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PDF Hosted at the Radboud Repository of the Radboud University Nijmegen PDF hosted at the Radboud Repository of the Radboud University Nijmegen The following full text is a publisher's version. For additional information about this publication click this link. http://hdl.handle.net/2066/196838 Please be advised that this information was generated on 2021-09-24 and may be subject to change. Tessa van Middelaar °270 522 17x 0,19 140/80 Blood pressure management to prevent dementia MEMORY UNDER PRESSURE: BLOOD PRESSURE MANAGEMENT TO PREVENT DEMENTIA Tessa van Middelaar ISBN 978-94-6284-154-3 Author T. van Middelaar Cover S. van Middelaar Layout Nikki Vermeulen | Ridderprint BV Printing Ridderprint BV | www.ridderprint.nl Funding The PhD position of T. van Middelaar was made possible by funding from ZonMw (The Netherlands Organisation for Health Research and Development, 733051041).as part of the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement n° 305374 and an EU Joint Programme - Neurodegenerative Disease Research (JPND) project. The preDIVA trial was supported by the Dutch Ministry of Health, Welfare and Sports (50-50110-98-020), the Innovatiefonds Zorgverzekeraars (innovation fund of collaborative health insurances, 05-234), and ZonMw (The Netherlands Organisation for Health Research and Development, 62000015). The HATICE trial was funded by the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement number 305374. Financial support by the Dutch Heart Foundation and the Dutch Alzheimer’s Foundation for the publication of this thesis is gratefully acknowledged © Tessa van Middelaar, 2018 All rights reserved. No part of this book may be reproduced in any form or by any means without prior permission of the author. MEMORY UNDER PRESSURE: BLOOD PRESSURE MANAGEMENT TO PREVENT DEMENTIA Proefschrift ter verkrijging van de graad van doctor aan de Radboud Universiteit Nijmegen op gezag van de rector magnificus prof. dr. J.H.J.M. van Krieken, volgens besluit van het college van decanen in het openbaar te verdedigen op maandag 5 november 2018 om 16:30 uur precies door Tessa van Middelaar geboren op 6 juli 1989 te Woerden Promotoren Prof. dr. W.A. van Gool (Universiteit van Amsterdam) Prof. dr. C.J.M. Klijn Copromotoren Dr. E. Richard Dr. E.P. Moll van Charante (Universiteit van Amsterdam ) Manuscriptcommissie Prof. dr. W.J.J.. Assendelft Prof. dr. M. Muller (Vrije Universiteit Amsterdam) Prof. dr. F.R.J. Verhey (Universiteit Maastricht) TABLE OF CONTENT Introduction · Chapter 1 – General introduction 7 Part I – Blood pressure in late life and dementia · Chapter 2 – Blood pressure-lowering interventions to prevent dementia: 15 a systematic review and meta-analysis · Chapter 3 – Lower dementia risk with different classes of antihypertensive 37 medication in older patients · Chapter 4 – Visit-to-visit blood pressure variability and the risk of dementia in 53 older people · Chapter 5 – Prescribing and deprescribing antihypertensive medication in 71 older people by Dutch general practitioners: a qualitative study Part II – Methodological challenges in prevention trials · Chapter 6 – Modifiable dementia risk score to study heterogeneity in 85 treatment effect of a dementia prevention trial: a post hoc analysis in the preDIVA trial using the LIBRA index · Chapter 7 – Older Europeans’ reasons for participating in a multinational 107 eHealth prevention trial: a cross-country comparison using mixed methods (ACCEPT-HATICE) · Chapter 8 – Engaging older people in an internet platform for cardiovascular 127 risk self-management: a qualitative study among Dutch HATICE participants · Chapter 9 – Effect of antihypertensive medication on cerebral small vessel 143 disease: a systematic review and meta-analysis General discussion and summary · Chapter 10 – General discussion 165 · Chapter 11 – Summary 181 · Chapter 12 – Dutch summary (Nederlandse samenvatting) 187 Appendices · References 197 · List of abbreviations 209 · List of contributing authors 211 · Data management statement 215 · List of publications 216 · PhD portfolio 218 · Curriculum Vitae 221 · Acknowledgements (Dankwoord) 222 · Donders Graduate School for Cognitive Neuroscience 225 · Dissertations of the disorders of movement research group, Nijmegen 226 GENERAL INTRODUCTION General introduction DEMENTIA 1 The number of people with dementia worldwide is projected to triple in the coming thirty years, from 47 to 135 million.1 This amplification is mainly driven by population ageing; an increase in the number and proportion of older people.2 Dementia is a clinical diagnosis characterised by cognitive impairment that interferes with daily functioning.3 It has major impact on society at the micro- and macro-level. People with dementia have severely impaired quality of life, and face increasing disability and reduced life expectancy.4,5 The functional dependence associated with dementia leads to an increased burden on (in) formal caregiving.6 The community as a whole is affected by costs of health- and social care, and loss in productivity, mainly due to informal care.5 The combined annual costs are estimated at almost 700 billion euros worldwide.5 Therefore, the G8 countries have agreed to take global action to reduce the dementia prevalence and burden, and have identified dementia prevention as a major public health priority.7 The two main subtypes of dementia are Alzheimer’s disease and vascular dementia.8 The first is neuropathologically characterized by beta-amyloid depositions (“plaques”) and hyperphosporylated tau (“tangles”), and the second by cerebrovascular lesions. It was long presumed that the two diseases occurred exclusive of one another. However, in the last decades it became apparent that the majority of persons with dementia have both neurodegenerative and cerebrovascular pathology.9 They also share common risk factors.10 The most influential risk factor for dementia is age, with around 80% of persons with dementia being 75 years or older.11 Yet, more noteworthy are the potentially modifiable risk factors; midlife hypertension, diabetes, midlife obesity, physical inactivity, depression, smoking, hyperlipidaemia and low educational attainment.10,12 Up to a third of dementia cases may be attributable to these modifiable risk factors.10 DEMENTIA PREVENTION TRIALS The window of opportunity for interventions aimed at preventing dementia is large. It has been estimated, that if modifiable risk factors could be reduced by 10%, this could lead to a reduction in the prevalence of Alzheimer’s disease of 8% within forty years.10 This would sum up to 8.8 million people in whom dementia could be prevented. Initially, randomised controlled trials (RCTs) only included cognitive impairment and dementia as secondary outcome measures.13 In the last three years, the first trials with cognition or dementia as primary outcome have been published. The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) and Multidomain Alzheimer Preventive Trial (MAPT) showed that a multi-domain intervention targeting several dementia risk factors could potentially have a beneficial effect on cognition within 2-3 years in an at risk population.14,15 The Prevention of Dementia by Intensive Vascular Care (preDIVA; box 1) trial, 9 Chapter 1 however, did not show a beneficial effect on prevention of dementia within 6-8 years, in a general population aged 70-78 years.16 Researchers from these three trials united their efforts in the design and execution of the Healthy Ageing Through Internet Counselling in the Elderly (HATICE; box 1).17 This thesis is based on post hoc analyses in the preDIVA trial and two sub-studies in the HATICE trial. Box 1 - Description of the preDIVA and HATICE trial Prevention of Dementia by Intensive Vascular Care (preDIVA) is a Dutch cluster- randomised controlled trial (RCT), which ran from 2006-2016.16 The trial studied the effect of nurse-led vascular care during 6-8 years on incident all-cause dementia. Participants randomised to the intervention group had four-monthly visits to a practice nurse during which lifestyle and medical advice was given regarding blood pressure, cholesterol, weight, smoking, physical activity and diet. Participants in the control group received standard care. For the trial community-dwelling people aged 70-78 years, without dementia, were recruited at baseline. Every two years all participants visited a trial nurse, during which primary and secondary outcome measures were assessed, including cardiovascular risk parameters and cognition. After 6-8 years an independent outcome adjudication committee validated all possible dementia cases based on clinically available data. Healthy Ageing Through Internet Counselling in the Elderly (HATICE), is an international RCT which ran from 2015-2018 on the effect of an internet intervention for cardiovascular self-management to reduce the risk of cardiovascular disease and dementia.17 For HATICE, people aged 65 years and older at increased cardiovascular risk were recruited to participate in the Netherlands, Finland and France. Intervention participants gained access to an interactive internet platform with remote support by a coach and several other functionalities to facilitate self-management, such as the ability to enter measurements and set goals.18 The control group gained access to a platform with static information. After 18 months the effect of the intervention on a composite score containing systolic BP, low-density lipoprotein cholesterol and body-mass index, was assessed. BLOOD PRESSURE AND COGNITION
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