Dementia & Neurodegeneration

Question 1

What are the 3 ways in which axons can become degenerated?

Answer 1

Wallerian - distal degeneration of both axon and myelin (often by trauma - DAI)
Axonal - ‘dying back’ from cell body towards dendrite
Demyelination - loss of oligodendrocytes/Schwann cells (MS/GBS)

Question 2

Outline PNS degenerative disorders

Answer 2

Diabetic Neuropathy - axonal degeneration from hyperglycaemia, nociceptive + neuropathic pain
MND - UMN and LMN lesions by degeneration of motor pathways affecting outflow from anterior horn cells
GBS - autoimmune demyelinating disorder

Question 3

Outline CNS degenerative disorders

Answer 3

MS - autoimmune inflammatory demyelinating disorder
PD - degeneration of DA neurones in SN and Lewy Body accumulation intracellularly (inclusion)
HD - autosomal dominant CAG repeats, GABAergic neurone loss in striatum and reduced ACh transmission - shrunken caudate head
Prion diseases - CJD, vCJD, Spongiform encephalopathies by PrPc -> PrPsc transmissible or genetic

Question 4

What are the different types of Dementia?

Answer 4

Alzheimer’s - loss of ACh transmission
Vascular - reduced cerebral blood flow
Dementia with Lewy Bodies - a-synuclein Lewy body inclusion
Frontal Temporal - atrophy of frontal/temporal lobes (Pick’s)
Normal Pressure Hydrocephalus - CSF build up without raised ICP

Question 5

How is Normal Pressure Hydrocephalus characterised both by symptoms and on imaging?

Answer 5

Ventriculomegaly

Urinary incontinence, gait disturbance, cognitive decline, ocular changes sometimes

Question 6

How are Parkinson’s disease and Dementia with Lewy Bodies different?

Answer 6

LBD a-synuclein deposits typically throughout cortex, symptoms present with Parkinsonism + hallucinations + memory loss/fluctuations in cognition

PD bradykinesia + tremor from reduced DA neurones from SNPC (a-synuclein inclusion) and memory loss/cognitive impairment not until later stages

Question 7

How does Alzheimer’s present on imaging? What is the treatment?

Answer 7

First thing to degenerate is hippocampus and medial temporal lobes
FMRI shows hypometabolism in posterior cingulate and bilateral parietal-temporal regions
Post-mortem will confirm histology of B-amyloid plaques and Tau neurofibrillary tangles
Gross morphology is cerebral atrophy

Cholinesterase inhibitors for mild-moderate: Donepezil, Galantamine, Rivastigmine

Severe treated with NMDAr antagonists Memantine

Question 8

What investigations can be used for Dementia?

Answer 8

History from patient but family member/friend too

Cognitive tests: MMSE, GPCOG

Neuroimaging: CT, MRI, fMRI

Bloods for B12/Folate/TFT/CRP

Question 9

Dementia is characterised by global deterioration in…

Answer 9

Cognition - memory, orientation, concentration, speech
Behaviour
Personality

= affect work, social function and relationships

Question 10

What’s a cerebrovascular cause of dementia?

Answer 10

Multi-infarct

Question 11

Which types of dementia fall into the acute, subacute and chronic clinical courses?

Answer 11

Acute (weeks) - infective/encephalitis/paraneoplastic

Subacute (months) - Thiamine deficiency (Werncike’s), CJD, vCJD, Inflammatory (vasculature, sarcoidosis)

Chronic (years) - AD, multi-infarct, Pick’s disease, HD

Question 12

What are some cortical types of dementia and their features?

Answer 12

Frontotemporal
CJD
Alzheimer’s

Higher cortical abnormalities
Dysphasia
Agnostic
Apraxia

Question 13

What are some subcortical types of dementia and their features?

Answer 13

Normal pressure hydrocephalus
PD
HD

Apathetic
Forgetful
Slow
Impaired visuospatial abilities
Depression of mood

Question 14

What are 2 types of subcortical AND cortical dementia?

Answer 14

Multi-infarct

Cortical Lewy body disease

Question 15

What does imaging in Alzheimer’s disease show?

Answer 15

Early imaging will be normal

Later: neocortical/hippocampus atrophy, medial temporal lobe atrophy

Functional imaging: hypometabolism in posterior cingulate and bilateral parieto-temporal regions

Question 16

What type of neurones are lost in DLB?

Answer 16

Dopamine and Acetylcholine

Question 17

How can you tell fronto temporal dementia on imaging?

Answer 17

Focal atrophy of frontal or temporal lobes

Question 18

What are the 3 cardinal features of normal pressure hydrocephalus? What’s its sign on imaging? How is it treated?

Answer 18

Gait disturbance
Cognitive decline
Urinary incontinence

Ventriculomegaly on imaging

CSF shunt inserted ventriculoperitoneal to drain CSF into abdomen, maybe third ventriculostomy

Question 19

What are the two main classes of drugs used to treat dementia and in which cases are they used?

Answer 19

Anticholinesterases (AChE inhibitors to prolong ACh in cleft) used in mild-moderate dementia (Donepezil Galantamine, Rivastigmine)

Glutamate receptor antagonists (NMDAr to prevent neuronal excitability and cell death) for moderate-strong dementia (Memantine)

Question 20

What are the three features of DLB? What class of drug for one of the symptoms is a problem?

Answer 20

Dementia + Parkinsonism + Hallucinations

Antipsychotics can’t be used to treat hallucinations in DLB as they will exacerbate the Parkinsonism symptoms (as they block DA pathways to slow hyperactivity/psychotic behaviours seen in Schiz)

Question 21

What are the two forms memory can be divided into? Where are these different memories stored?

Answer 21

Procedural (expressed through motor functions) and Declarative (recognition/naming)

Procedural memory involved cerebellum, basal ganglia and pre motor cortex = long lasting and can be performed without conscious recollection

Declarative memories are rapidly learned and rapidly forgotten - rely on connection between hippocampus and cortex

Question 22

What’s anterograde amnesia?

Answer 22

Inability to form new memories due to fault in consolidation of new experience into long term memory

Damage usually in temporal lobes - hippocampal gyrus

Question 23

What’s retrograde amnesia?

Answer 23

Inability to recall events prior to precipitating event eg a car crash

Failure of long term memory

Question 24

What’s episodic memory?

Answer 24

Remembrance of autobiographical information located in time and personal experience

Question 25

What’s semantic memory? What type of memory do semantic and episodic make up?

Answer 25

Knowledge of facts and general knowledge

Semantic and episodic memories are types of declarative/explicit memory - consciously recalled information