Research topic

The SMART-MR study is a single-center prospective cohort study among non-demented individuals with vascular disease referred to the University Medical Center (UMC) Utrecht, the Netherlands. The SMART-MR cohort forms a unique population of independently living individuals with symptomatic atherosclerotic disease and aims at investigating risk factors and consequences of brain changes on MRI and changes in cognition.

Study description

Recruitment and participants

Recruitment of participants and baseline examinations started in 2001. The UCC-SMART cohort – of which the SMART-MR is a sub-study - recruited participants newly referred to the University Medical Center Utrecht with symptomatic or asymptomatic vascular disease. Participants of the SMART cohort with symptomatic vascular disease, i.e. manifest coronary artery disease, cerebrovascular disease, peripheral arterial disease, or an abdominal aortic aneurysm, and without contraindications for brain imaging, were invited to participate in the SMART-MR study. Written informed consent was obtained from all participants. All participants of SMART-MR still alive were invited for follow-up measurements, including MRI of the brain and neuropsychological testing, in January 2006 (wave 2) and November 2013 (wave 3). The most recent, third wave was completed in October 2017. Retention rates of SMART-MR are 58% and 44% for wave 2 and wave 3, respectively, with 87% of the participants at baseline being alive at wave 3.

Inclusion criteria for SMART-MRExclusion criteria for SMART-MR

Participants from SMART study with at one of the following diseases:

- Manifest coronary artery disease
- Cerebrovascular disease
- Peripheral arterial disease
- Abdominal aortic aneurysm

Minors or incapacitated individuals

MR contraindications (metal objects in body, claustrophobia, pregnancy)

Diagnosis of terminal malignancy

Willingness to participate in longitudinal follow-up and additional testingLack of independence in daily activities (Rankin scale > 3)
Willingness and ability to provide written informed consentLack of fluency in Dutch

Referral back to the referring specialist


At baseline SMART-MR participants completed questionnaires about risk factors, medical history, lifestyle and functioning before their visit to the clinic. At the clinic they underwent a medical examination, laboratory tests, comprehensive cognitive testing, and 1.5T magnetic resonance imaging (MRI) of the brain.

At the first follow-up (wave 2), after 4 years on average, measurements were repeated and the following were added as part of the SMART-Medea study: presence and history of depression (Composite International Depression Interview), severity of depressive symptoms (Patient-Health-Questionnaire-9), psychosocial vulnerability, psychosocial stressors early and later in life, measurement of salivary cortisol, as well as a T1-weighted three-dimensional (3D) fast field-echo (FFE) sequence for measuring hippocampal volumes.

During the second follow-up (wave 3), questionnaires and brain outcomes were assessed, including 1.5T MRI and neuropsychological examinations. In addition, around 200 participants also underwent 7T brain MRI. Furthermore, starting in 2006, participants completed bi-annual questionnaires of depressive symptoms and subjective cognitive decline during 10 years of follow-up.

The cohort is continuously monitored for vascular events and mortality through yearly questionnaires and additionally evaluated by physicians of the UCC-SMART Study Endpoint Committee. Finally, a linkage with the Central Bureau of Statistics / Centraal Bureau voor de Statistiek, the Dutch Hospital Data foundation and the Netherlands Cancer Registry is obtained.

A detailed description of the (SMART-MR) study design can be found at:


The Netherlands Consortium of Dementia Cohorts (NCDC)

NCDC consists of nine Dutch cohort studies including the SMART-MR study. The main objective of this project is to unravel the pathophysiology of dementia with a specific focus on amyloid and vascular pathologies in order to find clues for primary prevention by performing a pooled analysis of cohorts on aging and dementia. 

Early detection of semantic loss in preclinical Alzheimer’s disease

This study investigates if analyzing letter and category fluency through the psycholinguistic features of lexical frequency, age of acquisition, and neighborhood density can disambiguate semantic processing from executive function within task performance of racially/ethnically and educationally diverse individuals in a preclinical phase of Alzheimer’s disease.

Detection of early cognitive impairment through language in Alzheimer’s disease 

Biological markers of Alzheimer’s pathology do not relate one-to-one with eventual clinical symptoms of cognitive impairment. Thus, there is a need for early cognitive markers. This project investigates a new score of a widely used neuropsychological test using language features to identify the earliest cognitive changes associated with Alzheimer’s disease.

Prognosis of ischemic stroke in different imaging phenotypes

In clinical practise the stroke symptoms and imaging findings do not always overlap. The objective of this study is to investigate whether the clinical or radiological prognosis of ischemic stroke are different depending on the imaging phenotypes and symptom-imaging mismatch.

Linkage with Centraal Bureau voor de Statistiek (CBS) / Statistics Netherlands

Data from CBS are linked to SMART-MR participants and are analyzed within the secure CBS environment. Thereby, information on important clinical endpoints can be obtained to enrich the dataset.



Click here for a list of all publications.


Click here for a list with all dissertations.


Mirjam I. Geerlings

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