive function in Alzheimer’s?
- Visuospatial impairment
- Dysphagia
- Apraxia
- Agnosia
When does impairment of executive functions start in Alzheimer’s?
At the disease progression stage
What can visuospatial impairment result in practically in Alzheimers?
- Getting lost
- Impaired driving
What might dysphagia include in Alzheimer’s?
- Word finding difficulties
- Global aphasia
- Perseveration
What is global aphasia?
Impairment of language, affecting the production or comprehension of speech and the ability to read and write
What is perseveration?
Uncontrollable repetition of a particular response such as a word, phrase, or gesture
What is apraxia?
The inability to carry out previously learned purposeful movements, despite normal coordination and strength
What is agnosia?
Impaired recognition of sensory stimuli, not attributed to sensory loss or language disturbance
What are the non-cognitive symptoms of dementia?
- Hallucinations
- Delusions
- Depression
- Apathy
- Abnormal behaviour, including wandering, aggression, and restlessness.
What is the ICD-10 criteria for Alzheimer’s disease? The general criteria for dementia must be met. There should be no evidence for any other possible cause of dementia, or systemic disorder.
The general criteria for dementia must be met. There should be no evidence for any other possible cause of dementia, or systemic disorder.
What are the ICD-10 criteria for early onset Alzheimer’s disease?
General criteria for Alzheimer’s must be met, and age of onset <65.
Presence of at least one of;
- Relatively rapid onset and progression
- In addition to memory impairment, there is aphasia, agraphia (reduced ability to communicate through writing), acalculia (inability to perform mathematical tasks), or apraxia
What are the ICD-10 criteria for late onset Alzheimer’s disease?
General criteria for Alzheimer’s must be met, and age of onset >65.
Presence of at least one of;
- Slow, gradual onset and progression
- Predominance of memory impairment over intellectual impairment
When does vascular dementia normally present?
Late 60’s or early 70’s
Describe the progression of vascular dementia
It is a stepwise rather than continuous deterioration
What are the symptoms of vascular dementia?
- Memory loss
- Depression
- Apathy
- Personality changes
- Confusion
- Neurological symptoms or signs
What neurological symptoms and signs are present in vascular dementia?
- Unilateral spastic weakness of limbs
- Increased tendon reflexes
- Extensor plantar response
- Pseudobulbar palsy
What are the symptoms of Lewy-Body dementia?
- Day to day fluctuations in cognitive performance
- Recurrent visual hallucinations
- Motor signs of parkinsonism, including tremor, rigidity, and bradykinesia
When are people diagnosed with Parkinson’s disease with dementia, rather than Lewy-body dementia?
When they develop dementia 12 months after being diagnosed with Parkinson’s
When are people diagnosed with Lewy-body dementia, rather than Parkinsons?
When dementia and parkinsonian features appear within 12 months of each other
When does fronto-temporal dementia usually occur?
Between the age of 50-60
In what manner does fronto-temporal dementia develop?
Insidiously
How does fronto-temporal dementia present?
- Early personality changes, including disinhibition, apathy, and restlessness
- Worsening of social behaviour
- Repetitive behaviour
- Language problems
What happens to memory in the early stages of fronto-temporal dementia?
It is preserved
What happens to insight in fronto-temporal dementia?
It is lost early
How does Huntington’s disease present?
Main features are abnormal choreiform movements of face, hands, and shoulders, alongside gait abnormalities. Dementia presents later.
When does normal pressure hydrocephalus normally present?
After 70
What are the features of normal pressure hydrocephalus?
- Dementia
- Urinary incontinence
- Wide gait
When does CJD usually present?
Before 65
Describe the progression of CJD?
It has a rapid progression, and death within 2 years
How does CJD present?
There is disintegration of virtually all higher cerebral functions, and the dementia is associated with neurological signs
How is dementia investigated?
- History
- MSE and MMSE
- Blood tests
- Other non-routine investigations can be carried out, guided by clinical assessment
- Assessment of functional capacity
How is dementia classified on the basis of MMSE?
- Normal 25-30
- Mild 21-24
- Moderate 10-20
- Moderate-severe 10-14
- Severe <10
What should be asked about in an assessment of functional capacity in dementia?
- Dressing
- Continence
- Self-care
- Shopping/housework
- Ability to manage financial affairs
- Social contacts
- Safety in the home
- Ability to cook
- Nutrition
- Orientation
What are the differential diagnoses in dementia?
- Normal ageing and mild cognitive impairment
- Delirium
- Trauma, including stroke, hypoxic brain injury, or traumatic brain injury
- Depression
- Late onset schizophrenia
- Amnesic syndrome – severe disruption in memory with minimal deterioration in cognitive functioning
- Learning disability
- Substance misuse
- Drug side effects, e.g. from opiates or benzodiazepines
What are the aims of treatment in dementia?
- Promote independance
- Maintain function
- Treat symptoms, including cognitive, non-cognitive (hallucinations, delusions, anxiety etc), behavioural, and psychological
What are the non-pharmacological management options in dementia?
- Social support, including support groups such as the Alzheimer’s society
- Increasing assistance with day-to-day activity
- Information and education
- Community dementia team input
- Home nursing and personal care
- Community services such as meals-on-wheels, befriending services, day centres, respite care, and care homesa
What pharmacological agents are options in the management of dementia?
- Acetylcholinesterase inhibitors
- Memantine
What are acetylcholinesterase inhibitors recommended for in dementia?
The treatment of mild to moderate Alzheimer’s.
They can also be used in dementia with Lewy bodies in cases where non-cognitive symptoms cause significant distress
Give 3 acetylcholinesterase inhibitors that are options in the management of dementia
- Donepezil
- Galanatamine
- Rivastagmine
What kind of drug is memantine?
NMDA receptor antagonist
Where is memantine an option in dementia?
In moderate Alzheimer’s in those who are intolerant of, or have a contraindication to, acetylcholinesterase inhibitors, or in severe Alzheimer’s disease
What is the purpose of pharmacological management in Alzheimer’s disease?
Palliative only.
Describe the benefit of pharmacological agents in Alzheimer’s disease
Provides only a modest short-term benefit
Have any of the currently available pharmacological agents for Alzheimer’s been shown to alter the underlying neurodegenerative process?
No
What can be used for challenging behaviour in dementia if non-pharmacological strategies have been ineffective?
A short course of antipsychotic, e.g. resperidone
What can happen if anti-psychotics are used in Lewy body dementia?
They can cause severe adverse effects, including neuroleptic sensitivity reactions, or worsening of extrapyramidal features
What can be used for low mood in dementia?
Antidepressants
Why is it theorised that acetylcholinesterase inhibitors will improve Alzheimer’s disease?
It has been shown that there is a link between the progressive loss of cholinergic neurons and cholinergic transmission within the cortex, to the memory loss that is a hallmark symptom of Alzheimer’s disease. Inhibiting AChE within the CNS will improve cholinergic transmission in the neurones that are still functioning, and so improve the memory loss symptoms
What is the mechanism of action of all AChE inhibitors apart from galantamine?
They are non-competitive inhibitors of AChE, with some selectivity for AChE in the CNS compared to the periphery
What is the mechanism of action of galantamine?
It is a competitive inhibitor of ACh, and may also act as an allosteric modulator of the nicotinic receptor in the CNS, and therefore secondarily may increase the cholinergic neurotransmission through a separate mechanism
How effective are AChE inhibitors at managing Alzheimer’s?
At best, they provide a modest reduction in the rate of loss of cognitive function in Alzheimer’s disease
What are the adverse effects of acetylcholinesterase inhibitors?
- Tremors
- Bradycardia
- Nausea
- Diarrhoea
- Anorexia
- Myalgia
What monitoring is required in patients who are on acetylcholinesterase inhibitors?
You should perform a pulse check at every appointment
What should be done before starting treatment with acetylcholinesterase inhibitors?
ECG
How does rivastigmine differ from other acetylcholinesterase inhibitors in terms of potential for interactions?
Rivastigmine does not interact with drugs that alter the activity of cytochrome P450 enzymes, whereas other agents are substrates for cytochrome P450-dependant enzymes, and so have the potential for interactions
What is the importance of glutamate receptors in memory?
Stimulation of glutamate receptors in the CNS appears to be critical for formation of certain memories
How might glutamate receptors be involved in pathologies of the brain?
Overstimulation of glutamate receptors, particularly of the NMDA type, has been shown to result in excitotoxic effects on neurons, and it has been suggested as a mechanism for neurodegenerative or apoptotic processes
How is it theorised that stimulation of NMDA receptors leads to apoptosis?
Binding of glutamate to the NMDA receptor assists in the opening of an associated ion channel that allows sodium ions and calcium ions to enter the neuron. The intracellular calcium can activate a number of processes that ultimately damages neurones, and leads to apoptosis.
Why are antagonists of NMDA-glutamate receptors clinically useful?
They are often neuroprotective, preventing the loss of neurones following ischaemic and other injuries
What is the mechanism of action of memantine?
It physically blocks the NMDA receptor-associated ion channel. At therapeutic doses, only a fraction of these are blocked. This partial blockage allows memantine to limit calcium influx into the neuron, such that toxic intracellular levels are not achieved during NMDA-receptor overstimulation, while still permitting sufficient calcium to flow through unblocked channels to preserve other vital processes
What are the adverse effects of memantine?
Memantine is well tolerated, with few dose-dependant adverse effects. Expected side effects, such as confusion, agitation, and restlessness are indistuguishable from the symptoms of Alzheimer’s disease
What is the bioavailability of memantine?
100%
Where is memantine metabolised?
Liver
How is memantine excreted?
Renally
What are the rules regarding dementia and driving?
After a diagnosis of dementia is made, patients are obliged to contact the DVLA. They may be able to continue driving subject to medical reports and annual review
What early discussions need to be made after a diagnosis of dementia?
Early discussions about advance planning prior to cognitive deterioration. Topics include advance statements or decisions, lasting power of attorney, and preferred place of care plans
What is important to consider in vascular dementia?
Cardiovascular risk factor modification, as the course can be changed
