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

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- 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

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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)

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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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