5) Dementia

Question 1

What is the main risk factor for neurodegenerative diseases causing dementia?

Answer 1

Old age

Question 2

To what extent (%) can lifestyle modifications reduce the risk of dementia? Which lifestyle factor has the greatest impact?

Answer 2

40%
Greatest impact = early education

Other preventative factors:
* stop smoking
* social connections
* address health conditions (depression, hypertension, diabetes/obesity)

Question 3

What is the most common dementia-causing neurodegenerative disease?

Answer 3

Alzheimers Disease
(ca. 75% of all dementia = either AD or a mix of AD + vascular dementia)

Question 4

What is the difference between subjective cognitive decline (SCD) and mild cognitive impairment (MCI)?

Answer 4

Subjective Cognitive Decline (SCD) occurs when individuals perceive cognitive impairments, such as memory or thinking difficulties, that aren’t yet detectable through standardized tests. SCD typically precedes Mild Cognitive Impairment (MCI), which involves measurable cognitive decline beyond normal aging and carries a higher risk of progressing to dementia.

Question 5

What does the amyloid hypothesis of AD explain?

Answer 5

It explains how Alzheimers leads to neurodegeneration.

1. Amyloid-Beta (Aβ) accumulates in excess.
2. This excess of Aβ aggregates into soluble oligomers (which are neurotoxic) + amyloid fibrils (which form plaques).
3. Soluble oligomers trigger neuroinflammation + increased tau.
4. This causes neurodegeneration.

Question 6

What is the most accurate tool for diagnosing AD? What other methods are there?

Answer 6

Biomarkers can diagnose Alzheimer’s with high accuracy, even in the preclinical stage. (e.g. measuring tau in blood, or measuring amyloid + tau in CSF — cerebrospinal fluid)

Other methods include:
* psychometric tests (e.g. clock drawing)
* imaging (e.g. scanning for neurodegeneration)

The “AT(N) System” combines these, diagnosing AD based on a person’s combination of amyloid pathology (A), tau pathology (T), and neurodegeneration (N).

Question 7

To what extent does genetics affect a person’s risk of developing Alzheimer’s?

Answer 7

Genetics is highly important to individual risk, but polygenic risk scores have not been established yet to help calculate this risk more precisely.

While there is a monogenic variant of Alzheimer’s disease (“familial AD”) that is caused by mutations in specific genes, this form is rare. The vast majority of AD cases are polygenic (“sporadic AD”) and result from a complex interplay of genetics + other factors (environment, lifestyle).

Question 8

Treatments such as aducanumab have recently proven to slow the progression of Alzheimer’s. What part of AD pathology do these treatments target?

Answer 8

Anti-amyloid treatments like aducanumab target beta-amyloid (Aβ) plaques by using antibodies that bind to the plaques, facilitating their removal.

Early administration is critical — amyloid reduction is most effective before tau pathology and neurodegeneration have significantly progressed. (There is a “point of no return” beyond which tau pathology no longer needs amyloid to progress.)

Question 9

The biological stages of AD describe the distribution and severity of tau pathology, using Tau-PET imaging.

What are the stages of Alzheimer’s spread in the brain?

Answer 9

1. Transentorhinal stage
2. Limbic stage
3. Neocortical stage

Question 10

The clinical stages of AD describe how cognitive function progressively declines.

What are these clinical stages?

Answer 10

1) No cognitive decline / preclinical
2) Subjective cognitive decline (SCD)
3) Mild cognitive impairment (MCI)
4) Mild to severe dementia