🧠Neurology🧠 - Dementia

Question 1

What is the most common cause of dementia?

Answer 1

Alzheimer’s disease

Question 2

What characterises dementia?

Answer 2

Fatal neurodegenerative disease
Progressive cognitive, social and functional impairment

Question 3

What are the current treatment options for dementia?

Answer 3

No cure
Acetylcholinesterase inhibitors have modest symptomatic benefit in early stages (ΔMMSE = 1)

Question 4

Outline the progression of dementia

Answer 4

Question 5

Why is it hard to accurately diagnose dementia?

Answer 5

Follows a heterogenous course - great variety in rate of progression as well as symptoms and severity
Often presents with multiple co-morbidities

Question 6

What are the cerebral issues that present with dementia?

Answer 6

Parenchymal ischaemic changes
Vessel wall pathology

Question 7

What step of the clinical consultation pathway does the diagnosis most heavily rely on for dementia?

Answer 7

History

Question 8

What is the patient interview checklist for suspected dementia?

Answer 8

Cognitive skills
Sensory issues
Behaviour/mood
Chronology of each

Question 9

What is a functional definition of dementia?

Answer 9

Severe loss of memory and other cognitive abilities which
leads to impaired daily function (regardless of the underlying cause)

Question 10

How can a patient’s cognitive impairment be measured?

Answer 10

MMSE (shown below)
+/- ACE III (more memory focused)

Question 11

What blood test should be done for a patient presenting with dementia like symptoms?

Answer 11

Blood tests with aims to eliminate possibilities of alternate diagnoses
FBC
Inflammatory markers
Thyroid function
Glucose
B12 + folate
Clotting
Syphilis serology
HIV
Caeruloplasmin

Question 12

What are the 4 main types of dementia?

Answer 12

Alzheimer’s disease
Vascular dementia
Lewy body dementia
Frontotemporal dementia (FTD)

Question 13

How does Alzheimer’s present and what is the suspected underlying mechanism?

Answer 13

Subtle, insidious presentations
Cerebral-cortical atrophy
Beta-amyloid plaques - form toxic aggregates between nerve cells
Synaptic deterioration and neuronal cell death
Neurofibrillary tangles found in brain cells - protein called tau

Question 14

How do the beta-amyloid plaques arise in Alzheimer’s?

Answer 14

APP normally cleaved by alpha secretases. AD—> Aberrant cleavage by beta + gamma secretases—> amyloid beta—> aggregates into insoluble amyloid plaques—> interfere with neuronal communication—> inflammation

Question 15

How do neurofibrillary tangles arise in Alzheimer’s?

Answer 15

Tau protein usually involved in microtubule assembly - essential for neuronal growth and development
Amyloid beta plaques trigger tau hyperphosphorylation—> oligomerisation—> aggregate in NFT—> disrupt microtubular system—> impaired neuronal growth, transport and communication—> reduced neuronal function and apoptosis (⇒ atrophy especially in hippocampus and temporal regions) & degeneration of cholinergic nuclei (low acetylcholine)

Question 16

How does vascular dementia present and what is the suspected underlying mechanism?

Answer 16

Related to cerebrovascular diseases with a classical step-wise deterioration + multiple infarcts
Associated with reduced blood supply to brain and diseased vessels plus multiple infarcts
Atherosclerosis—> vascular occlusion—> TIA/strokes—> deterioration of cognition
Abrupt onset (stroke) or gradual (accumulation of injuries to small vessels)

Question 17

How does Lewy body dementia present and what is the suspected underlying mechanism?

Answer 17

Insidious onset, progressive with fluctuations
Cognitive impairment before/within 1 year of onset of Parkinsonian symptoms
Visual symptoms such as hallucinations and fluctuating cognition
Aberrant deposits of alpha-synuclein protein predominantly in primary motor cortex; deposits= Lewy bodies

Question 18

How does FTD present and what is the suspected underlying mechanism?

Answer 18

Insidious onset, then rapid progression
Behavioural changes (e.g. disinhibition, socially inappropriate behaviour, poor judgement, apathy etc..)
Frontal and temporal atrophy
Neuronal atrophy of frontal and temporal lobes due to presence of phosphorylated tau or TDP-43 (transactive response DNA-binding protein 43)
Genetic- autosomal dominant
Semantic dementia—> effect on temporal lobe—> impaired understanding of language
Obsessions, diet, lack of interest

Question 19

What disorders/conditions can mimic presentations of dementia?

Answer 19

Depression
Delirium
Ageing

Question 20

What does “management” entail, in the context of dementia?

Answer 20

Acetylcholinesterase inhibitors
Watch and wait
Treating behavioural/psychological
symptoms
OT/Social services
Specialist therapies

Question 21

What are the most classic signs of Alzheimer’s?

Answer 21

Memory problems
Cognition issues
Lack of insight

Question 22

What are the most important parts of the consultation in a patient presenting with dementia-like symptoms?

Answer 22

History
Both from patient and collateral from relative

Question 23

Give some typical collateral history for a patient with Alzheimer’s

Answer 23

Family says:
* Patient asks the same questions every day,
* Makes mistakes with respect to taking medication
* Still drives, but could not find his way to son’s house last month, even
though going for several years
* Will watch film/TV programme for the second time without realising
* Increasingly irritable

Question 24

What might be evident in a patient with Alzheimer’s upon examination?

Answer 24

Head-turning sign - looks to relatives for help with questions
Vague about recent news events and sports results
Not certain about route to hospital
MMSE (Mini Mental State Examination)
ACE (Addenbrooks Cognitive Assessment).
Neuropsychology – profound impairment of episodic memory, particularly in relation to
recently learned material.
Episodic memory:
Memory for particular episodes in life
Dependent on the medial temporal lobes, including the hippocampus

Question 25

How is Alzheimer’s diagnosed?

Answer 25

Can only be certain post-mortem
Probable Alzheimer’s on brain MRI
Person is that patient - however disease also takes significant toll on partner/carer/family

Question 26

Where in the brain is most affected by Alzheimer’s in the context of reduced cognition and impaired memory formation?

Answer 26

Hippocampus

Question 27

How can Alzheimer’s be effectively diagnosed?

Answer 27

CSF beta-amyloid and tau levels

Question 28

How does Lewy body dementia present in clinic?

Answer 28

Associated with fluctuating cognition
Different cognitive profile to Alzheimer’s Disease
Often visual hallucinations
REM sleep disorder
Development of symptoms associated with Parkinson’s Disease
High risk of falls

Question 29

How do Lewy bodies form (not essential knowledge)

Answer 29

Question 30

How would you expect someone to present in clinic with FTD?

Answer 30

Speech issues
Memory problems
Behavioural changes, socially inappropriate behaviour
Lack of self care
Some motor issues with fine movement
MRI will show volume loss in temporal and frontal lobes