Chapter 19: Alzheimer disease

Question 1

DSM criteria for dementia

Answer 1

1. Significant cognitive decline in one or more cognitive domains
2. Concerns about the cognitive decline
3. Substantial impairment in cognitive performance
4. Interference with independence in daily activities
5. Not due to a delirium or other disorders

Question 2

DSM criteria for Alzheimers (overlapping term)

Answer 2

1. Insidious onset and gradually progressive course
2. Cognitive impairment in at least 2 domains
3. No evidence for another disease that could explain the cognitive symptoms

Question 3

Evidence for Dementia, Alzheimers and cognitive decline

Answer 3

• Information form informants
• Cognitive testing
• Neuroimaging
• Cerebrospinal fluid analysis
• Genetic mutation

Question 4

DSM criteria for mild cognitive impairment (MCI)

Answer 4

1. Modest cognitive decline
2. Concerns about mild decline compared with previous level of functioning.
3. Modest impairment in cognitive performance documented by objective cognitive assessment.
4. No over interference with daily independent activities (but they may require more time and effort)
5. Not caused by a delirium or other mental disorders

Difference between MCI and dementia: people with MCI are still able to function independently in daily life.

Question 5

MCI as a form of Alzheimers

Answer 5

1. A cognitive profile that is typical for early Alzheimers disease
2. A positive biomarker reflecting Alzheimers disease

(Not everybody with MCI is in the prodromal stage of Alzheimers, some people develop other forms of dementia and some never develop dementia.)

Question 6

Neuropathology and prevalence

Answer 6

Woman have a higher chance (1/3) of developing dementia than men (1/7). After a diagnosis people usually survive for 7-10 years.

Question 7

Biology of Alzheimers

Answer 7

Abnormal accumulation and deposition of extracullular plaques of the amyloid-beta protein and intracellular tangles of the protein tau, which lead to degeneration of nerve cells and ultimately brain atrophy.

Question 8

How to find Alzheimers in the brain

Answer 8

It can only truly be confirmed with an autopsy-based neurology examination. But can also be established with:
- CT scans
- MRI
- molecular imaging
- cerebrospinal fluid

Question 9

Amyloid cascade hypothesis

Answer 9

The cause of Alzheimers is the abnormal accumulation / overproduction of the amyloid-beta protein. People with mutations in the Precursur Protein gene show an overload in amyloid-beta and eventually develop Alzheimers, because the overload causes an increase in the tau protein, which leads to synapse loss –> neuronal death –> cognitive decline –> dementia.

(But 1/3 of older people have an overload of the amyloid-beta protein, so what causes dementia is unsure).

Question 10

Vascular hypotheses

Answer 10

Vascular risk factors (obesity etc.) lead to reduced blood flow and oxygen deficiency in the brain. This leads to stiffening of the arterial walls, but also to a metabolic reaction that causes an overproduction of the amyloid-beta protein and neurodegeneration.

Question 11

Consensus about the 2 hypotheses of Alzheimer development

Answer 11

A lot of scientists agree that both hypothesis complement each other in the development of Alzheimers disease.

Question 12

Familiar Alzheimers disease

Answer 12

The genetic mutation in the amyloid precursor protein gene, the presenilin-2 1 or presenolin-2 gene almost certainly leads to the development of Alzheimer’s disease. This is something passed down to other generations, but not many people have this mutation.

Question 13

Clinical Dementia Rating scale (CDR)

Answer 13

An instrument that measures cognitive and functional decline on 6 domains:
1. Memory
2. Orientation
3. Problem solving ability
4. Social activities
5. Home and hobbies
6. Personal care

Question 14

Amnestic MCI pre-dementia stage (CDR 0.5)

Answer 14

Mostly episodic memory deficits (antrograde amnesia) due to neuronal loss of the hippocampus. Performing certain complex activities can be more challenging.

Question 15

Mild dementia (CDR 1)

Answer 15

Problems with language production, orientation in time and place and planning and performing activities. Deficit in mental flexibility and divided attention. Problems in performing higher order activities of daily living (driving, cooking).

Question 16

Moderate dimentia (CDR 2)

Answer 16

More extensive cognitive impairments occur and the episodic memory deficits start to show in more distant path. The more basic activities of daily life become more difficult.

Question 17

Severe dimentia (CDR 3)

Answer 17

Severe cognitive loss and being completely dependent on the environment. Patients are often confused, have difficulty communicating and show deficits in basis moto functions (like chewing).

Question 18

Brain changes in Alzheimers

Answer 18

Typical pattern of grey matter volume loss. This starts in the medio-temporal lobe and goes to the posterior and frontal cortical regions. It eventually becomes global cortical atrophy.

(Measured with the MTA: medio-temporal atrophy scale)

Question 19

Atypical variants of Alzheimers disease

Answer 19

1. Posterior cortical atrophy (PCA): visual agnosia, but the memory remains intact.
2. Legppenis variant primary progressive aphasia (lvPPA): language and communication deficits.
3. The behavioral/dysexecutive variant: behavioral changes, impairment in executive functioning and in social cognition.
4. Early-onset Alzheimers disease: starts early in life and has a rapid disease progression.

Question 20

Neuropsychiatric symptoms of Alzheimers

Answer 20

• Agitation
• Depression
• Anxiety
• Apathy
• Delusions
• Hallucinations
• Sleep impairment

Question 21

Treatment of Alzheimers

Answer 21

Cholinestrase inhibitors are the standard form of therapy for the treatment of Alzheimers. These drugs decrease te breakdown of acetylcholine, which results in more acetylcholine in the synaptic cleft and more communication between nerve cells. This can stabalize the symptoms.