B1: Dementia Flashcards
What is the most common initial dementia symptom?
Impaired ability to learna nd retain new information
Impairments of higher cognitive functions deteriorate over months to years, resulting in complex isorder with multiple cognitive, emotional and behavioural abnormalities
Implications (for memory) of medial temporal lobe excision (including amygdala, cortex and part of hippocampus) to stop severe seizures?
- Long term memory mainly retained, with partial retrograde amnesia
- Profound anterograde amnesia
- Working memory and procedural memory are normal
Thus: constant rehearsal can lead to learning new tasts (involves cerebellum)
and distraction from tasks will cause them to forget them
Role of hippocampus in memory
- creating spacial map of environment
- lesions to hippocampus can cause defecits in working memory
- Links things happening all the time
- Hippocampus + temporal lobe are necessary for relational memory (due to this linking)
Role of Striatum in memory
Procedural learning -> habit formation etc
Role of neocortex in memory
working memory, temporary storage (e.g. repeating number so don’t forget it)
Describe Hebbian Learning
A form of synaptic plasticity, where synaptic efficacy results in strengthening of the ‘wiring’ between certain neurons.
synaptic inefficiency leads to weakinging of the wiring between neurons
(i.e. if firing of A triggers response in B, that synapse will be strengthened. If firing of C does not elicit response in B, that synapse will be weakened)
How does synaptic plasticity work? (basics)
Changes in dendritic morphology (spine shape, size and number) alters synaptic strength - i.e. synapses can be potentiated or depressed
*spines are protrusions on endrites that can change in morphology over minutes or hours -> have effect on synaptic efficacy
Long Term Potentiation (LTP)
Long Term Depression (LTD)
can occur due to changes in protein composition at the post-synaptic density
LTP/LTD modifies the post-synaptic neuron’s response to glutamate signals -> either by increasing or decreasing the subsequent response.
What is associative learning?
learning that occurs due to associating two things together (typically stimulus and response -> learning that a given stimulus leads to a certain response, or associating 2 stimuli together)
Thought to be key to the formaiton of declarative memory (conscious recall of facts etc)
What is the relationship between Associative learning and Long Term Potentiation (LTP)
Long Term Potentiaiton (LTP) is triggered by either:
- high frequency stimulation
or by
-Synchronous activation of synapses (leading to v strong depolarization of the postsynaptic CA1 neuron)
E.g. Sight and smell of a rose occur simultaneously
-> inputs may undergp LTP, resulting in association (associative learning) between the two stimuli
How does LTP modify the postsynaptic neuron’s response to glutamate signalling from presynaptic neuron?
There are 3 tyoes of glutamate receptors at a synapse:
- NMDA
- AMPA
- mGulR
NMDA receptors are voltage-sensitive and, at rest, are blocked by Mg++. Membrane depolarisation releases the Mg++ block, meaning that glutamate can bind.
NDMA receptor opening -> Ca++ influx
An LTP (effective and strong) stimulus produces a strong Ca++ signal via activation of many NDMA receptors
This in turn causes more AMPA receptors to be inserted into the membrane.
What are the 3 types of glutamate receptors?
NMDA
AMPA
mGluR
What is the relationship between LTP/LDP Ca++ signalling, and AMPA receptor expression
In LTD, there is low synaptic efficacy, and thus weak NMDA receptor activation and weak Ca++ signals. Weak Ca++ signals = AMPA receptors are internalised
In LTP, there is high synaptic efficacy, and thus strong NDMA receptor activation and strong CA++ signals. This causes more AMPA receptors to be recruited to membrane
How does LTP (long term potentiation) affect synaptic plasticity
High Ca++ influx associated with LTP leads to CAMKII activation. This leads to:
- Polymerisation of actin (necessary for dendrite spine maturation)
- Activation of local mRNA translation, for production of more NDMA and AMPA receptors, and more scaffold proteins, etc. being inserted into the membrane and postsynaptic density.
= Stronger synapse
How does LTD (long term depression) affect synaptic strength?
Low Ca++ influx associated with LTD leads to activation of Calcineurin
Calcineurin activation leads to:
- Depolymerisation of actin
- Dephosphorylisation of proteins such as AMPA receptors -> increased endocytosis of receptors
= Weaker Synapse
What changes occur in dendritic spines in response to learning?
In response to learning new motor tasks:
- Formation of new spines
- Stabilization of dendritic filopodium
- Direct emergence of new spines towards nearby axon(s)
- Elimination of unused spines
Which receptor types are part of learning and memory formation?
- ACh R
- Glutaminergic Rs: NDMA, AMPA mGluR
- Inhibitory receptors: GABAa,b,c and Glycine
What are the overarching principles we know from studying LTP and LTD?
- Learning and memory can result to modifications to synaptic transmission
- These synaptic modifications can be triggered by conversion of neural activity into intracellular second messengers (i.e. intracellular cascades that result in production or deconstruction of proteins to increase/decrease receptor expression, or increase/decrease spine production)
- Memories can result from alterations in existing synaptic proteins
To diagnose dementia, what symptoms/signs need to be confirmed?
At least 2 of:
- Impaired new learning
- Impaired STM
- Apraxia (disordered motor planning)
- Agnosia (inability to recognise people, things, objects, smells, tastes, etc)
- Language Disturbance
- Loss of executive functions
*Note: attention and concentration are usually unimpaired in mild dementia
Why is it important to diagnose the type of dementia?
Although there is no known ‘cure’ for most dementias, it is important to diagnose the type so that we can help the patient and family to:
- Access information to help them deal with the specific functional difficulties
- Find beneficial treatments specific for the type
- Avoid drugs known to aggrevate problems
- Make plans for the future (prognosis)
What are some alternative causes of cognitive imairment that should be considered before diagnosing dementia?
- Delirium (disordered attention, recent onset days-weeks, flactuation of symptoms over hours)
- Depression (*often coexists with dementia)
- Drug Effects
commonly: anticholinergics, sedatives, hypnotics, antipsychotics, analgesics (these often cause features of delirium)
List dementia subtypes:
Alzheimers Vascular Dementia Dementia with Lewy Bodies Parkinson's Disease with Dementia Frontotemporal Dementia Post-Traumatic Dementia Toxic Encephalopathy
Features of ALzheimers
Memory impairment Language impairment Executive function impairment Motor function impairment Agnosia
Features of vascular dementia
Progressive -> associated with physical signs of stroke of history of transient ischaemic attack
Features: dementia with lewy bodies
Progressive dementia At least 2/3 of: - flactuating cognition - visual hallucinations - Parkinsonism
*severely intolerant to adverse effects of antipsychotics
some evidence for efficacy of cholinesterase inhibitors
Features: parkinsons w/ dementia
Ability to function is related to adequacy of dopa replacement. Often worse in ‘off’ periods
*may be part of spectrum of disease with dementia w/ lewy bodies
Features: frontotemporal dementia
Tends to affect younger patients ( with changes to behaviour and personality is common
Delusions common
Aphasia
Memory relatively spared
Mini mental state examination is unreliable here*
Seteriorates w/ use of antipsychotics
Features: post-traumatic dementia
History of injury w/ consistent imaging
Not progressive
**Appears to increase risk of later developing alzheimers
Features: Toxic encephalopathy
History of toxin exposure - e.g. chronic alcohol abuse
Describe the non-pharmacological treatment of dementia
- Monitor general health
- CV risk factors
- Optimise health and thus ability for independence - Psychosocial Interventions for Carers
- Teaching specific problem-solving skills
- Involvement also of extended family and other carers
- Can help reduce psychological burden on carers
- Thus also reduces need for institutionalised care of dementia patient - Community Based Occupational Therapy
- Aims to improve the patient’s daily function
- *Maintaining cognitive, physical and social activity
- improves quality of life for patient
- Reduces the burden of care
For which non-pharmacological treatments is there no supportive evidence for, based on Cochrane reviews?
- Aromatherapy
- Music Therapy
- Transcutaneous electrical nerve stimulation (TENS)
- Bright light therapy
