Minor
Hot topics in neurology and psychiatry 2
Week 9
Introduction dementia 2
MRI biomarkers for neurodegeneration 4
PET biomarkers for neurodegeneration 5
CSF biomarkers for neurodegeneration 8
Week 10
Impact of depression 1 8
Impact of depression 2 9
Dementia with Lewy bodies 11
Vascular cognitive impairment and dementia 14
Frontotemporal dementia 19
Parkinson neuropsychiatry 21
Parkinson neurology 27
Week 11
Depression 1 30
Depression 2 32
Depression 3 37
Biomarkers 38
Week 12
OCD 39
rTMS 42
OCD & rTMS 43
Genetics of dementia disorders 48
Medical ethics & catatonia/GHB 51
Week 13
Sleep & sleep disturbances 54
Trauma & TMR 57
Microscopy and pathology 60
Week 14
Big data 65
Machine learning and smartphone applications 66
Trials and disease heterogeneity 68
Anxiety disorders 70
Week 15
Staging in bipolar disorders 71
iPSC 75
Tau spreading 77
What have we learned 78
Articles 79
1
,Lecture 1 introduction dementia
Most common causes:
• Alzheimer’s disease 60-70%
• Lewy body dementia 10-25%
• Frontotemporal dementia 10-15%
• Vascular dementia 10-20%
Dementia de nition
DSM-5 major cognitive disorder
• Evidence of significant cognitive decline from previous level performance in one or more
cognitive domains: complex attention, executive function, learning, language,
visuoconstruction, or social cognition
• Decline objectified by tests or clinical assessment
• Cognitive deficits interfere with independence in every day activities
• Does not occur exclusively in the context of a delirium
• Can not be explained by other mental disorder, such as depression
Dementia is the number one cause of mortality in the Netherlands and the most expensive
disease
Prevalence
260.000 patients
1 out of 3 in people aged 80 years
1 out of 2 in people aged 90 years
Incidence
Life time risk 20%
Dementia is a syndrome of multiple cognitive impairments (including memory) and Alzheimers
disease is one of the causes of dementia
1. Alzheimers disease 60-70%
2. Lewy body dementia 10-25%
3. Frontotemporal lobe dementia 10-15%
4. Vascular dementia 10-20%
1. Alzheimers disease
Genetics:
• Heritability +/- 60%
• 2-5% autosomal dominant mutations in amyloid related genes
• Risk genes:
- Inflammation-related (eg TREM2)
- Lipid metabolism-related (eg APOE)
- Amyloid related (eg ADAM10)
Typical patient
• Age > 75 years
2
fi
,• Short term memory
• Loss of planning, organization
• Insecure, depressive and anxious
• Denial, shame for stigma
Atypical patient
• Age < 65 years
• Visual problems (posterior cortical atrophy)
• Behavioral problems (frontal variant)
• Language problems (logopenic aphasia)
Pathology
In the cortex there are amyloid plaques and tau tangles
Biomarker of Alzheimers disease in atrophy in the brain
and amyloid and tau on PET scan
In CSF beta amyloid is decreased and tau is increased in
Alzheimers patients -> this is due to the fact that tau is in
neurons and neurons keep secreting tau but amyloid clumps
together and forms plaques
CSF normal values
• Amyloid beta 1-42 cut-off: < 550 pg/ml
• Total tau cut-off: > 375 pg/ml, phospho tau cut-off: > 52 pg/ml
The amyloid cascade
5 to 10 years between stages
Normal memory when there are
amyloid plaques -> mild memory
impairment when there is atrophy
and tau tangles -> dementia
Take home message
• Protein aggregation central feature of dementing disorders
• On the basis of symptoms and atrophy patterns is it difficult to know which proteins aggregate
• Clinical criteria provide and probability diagnosis
• Molecular biomarkers are needed for an accurate diagnosis
• New therapeutic strategies are under development
3
, Lecture 2 MRI biomarkers for neurodegeneration
MRI protocol dementia
• 3D T1-weighted images (+ coronal MPR)
- Evaluation of (medial temporal lobe) atrophy
• Axial FLAIR & T2
- Vascular pathology
• Axial T2 * gradient-echo or SWI
- Microbleeds
• DWI
- Creutzfeldt-Jakob (accumulation of proteins in the brain)
Primary gray matter loss
MTA is medial temporal lobe atrophy -> the hippocampus
- The hippocampus is one of the first areas affected in Alzheimer’s
disease -> absence of MTA rules against AD
GCA is global cortical atrophy scale -> to see how much of the sulci
are open
PCA (Koedam score) is parietal cortical atrophy -> to see if the part
between the parietal sulci and the occipital sulci is shrinking
Vascular pathology
WMH (Fazekas scale) -> often with FLAIR to see white
matter lesions
Infarcts
- Thalamic infarct bilaterally -> diagnosis is vascular dementia
Lacunes
Medial microbleeds: vascular origin
Lobar microbleeds: cerebral amyloid
angiopathy (CAA)
4
Hot topics in neurology and psychiatry 2
Week 9
Introduction dementia 2
MRI biomarkers for neurodegeneration 4
PET biomarkers for neurodegeneration 5
CSF biomarkers for neurodegeneration 8
Week 10
Impact of depression 1 8
Impact of depression 2 9
Dementia with Lewy bodies 11
Vascular cognitive impairment and dementia 14
Frontotemporal dementia 19
Parkinson neuropsychiatry 21
Parkinson neurology 27
Week 11
Depression 1 30
Depression 2 32
Depression 3 37
Biomarkers 38
Week 12
OCD 39
rTMS 42
OCD & rTMS 43
Genetics of dementia disorders 48
Medical ethics & catatonia/GHB 51
Week 13
Sleep & sleep disturbances 54
Trauma & TMR 57
Microscopy and pathology 60
Week 14
Big data 65
Machine learning and smartphone applications 66
Trials and disease heterogeneity 68
Anxiety disorders 70
Week 15
Staging in bipolar disorders 71
iPSC 75
Tau spreading 77
What have we learned 78
Articles 79
1
,Lecture 1 introduction dementia
Most common causes:
• Alzheimer’s disease 60-70%
• Lewy body dementia 10-25%
• Frontotemporal dementia 10-15%
• Vascular dementia 10-20%
Dementia de nition
DSM-5 major cognitive disorder
• Evidence of significant cognitive decline from previous level performance in one or more
cognitive domains: complex attention, executive function, learning, language,
visuoconstruction, or social cognition
• Decline objectified by tests or clinical assessment
• Cognitive deficits interfere with independence in every day activities
• Does not occur exclusively in the context of a delirium
• Can not be explained by other mental disorder, such as depression
Dementia is the number one cause of mortality in the Netherlands and the most expensive
disease
Prevalence
260.000 patients
1 out of 3 in people aged 80 years
1 out of 2 in people aged 90 years
Incidence
Life time risk 20%
Dementia is a syndrome of multiple cognitive impairments (including memory) and Alzheimers
disease is one of the causes of dementia
1. Alzheimers disease 60-70%
2. Lewy body dementia 10-25%
3. Frontotemporal lobe dementia 10-15%
4. Vascular dementia 10-20%
1. Alzheimers disease
Genetics:
• Heritability +/- 60%
• 2-5% autosomal dominant mutations in amyloid related genes
• Risk genes:
- Inflammation-related (eg TREM2)
- Lipid metabolism-related (eg APOE)
- Amyloid related (eg ADAM10)
Typical patient
• Age > 75 years
2
fi
,• Short term memory
• Loss of planning, organization
• Insecure, depressive and anxious
• Denial, shame for stigma
Atypical patient
• Age < 65 years
• Visual problems (posterior cortical atrophy)
• Behavioral problems (frontal variant)
• Language problems (logopenic aphasia)
Pathology
In the cortex there are amyloid plaques and tau tangles
Biomarker of Alzheimers disease in atrophy in the brain
and amyloid and tau on PET scan
In CSF beta amyloid is decreased and tau is increased in
Alzheimers patients -> this is due to the fact that tau is in
neurons and neurons keep secreting tau but amyloid clumps
together and forms plaques
CSF normal values
• Amyloid beta 1-42 cut-off: < 550 pg/ml
• Total tau cut-off: > 375 pg/ml, phospho tau cut-off: > 52 pg/ml
The amyloid cascade
5 to 10 years between stages
Normal memory when there are
amyloid plaques -> mild memory
impairment when there is atrophy
and tau tangles -> dementia
Take home message
• Protein aggregation central feature of dementing disorders
• On the basis of symptoms and atrophy patterns is it difficult to know which proteins aggregate
• Clinical criteria provide and probability diagnosis
• Molecular biomarkers are needed for an accurate diagnosis
• New therapeutic strategies are under development
3
, Lecture 2 MRI biomarkers for neurodegeneration
MRI protocol dementia
• 3D T1-weighted images (+ coronal MPR)
- Evaluation of (medial temporal lobe) atrophy
• Axial FLAIR & T2
- Vascular pathology
• Axial T2 * gradient-echo or SWI
- Microbleeds
• DWI
- Creutzfeldt-Jakob (accumulation of proteins in the brain)
Primary gray matter loss
MTA is medial temporal lobe atrophy -> the hippocampus
- The hippocampus is one of the first areas affected in Alzheimer’s
disease -> absence of MTA rules against AD
GCA is global cortical atrophy scale -> to see how much of the sulci
are open
PCA (Koedam score) is parietal cortical atrophy -> to see if the part
between the parietal sulci and the occipital sulci is shrinking
Vascular pathology
WMH (Fazekas scale) -> often with FLAIR to see white
matter lesions
Infarcts
- Thalamic infarct bilaterally -> diagnosis is vascular dementia
Lacunes
Medial microbleeds: vascular origin
Lobar microbleeds: cerebral amyloid
angiopathy (CAA)
4
