10 - AD

Question 1

What is dementia?

Answer 1

Dementia is an umbrella term for many other conditions of the brain
→ there is not one specific disease, but a mix of symptoms
→ Significant loss of intellectual abilities such as memory capacity, severe enough to interfere with social or occupational functioning

Question 2

What are some of the criteria for the diagnosis of dementia?

Answer 2

→ Impairment of attention, orientation, memory, judgment, language, motor and spatial skills, and function
→ By definition, dementia is not due to major depression or schizophrenia
→ these declines interfere with everyday activities
→ wandering is a common symptom of dementia, which is very problematic if they live alone; they’ll wander around the house and be unaware of where they are and how to get “back home” even if they are already home

Question 3

True or false: Dementia is sudden, meaning the symptoms all strike at once at a certain severity level.

Answer 3

False: Dementia is progressive, meaning the symptoms will continue to get worse as more brain cells lose connection with each other and eventually die

Question 4

True or false: Dementia is not a normal part of aging.

Answer 4

True

Question 5

Someone can have brain changes that resemble…

Answer 5

More than one type of dementia
→ ½ of the people with brain changes from AD, at autopsy could also be categorized as having a secondary dementia, like vascular dementia; this is mixed dementia
→ doctor will look at your report and not be sure where to categorize you, because you have more than one type

Question 6

Dementia-like symptoms can be observed without ___ ___ ___.

Answer 6

Progressive brain changes
→ there are some treatable conditions that produce symptoms similar to dementia (p.ex dementia)
→ doctors will typically do multiple tests to determine the underlying issues to verify what the problem is exactly, because sometimes the problem can be treated

Question 7

With Alzheimers, it is difficult to predict… (3)

Answer 7

• Symptoms; the order they will appear; or its progression rate
  → but one of the first things that will be affected is cognition
  → Symptoms may be minimal in beginning with them slowly progressing

Question 8

What are some areas affected by AD? (4)

Answer 8

1) Cognition; ability to understand, think, communicate, remember
→ confusion, memory loss (first its recent memories, then long-term memories)
→ this is a deciding factor in differentiating dementia from depression
2) Emotions and mood
→ may lose interest in things that you previously enjoyed
→ become less expressive, withdrawn or aggressive
3) Behaviour
→ react in ways that you normally didn’t before; seeming out of character
→ p.ex: frequent outburst when in the past you were more calm; may seem restless; repeating the same words or actions
4) Physical abilities; coordination, mobility
→ p.ex: eating, bathing, getting dressed

Question 9

What is AD characterized by?

Answer 9

• Characterized by plaque and tangle build-up in the brain
  → plaque: deposits of protein (beta-amyloid)
  → beta-amyloid buildup and prevents the transfer of information in the brain, causing cells to die

Question 10

Name the AD stages.

Answer 10

1) Early stage
2) Middle stage
3) Late stage

Question 11

Elaborate on the first stage of AD; time in stage and characteristics

Answer 11

Early stage
- time in stage: starts 20 years before diagnosis (typically 1 - 9 years)
- changes in the brain occur long before symptoms start to show
→ marked by memory loss
→ begins in the hippocampus and the intarinal cortex
→ both of which are crucial for memory formation and navigation
→ not yet near the frontal cortex, but memory is the first to go
- disorientation to time and space
- poor judgment
- personality changes

Question 12

Elaborate on the second stage of AD; time in stage and characteristics

Answer 12

Middle stage
- Time in stage: 2 - 10 years
- progressed beyond the hippocampus and intarinal cortex
→ occipital lobe, touching on the parietal lobe
- Increased memory problems
- Difficulties with speech
- restlessness
- irritability and loss of impulse control

Question 13

Elaborate on the third stage of AD; time in stage and characteristics

Answer 13

Late stage
- time in stage: ranges from 1 - 5 years
- once in the late stages, the onset is much quicker
- Incontinence of urine and feces
- Loss of motor skills
- Decreased appetite
- Have great difficulty with speech and language
- May not recognize family or even oneself in a mirror
- Loses most (or all) of self care abilities
- Decreased ability to fight off infection

Question 14

Explain the case of the first Alzheimers patient.

Answer 14

Auguste D., age 51
- First person to be diagnosed with AD; case was studied by Alzheimer
→ trouble sleeping, drag sheets across the house, scream for hours through the night; rapid mood changes from anxiety to mistrust; couldn’t write her name, would start but couldn’t finish it
→ with time, every symptom increased (progressed confusion, aggression, etc)
- Problems with:
→ Memory
→ Unfounded suspicions that her husband was unfaithful
→ Difficulty speaking and understanding language
- Rapid decline
- Died of infections from bedsores and pneumonia

Question 15

What did Alzheimer see on autopsy?

Answer 15

• Dramatic atrophy, especially of cerebral cortex
  → memory, reasoning, language
• Widespread fatty deposits in small blood vessels throughout the brain
  → this vascular abnormality suggested compromised blood flow
  → reduced amount of central nutrients and oxygen going through the brain
• Dead and dying brain cells
  → cells were responsible for transferring information between neurons and hemispheres
• Abnormal protein deposits in and around cells (illustration)
  → tangles: twisted fibers around the neuron themselves

Question 16

What are the brain changes seen in AD?

Answer 16

• Atrophy
• Senile plaques: buildup of beta-amyloid may interfere with neuronal communication
  → dense clusters
  → disrupt communication between the brain cells
  → everyone has beta-amyloid in their brains, but those with AD have an excess of it; we have to consider the amount of amyloid and other factors on top of that (atrophy and tangles) to consider diagnosis
• Neurofibrillary tangles: threads of tau protein become twisted
  → tangles effectively block connections and transportation between cells that is essentially needed to sustain cell health
  → biomarkers change from normal, to maximally abnormal as a function of the disease stage
  → the bottom is NOT 0, we all have these factors
  → researchers consider demographic factors, age, genetics, socioeconomic factors, education, etc. being indicators of cognitive reserve

Question 17

Cerebrovascular disease is observed in over __% of people with AD.

Answer 17

70

Question 18

How can cerebrovascular disease help to look at AD?

Answer 18

• In addition to neurodegeneration, we can also use an MRI to look at changes between normal aging in AD by examining cerebrovascular diseases where there is reduced blood flow and damage to small vessels in the brain, which can impact the health of the brain tissue
• These vascular changes are often seen as white matter hyperintensities, or small infarcts on MRI
• Often measured using white matter hyperintensities (WMHs)
• Cerebrovascular disease very important when examining changes in cognition, age and cognitive decline
  → most commonly measured with cerebrovascular lesions (WMH) as they’re observed in both aging and dementia
  → more likely to occur in people with high blood pressure, people who smoke, etc.

Question 19

True or false: Similar to AD-specific pathology, cerebrovascular pathology is known to occur before declines in cognition

Answer 19

True

Question 20

___ are the fourth component to look at with an MRI for AD

Answer 20

Infarcts

Question 21

What are the risk factors for AD?

Answer 21

• Age
• Genetics/Heredity
• Mild cognitive impairment: objective memory impairment but no dementia
• Health status: high blood pressure, high cholesterol, poorly controlled diabetes
• Education is a protective factor
• for most of these risk factors, the mediating pathways are unknown, so we don’t know which one of these amyloid and tau are acting on
  → we just know that they’re the risk factors and they’re interacting with them

Question 22

What have we found about prevention of AD?

Answer 22

• Most studies have focused on modifying vascular and lifestyle risk factors
• AD is multifactorial therefore multicomponent interventions that target several risk factors simultaneously may be needed for optimal preventative effects
• FINGER Study (Ngandu et al., 2015):
  → 2 year intervention program which included: nutritional guidance, physical exercise, cognitive training, social stimulation, and management of vascular and metabolic risk factors
  → Improved/maintained cognitive functioning in older adults at risk of dementia
  → ⅓ of AD cases are attributable to 7 modifiable risk factors
  → factors: (1) low education; (2) midlife hypertension; (3) midlife obesity; (4) physical inactivity; (5) diabetes; (6) smoking; (7) depression
  → these factors are preventative

Question 23

According to the FINGER study, what are the 7 modifiable risk factors of AD?

Answer 23

(1) low education; (2) midlife hypertension; (3) midlife obesity; (4) physical inactivity; (5) diabetes; (6) smoking; (7) depression

Question 24

True or false: Plaques form inside the cells and tangles form outside the cells

Answer 24

False: Plaques are outside, tangles are inside

Question 25

Explain how the hippocampus is related to AD and what this means for memories

Answer 25

• First area of the brain affected
• Has a vital role in memory formation
• They may struggle to remember what they have just done or said
• More recent memories are usually lost first
  → older memories depend less on the hippocampus, but rather other parts of the brain hold those memories, this is why older memories stay longer

Question 26

True or false: Someone may recall emotions about someone or something even if they cannot recall why they have those emotions

Answer 26

True