Dementia

Question 1

Frontal lobe damage

Answer 1

Impaired judgement, abstract reasoning, strategic planning, emotional restraint, control of appetite and continence

Question 2

Medial temporal lobe damage - hippocampus, amygdala, limbic - damage

Answer 2

Memory disorders

Hallucinations

Question 3

Temporal neocortex damage

Answer 3

Receptive dysphasia and automatisms

Question 4

Occipital lobe damage

Answer 4

Failure of visual sensory systems

Question 5

Parietal lobe damage

Answer 5

Impairment of visuospatial skills, integration of sensory inputs, leading to sensory agnosias and apraxias

Question 6

Neurodegenerative dementia types

Answer 6

Alzheimer's
Lewy body dementia
Frontotemporal dementia
Huntington's disease + many others
Vascular dementia
Prion diseases

Question 7

Dementia classification categories

Answer 7

Ant/post

Cortical/subcortical

Question 8

Movement disorders examples

Answer 8

Parkinson’s
Parkinson plus syndromes
Huntington’s disease
Motor neuron disease

Question 9

Neurodegenerative dementias

Answer 9

Alzheimer’s
Frontotemporal dementia
Dementia with lewy bodies

Question 10

Tauopathies

Answer 10

Frontotemporal dementia

Alzheimer’s

Question 11

Ubiquinopathies

Answer 11

Frontotemporal dementia

Question 12

Synucleinopathies

Answer 12

Parkinson’s
Dementia with lewy bodies
MSA

Question 13

Normal pressure hydrocephalus - presentation

Answer 13

Triad of: dementia, gait disturbance, urinary incontinence

Question 14

Normal pressure hydrocephalus - types

Answer 14

NPH with preceding cause e.g. SAH, meningitis, trauma, radiation-induced

Idiopathic (50%)

Question 15

What would show triphasic waves?

Answer 15

Transmissible spongiform encephalopathies

Question 16

What does CBD stand for?

Answer 16

Corticobasal degeneration

Question 17

What is CBD?

Answer 17

Tauopathy

MRI shows phospho-tau filaments within the neuron from a brain of CBD

Question 18

What does VGKC Ab mean?

Answer 18

Voltage gated potassium antibodies

Question 19

What does VGKC Ab indicate and present?

Answer 19

Subacute memory loss
Psychiatric/behavioural disturbance 
Seizures
Hyponatraemia
65 yo median age; 2:1 M:F
Immunomodulation for treatment - if no tumours but a lot have tumours

Question 20

What proteins are involved in dementia

Answer 20

B-amyloiad
Tau
a-synclein
Ubiquitin

Question 21

What are amyloid proteins?

Answer 21

INsoluble fibrous protein aggregates sharing specific structural traits

Question 22

What do tau proteins do?

Answer 22

A group of proteins that stabilise microtubules in neurons

Six isoforms - if defective, microtubules become unstable and dysfunctional

Question 23

Amyloid cascade model

Answer 23

1. a-secretase processing of APP is modulated by stimulation of ACh or 5HT receptors.
2. Within the neuron, PS1 associated with APP and traffics it with an endosomal vesicle, generating AB1-42
3. AB1-42 secreted and forms aggregates
4. activate microglia + react excitotoxically with neurons, forming plaques via interaction with ApoE and deposition of AB amyloid as plaque
5. Plaque formation degenerates neurons
6. Active microglia make positive feedback loop + enhances plaque

Question 24

a-Synuclein pathway

Answer 24

1. Monomer folds badly
2. forms b-sheet oligomer
3. Forms lewy body

Question 25

What is ubiquitin?

Answer 25

Small regulatory protein in almost all cells Directs proteins to cell compartments Can be attached to protein and label them for destruction

Question 26

Pathogenesis

Answer 26

1. Oxidative stress makes free radicals 2. Excitotoxicity: glutamine stimulation 3. Induction of apoptosis Cytokines, genetic factors, ageing and unknown aetiology

Question 27

Accumulation of abnormal proteins intracellular

Answer 27

Tau a-Synuclein Polyglutamine Ubiquitin

Question 28

Accumulation of abnormal proteins extracellular

Answer 28

Amyloid

Question 29

Macroscopic neuropathological findings of AD

Answer 29

Brain weight decrease - (1300 -> 1000) Atrophy in cerebral gyri (hippo, temp, parietal, frontal, cingulate - less so occipital) Atrophy in white matter + thin corpus callosum + brain stem + cerebellum Ventricular dilatation Pale substantia nigra + locus ceruleus

Question 30

Microscopic neuropathological findings of AD

Answer 30

Neuron loss from hippo,cerebral cortex Microvacuolation in cerebral neocortex Attenuation in white matter

Question 31

Braak staging system what is it?

Answer 31

Shows mild to severe infiltration of abnormal proteins

Question 32

Names of CERAD groups

Answer 32

Normal Definitive AD Probable AD Possible AD

Question 33

Macroscopic finding of dementia with lewy body (DLB)

Answer 33

Pale substantial nigra and LC??? | Atrophy in amygdala, cingulate, temp, parietal, frontal

Question 34

Microscopic finding of dementia with lewy body (DLB)

Answer 34

Neuronal loss from SN and LC | Accumulation of a-synuclein +ve bodies in neurons of SN, amygdala and later in the cerebral cortex

Question 35

DLB under microscope you see

Answer 35

Red bodies

Question 36

Vascular dementia features

Answer 36

Multi-infarct dementia (ischaemic damage to brain) Binswanger's dementia (pathology mainly in white matter - microinfarctions in white matter) Arteriolosclerosis (high pressure and become sclerotic, collagen fibres replace smooth muscle, less able to supply local region so loss of neurons)

Question 37

Frontotemporal dementia (pick's disease) under microscope

Answer 37

Balloon cells and pick bodies - ubiquitin and tau positive

Question 38

Abbreviations of major neuropathological diagnosis of dementias

Answer 38

``` Alzheimer’s Disease (AD) Frontotemporal lobar degeneration (FTLD) Dementia with Parkinsonism: Idiopathic Parkinson Disease (IPD) Dementia with Lewy Body (DLB) Corticobasal degeneration (CBD) Progressive Supranuclear Palsy (PSP) Vascular Dementia (VaD) Normal Pressure Hydrocephalus (NPH) Creutzfeldt-Jakob Disease (CJD) ```