clinical research in alzheimer’s disease: current status ... · pieter jelle visser, md, phd...
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![Page 1: Clinical research in Alzheimer’s disease: Current status ... · Pieter Jelle Visser, MD, PhD Department of Psychiatry, University of Maastricht. Maastricht . Alzheimer center, Department](https://reader034.vdocuments.mx/reader034/viewer/2022050122/5f51f4740a9e1f4b327a1726/html5/thumbnails/1.jpg)
Clinical research in Alzheimer’s disease:
Current status and future perspectives
Pieter Jelle Visser, MD, PhD
Department of Psychiatry, University of MaastrichtMaastricht
Alzheimer center, Department of Neurology, VUMC, AmsterdamThe Netherlands
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Auguste D. Case described by Alois Alzheimer in 1908
Tangles
Plaques
Atrophy
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Patient from the Dementia Research Centre, London. Courtesy slidPatient from the Dementia Research Centre, London. Courtesy slide Nick Fox.e Nick Fox.
1 year before 1 year before diagnosisdiagnosis
2 years after 2 years after diagnosisdiagnosis
5 years after 5 years after diagnosisdiagnosis
William William UtermohlenUtermohlen –– self portraitsself portraits
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Alzheimer’s disease in Europe
1 out of 5 gets Alzheimer’s disease
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Alzheimer’s disease in Europe
Number of cases Societal costs (€)2009 6.000.000 72.000.000.000
1 out of 5 gets Alzheimer’s disease
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Alzheimer’s disease in Europe
Number of cases Societal costs (€)2009 6.000.000 72.000.000.000
2039 12.000.000 144.000.000.000
1 out of 5 gets Alzheimer’s disease
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The amyloid cascade hypothesis
Abnormal beta amyloid processing
Neuronal dysfunction/neuronal death
Cognitive impairment
Impaired activities daily living
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Clinical research
• Diagnosis• Prognosis• Therapy
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Diagnosis
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Clinical criteria Alzheimer’s disease
McKhann 1984:– Demented
• Memory impairment• Impairment in other cognitive domain• Both interfere with activities daily living
– No other disorder causing symptoms
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Atrophy on MRI
Alzheimer Control
Markers in cerebrospinal fluid
0
100
200
300
400
500
600
700
800
Beta amyloid Tau
AlzheimerControl
Plaques on PET scan
Control
Alzheimer
Hypometabolism on PET scan
Control
Alzheimer
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0%
25%
50%
75%
100%
Controls Subjective complaints Memory impairment
32%
52%
78%
Alzheimer pathology in non- demented subjects
Results from EC funded DESCRIPA study
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Prognosis
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Course of AD
DeathDementiaComplaintsDisease
onset
10 years5-10 years10-20 years
Asymptomatic
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Acceleration of decline
Jack et al 2008
Change in cognition over time
Time AD diagnosis
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% c
hang
e in
bra
in v
olum
e
time (years)0 2 4 6
-15
-10
-5
0
Fox et al., UCL London
Heterogeneity in progression
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Therapy
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Alzheimer treatment
• Current:– Symptomatic
• Future:– Treatment underlying disease process
• Prevention beta amyloid production• Prevention aggregation of beta amyloid• Stimulation removal beta amyloid
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Vaccinination against beta amyloid
Bombois et al 2007; Van Broeck et al. 2007
Untreated patient Vaccinated patient
Plaques
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Future perspectives
• Diagnosis– Diagnosis Alzheimer’s disease in non-demented subjects– Standardization tests
• Prognosis– Predictors of decline
• Therapy– Testing new therapies (set-up trial networks)– Development outcome measures
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Funding
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National funding
• Large scale programmes for dementia research:– France– Germany– United Kingdom– Sweden– Ireland– The Netherlands
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European funding
• Current funding fragmented– Framework programme
• No specific Alzheimer programme– ERA-Net– Innovative Medicine Initiative
⇒European Alzheimer programme needed
⇒Joint Programming?
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