Dementia Flashcards

1
Q

What are the different categories of dementia?

A

Dementia is a complex syndrome with many causes. There are specific genes and molecular mechanisms that underlie Alzheimer’s disease however is complicated because there’s not one single cause that contributes to disease and because the symptoms of the disease only become obvious after the underlying pathology has progressed it’s difficult to have effective treatment for it
Alzheimer’s disease is the main cause of dementia 60% of patients. It is a physical condition caused by changes in the structure of the brain. This is due to a build-up of proteins, resulting in ‘plaques’ and ‘tangles’ which damage the brain cells’ ability to transmit electrical impulses and communicate with the body and eventually lead to brain cell death.
Vascular dementia accounts for 20% of patients.
Vascular dementia is the second most common type of dementia. It is caused by problems in the supply of blood to the brain cells, commonly due to strokes or a series of small strokes, known as Transient Ischaemic Attacks (TIAs), which cause areas of localised cell damage in the brain.
Dementia with Lewy bodies affects movement and motor control. The patient could have tremors which are also seen in Parkinson’s disease.
5% is due to frontotemporal dementia- can often be missed for the first 5 years of the syndrome but affects personality and speech.

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2
Q

What is Alzheimer’s disease?

A

Alzheimer’s disease is the most common form of progressive senile dementia primarily affecting individuals over the age of 65.
Familial Alzheimer’s disease can result in early onset (30-60 years).
The disease leads to the inevitable destruction of neurons, and ultimately death within 7 to 10 years.
Alzheimer’s is not “normal aging”.

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3
Q

What Alzheimer’s risk factors are there?

A

Risk factors include:
Advanced age
Genetic: (3-5% of cases?) Down’s syndrome (chromosome 21); presenilins (14, 1) and ApoE4 (19)
Cerebral perfusion
Head trauma
Female (1.4: 1)
Environmental

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4
Q

What happens in Alzheimer’s disease?

A

Alzheimer’s disease is associated with brain shrinkage and loss of neurons in many brain regions. Several areas of the brain are at risk and this is why there is such a wide range of symptoms and effects on the patients. the loss of cholinergic neurons in the hippocampus and frontal cortex is a feature of the disease and is thought to underlie the cognitive defect and the loss of short term memory that occurs.

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5
Q

What does the cerebral cortex do?

A

Involved in conscious thought and language.

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6
Q

What does the basal forebrain do?

A

Important in memory and learning

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7
Q

What does the hippocampus do?

A

essential to memory storage

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8
Q

What happens in the brain in AD?

A

The exact cause is unknown but we do know that ‘plaques’ and ‘tangles’ form in the brain due to two proteins called amyloid (plaques) and tau (tangles).
Amyloid protein is found in the brain when B secretase enzyme cleaves the amyloid protein it forms β amyloid which is more sticky compared to normal amyloid protein.

Results in a Build up of amyloid plaques

If the amyloid plaques form outside neurons
it get between neurons and prevents communication with memmory neurons resulting in memory loss.

This results in an inflammatory response - the increased inflamation and inflammation markers build up in blood vessels which weakens them and results in blood leakage

If the amyloid plaques are inside neurons.
Tau protein is inside the neurons
amyloid plaques activates kinase in the cell causing tau proteins to become tangled together = apoptosis
Cells die = atrophy shrinkage of the brain and an increase in ventricle size
synaptic loss is the principal correlate of disease progression and loss of cholinergic neurons contributes to memory and attention deficits

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9
Q

What is the amyloid hypothesis?

A

Cause of degeneration
The exact cause is unknown but we do know that ‘plaques’ and ‘tangles’ form in the brain due to two proteins called amyloid (plaques) and tau (tangles).
Amyloid is a naturally occurring protein which for a reason that is not yet understoodbegins to malfunction, creating beta amyloid which is toxic to the brain cells. Plaques form consisting of dead cells and amyloid protein.
Mutations of the Apolipoprotein E4 (ApoE4) enhance aggregation of β amyloid. ApoE is involved in transport and delivery of cholesterol to cell surface apoE receptors.
Tau protein naturally occurs in the brain and helps brain cells communicate with each other but for a reason that is not yet understoodit can become abnormal and “clump together” leading to death of the brain cells affected.

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10
Q

What is dementia?

A

Decline in cognitive ability, the decline is caused by cell loss. Syndrome rather than a disease, effects elderly people.

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11
Q

The Alzheimer’s brain is associated with loss of memory BECAUSE plaques and tangles build up leading to cell death.

A. Both the assertion and the reason are true statements, and the reason is a correct explanation of the assertion.
B. Both the assertion and the reason are true statements, but the reason is not a correct explanation of the assertion.
C. The assertion is true, but the reason is false.
D. The assertion is false, but the reason is in fact a true statement in its own right.
E. Both the assertion and reason are false.

A

A

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12
Q

What effect does β amyloid plaques have on the brain?

A

B amyloid plaques have on brain?
Plaques block the synapses slowing down electrical impulses not getting same communication lead to memory loss. On neurons stops communication and if it’s in neurons activate kinase which causes tou protein to tangle together.

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13
Q

How is dementia diagnosed?

A

GP will take a medical and family history of the person, and will screen them for mental health and cognitive issues by: asking questions, testing concentration, short term memory, mood and behaviour changes.
MMSE it includes tests of orientation, attention, memory, language and visual-spatial skills.
Early diagnosis is important and there are advantages to starting treatment early.

Clinical criteria

Cognitive testing: Mini-Mental State Examination (MMSE)
21-24 points mild dementia
10-20 points moderate dementia

Lab test dependent on history and clinical circumstances - Lab tests can rule out delirium caused by a infection or an underactive thyroid
The GP may then request blood tests, an MRI or CT scan to examine the structure of the brain, or request a chest X-ray to check for any chest conditions.

Exclusion of depression

Use of imaging:
MRI for early diagnosis and diagnosis of vascular or frontotemporal dementia
SPECT to differentiate subtypes – Lewy body dementia - SPECT- imaging technique uses a tracer to determine blood flow to specific areas–
Initial Assessment (2-3 months)

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14
Q

Advantages of MMSE?

A

This test is Relatively quick and easy to perform and can provide a method of monitoring deterioration over time

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15
Q

Disadvantage of MMSE

A

The disadvantage of this test is it had Poor sensitivity at detected mild/early dementia

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16
Q

What causes short term memory loss in AD?

A

Amyloid plaques

Neurofibrillary tangles

Loss of cholinergic neurones

Loss of cholinergic neurones and acetylcholinesterase (AChE) activity within the cortex in is thought to underlie much of the short-term memory loss seen in AD.

17
Q

What are cholinergic neurotransmission responsible for?

A

cholinergic neurotransmission is responsible for modulating important neural functions. The cholinergic system is involved in critical physiological processes, such as attention, learning, memory, stress response, wakefulness and sleep, and sensory information.

18
Q

What medication is used to manage mild - moderate alzheimers disease?

A

Acetylcholinesterase (AChE) inhibitors:
Cholinergic hypothesis: use drugs that enhance cholinergic transmission.
Donepezil (Arice)
Rivastigmine (Exelon)
Galantamine (Reminyl)

19
Q

What medication is used to manage mild - moderate alzheimers disease who are intolerant or have contradictions with AChE inhibitor?

A

Memantine (Ebixa):
For moderate dementia who are intolerant of or have contraindications to AChE inhibitor
Severe dementia
Non-competitive NMDA receptor antagonist
Differs from other drugs available as it alters glutamate transmission

20
Q

How do AChE inhibitors work?

A

They prolong the action of acetylcholine by inhibiting the action of the enzyme acetylcholinesterase

21
Q

How does Memantine differ from other drugs available?

A

Differs from other drugs available as it alters glutamate transmission Memantine works by blocking the receptors in the brain that glutamate would normally bind to. This decreases the harmful effect of glutamate in the brain and may help improve the symptoms of dementia. Memantine provides a modest cognitive improvement in motor or severe Alzheimer’s disease but does not appear to be neuroprotective

22
Q

Why are the side effects of AChE inhibitors? Why do we get side effects?

A

Side effects:
GI: nausea; vomiting; diarrhoea; gastric ulcers
breathlessness
bradycardia
headache; dizziness; fatigue; hallucinations
anorexia

The side effects are due to an increase in acetylcholine in the periphery and an overstimulation of parasympathetic nerves including:
Parasympathomimetic side effects

23
Q

What is the treatment of Alzheimers disease?

A

To treat people with an established diagnosis of AD who already take an AChE inhibitor:
Combine with memantine if they have moderate or severe disease
MMSE score 9 points of lower = severe dementia
Side effects of memantine include:
Headaches, dizziness, downiness
Constipation
Shortness of breath
Hypertension

24
Q

What is used to manage non-cognitive symptoms?

A

Antidepressants
Anxiolytics
Antipsychotics - should only be prescribed if the patient is at risk of causing themselves or others harm or if they are extremely distressed.
The evidence also showed that people living with dementia who discontinued antipsychotic medication had lower levels of mortality compared with those who continued.

Safe, low-stimulation environment
Use drugs to calm and reduce agitation and aggression without sedation
Use lowest effective dose

25
Q

What are some non - pharmacological interventions in dementia?

A

Advice and involvement of carers
Evaluate environment, privacy, communication, conflicts, staff attention and clinical leadership
Behaviour management:
Cognitive stimulation- different forms
Recreational and physical activities- mobility and conversation. Cognitive stimulation- to actively stimulate and engage people with dementia, providing an optimum learning environment

Aromatherapy for behaviour problems and aggression

26
Q

The patient is presenting confused with memory loss and after the MMSE test the patient has a score of 15.

What would be the drug of choice to reduce the symptoms of dementia?

What is the mode of action of the drug?
Name a side effect of the drug.

A

1) Score of 15 is mild therefore donepezil, going to maintain acetylcholine levels cholinergic neurons are very important for many processes

2) Mode of action of drug inhibits acetylcholinesterase enzyme stops acetylcholine breakdown
Side effect of drug, bradycardia, anorexia, GI upset.

Give an explanation of side effects, how does this drug cause side effect, it will increase acetylcholine in the periphery and that can lead to parasympathetic activation.
prolonged effect of acetylcholine in the CNS and periphery - more cholinergic transmission- more parasympathetic activity is activated which can cause more GI upset, anorexia, bradycardia. Also get anxiety, depression

27
Q

What are some psychosis symptoms?

A

Psychosis symptoms
Symptoms of psychosis include: difficulty concentrating. depressed mood. sleeping too much or not enough. anxiety. suspiciousness. withdrawal from family and friends. delusions. Hallucination

28
Q

What is Glutamate?

A

Glutamate is mostly concentrated in the brain and central nervous system, and functions as an “excitatory” neurotransmitter. Just as it sounds, an excitatory neurotransmitter “excites” or stimulates cells. Glutamate sends signals between nerve cells in the brain and body, and is especially vital for brain development, learning and memory.

29
Q

What is the cause of Alzheimers disease?

A

Causes of Alzheimer’s disease placks and tangles which build up in the brain lead to cell death. Amyloid protein in the brain if its cleaved by the beta secretase enzyme it can turn into beta amyloid. Normal amyloid protein is less sticky than the beta one. They start to aggregate together and form plaques if plaques are outside neurons they build up at synapses, synapses for electrical signalling communication therefore no communication which effects memory neurons are not available to communicate with each other. Cause an immune response which can lead to build of inflammation and inflammatory markers. Congregate at blood vessels weakening the blood vessel walls leading to blood leakage. All of these cause atrophy (shrinkage of brain) and cell death. The beta amyloid plaques can activate kinase inside neurons inside neurons cause tow proteins to become tangled. When they tangle apoptosis (programmed cell death) leads to shrinkage of brain.

If the plaques are inside neurons they activate kinases which cause tou protein to tangle together

30
Q

What causes short term memory loss?

A

Loss of cholinergic neurons which are present in the basal forebrain and hippocampus. Leads to cognitive defect (short term memory loss)

31
Q

What is the peripheral Nervous system?

A

The peripheral nervous system is one of two components that make up the nervous system of bilateral animals, with the other part being the central nervous system. The PNS consists of nerves and ganglia, which lie outside the brain and the spinal cord. The main function of the PNS is to connect the CNS to the limbs and organs, essentially serving as a relay between the brain and spinal cord and the rest of the body. Unlike the CNS, the PNS is not protected by the vertebral column and skull, or by the blood–brain barrier, which leaves it exposed to toxins.

32
Q

What is bradycardia?

A

Hear rate less than 60bpm

33
Q

What is Atrophy?

A

Shrinkage of the brain

34
Q

What is Apoe gene used for?

A

The APOE gene is involved in making a protein that helps carry cholesterol and other types of fat in the bloodstream.