Alzheimer’s and dementia from clinical
perspective (Prof. Dr. Engelborghs)
1. Epidemiology
AD is an incurable disease but treatable
Since 2023: dementia = 1st cause of death in Belgium
develops dementia
As age is main risk factor and given ageing population, number of people
with dementia is expected to have doubled in 2070
Dementia = umbrella term
o Symptoms
Memory loss
Change of personality
Less aware of danger/lack of insight
Special impairment/lack of orientation in space and time
o It doesn’t say anything about the cause of the disease
o People with dementia have symptoms in 3 pilars
Cognitive symptoms
Change of personality and behavior
Functional deficits: activities of daily living that can be very
basics are know very difficult
o Which disease causes dementia
Most common cause is AD: 60-75%
Vascular dementia: 20-30%
Dementia with Lewy bodies: 10-25%
Frontotemporal lobar degeneration (FTLD): 10-15% really
causes memory loss
The way that dementia represents is depended on the disease
2. Alzheimer’s disease (AD): the amyloid cascade
hypothesis
Not everyone with AD has dementia can’t diagnose dementia in the
stage of mild cognitive impairment
2.1. Amyloid cascade hypothesis
(1) First thing that happens in the brain is the formation of amyloid
plaques
o Amyloid is being formed based on the precursor protein formation
of amyloid of 42 amino acids insoluble clitting together in the
brain and forming plaques
o This is the first thing that happens in the brain for AD
(2) Second thing that happens
o Protein tau: basis of cytoskelet of neurons
o This protein gets phosphorylated leading to the effect that tau
protein loses its functions aggregates form deposits within the
neurons
Deposits are neurofibrillary tangles
1
, (3) Neurons start degenerating connect to each other
o Create brain network
(4) Number of synaps per neuron are decreasing brain network is
defected
(5) Loss of neurons themselves
o Brain shrinks
o Coronal section on the level of the temporal lobe
Hippocampus is important to transfer new information to your
permanent memory
Atrophy is maximal in hippocampus
Recent memory problems are the most common results from
this
If you’re able to wash these plaques away you can ‘cure’ AD
1 2
3
4
5
2.2. Sequence of spread of neurofibrillary tangles
Inner part of the right hemisphere
Red color shows you the spread of the neurofibrillary tangles
o The darker the denser the neurofibrillary tangles
Huge damage in the brain but not the whole brain is affected
o Some parts are more affected than other
o Darker spots so the disease started there
o Selectively defects brain region
Early dementia stage and damage is huge started very early
Mild cognitive impairment
People that have memory problems but no other symptoms don’t have
dementia because they don’t have symptoms in the other pilars
First symptoms of AD are seen here
10-20 years before the first symptoms
2
,3
, 2.3. The Alzheimer continuum
Shows that you spend the majority of the disease in the preclinical stage
o Building the pathology without showing symptoms
Mild cognitive impairment (MCI) is the first stage where you see symptoms
Only people with MCI and mild dementia can be treated
3. Diagnosing Alzheimer’s disease
3.1. (Biomarker) changes throughout the AD continuum
How do we diagnose AD? biomarkers of the disease are used
Colored curves are different markers they used in clinical practice
Move from normal to abnormal throughout the different stages of the
disease
o Preclinical
o MCI
o Dementia
Brown curve: activities of daily living (ADL)
o MCI have no functional deficits
Purple is neuropsychological examination
o Psychologist trained to diagnose deficits
o Testing different cognitive function through standardized cognitive
tests
Use battery of test to cover all cognitive domains
Someone of the age of 70 with this educational level should
score this
Score lower = deficits for this
Cognitive functions are normal for age and … = no problem
4
perspective (Prof. Dr. Engelborghs)
1. Epidemiology
AD is an incurable disease but treatable
Since 2023: dementia = 1st cause of death in Belgium
develops dementia
As age is main risk factor and given ageing population, number of people
with dementia is expected to have doubled in 2070
Dementia = umbrella term
o Symptoms
Memory loss
Change of personality
Less aware of danger/lack of insight
Special impairment/lack of orientation in space and time
o It doesn’t say anything about the cause of the disease
o People with dementia have symptoms in 3 pilars
Cognitive symptoms
Change of personality and behavior
Functional deficits: activities of daily living that can be very
basics are know very difficult
o Which disease causes dementia
Most common cause is AD: 60-75%
Vascular dementia: 20-30%
Dementia with Lewy bodies: 10-25%
Frontotemporal lobar degeneration (FTLD): 10-15% really
causes memory loss
The way that dementia represents is depended on the disease
2. Alzheimer’s disease (AD): the amyloid cascade
hypothesis
Not everyone with AD has dementia can’t diagnose dementia in the
stage of mild cognitive impairment
2.1. Amyloid cascade hypothesis
(1) First thing that happens in the brain is the formation of amyloid
plaques
o Amyloid is being formed based on the precursor protein formation
of amyloid of 42 amino acids insoluble clitting together in the
brain and forming plaques
o This is the first thing that happens in the brain for AD
(2) Second thing that happens
o Protein tau: basis of cytoskelet of neurons
o This protein gets phosphorylated leading to the effect that tau
protein loses its functions aggregates form deposits within the
neurons
Deposits are neurofibrillary tangles
1
, (3) Neurons start degenerating connect to each other
o Create brain network
(4) Number of synaps per neuron are decreasing brain network is
defected
(5) Loss of neurons themselves
o Brain shrinks
o Coronal section on the level of the temporal lobe
Hippocampus is important to transfer new information to your
permanent memory
Atrophy is maximal in hippocampus
Recent memory problems are the most common results from
this
If you’re able to wash these plaques away you can ‘cure’ AD
1 2
3
4
5
2.2. Sequence of spread of neurofibrillary tangles
Inner part of the right hemisphere
Red color shows you the spread of the neurofibrillary tangles
o The darker the denser the neurofibrillary tangles
Huge damage in the brain but not the whole brain is affected
o Some parts are more affected than other
o Darker spots so the disease started there
o Selectively defects brain region
Early dementia stage and damage is huge started very early
Mild cognitive impairment
People that have memory problems but no other symptoms don’t have
dementia because they don’t have symptoms in the other pilars
First symptoms of AD are seen here
10-20 years before the first symptoms
2
,3
, 2.3. The Alzheimer continuum
Shows that you spend the majority of the disease in the preclinical stage
o Building the pathology without showing symptoms
Mild cognitive impairment (MCI) is the first stage where you see symptoms
Only people with MCI and mild dementia can be treated
3. Diagnosing Alzheimer’s disease
3.1. (Biomarker) changes throughout the AD continuum
How do we diagnose AD? biomarkers of the disease are used
Colored curves are different markers they used in clinical practice
Move from normal to abnormal throughout the different stages of the
disease
o Preclinical
o MCI
o Dementia
Brown curve: activities of daily living (ADL)
o MCI have no functional deficits
Purple is neuropsychological examination
o Psychologist trained to diagnose deficits
o Testing different cognitive function through standardized cognitive
tests
Use battery of test to cover all cognitive domains
Someone of the age of 70 with this educational level should
score this
Score lower = deficits for this
Cognitive functions are normal for age and … = no problem
4
