Dementia Flashcards
Why can dementia be considered a Cinderella disease?
Because although has a very high health and social care cost (52% vs cancer’s 23%), little research funding is allocated to it (only 6% compared to cancer’s 71%)
What are the 2 approaches in looking at the clinical features of dementia?
The historical method
The precise/deductive method -> clinical approach
What does the historical approaches to dementia include?
Looking for senility, poor memory, global decline
Why is the precise/deductive method of assessing the clinical features of dementia better than historical approaches?
It tells you more about diesease pathogenesis and allows you to identify the different types of dementia
What clinical assessments exist for dementia?
Witness account Blood tests Examination Imagine Neuropsychology EEG
Why are EEGs useful for assessing dementia?
Because many people suffering from epilepsy get Alzheimer’s
Is neuroimaging a good diagnostic tool for dementia?
No, but it is good at ruling out other causes (e.g. brain tumour, stroke, hydroencephalus)
What are the things you think about in a clinical neurological examination?
Where? - localisation
When? - time course of illness
What? - investigations
So what? - treatment
What part of the CNS does dementia affect?
The cortex
What are symptoms?
Something the person/witness observes
What are signs?
They can be elicited in the clinic by the clinician
What are the symptoms of someone with frontal lobe damage?
Disinhibition Apathy Change in sexual/eating behaviour OCD Loss of insight and empathy Difficulty with planning/multi-tasking slowing
Frontal-language:
Poverty of speech
mutism
What are signs of frontal lobe damage?
Verbal fluency Frontal release signs cognitive estimates motor sequencing utilization behaviour
Frontal-language: short sentences agrammatical phonemic paraphasias oro-buccal dyspraxia
What are frontal release signs?
Primitive reflexes that are normally present in infants. include the grasp, snout, root, and suck reflexes.
What are utilization behaviours?
The appropriate usage of an object by a patient, however at an inappropriate situation.
What is motor sequencing?
The ability to move the body with appropriate sequencing and timing to perform bodily movements with refined control.
What are phonemic paraphasias?
Substitution of a word with a nonword that preserves at least half of the segments and/or number of syllables of the intended word. (maybe like “That’s a hippopotamus” –> “That’s a hippocampus”)
What is oro-buccal dyspraxia
Difficulty moving mouth
What is Broca’s aphasia characterised by?
Short sentences - agrammatic telegraphic speech
How do you test verbal fluency?
Get people to say words that e.g. start with the same letter. Most people can get 12 words per min.
Do the symptoms displayed by the patient help diagnose the cause of the brain damage?
No, only the part of the brain damaged
What are symptoms of left temporal damage?
“deaf”
Not following commands/ instructions
What are signs of left temporal damage?
Preserved grammar
Semantic paraphasias
Anomia
What is semantic paraphasia?
Substituting a related or unrelated (sometimes distinguished as verbal paraphasia) word for the apparently intended or correct word.
maybe like “I’m bipolar” –> “I’m polar-bear”)
Why do people with left temporal lobe damage have problems with word selection?
Because the left temporal lobe is involved with:
- processing of verbal versus non-verbal inputs
- word retrieval
- social content of the stimuli
What are symptoms of left parietal damage?
Difficulty with writing, spelling, calculations
What are signs of left parietal damage?
Dyspraxia (miming and hand positions)
Dyslexia
Acalculia
Myoclonus
Corticoal Sensory loss
What are symptoms of occipital lobe damage?
Hallucinations
Virual misperception (e.g. visual snow)
What are signs of occipital lobe damage?
Loss of colour vision
Visual disorientation (optic ataxia - can’t grab things in front of them)
Asimultanagnosia - loss over movement perception
What is asimultanagnosia?
Inability of an individual to perceive more than a single object at a time
What are symptoms of right parietal damage?
Spatial inattention
Dressing apraxia
What are signs of right parietal damage?
Constructional apraxia
Sensory innatention
myoclonus
Cortical sensory loss
What are signs of right temporal damage?
Prosopagnosia (cannot recognise faces)
Poor topographical memory (doesn’t remember routes)
What are the symptoms of right temporal damage?
Getting lost
Difficulty with face recognition
What are symptoms of mesial temporal damage?
Forgetful
What are signs of mesial temporal damage?
Disorientation
Poor episodic memory
Which is the first area of the brain to be affected by alzheimers?
Mesial temporal (contains the hippocampus and parahippocampus
What would you see if you did an autopsy of an alzheimer’s brain?
Amyloid plaques occurring diffusely through the cerebral cortex
Tau neurofibrillary tangles
Neurodegeneration- enlarged ventricals, shrinking of hippocampus, shrinkage of cerebral cortex (grey and white matter)
Which neurons are most affected by alzheimers?
Cholinergic neurons are lost
How do amyloid plaques form?
Amyloid molecules usually sit in cell membrane but they become sticky and form plaques
What are neurofibrillary tangles?
Insoluble twisted fibers found inside the brain’s cells.
These tangles consist primarily of a protein called Tau, which forms part of a structure called a microtubule
Cholinergic neurons are the most affected
How common is alzheimers?
Very (1.4% UK pop, x10 more than PD)
What are the early clinical features of alzheimer’s disease?
Disorientation
Day to day memory impairment
Mild naming problems
What are later features of Alzheimers?
Receptive dysphasia (difficulty understanding)
Motor retardation
Visuo-spatial disorientation
Myoclonus
What probably causes myoclonus in alzheimers?
Damage to inhibitory neurones
Name a test often used to localise the part of the brain damaged by alzheimers and explain its steps
Folstein Mini-Mental State Examination (MMSE):
- Orientation (0-10): what day is it?, what floor are we on? etc - checks mesial temporal
- Immediate recall (0-3): Ask them to repeat words - frontal
- Attention and calculation (0-5) Count back from 100 - check left parietal
- Recall(0-3): Remember words I said before? - mesial temporal
- Language(0-3): what is this? show a watch - left temporal
- Praxis (0-3): Take paper and fold in half - parietal
- Language and reading comprehension (0-1): do as it says on the paper - temporal
- Praxis: Write a sentence - parietal
Discribe Alzheimers prodrome
Memory tests start to change about 10 years before symptoms
Amyloid markers build up starting about 20 years before onset
How does the progression of language comprehension and memory test compare in alzheimers?
Memory tests begin to worsen long before onset and reach a plateau after onset
Language comprehension test begin to get worse about 5 years before onset and the continue to get worse after
What tracks with Alzheimers progression?
Amyloid pathology does not track with disease process well
Tau pathology does
What happens to the Tau and Amyloid concentration in the CSF as disease progresses?
You can see amyloid in spinal fluid, this decreases when the disease starts probably because they are turning into plaques
Tau pathology starts way before disease starts
Tau increases in the CSF
Describe typical AD progression
Memory problems –> executive dysfunction, praxis, language, complex visual impairments –> spatial function
What is an APP mutation
You will get Alzheimer’s disease (people in 20s in the families have 50% chance of getting it)
These are the people who were studied to learn about the AD prodrome
What are the current treatments for AD?
Supportive care: physiotherapy, social support
Treat vascular risk factors: there is interplay between vascular risk factors and AD
Cholinesterase inhibitors
Multidisciplinary care
Chilnesterase inhibitors increase AD life expectancy.
TRUE or FALSE
FALSE
They only help control symptoms
What is Gantenerumab and what does it do?
It was a Mab which was meant to bind to beta-amyloid plaques, dissassemble them and stimulate phagocytosis to remove them.
It didn’t work
Name another Mab being trialed against AD
Crenuzumab
Can recognize different forms of amyloid-beta aggregates and plaques.
It stimulates the cellular ingestion of amyloid plaques and limits the release of cell signalling molecules (cytokines) that promote inflammation.
What is the amyloid cascade hypothesis
It proposes that the deposition of β-amyloid (Aβ) is the initial pathological event in AD, leading to the formation of plaques, tau-immunoreactive neurofibrillary tangles (NFT), neuronal loss, and ultimately, clinical dementia.
What kills people with AD?
Immobility leads to pneumonia and pulmonary embolisms
What is the most common cause of early onset dementia?
FTLD:AD = 1:1 ratio
What are the clinical features of frontotemporal dementia?
Insidious onset and gradual progression
Early decline in social interpersonal conduct
Early impairment in regulation of personal conduct
Early emotional blunting
Early loss of insight
What part of the brain does sematic dementia mainly affect?
Left temporal lobe
What are the diagnostic features of SD?
Insidious onset and gradual progression
Language disorder characterised by: Progressive, fluent , empty spontaneous speech
Loss of word meaning, manifested by impaired naming and comprehension
Sematic paraphasias
What are the clinical diagnostic features of progressive nonfluent aphasia?
Insidious onset and gradual progression
Nonfluent spontaneous speech with at least one of the following: agrammatism, phonemic paraphasias, anomia
II. Supportive diagnostic features -Speech and language
- Stuttering or oral apraxia
- Impaired repetition
- Alexia, agraphia
- Early preservation of word meaning
- Late mutism
What area of the brain does progressive nonfluent aphasia affect?
Frontal lobe (Broca’s area)
What 3 molecules are found in FTLD?
Tau, FUS, TDP-43
What are the 3 phenotypes of FTLD?
Sematic dementia
Behavioural variant frontal temporal dementia
Progressive nonfluent aphasia
How is FTLD different from AD?
Memory is usually normal at first but e.g. can’t look after kids (innapropriate punishing)
Can’t plan
Massive frontal atrophy
Onset is 50s not 60s
What is the central feature of dementia with Lewy bodies
Progressive cognitive decline with resultant functional impairment
Essential features for diagnosis:
Fluctuating cognition and pronounced variations in attention and alertness
Recurrent visual hallucinations (well formed, detailed)
Spontaneous motor features of Parkinsonism
Where else are lewy bodies found?
Parkinson’s
What are features of dementia with Lewy bodies which are supportive of the diagnosis?
Repeated falls
Syncope
Transient loss of consciousness
Neuroleptic sensitivity
Systematized delusions
Hallucinations
What is the most common dementia after AD?
DLB
How do you treat DLB?
May respond to cholinesterase inhibitors
What cells are damaged most in DLB?
Cholinergic neurons
