Microstructural White Matter Abnormalities and Cognitive Functioning in Type 2 Diabetes

221 Pages·2012·4.06 MB·English

Vascular Cognitive Impairment:
risk factors and brain
MRI correlates
Yael Reijmer
Cover image: Els Freeke
Lay-out: Roy Sanders
Printed by: Ridderprint
ISBN: 978-90-393-5728-6
© 2012 Y.D. Reijmer
All rights reserved. No part of this publication may be reproduced or transmitted
in any form or by any means, without permission in writing from the author. The
copyright of the articles that have been published has been transferred to the
respective journals.
Vascular Cognitive Impairment:
risk factors and brain
MRI correlates
Vasculaire cognitieve beperkingen: risicofactoren en
gerelateerde hersenschade op MRI
(met een samenvatting in het Nederlands)
Proefschrift
ter verkrijging van de graad van doctor aan de Universiteit Utrecht
op gezag van de rector magnificus, prof.dr. G.J. van der Zwaan,
ingevolge het besluit van het college voor promoties
in het openbaar te verdedigen op
donderdag 9 februari 2012 des middags te 4.15 uur
Door
Yael Dorit Reijmer
Geboren op 7 januari 1982 te Jeruzalem, Israel
Promotor: Prof.dr. L.J. Kappelle

Co-promotoren: Dr. G.J. Biessels
Dr. E. van den Berg
Financial support by the Dutch Heart Foundation and the Diabetes Fonds for the
publication of this thesis is gratefully acknowledged.
Additional financial support was generously provided by the Alzheimer Nederland
(Bunnik), Internationale Stichting Alzheimer Onderzoek and Boehringer Ingelheim.

Contents
Chapter 1 General introduction and outline of the thesis 9
Part I: The development of VCI over time
in individuals with type 2 diabetes mellitus
Chapter 2 Cognitive dysfunction in patients with type 2 diabetes 21
Chapter 3 A 4 year follow-up study of cognitive functioning in patients 51
with type 2 diabetes mellitus
Chapter 4 Accelerated cognitive decline in patients with type 2 67
diabetes: MRI correlates and risk factors
Part II: Exposure to vascular risk factors and VCI
Chapter 5 Development of vascular risk factors over 15 years in 85
relation to cognition: the Hoorn study
Chapter 6 Dementia risk score predicts cognitive impairment after a 105
period of 15 years in a non-demented population
Chapter 7 The metabolic syndrome, atherosclerosis and cognitive 117
functioning in a non-demented population: the Hoorn study
Part III: Microstructural white matter correlates of VCI
Chapter 8 Constrained spherical deconvolution based tractography and 139
cognition in Alzheimer’s disease
Chapter 9 Microstructural white matter abnormalities and cognitive 159
functioning in type 2 diabetes: a diffusion tensor imaging study
Chapter 10 General discussion 177
Chapter 11 Summary 191
Nederlandse samenvatting 197
List of publications 205
Acknowledgements 209
Dankwoord 213
Curriculum Vitae 219

Chapter 1
General introduction
Chapter 1
Vascular cognitive impairment
Dementia affects around 7% of the general population over 65 years, and 30% of
people over 80 years.1,2 The prevalence of dementia is expected to double over
the next 30 years3, making disorders of cognition a priority for healthcare and
social-care services.
Alzheimer’s disease and vascular dementia are the two most common forms of
dementia, accounting for over 75% of all dementia cases.4 Although Alzheimer’s
disease and vascular dementia have been considered two separate entities for
decades, we now know that the majority of older individuals with dementia
show mixed pathology, despite the clinical diagnosis.5 In fact, there is probably
a continuum in underlying pathologies ranging from patients with pure vascular
dementia to pure AD6. The close relation between vascular dementia and
Alzheimer’s disease is further supported by studies showing that risk factors for
cerebrovascular disease such as hypertension, obesity, hypercholesterolemia, and
hyperglycemia are also risk factors for Alzheimer’s disease.7,8 These findings have
lead to the introduction of the concept ‘vascular cognitive impairment’ (VCI). VCI
refers to all forms of mild to severe cognitive impairment associated with, and
presumed to be caused by, cerebrovascular disease.9 Given the important role of
cerebrovascular disease in the development of cognitive decline, further research
into progression rates, risk factors and imaging changes of VCI is needed to gain
insight in possible mechanisms and to develop effective treatment strategies.
The current emphasis in the literature on VCI is on the late stages of cognitive
decline, i.e. dementia. However, twice as many people suffer from more mild forms
of cognitive impairment.10,11 Examination of underlying mechanisms of these
early stages of cognitive dysfunction is relevant, because treatment benefits are
expected to be largest when the underlying brain damage is still relatively modest.
Moreover, mild cognitive deficits are a problem by itself, leading to complaints
and affecting functional abilities, also in individuals who will not progress to
dementia.12,13 Addressing mild cognitive deficits will therefore help to identify a
much larger group of individuals who can benefit from treatment strategies.
The present thesis focuses on these milder forms of vascular related cognitive
impairment by addressing i) their course of development (first part), ii) vascular
risk factors (second part), and iii) cerebral white matter correlates (third part).
The following paragraphs will give a short introduction to the different research
questions addressed in each chapter.
10