Week 3- dementia

Question 1

What is dementia?

Answer 1

An acquired and persistent generalised disturbance of higher mental functions in an otherwise fully alert person.

Question 2

What is the difference between primary and secondary dementias?

Answer 2

Secondary dementias are other disorders giving rise to dementia. Whereas primary is just the dementia alone.

Question 3

Give examples of primary dementias?

Answer 3

Alzheimer’s disease, Lewy body dementia, Picks disease, Huntington’s disease.

Question 4

Describe Alzheimer’s disease?

Answer 4

Progressive impairment of higher intellectual function. Associated with mood and behaviour changes. As it progresses- progressive disorientation, memory loss and aphasia indicating severe cortical dysfunction.

Question 5

Macroscopically- what changes would you see in the brain in a patient with Alzheimer’s disease?

Answer 5

Atrophy of the cortex- typically affecting frontal and parietal lobes.
Reduction in weight
Narrowing of gyri and widening of the sulci.
Compensating dilatation of the ventricles.
Brainstem and cerebellum are normal.

Question 6

Microscopically- what changes would you see in a brain of a patient with Alzheimer’s disease?

Answer 6

Neuronal loss with associated astrocyte proliferation. Gliosis.
Neurofibrillary tangles (intracytoplasmic accumulations of microtubules and proteins called Tau)
Neuritic plaques- formed by A beta amyloid plaques. Surrounding astrocytes and microglia.

Question 7

What is the importance of amyloid AB in Alzheimers disease?

Answer 7

It forms the central element of the neuritic plaques. Also found in patients with trisomy 21 (downs syndrome)- meaning they have early onset Alzheimer’s.

Question 8

Genes associated with Alzheimers and inheritance

Answer 8

Implicated genes are the amyloid precursor protein (APP) and presenillin 1 and 2.
May have a familial connection.

Question 9

Who is affected by Alzheimers disease?

Answer 9

Its a disease of the elderly (over the age of 65).

Question 10

Brief pathogenesis of Alzheimer’s?

Answer 10

Depositation of Alpha- beta amyloid is the initial event. These form neuritic plaques which activate inflammatory cells.
Real disruption is caused by a-beta oligomers that get into the synaptic cleft.

Question 11

What is amyloid angiopathy?

Answer 11

A beta peptide accumulates in vessel walls- can disrupt the blood brain barrier. Stains Congo red.

Question 12

Describe Lewy body dementia?

Answer 12

This is the third most common form of dementia. It is a progressive dementia with hallucinations and fluctuating levels of attention/cognition.

Question 13

How does Lewy body dementia differ from Alzheimers disease?

Answer 13

Lewy body dementia fluctuates in severity on a day to day basis.

Question 14

What features present early in Lewy body dementia?

Answer 14

Parkinson features present at onset or shortly after.

Question 15

Describe features of Parkinson’s?

Answer 15

Loss of facial expression, pill rolling resting tremor, rigidity, slow and difficult initiation of movement.

Question 16

Describe the pathology of Lewy body dementia?

Answer 16

Degeneration of the substantia nigra as seen in Parkinson’s.
Accumulation of lewy bodies in vulnerable sites.

Question 17

Macroscopically- what will the substantial nigra look like in Lewy body dementia?

Answer 17

Loss of pigment- pale.

Question 18

Microscopically- what does Lewy body dementia present as?

Answer 18

Loss of pigmented neurones
Reactive gloisis
Remaining neurones show Lewy bodies. Lewy bodies are eosinophilic, round, elongated bodies with a dense core and surrounding pale halo.

Question 19

What is Huntington’s disease and what is the classic triad?

Answer 19

A neuropsychiatric disorder that presents in the younger population.
Triad of emotional, cognitive and motor disturbances.

Question 20

Symptoms of Huntington’s disease?

Answer 20

Chorea (dance like movements) 
Myoclonus (spasmodic jerky contractions of a group of muscles)
Clumsiness
Slurred speech
Depression
Irritability
Dementia develops later.

Question 21

How is Huntington’s disease inherited?

Answer 21

Autosomal dominantly

Question 22

Describe the macroscopic appearance of a sufferer of Huntington’s disease’s brain?

Answer 22

Atrophy of the basal ganglia- especially the caudate nucleus.

Question 23

What is Pick’s disease also known as?

Answer 23

Fronto-temporal dementia

Question 24

Describe Picks disease

Answer 24

Progressive dementia affecting a slightly younger age group than Alzheimers disease and Lewy body dementia. Characterised by progressive changes in character and social deterioration leading to impairment of intellect, memory and language.

Question 25

Describe what happens to the brain in Picks disease?

Answer 25

Extreme atrophy of the cerebral cortex especially in the frontal and temporal lobes. Huge degree of atrophy means the brain can weigh less than 1kg.

Question 26

Microscopically what happens to the brain in Picks disease?

Answer 26

Neuronal loss and gliosis. 
Picks cells (swollen neurones) are the histological landmark.

Question 27

Describe multi-infarct dementia?

Answer 27

Disorder involving a deterioration in mental function due to progressive damage.

Question 28

What occurs to the brain (pathophysiology) in multi-infarct dementia?

Answer 28

Successive, multiple cerebral infarcts cause increasingly larger areas of cell death. When a sufficient area of the brain is damaged, dementia occurs.

Question 29

Who gets multi-infarct dementia?

Answer 29

Commonly over the age of 60 however also seen in middle aged hypertensives.

Question 30

Sufferers of multi-infarct dementia are aware of their mental deficit and can develop depression. T or F

Answer 30

True.

Question 31

What differentiates multi-infarct dementia from the other dementias?

Answer 31

The other dementias tend to be relatively smoothly progressing, whereas multi-infarct dementia shows a step-wise change in neurological function.

Question 32

Morphological appearance of multi-infarct dementia?

Answer 32

Large vessel infarcts.
They will be scattered throughout hemispheres. Atheroma of large cerebral arteries provoke thromboemboli. Also lacunar infarcts add to these.

Question 33

What is key in a history to ascertain with a patient with dementia?

Answer 33

How it affects their activities of daily living e.g. finances, medications etc.

Question 34

What is vascular dementia also known as? What can point you towards this diagnosis?

Answer 34

Also known as multi-infarct dementia.
Lots of infarcts amounting to progressive cognitive decline. Look for evidence of vascular pathology e.g. hypertension, previous strokes etc.

Question 35

Which dementia is most likely to cause behavioural and personality change?

Answer 35

Frontotemporal dementia.

Question 36

What drugs can be offered as aid for Alzheimers patients to try to prevent further cognitive decline?

Answer 36

Acetylcholinesterase inhibitors- e.g. Donepezil, Rivastigmine and galantine
And also some evidence for use in Parkinson’s dementia
Be wary in peptic ulcer disease.

Also folic acid and B vitamins.

Question 37

What drug may improve behavioural symptoms in Lewy body dementia?

Answer 37

Rivastigmine.

Question 38

In late stage dementia, what drug may be affective against further cognitive decline?

Answer 38

Memantine- an NMDA antagonist

However side effects include hallucinations, confusion, hypertonia, hypersexuality.

Question 39

What drug can be used to target beta amyloid?

Answer 39

Solanezumab- can be used in mild Alzheimers disease patients.