CNS Week 4 Dementia Flashcards
Demographic of the population most likely to get dementia
66% are women (could be due to age being a risk factor and women living longer)
1/3 people over 65 will get dementia
Signs and symptoms of dementia that you should look out for
- struggling to remember recent events but easily recalling things from the past
- finding it hard to follow conversations or TV programmes
- forgetting names of friends or objects
- repeating yourself or losing the thread of what you are saying
- issues with thinking and reasoning
- feeling anxious, depressed or angry about forgetfulness
- confused even in familar environment
- decline in ability to talk, read or write
Psychological disturbances in dementia
Delusions and hallucinations
Anxiety and depression
Behavioural disturbances in dementia
Apathy, aggression, purposeful walking (walking but forgetting where theyre going)
Abnormal vocalisation
Biological distubrances in dementia
Sleep and appetite
What factors does the clinical dementia rating take into account
Memory Orientation Judgement and problem Community affairs Home and hobbies Personal care
What is a dementia friendly community
A place where people with dementia are understood respected and supported
Uses measures eg sign posts on the floor rather than walls as PwD tend to look down when they walk
Process of a dementia diagnosis being made
Visit to GP: signs / symptoms are noticed by PwD or informant- a feeling that something isnt quite right
Screening tests eg MMSE
Referral to MAS: diagnostic assessments undertaken eg neuropsychological testing, CT head scan, blood testing for biomarkers
Diagnosis disclosed at MAS: the healthcare professional at the MAS will disclose a diagnosis after discussion with the PwD and their supporters
Why are scans and biomarkers less helpful in diagnosing old people with dementia
Because a mixed pathology is very common
How do south asian families view dementia
Tend to seek help later as they may prefer to manage symptoms within the family
Older people are shown respect in south asian cultures by no longer being asked to do household chores so impairments can go unnoticed
How do sub-saharan african cultures view dementia
May perceive dementia as witchcraft or possession and can turn to alternative care such as herbs, prayers or traditional healers
Define dementia
An umbrella term that describes a collection of symptoms that are caused by disorders affecting the brain. It is not one specific disease
Affects thinking, behaviour and the ability to perform everyday tasks and brain function is affected enough to interfere with the persons normal social or working life
What is alzheimers disease
The most common type of dementia
Accounting for approximately 40-70% of all dementias
Caused by build up of protein in the brain (amyloid beta and tau)
Insidious onset and gradual progression
Slightly more predictable than other dementias
What is vascular dementia
The second most common type of dementia
Accounting for approximately 15-25% of all dementias
Caused by interrupted blood flow to the brain which causes cells to die
What is lewy body dementia
Accounts for approximately 2-20% of all dementias
Deposits of protein called lewy bodies that interrupt the chemical transmission of impulses
Symptoms of lewy body dementia
Problems with attention and alterness that can fluctuate throughout the day, memory, visual hallucinations which may be distressing, delusions such as thinking there are strangers in the house or that family members have been replaced by imposters, movement problems such as shuffling when walking and balacne problems
What are some other types of dementia
Demenita associated with parkinsons disease and huntingtons disease
Head trauma
Human immunodeficiency virus
Alcohol related dementia
Crutzfedlt jakob disease
Corticobasal degeneration and progressive supranuclear palsy
Link between neuropathology and presentation in alzheimers disease
Cell death and difficulties in cells communicating with each other begins in the hippocampus (memory)
Degeneration spreads to areas concerned with language so we start to have problems comprehending and forming speech
Then to the fronal lobes - problems with decison making and planning actions
What reduces the risk of developing alzheimers disease
Activities than strengthen our neural connections or create extra connections eg white collar jobs, edication, stimulating activities such as reading, museums, sport and sudoku
What
Symptoms of vascular dementia
Problems with thinking speed, concentration and communication, anxiety and depression, memory problems and confusion
Treatment of vascular dementia
No way of reversing the damage so treatment is about secondary prevention
Use drugs that act on the cardiovascular system eg blood pressure / statins
Lifestyle changes- people with dementia might need extra support to make these changes
What is levodopa
A drug often given to people with parkinsons disease to help with movement - increases the amount of dopamine precursor available
Sometimes given to people with dementia lewy bodies but is less effective for them
What is frontotemporal dementia
Affecting less than 5% of all people with dementia and generally with a younger onset (55) Affects frontal (executive function and damage here can lead to a loss of inhibitions, difficulty expressing sympathy or empathy, loss of interest and motivation, difficulties in planning and temporal lobes (language, communication so damage here can lead to difficulties with speech, understanding sentences and finding the right words
What is mild cognitive impairment
A concept developed to describe the transitional phase between normal and pathological ageing
Criteria include objective impairment in memory or other cognitive domain, intact general cognitve functioning, intact activies of daily living, absence of dementia, presence of subjective memory complaints
People with MCI are at increased risk of progression to dementia compared to people without cognitve impairment
Link of social networks and risk of dementia
People with cognitive impairment have less rich social networks than those without
Having weaker social networks is associated with a higher likelihood of having anxiety and depression
Both relatives and friends are important
Describe the 3 componenets of reality orientation
24 hour - staff present information related to orientation every time they interact with people and give a commentary on what is happening
Small groups of 5 or 6 and 2 staff
Sessions begin with an introduction and a discussion of current information and orientation and then activities to enhance social interaction and learning
Attitude therapy - staff tailor their attitudes towards patients / residents personalities
This can vary from friendliness through no demand and matter of fact to kind firmness
What is reminisence therapy
Using memory triggers to provide a tangible focus for reminisence
Maintaining the persons identity and assisting in social interaction through sharing memories and experiences
What is cognitive stimulation therapy
1) experimental learning using all 5 senses to promote cognitive stimulation and memory processes
2) focused psychological interventions relevant to the difficulties of everyday living
3) acknowledgement of the emotional lives and enhancement of the cognitive skills of people with dementia
4) implicit learning rather than explicit ‘teaching’. Extensive rehearsal and consolidation of essential information about themselves and their world
5) the reciprocal, psychological processes in which people with dementia and those who care for them learn more about each others capabilites and vulnerabilities
Benefits of cognitive stimulation therapy for PwD
Opportunities to engage in pleasurable and mentally stimulating activities
Improved cognition
Improved communication
Maintenance of daily skills
The supportive environment and opportunities for social interaction help to boost confidence
Benefits of cognitive stimulation therapy for carers
A break whilst the PwD is attending the group
Carer delivered iCST helped carers and PwD to become closer
Strengthen the care giving relationship
Define learning
The process by which we acquire new information about the world
Define memory
The product of learning - the persistence of learning in the brain in a manner that enables us to call it up later
What are the general stages of memory
Encoding: the processing of information ready for storage
Storage: the maintenance of a permanent record, trace or ‘engram’ representing the encoded information
Retrieval: the ‘bringing to mind’ of a stored representation of information, an event or actions
What is sensory memory
Duration of milliseconds- seconds
Echoic and iconic sensory traces
Larger capacity than STM - icon thought to contain about 12 items but they fade too fast for verbal report
Echoic trace thought to last 10 seconds
Items shift from sensory to STM through attention
What is short term memory
Duration of seconds
Capacity of 7 +/-2 items (miller
Chunking information creates larger items
Items can be maintained in STM by active rehearsal; if rehearsal is blocked, items decay over time
Items shifted from STM to LTM via rehearsal
What is LTM
Unlimited capacity store
Duration measured in hours - years
Information can be lost from LTM through interference of new malterial on old
Items can enter LTM only via STM according to the modal model
What is working memory
The collection of strucures and processes used for temporarily storing and manipulating information eg digit span and digit span backwards
What is amnesia
A condition characterised by deficits in the recall and recognition of facts and events experienced
STM abilities and intelligence often remain relatively unimpaired
What are the 2 types of amnesia
Retrograde amnesia: before the onset of brain damage
Anterograde amnesia: after the onset of brain damage
What are the causes of amnesia
Organic: the result of damage to the brain through trauma, disease, or drugs
Functional: the resuly of psychological factors
What is episodic memory
Length of storage: minutes to years
Explicit declarative awareness eg remembering a short story, what you had for dinner last night, your birthday
What is semantic memory
Length of storage of memory: minutes to years
Explicit declarative awareness eg knowing the PMs during WWII, the colour of an elephant, how a fork is different to a comb
What is procedural memory
Length of storage of memory: mins to years
Explicit or implicit, declarative or nondeclarative awareness eg driving a car, lerning the sequence of numbers on a mobile without trying
What is working memory
Length of storage of memory: seconds to minutes
Explicit, declarative awareness
Eg phonologic: keeping a phone number in your head, mentally following a route in your mind
Neuropathology of AD
Amyloid plaques Neurofibrillary tangles B-amyloid pathology and tauopathy Synaptic dysfunction and neuronal loss Reactive gliosis and microgliosis
Histopathology of AD
Neuritic plaques: extracellular B-amyloid depositions and dystrophic neurites, activated microglia
Neurofibrillary tangles: intracellular acetylated paired helical filaments of hyperphosphorylated tau
What is dementia with lewy bodies
Clinically similar to AD
May not have parkinsons
Varying degrees of B amyloid plaques
Neocortical neurofibrillary tangles are less frequent in DLB
What is the difference between lewy body dementia and dementia with lewy bodies
Lewy body dementia includes PD
Whereas dementia with lewy bodies doenst
What are the subtypes of dementia with lewy bodies
Brainstem predominant DLB
Limbic DLB
Neocortical or diffuse DLB
Cerebral DLB
Explain how symptoms can vary in frontotemporal dementia
If the frontal lobe is more affected then behaviour is affected first
If the temporal lobe is more affected then language is affected first
Structural neuroimaging techniques for dementia
Computed tomography
Magnetic resonance imaging
Functional neuroimaging techniques for dementia
Functional MRI Magnetic resonance spectroscopy SPECT (if this is positive most likely DLB) Positive emission tomography Diffusion tensor imaging
Different types of B amyloid peptides
AB1-40 and AB1-42
AB1-42 aggregates faster, seeds plaques and more neurotoxic
Most familial AD mutatiosn increase the levels of AB1-42
Describe the amyloid cascade hypothesis
Reduced breakdown clearance, mutations and risk factors all increase B amyloid.
Cuases more plaques, tangles and neurotransmitter changes
Plaques and tangles lead to neuronal loss which increases neurotransmitter changes and has a 2 way relationship with synapse loss
What does Tau protein do
It is stable and binds to elements in the neuronal membrane
They are abundant in the CNS neurons and have roles in maintaining stability of microtubules in axons
What is tauopathy
Phosphorylation negatively regulates binding of tau to microtubules
Highly phosphorylated during development and in AD
Insoluble ubiquitinated phosphorylated Tau form filamentous inclusions in neuronal cell bodies, processes and glia
Conditions associated with tauopathies
AD Pick’s disease Frontotemporal dementia with parkinsonism linked to chromosome 17 Progressive supranuclear palsy Corticobasal degeneration Postencephalitic parkinsonism Niemann pick’s disease
Describe synucelinopathy
Aggregation of a-synuclein is the key inital step in the formation of lewy bodies
Neurotoxic a-synuclein oligomers
Extracellular a-synuclein oligomers can transmit lewy pathology
Neurobiology of DLB
B-glucocerebrosidase 1 deficiency Microglial dysfunction Mitochondrial dysfunction Autophagy lysosome pathway impairment Ubiquitin protease system impairment Oxidative stress
Indicative biomarkers of DLB
Reduced dopamine transporter uptake in basal ganglia demonstrated by SPECT or PET scan
Low uptake in 123iodine- MIBG myocardial scintigraphy
Polysomnographic confirmation of REM sleep wihtout atonia
Supportive biomarkers of DLB
Relative preservation of medial temporal lobe structures
Generalised low uptake on SPECT / PET with reduced occipital activity +/- the cingulate island sign on FDG-PET imaging
Prominent posterior slow wave activity on EEG with periodic fluctuations in the pre-alpha / theta range
Role of DNA methylation in epigenetics
The methyl group (an epigenetic factor found in some dietary sources) can tage DNA and activate or repress genes and change the histone structure which alters the availability of genes in the DNA to be activated
What is causing population ageing
Decreasing fertility and increasing life expectancy
Implications of population ageing
Healthcare utilisation, shrinking workforce, older retirement age, pensions, public finances
Define dementia
An acquired, persistnet impairment of mental abilities often accompanied by changes in personality and behaviour (aggression, wandering)
Impaired daily living, occupational functioning and social interaction
Caused by disease or head trauma and often associated with increasing age (exc downs syndrome, and early onset dementia)
What is mild cognitve impairment
A pre clincial stage of dementia
Not 100% cognitive functioning
Pathological casues of dementia
AD
Vascular
Frontal temoral
Lewy body
Breakdown of the cost of dementia in the UK
Costs over £26bn
£12bn for cancer, £8bn for coronary heart disease and £5bn for stroke
Cost is actually higher as PwD are usually cared for by unpaired carers eg family members
Protective factors of dementia
Educational attainment Social engagement Mental stimulation Physical activity Diet (eg fish intake)
Risk factors for dementia at different points throughout life
Birth: ApoE E4 allele
Early life: less education
Midlife: hearing loss, hypertension, obesity
Late life: smoking, depression, physical inactivity, social isolation, diabetes
Drug treatment for dementia
Approval for a limited number of drugs
Cholinesterase inhibitors (galantamine, rivastigmine, donepezil)
Memantine (N-methyl D aspartate antagonist; glutamate)
Only approved for mild - moderate cases
Dont work in everyone
Side effects: gastrointestinal, insomnia, nausea, vomiting
Non pharmacological interventions for dementia
Physical activity, caloric restriction, cognitive training/therapies eg cognitve stimulation therapy and vitamin supplementation
Benefits of an ageing population
Reflectes success in medicine and technology (childhood disease) as well as advancement in social and environmental conditions
Resource for families and communities in the form of knowledge
Challenges of an ageing population
Strain pension and social security systems (many LIC where people dont have access to pensions)
Increase demand for acute and primary health care
Require a larger and better trained health workforce
Increase the need for long term care
What is the individual impact of dementia
Years lived with disability not mortality
Impact on quality of life (cognitive and functional disability)
Contributes much more than other chronic illness to disability, need for care, carer strain, financial strain
How can the behaviour of the EO muscles be used to examine the cranial nerves that innervate them
CNII, CNIII, CNIV and CNVI usually tested together
Test includes:
Range and accuracy of eye motion (tracking an object)
Pupillary light reflex (shining light into one pupil should
cause both to dilate)
Ptosis (drooping eyelid)
What are cranial nerve palsies
Affect CN III, CN IV and CN VI often found by opticians and referred to opthalmology
Often found with strabismus (squint) and diplopia (double vision)
Common causes of cranial nerve palsy
Trauma
Neoplasm / tumour
Something vascualr eg diabetes and hypertension
Things to consider in treatment of cranial nerve palsy
Affected nerve (cranial nerve examination)
Direction of diplopia (horizontal, vertical, oblique)
Age of onset
Role of fixational eye movements in pathology
Certain visual disorders influence unconscious eye movement behaviour
Eg they are exaggerated by a factor of 4 in macular disease
What are the smallest eye movements
Tremors
Difference in clincal manifestation of DLB and AD
AD is mainly about progressive memory or other non-amnestic symptoms
DLB typically has fluctuating cognition, recurrent visual hallucinations, REM sleep behaviour disorder, plus symptoms of parkinsonism
What brain structures are implicated in AD
Begins in the hippocampus and medial temporal lobe spreading upwards and outwards to affect other cortical regions
As a result memory is usually affected also language and later other areas such as visuospatial skills
Executive problems quite common due to frontal lobe involvement
what neuropathological findings are seen in alzheimers disease at post mortem stage
Typically cerebral atrophy, especially medial temporal lobe structures but also often inferior temporal and frontal areas
Consequent ventricular enlargement
Microscopically neurofibrillay tangles of hyperphosphorylated tau protein and beta amyloid plaques
Describe the genetic component to alzheimers
1) single genes with autosomal dominant inheritance that causes AD eg presenilin mutations
2) ApoE e4 is a gene conferring increased risk of AD or at least of developing AD at an earlier age
What are the tests done to determine dementia
Clinical assessment - history, collateral history, mental state examination, cognitive testing
Blood tests
Neuroimaging
How does dementia look on an MRI
Ventricles may be enlarged - depends on the degree of cerebral atrophy which can be variable
Whay is montreal cognitive assessment (MOCA) and what does it entail
A short neuropsychological scheldule designed as an alternative to the MMSE aimed especially at early dementia / MCI
Tests: orientation, attention, naming, language, memory, delayed recall, abstraction and visuospatial / executive
What are normal MOCA and ACE-III scores for a person without dementia
MoCA= 26/30 and above; ACE-III various figures quoted between 82-88/100
Higher cutoff has greater sensitivity but lower specificity
Differentials for an older patient presenting with memory loss
Dementia MCI Depression Alcohol misuse Medication with anticholinergic side effects Delirium
How is alzheimers dementia different to another type of dementia
Progressive memory impairment over a period of time plus a lack of symptoms to suggest another cause eg DLB or depression suggests AD
Action of donepezil and how it helps in the management of dementia
Acetylcholinesterase inhibitor
Inhibits breakdwon of ACh at synapses thus increasing availability of ACh to muscarininc and nicotinic receptors
ACh is important in memory function however action of AChEIs seems to be as much on alertness as upon improving memory
How do urine infections cause delirium
Pathophysiology isnt completely understood
Various hypotheses:
- changes in neurotransmitters, altered neuroinflammatory processes and oxidative stress
What causes death in dementia
In severe dementia people become physically frail and immobile and their swallowing reflex may be impaired
Vulnerable to conditions that affect frail, immobile people
Often eventually die of pneumonia
Define quality of life
The level of satisfaction and comfort that a perosn enjots
Life gains its quality from the ability and capacuty of the individual to satisfy his or her needs
What is response shift
The potential of a subjects views, values or expectations changing over the course of a study, thereby adding another factor of change on the end results
What is SIDECAR
The scale measuring the impact of dementia on carers
Describe end of life care in dementia
No proven effective interventions on QoL in advanced dementia
Several interventions effective in diminishing mediatiors of QoL ie challening behaviour, mood, sleeping disorders, including pain treatment
What symptoms do people with end of life dementia experience
Confusion Pain Low mood Constipation Loss of appetite
(Similar to cancer but people with dementia experience them for much longer
Barriers to pain recognition in dementia
Person with dementia may not be able to remember the pain they experienced earlier
The person with dementia may not be able to verbally communicate what they are feeling
May not be able to identify where their pain is located
Belief that behaviours resulting from the pain are symptoms of the dementia
How to assess pain in dementia
Asking the patient directly is best
Poor STM: people may not remember their pain
Speech problems- may have difficulty describing their pain
May no longer understand the concept of ‘pain’
May lose abstract concepts of severity
May need to use alternative expressions eg ‘sore’
Ask relatives for any individual pain indicators
Review health records
Barriers to good palliative care in dementia
Lack of care continuity across the whole trajectory of dementia
Continuity in a palliative care approach in dementia is often not acheived well in the UK largely because of the commissioning divide across health and social care
What is the role of the obicularis oculi
Has 2 parts (palpebral) and (orbital)
P- involved in blinking
O- needed if you are scrunching the eye shut
Goes to just below the cheek bone
What is the role of the levator palpebrae superioris
Used for opening the eye
What are the origins and insertions of the recti muscles (EO)
Recti superior originate in a common tendinous ring
Insert into the sclera
Role of the optic nerve
Takes information away from the back of the eye
Is cranial nerve 2
Origin and insertion of the oblique muscles (EO)
Superior oblique originates in sphenoid bone
Inferior oblique originates in maxilla
They both hook through the trochlear and back on self and insert into the sclera
What are saccades
Intentional eye movements that are fast and omnidirectional
What are FEMs
Fixational eye movements (The eyes are never stationary) 3 types: - microsaccades - drifts - tremors
Describe the roles of the different types of fixational eye movements
Drifts: move the image across the retina
Microsaccafes: snap it back to the centre
Adaptation: causes the image to fade over time
Describe testing of cranial nerves 2,3,4,6
Range and accuracy of eye motion eg tracking an object
Pupillary light reflex (shining light into one pupil, should cause both to dilate)
Ptosis (drooping eyelid)
What cranial nerves do cranial nerve palsies affect and what are the causes
CN III, IV and VI
Causes: trauma, neoplasm / tumour, vascular eg diabetes, hypertension
What are opsins
Photosensitive proteins (rhodopsin / conopsin) Contain vitamin A
What is the function of photoreceptors
Dark: Na + channel open, Na+ / K+ ATP-ase pump active, cell at baseline depolarised (-40mV)
Light: Na+ channel closed, positive ions build up in the synpase, cell hyperpolarised (more -ve), glutamate prevented from release to bipolar cells
Role of choroid layer
Absorbs light
Role of rods
120 million per eye In the periphery Monochrome colours Low resolution Many : 1 with ganglion cells
Role of cones
6 million per eye In the fovea Detect colour High resolution 1:1 with ganglion cells
Describe cataracts
Increased opacity / cloudiness of the lens (sometimes cornea)
Most common cause of low vision registration worldwide
Key factors:
- gradual onset
- can be 1 or both eyes
- manifests as gradual degradation of acuity, diplopia, reduced sensitivity to colour
- simple surgical treatment
Risk factors for cataracts
Age Trauma Radiation Smoking Genetics
Describe glaucoma
Increased intra-ocular pressure (IOP)
- fluids in the eye maintain structure - typically 10mmHg
- if the outflow is blocked, pressure can build (above 21 mmHg is considered high)
- constricts the optic nerve and artery
- results in loss of peripheral visual field
Describe macular degeneration
Dry, age related
- if the eye stops clearing debris properly, drusen can build up
- this can block or damage photoreceptors, particularly in the fovea (macula)
- loss of centra visual field
Describe the key factors of a detached retina
The detached retina has been pulled away from the choroid layer
- often connected to trauma (particularly in myopic patients)
- sudden appearance of ‘floaters’- dark spots that float in the field of vision
- sudden short flashes of light in one eye
Describe colour vision deficiency (colour blindness)
Typically genetic but can develop due to other eye diseases
Red-green is most common
XX chromosomes: 0.5% chance due to the gene being carried on the X chromosome
XY: there is an 8% chance that you are coloour blind
What is giant cell / temporal arteritis
Inflammation of some very important arteries
May affect blood supply to the optic nerve, causing arteritic anterior ischemic optic neuropathy
- reduced visual acuity
- diplopia
- acute loss of vision
What happens at the optic chiasm
Projections from the contralateral hemifield switch sides at the optic chiasm
Role of the optic tract
Projects to the LGN in the thalamus and some projections to the hypothalamus
What do lesions in the optic nerve lead to
Monocular blindness
What do lesions in the optic chiasm lead to
Temporal hemianopia
What do lesions in the optic tract lead to
Left or right hemianopia
What do lesions in the optic radiations pathways lead to
Upper or lower hemianopia
Upper VF defects sometimes caused by temporal lesions
What is the 2 stream model in the visual cortex
Post V1, information is transmitted via 2 pathways
Dorsal stream: the ‘where’ or ‘how’ pathway
Associated with motion, location, saccadic control
Ventral stream: the ‘what’ pathway
Associated with object recognition and memory
