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The importance of the brain diseases inelderly population in Europe:
Presentation of the Lancet NeurologyDementia Commission Paper on Alzheimer’sDisease
Bengt Winblad and Angel Cedazo-MinguezKarolinska Institutet. Center for Alzheimer ResearchHuddinge, Sweden
BRAIN AWARENESS WEEKEuropean ParliamentMarch 15, 2016
2016-03-16Bengt Winblad and Ángel Cedazo-Mínguez 2
- Health economics in AD- Epidemiology- Prevention
- Genetic risk- Disease Biology- Diagnosis and Biomarkers
- Pharmacological treatment- Non-pharmacologicaltreatment
- Formal and informal care- Ethics
Acknowledgements
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Maria Ankarcrona Angel Cedazo-Minguez Susanne Frykman Miia Kivipelto Janne Johansson Francesca Mangialasche Patricia Mecocci Lars Tjernberg Gunilla Johansson
Extracted from the ADI World Alzheimer Report, August 2015
Bengt Winblad and Ángel Cedazo-Mínguez
Epidemiology
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Prevention
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RISKS FACTORS PROTECTIVE FACTORS
• Cardiovascular diseases• Diabetes mellitus and pre-diabetes• Midlife hypertension• Midlife overweight and obesity• Midlife high serum cholesterol
• Saturated fats• Hyperhomocysteinaemia• Deficiencies in vitamins
• Sedentary lifestyle• Depression• Traumatic brain injury
• Antihypertensive drugs• Statins• Hormone replacement therapy• Non-steroidal anti-inflammatory drugs
• Mediterranean diet• Polyunsaturated fatty acids• Vitamin B6, vitamin B12, and folate.Antioxidant
• Physical activity• High education and socioeconomicstatus• High work complexity• Rich social network and socialengagement
6
FINGER MAPT Pre-DIVA
Multidomainintervention
Vascular care, Diet,Exercise, Cognitivetraining
Diet, Exercise,Cognitive training,Omega-3
Nurse-lead intensivevascular care
Age, yrs 60-75 70 - 70-78
Sample size 1200 1680 3535
Inclusion criteria Dementia Risk Score>6 and mild degree ofcognitive impairment
Frail elderly people(subj memory complaint,slow walking speed,limitation in IADL)
All elderly within GPpractices
Study design Multi-center,randomized, single-blind, parallel group
Multi-center,randomized, controlledtrial
Multi-cite, open,cluster-randomizedparallel group
Intervention period 2 yrs 3 yrs 6 yrs
Primary outcome Neuropsych testbattery, Trail Making,Stroop, Dementia
Change in cognitivefunction (Grober andBuschke memory test)
Dementia, Disability
Study completion 2014(Lancet 2015, Ngandu et al)
2015 20152016-03-16Bengt Winblad and Ángel Cedazo-Mínguez
Genetics of AD.Deterministic Mutations or Individual Risk.
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CholesterolmetabolismCholesterolmetabolism
Membrane/vesicle
recycling
Membrane/vesicle
recycling
InflammationInflammation
Glucosemetabolism
Glucosemetabolism
Aβ accumulationAβ accumulation
Uncovered mechanisms
From Genetics to Precision Medicine
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Disease Pathology
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Abeta plaquesNFTs
Disease Biology
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AD Diagnosis Marching Leftward
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Standarddiagnosis
Duboisresearch criteria:“early AD”
ModifiedDubois criteria:“earlier AD”
PresymptomaticAD
No symptoms
Very mildsymptoms+ amyloidbiomarker
Episodicmemoryimpairment+ any
biomarker
Dementia
Onsetof ADpath
Need to define subtypes:
Individualization for Personalized Medicine
Therapy in AD: The first hundred yearsand looking forward……….
Thecholinergichypothesis
1906 1910 200419821974 1997
MemantineNMDA
UncompetitiveReceptor
Antagonist
2010 2020
Acetylcholinesteraseinhibitors
First Disease Modifying Rx?Amyloid and tau lowering?
Next generation targets?
March 12, 2016 12Bengt Winblad
Ongoing clinical trials in Alzheimer disease
β amyloidTau
CholinergicsOthers
Mangialasche et al, modified 2013 from Lancet Neurology, 2010
Aß production
Aß clearanceAß aggregation
CAD106
Research - the way forward to treatment
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Formal and Informal Care for Patients
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• The care of patients with dementia does notfit easily into typical health-care deliverysystems
• Worldwide, the burden of care often fallson family members
• The long-term care of people with dementiabegins at home with a collaborativepartnership between informal and formalcaregivers.
• Institutional care for patients with severedementia is demanding and costly
• Effective assisted care and nursing homeswith skilled staff will become increasinglyimportant
Ethical Considerations
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Doing good not causing harm,respecting patient autonomyand striving for justice for all
End-of-life care in dementia canbe improved by advance careplanning (as a routine part ofprimary care) to improvequality of life
Benefits and disadvantages ofearly diagnostics (risk for falsepositive) should be assessedfrom both the biomedical andthe patients’ perspectives
Increased internationalcollaboration in research willdemand harmonised ethicalstandards on national andinternational (EU) level.
Assessment of competency toconsent cannot be based ondiagnosis or staging, but onindividual assessment tomaximise patients’ autonomy
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