S9) Cortical Dysfunction and Dementia Flashcards
What is dementia?
Dementia is the progressive decline in higher cortical function leading to a global impairment of memory, intellect and personality which affects the individual’s ability to cope with activities of daily living
Identify four common causes of dementia
- Alzheimer’s disease
- Dementia with Lewy bodies
- Vascular dementia
- Fronto-temporal dementia
What are the reversible causes of dementia?
- Depression
- Trauma
- Vitamin deficiency
- Alcohol
- Thyroid disorders
Identify a rare cause of dementia
Creutzfeldt-Jacob disease – a rare and fatal condition that affects the brain
How does dementia present?
- Memory deficit
- Behavioural changes
- Physical changes
- Language disorder
- Visuospatial disorder (temporal)
- Apraxia (temporal)
Explain how dementia presents with a memory deficit
Memory deficit – struggle to learn new information, short term memory loss
Hippocampus/temporal
Explain how dementia presents with behavioural changes
Behavioural changes – altered personality, disinhibition, labile emotions, wandering
pre frontal cortex atrophy
Explain how dementia presents with physical changes
Physical changes – incontinence, reduced oral intake, difficulty swallowing
limbic system (hippocampus)
Explain how dementia presents with a language disorder
Language disorder – anomic aphasia, difficulty understanding language
primary motor cortex, brooks and wernickers
Explain how dementia presents with a visuospatial disorder
Visuospatial disorder – unable to identify visual and spatial relationships between objects
Explain how dementia presents with apraxia
Apraxia – difficulty with motor planning resulting in inability to perform learned purposeful movements
What investigations would one request for a patient presenting with dementia?
- Full history + MMSE (collateral from family)
- Full neurological examination
- Blood tests – TFTs, Vitamin B12 (reversible causes)
- CT/MRI head
Pet Ct - Memory Clinic follow
up
Which method is used to differentiate between delirium and dementia?
Confusion assessment method (CAM score)
A CAM Score of 2/more indicates delirium rather than dementia.
What does the CAM score entail?
- Acute change / fluctuating mental status
- Altered consciousness – hypo/hyperactive
- Inattention
- Disorganised thinking
How does a patient with dementia’s brain present on CT scans?
- Transverse CT head showing dilation of ventricles and generalised atrophy
- NB. features on scan don’t always correlate with clinical picture

Explain how a patient’s brain with dementia presents on an MRI scan
Axial and coronal sections of T1 weighted MRI brain showing hippocampal atrophy

Describe the rate of progression of cognitive decline in the following forms of dementia:
- Vascular dementia
- Alzheimer’s disease
- Lewy-body dementia

Describe the macroscopic pathology of Alzheimer’s disease
- Loss of cortical and subcortical white matter causing gyral atrophy with narrow gyri and wide sulci
- Marked ventricular dilation reflecting loss of white matter
→ hippocampus often affected first

Describe the microscopic pathology of Alzheimer’s disease
- Amyloid-Beta plaques
- Neurofibrillary tangles

Outline the mild, moderate and severe stages of Alzheimer’s disease
- Mild: 2-4 years, minor memory loss, difficulty learning and remembering new information, long term memory and reasoning intact
- Moderate: 2-10 years, withdrawal, confusion, poor judgement, increasing difficulty in self-care, anger, anxiety, frustration
- Severe: 1-3 years, incapacitated, patients do not recognise people, loss of bodily functional control, violent episodes of aggression
Describe the pathophysiology of dementia with Lewy bodies
Lewy bodies in the cortex and substantia nigra

Identify four clinical features of dementia with Lewy Bodies
- Substantial fluctuations in the degree of cognitive impairment over time
- Parkinson’s symptoms (repeated falls)
- Visual hallucinations
- Frequent falls
(if movement disorders follow after dementia we call it Parkinson’s, if it precedes movement disorder we call it dementia with Lewy bodies)
Describe the pathology of vascular dementia
- Arteriosclerosis of the blood vessels supplying the brain
- Diffuse small vessel disease vs infarcts (large vessel disease)
- Results in decreased/cut off blood supply to specific part of brain
→ can occur in multiple sites In the brain
Describe the clinical features of vascular dementia
Abrupt, step-wise decline in cognitive function related to vascular episode
Describe the management of vascular dementia?
Assess cardiovascular risk – treat hypertension/high cholesterol
Frontotemporal dementias are a diverse group of conditions with similar presentation but different pathologies.
Identify some
- Frontotemporal lobar degeneration (FTLD) with tau pathology
- Pick’s disease
- Familial tauopathies
Describe three clinical features of fronto-temporal dementias
- Alteration of social behaviour and personality: agitation, depression
- Impaired judgment and insight – gambling, taking off clothes, inappropriate comments
- Speech output falls eventually to a state of mutism
Outline the holistic approach for managing dementia in terms of:
- Memory aid
- Therapies
- Drugs
- Social care

What is a seizure?
A seizure is a sudden irregular discharge of electrical activity in the brain causing a physical manifestation such as sensory disturbance, unconsciousness or convulsions
What are convulsions?
Convulsions are uncontrolled shaking movements of the body due to rapid and repeated contraction and relaxation of muscles
What is an aura?
An aura is a perceptual disturbance experienced by some prior to a seizure e.g. strange light, unpleasant smell, confusing thoughts
What is epilepsy?
Epilepsy is a neurological disorder marked by sudden recurrent episodes of sensory disturbance, LOC or convulsions, associated with abnormal electrical activity in the brain
What is status epilepticus?
Status epilepticus are epileptic seizures occurring continuously without recovery of consciousness in between (generalised seizure – medical emergency)
How can seizures be classified?

Partial seizures only occur in part of the brain.
What are the two types of partial seizures and how do they differ?
- Simple – same consciousness
- Complex — consciousness is impaired
Identify two types of partial seizures
- Temporal lobe epilepsy – following seizure with fever or an early injury to the brain
- Frontal lobe epilepsy
Describe the five different types of generalised seizures

- Tonic-clonic – 1st tonic (muscles tense) 2nd clonic (convulsions)
- Absence – daydreaming
- Myoclonic – brief shock-like muscle jerks
- Atonic – ‘without tone’, drop attack
- Tonic – increased tone
What investigations can one request for a patient presenting with epilepsy?
- Clinical history
- EEG
- MRI
Describe the clinical history one must take before, during and after a seizure
- Before – PMH, FH, triggers, aura, first sign/symptom
- During – description of seizure, duration, abrupt/gradual end
- After – post-ictal state, tongue-biting, incontinence, neurological deficit
What is the differential diagnosis for a patient seeming to present with epilepsy?
- Vascular: stroke, TIA
- Infection – abscess, meningitis
- Trauma – intracerebral haemorrhage
- Autoimmune – SLE
- Metabolic – hypoxia, electrolyte imbalance, hypoglycaemia, thyroid dysfunction
- Iatrogenic – drugs, alcohol withdrawal
- Neoplastic – Intracerebral mass
The EEG is not diagnostic but supports a diagnosis.
Explain when an EEG is used to assess a patient presenting with epilepsy
- In first unprovoked seizure – assess risk of seizure recurrence (unequivocal epileptiform activity on EEG)
- Standard EEG assessment involves photic stimulation and hyperventilation – patient warned that it may induce a seizure

What are the contra-indications for an EEG?
Do not use if:
- Probable syncope (risk of false positive result)
- Clinical presentation supports diagnosis of non-epileptic event
- In isolation to make a diagnosis of epilepsy
What should be considered if an EEG is unclear?
- Repeated standard EEGs
- Sleep EEGs (sleep deprivation or melatonin in children/young people)
- Long-term video or ambulatory EEG
What other investigations can one request for a patient presenting with epilepsy?
To exclude other suspected causes of seizure:
- ECG as standard in adults
- MRI – in all patients with new-onset seizures
Outline the initial management for a patient presenting with epilepsy

What are the restrictions on driving with epilepsy?
- If suffers epilepsy when awake → licence is taken away until 1 year seizure-free
- If due to medication change → licence is taken away until 6 months seizure-free
- Seizures whilst asleep or don’t affect driving or consciousness → assessment of case by DVLA
- If one-off seizure then → licence is taken away until 6 months seizure-free and assessment by DVLA
What is an amyloid precursor protein?
→ protein that helps repair damaged neurones
→ periodically replaced and chopped up into smaller soluble parts via enzymes
→ These allow them to be disposed
what enzymes break down the amyloid precursor protein
alpha and gamma secretase
if Beta amylase gets involved in amyloid proteins what happens
→ amyloid proteins are broken down into insoluble molecules
they then start to form beta amyloid plaques
these fill space in between neurones and so slow down transmission
what pathological functions can plaques do
→ cause inflammatory response
→ neuronal death
→ if they deposit around blood vessels they can cause antipathy, weakened blood vessels can bleed
what are tau proteins
→ They stabilise microtubules within the neuronal cytoskeleton (these mobilise nutrients around the cytoskeleton)
how do beta amyloid plaques damage tau proteins
→ hyperphosphorylation of tau proteins (picks disease)
→ change shape of tau proteins
→ Tau proteins can’t support cytoskeleton = neuronal death
→ Tau proteins start to tangle = tau tangles
what medication removes amyloid plaques
aducanumab
which neurotransmitter is reduced in alzhimers
Ach
it is essential for processing memories and learning
types of Alzheimer’s
what psychotic features does dementia have
→ hallucinations
→ delusions (false beliefs)
why do people with dementia have insomnia and drowsiness
reduced cortical activity
what other disease could be giving a similar presentation to dementia
o Hypothyroidism
o Hypercalcaemia
o B12 deficiency
o Normal pressure hydrocephalus
Abnormal gait Incontinence Confusion
neurones involved With dementia
o Cholinergic (treatments target
this)
o Noradrenergic
o Serotonergic
o Those expressing
somatostatin
risk factors for vascular dementia
Previous stroke / MI etc o Hypertension
o Hypercholesterolaemia
o Diabetes
o Smoking
what is the pathology of Lewy body dementia
→ misfolding of protein alpha - synuclein
→ Forms spherical intracytoplasmic inclusions
→ Deposits found:
Substantia nigra
T emporal lobe
Frontal lobe
Cingulate gyrus (found just above the
corpus callosum)
why should you avoid giving someone with dementia with Lewy bodies antipsycotics
Do not give antipsychotics (dopamine antagonists)
as can cause neuroleptic malignant syndrome, a psychiatric emergency
Fever
Encephalopathy (confusion)
Vital signs instability (tachycardia,
tachypnoea (v.sensitive sign), fluctuating
BP)
Elevated creatine phosphokinase
Rigidity (caused by dopamine antagonism)
what is the second most common type of dementia and their symptoms
Fronto-temporal
→ effect younger patients
Behavioural disinhibition
o Inappropriate social behaviour
o Loss of motivation without depression (caused by
damage to anterior cingulate cortex) o Repetitive/ritualistic behaviours
o Non fluent (Broca type) aphasia
have an MI scan you will see either bi-temporal or unilateral atrophy
pathology of AIDS dementia complex
→ patients with AIDS more likely to live longer due to meds
→ Entry of HIV infected macrophages into the brain is thought to lead to indirect damage to neurones
Clinical features:
o Cognitive impairment
Psychomotor retardation (slow thoughts and
movements, also seen in depression) o Tremor
o Ataxia
o Dysarthria
o Incontinence
drugs to treat dementia with
Drugs
o Acetylcholinesterase inhibitors (e.g. donepezil,
rivastigmine, galantamine)
Alzheimer’s disease
o NMDA antagonists (e.g. memantine)
Useful for treating agitation NMDA antagonist
what is delirium
→ acute confused state, reversible and an organic cause
→ neuronal damage and inflammation
Rapid onset of confusion
Clouded consciousness (may be drowsy)
Fluctuating course
Maybe transient visual hallucinations
Often exaggerated emotional responses (e.g. aggression)
types of delirium
→ hypoactive
→ hyperactive
describe features of hypoactive delirium
Withdrawn
Quiet
Sleepy
Consequently more likely to be missed / confused with
something else
describe features of hyperactive delirium
- Restless
- Agitated
- Aggressive
Mood may rapidly fluctuate
Persecutory delusions (narrative of elusion often not coherent)
Symptoms worse at start and end of day
Maybe related to changes in endogenous cortisol levels
Causes of delirium
management of people suffering with delirium
Find and treat the underlying cause
Prognosis
Increases risk of dementia
Associated with mortality
These patients often have lengthy hospital stays and
have a high risk of re-admission