Prevention of Dementia by Intensive Vascular Care - preDIVA-trial Edo Richard Department of Neurology Academic Medical Centre University of Amsterdam The Netherlands Academic Medical Centre No conflict of interest Alzheimer’s Disease International 2012 - London

Vascular factors and dementia hypertension DM adiposity lipids smoking physical exercise Epidemiology Radiology Pathology + + Vascular lesions plaque tangle Clinical trials hypertension

EVA-trial Evaluation of Vascular Care in Alzheimer Alzheimer with vascular lesions N=130 mean age 76 y no effect on: cognition disability mortality standard care vascular care 3-monthly visits multicomponent intervention vascular risk factors 2-year follow-up p=0.03 Richard et al. J Am Geriatr Soc 2009;57:797-805 Richard et al. Stroke 2010;41:554-556

Dementia prevention? Prevention of Dementia by Intensive Vascular Care Start in 2006

Open, cluster-randomised trial 116 GP practices 3534 subjects 70-78 Y Dementia?  excluded Cluster randomisation Standard care Vascular care (nurse led) Component intervention BP lifestyle, medication smoking quit, counseling exercise advice, exercise program overweight BMI>25: advice; BMI>30: dietician cholesterol CVD: statin no CVD: in case TC/HDL >5: statin glucose if > 6.1 mmol/l: stepped protocol 4-monthly visits Secondary outcomes: stroke myocardial infarction depression mortality 2 year: dementia / handicap 4 year: dementia / handicap 6 year: dementia / handicap Richard E. et al. Alzheimer Dis Assoc Disord 2009; 23:198-204

2-yearly assessments Clinical assessment Clinimetrics Cardiovascular events Medication BP BMI Lifestyle advices Clinimetrics MMSE VAT GDS ALDS (AMC Linear Disability Scale) Laboratory assessment Lipids, glucose, HcY, CRP DNA storage (baseline) Dementia diagnostics when indicated

Baseline lack of physical exercise 40% smoking 12% Systolic BP BMI Total cholesterol % % % 39% 21% 23% <120 140-160 >180 120-140 160-180 lack of physical exercise 40% smoking 12%

Window of opportunity Number of vascular risk factors % 12% Richard E. et al. Alzheimer Dis Assoc Disord 2009; 23:198-204

Methodological considerations Timing of intervention Target population Outcome measures Type of intervention (multi-component)

Proceedings www.edpi.org Last patient out 3534 2000 1000 Jan 2007 Jan 2009 Jan 2011 Jan 2013 Jan 2015 First patient out www.edpi.org

Acknowledgements Academic Medical Centre Neurology: Pim van Gool, MD PhD Lisa Eurelings, MD General practice: Eric Moll van Charante, MD PhD Suzanne Ligthart, MD Clinical trials bureau dept of Neurology: Carin Miedema General practices: All participating GPs (n= 116) All practice nurses (n=25) Funding: Dutch Ministry of health, Welfare and Sport Dutch Innovation Fund Health Insurances The Netherlands Organisation for Health Research and Development Academic Medical Centre