
Mirjam I GeerlingsAmsterdam UMC · Department of General Practice
Mirjam I Geerlings
PhD
About
375
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Introduction
Skills and Expertise
Publications
Publications (375)
Background
Aggregation of cohort data increases precision for studying neurodegenerative disease pathways, but efforts to combine data and expertise are often hampered by infrastructural, ethical and legal considerations. We aimed to unite various cohort studies in the Netherlands to enhance research infrastructure and facilitate research on dement...
Objectives
Aneurysmal subarachnoid haemorrhage (ASAH) is a severe stroke type, preventable by screening for intracranial aneurysms followed by treatment in high-risk individuals. We aimed to develop and validate a risk prediction model for ASAH in the general population to identify high-risk individuals.
Design
We used the population-based prospec...
Physical exercise is a promising intervention to improve brain white matter integrity. In the PAM study, exercise intervention effects on white matter integrity were investigated in breast cancer patients. Chemotherapy-treated breast cancer patients with cognitive problems were randomized 2–4 years post-diagnosis to an exercise (n = 91) or control...
INTRODUCTION
This study assessed the association of plasma biomarkers of endothelial dysfunction with cognitive performance and decline.
METHODS
Data from 9414 individuals from eight Dutch cohorts were included (Ø age‐range: 57–93 years). Plasma biomarkers of endothelial dysfunction (soluble intercellular adhesion molecule‐1 (sICAM‐1), soluble vas...
Background and Aims
The incidence of cerebrovascular disease (CVD) is rising among young adults (<55 years). The risk for CVD starts to form in early childhood and is comprised of genetic and environmental risk factors. The aim of this study is to investigate the relationship between early family socioeconomic status (SES), inherited risk, and CVD...
Individual participant data (IPD) meta-analysis provides important opportunities to study interaction and effect modification for which individual studies often lack power. While previous meta-analyses have commonly focused on multiplicative interaction, additive interaction holds greater relevance for public health and may in certain contexts bett...
Objective: We aimed to estimate the association of age, education, and sex/gender with semantic fluency performance as measured by the standard total number of words as well as novel item-level metrics and to descriptively compare associations across cohorts with different recruitment strategies and sample compositions. Method: Cross-sectional data...
Background: Current benefits of invasive intracranial aneurysm treatment to prevent aneurysmal subarachnoid haemorrhage (aSAH) rarely outweigh treatment risks, and thus most intracranial aneurysms remain untreated. Commonly prescribed drugs reducing aSAH incidence may provide leads for drug repurposing.
Objectives: We performed a drug-wide associat...
INTRODUCTION: Dementia is a multifactorial disease with Alzheimer’s disease (AD)
and vascular dementia (VaD) pathologies making the largest contributions. Yet, most
genome-wide association studies (GWAS) focus on AD.
METHODS: We conducted a GWAS of all-cause dementia (ACD) and examined the
genetic overlap with VaD. Our dataset includes 800,597 indi...
Background and objectives:
Current benefits of invasive intracranial aneurysm treatment to prevent aneurysmal subarachnoid hemorrhage (aSAH) rarely outweigh treatment risks. Most intracranial aneurysms thus remain untreated. Commonly prescribed drugs reducing aSAH incidence may provide leads for drug repurposing. We performed a drug-wide associati...
Aneurysmal subarachnoid hemorrhage (aSAH) can be prevented by early detection and treatment of intracranial aneurysms in high-risk individuals. We investigated whether individuals at high risk of aSAH in the general population can be identified by developing an aSAH prediction model with electronic health records (EHR) data. To assess the aSAH mode...
Background
Although behavioral mechanisms in the association among depression, anxiety, and cancer are plausible, few studies have empirically studied mediation by health behaviors. We aimed to examine the mediating role of several health behaviors in the associations among depression, anxiety, and the incidence of various cancer types (overall, br...
Background and purpose
Risk factors for stroke differ between women and men in general populations. However, little is known about sex differences in secondary prevention. We investigated if sex interacted with modifiable risk factors for stroke in a large arterial disease cohort.
Methods
Within the prospective UCC-SMART study, 13,898 patients (35...
Background and purpose
Arterial calcifications on unenhanced CT scans and vessel wall lesions on MRI are often used interchangeably to portray intracranial arterial disease. However, the extent of pathology depicted with each technique is unclear. We investigated the presence and distribution of these two imaging findings in patients with a history...
Background
Two of the main causes for dementia are Alzheimer's disease (AD) and vascular pathology, with most patients showing mixed pathology. Plasma biomarkers for Alzheimer's disease‐related pathology have recently emerged, including Aβ (amyloid‐beta), p‐tau (phosphorylated tau), NfL (neurofilament light), and GFAP (glial fibrillary acidic prote...
Depression, anxiety and other psychosocial factors are hypothesized to be involved in cancer development. We examined whether psychosocial factors interact with or modify the effects of health behaviors, such as smoking and alcohol use, in relation to cancer incidence. Two‐stage individual participant data meta‐analyses were performed based on 22 c...
Introduction: Calcifications of the intracranial internal carotid artery (iICA) can lead to an increased risk for stroke. Two types of iICA calcification are known: those affecting the tunica intima or the tunica media. In extracranial arteries, risk factors and calcification patterns are different in women and men, but little is known regarding th...
Background
Microvascular dysfunction is involved in the development of various cerebral disorders. It may contribute to these disorders by disrupting white matter tracts and altering brain connectivity, but evidence is scarce. We investigated the association between multiple biomarkers of microvascular function and whole‐brain white matter connecti...
Several lines of evidence have indicated that depression might be a prodromal symptom of Alzheimer’s disease (AD). This systematic review and meta-analysis investigated the cross-sectional association between amyloid-beta, one of the key pathologies defining AD, and depression or depressive symptoms in older adults without dementia. A systematic se...
Background
Depression has been associated with an increased risk of Alzheimer’s disease (AD), but the biological mechanisms are still not fully understood. Plasma biomarkers, such as amyloid‐beta, tau, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL), have been associated with AD pathophysiology. However, the relationship with...
Background
Microvascular dysfunction may contribute to the development of various cerebral disorders, including cognitive dysfunction, dementia, and certain forms of depression. The suggested mechanism through which microvascular dysfunction contributes to these disorders is by disrupting white matter tracts and altering brain connectivity, but evi...
Introduction: The prevalence of unruptured intracranial aneurysms (UIAs) in the general population is 3%. Aneurysmal subarachnoid hemorrhage (aSAH) can be prevented by screening for UIAs followed by monitoring and, if needed, preventive neurosurgical or endovascular treatment of identified UIAs. Therefore, we developed a diagnostic model for presen...
Background:
Exercise is a promising intervention to alleviate cognitive problems in breast cancer patients, but studies on mechanisms underlying these effects are lacking.
Purpose:
Investigating whether an exercise intervention can affect cerebral blood flow (CBF) in cognitively impaired breast cancer patients and to determine if CBF changes rel...
Objectives
Semantic fluency is a prominent neuropsychological task, typically administered within the category ‘animals’. With the increasing development of novel item-level metrics of semantic fluency, a concern around the validity of item-level analyses could be that personal background factors (e.g., hobbies like birdwatching or fishing) may dis...
Background
Early identification of dementia is crucial for prompt intervention for high-risk individuals in the general population. External validation studies on prognostic models for dementia have highlighted the need for updated models. The use of machine learning in dementia prediction is in its infancy and may improve predictive performance. T...
Background
Depression and anxiety have long been hypothesized to be related to an increased cancer risk. Despite the great amount of research that has been conducted, findings are inconclusive. To provide a stronger basis for addressing the associations between depression, anxiety, and the incidence of various cancer types (overall, breast, lung, p...
Purpose
In this study, we aim to understand whether and how performance in animal fluency (i.e., total correct word count) relates to linguistic levels and/or executive functions by looking at sequence information and item-level metrics (i.e., clusters, switches, and word properties).
Method
Seven hundred thirty-one Dutch-speaking individuals with...
Background
The need persists for sensitive, low‐cost, and high‐access cognitive markers to complement biomarker information in the earliest stages of Alzheimer’s disease. Sensitive cognitive markers may be derived from information at the item level of neuropsychological tests. We investigated if item‐level metrics add information beyond total score...
In normal aging, the cognitive domain of semantic memory remains preserved, while the domain of episodic memory declines to some extent. In Alzheimer's disease dementia, both semantic and episodic memory become impaired early in the disease process. Given the need to develop sensitive and accessible cognitive markers for early detection of dementia...
Alzheimer's disease (AD) is the most common cause of dementia, characterized by the aggregation of amyloid-beta (Aβ) proteins into plaques. Individuals with AD frequently show mixed pathologies, often caused by cerebral small vessel disease (CSVD), resulting in lesions such as white matter hyperintensities (WMH). The current systematic review and m...
Background
Diagnosis of cerebrovascular disease is based on both clinical and radiological findings, however, they do not always correlate.
Aims
To investigate ischemic stroke recurrence and mortality in patients with different imaging phenotypes of ischemic cerebrovascular disease.
Methods
Within the SMART-MR study, a prospective patient cohort...
Purpose
The Utrecht Cardiovascular Cohort–Second Manifestations of Arterial Disease (UCC-SMART) Study is an ongoing prospective single-centre cohort study with the aim to assess important determinants and the prognosis of cardiovascular disease progression. This article provides an update of the rationale, design, included patients, measurements an...
The emergence of COVID-19 was rapidly followed by infection and the deaths of millions of people across the globe. With much of the research and scientific advancement rightly focused on reducing the burden of severe and critical acute COVID-19 infection, the long-term effects endured by those who survived the acute infection has been previously ov...
Specific subfields within the hippocampus have shown vulnerability to chronic stress, highlighting the importance of looking regionally within the hippocampus to understand the role of psychosocial factors in the development of neurodegenerative diseases. A systematic review on psychosocial factors and hippocampal subfield volumes was performed and...
Early identification of dementia is crucial for prompt intervention and better outcomes for high‐risk individuals in the general population. The use of machine learning in dementia prediction has allowed for highly accurate models that could aid in early classification; however, they have focused on expensive predictors. Exploring predictors that a...
Biomarkers for Alzheimer’s disease (AD), including amyloid‐beta (Abeta) and phosphorylated‐tau have recently been accurately detected in blood. Non‐specific biomarkers such as neurofilament light (NFL) and glial fibrillary acidic protein (GFAP) have been added as complementary biomarkers to fully investigate AD etiology in vivo. This has increased...
Background
Physical exercise in cancer patients is a promising intervention to improve cognition and increase brain volume, including hippocampal volume. We investigated whether a 6-month exercise intervention primarily impacts total hippocampal volume and additionally hippocampal subfield volumes, cortical thickness and grey matter volume in previ...
Background
Specific subfields within the hippocampus have shown vulnerability to chronic stress, highlighting the importance of looking regionally within the hippocampus to understand the role of psychosocial risk factors in the development of neurodegenerative diseases. The current study had two aims: to perform a systematic review on psychosocial...
Background
The current study aimed to assess if the relation between depression and dementia could be explained by allostatic load (AL) profiles, as well as assessing their risk on incident all-cause dementia, Alzheimer’s disease (AD), and non-AD dementias.
Methods
The study included individuals without dementia at baseline from the population-bas...
Asymptomatic low-grade carotid artery stenosis (LGCS) is a common finding in patients with manifest arterial disease, however its relationship with brain MRI changes and cognitive decline is unclear. We included 902 patients (58 ± 10 years; 81% male) enrolled in the Second Manifestations of Arterial Disease - Magnetic Resonance (SMART-MR) study wit...
Objective: A critical need persists to develop sensitive and high-access cognitive markers for early detection of dementia. Among older adults without dementia, we investigated if item-level metrics of semantic fluency related to episodic memory decline above and beyond traditional neuropsychological measures and total fluency score.Method: Partici...
Introduction: Coronavirus disease 2019 (COVID-19) has caused >3.5 million deaths worldwide and affected >160 million people. At least twice as many have been infected but remained asymptomatic or minimally symptomatic. COVID-19 includes central nervous system manifestations mediated by inflammation and cerebrovascular, anoxic, and/or viral neurotox...
Introduction:
It has been hypothesized that carotid artery stenosis (CAS) may lead to greater atrophy of subserved brain regions; however, prospective studies on the impact of CAS on progression of hemispheric brain atrophy are lacking. We examined the association between CAS and progression of hemispheric brain atrophy.
Methods:
We included 654...
Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify associ...
Objectives:
DISH has been associated with increased coronary artery calcifications and incident ischaemic stroke. The formation of bone along the spine may share pathways with calcium deposition in the aorta. We hypothesized that patients with DISH have increased vascular calcifications. Therefore we aimed to investigate the presence and extent of...
White matter hyperintensity (WMH) shape has been associated with the severity of the underlying brain pathology, suggesting it is a potential neuroimaging marker of WMH impact on brain function.
In 563 patients with vascular disease (58±10 years), we examined the relationship between WMH volume, shape and cognitive functioning. WMH volume and shape...
BACKGROUND AND PURPOSE: The clinical relevance of cortical microinfarcts has recently been established; however, studies on microinfarcts in the deep gray matter are lacking. We examined the risk factors and MR imaging correlates of microinfarcts in the deep gray matter on 7T MR imaging and their relation to cognitive functioning. MATERIALS AND MET...
Background
Up to 60% of breast cancer patients treated with chemotherapy is confronted with cognitive problems, which can have a significant impact on daily activities and quality of life (QoL). We investigated whether exercise training improves cognition in chemotherapy-exposed breast cancer patients 2–4 years after diagnosis.
Methods
Chemotherap...
Background and purpose:
The clinical relevance of cortical microinfarcts has recently been established; however, studies on microinfarcts in the deep gray matter are lacking. We examined the risk factors and MR imaging correlates of microinfarcts in the deep gray matter on 7T MR imaging and their relation to cognitive functioning.
Materials and m...
Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 ris...
Perivascular spaces (PVS) are believed to be involved in brain waste disposal. PVS are associated with cerebral small vessel disease. At higher field strengths more PVS can be observed, challenging manual assessment. We developed a method to automatically detect and quantify PVS.
A machine learning approach identified PVS in an automatically positi...
Background and aims
Pseudoxanthoma elasticum (PXE) is a genetic disorder characterized by systemic calcification of elastin fibers. Additionally, PXE is associated with an increased risk of stroke. It has been hypothesized that this may be caused by accelerated (intracranial) atherogenesis, as a consequence of specific genetic mutations underlying...
Objectives
Stroke is the second most common cause of death and a major cause of disability. Besides the physical consequences, depressive symptoms are frequent in the aftermath after stroke. Every year, approximately 15 million stroke survivors worldwide are at risk of developing post-stroke depression. In this study we describe the natural course...
Objective
Investigate associations of cognitive and brain reserve with trajectories of memory decline in mid-life and late-life, and whether the relationship of memory decline with atrophy differs as a function of reserve.
Methods
Participants were 989 Dutch middle-aged to older adults from the SMART-MR prospective cohort, followed up to 12 years...
Background:
Late-life depression (LLD) is related to an increased risk of developing dementia; however, the biological mechanisms explaining this relationship remain unclear.
Objective:
To determine whether the relationship between LLD and dementia can be best explained by the glucocorticoid cascade or vascular hypothesis.
Methods:
Data are fr...
Objective
To investigate socio-demographic and medical predictors of incident mild cognitive impairment (MCI) and subsequent course of MCI at follow-up, including sustained MCI diagnosis, classification as cognitively normal, and progression to dementia.
Methods
Within a community-based cohort, diagnoses of MCI were made using a published algorith...
Background
The biological underpinnings of the relationship between depression and dementia are currently not completely understood. Previous research has highlighted the role of vascular, metabolic, inflammatory, and stress markers in the role of both depression and dementia. Allostatic load has been an all‐encompassing term to describe these biol...
Background
Worse semantic than letter fluency performance is a clinical marker of Alzheimer’s disease (AD), but the longitudinal course of performance on these tasks in pre‐dementia stages remains undefined. This study investigated how many years before clinical AD the performance on the two verbal fluency tasks starts to diverge, and if this proce...
Objectives
Earlier retrospective studies have suggested a relation between diffuse idiopathic skeletal hyperostosis [DISH] and cardiovascular disease, including myocardial infarction. The present study assessed the association between DISH and incidence of cardiovascular events and mortality in patients with high cardiovascular risk.
Methods
In th...
Late-life depression (LLD) increases risk for dementia and brain pathology, but possibly this is only true for one or more symptom profiles of LLD.
In 4354 participants (76±5 years; 58% female) from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, we identified five LLD symptom profiles, based on the Geriatric Depression Scale-15 (n...
Abstract
Objectives
Psychosocial factors have been hypothesized to increase the risk of cancer. This study aims (1) to test whether psychosocial factors (depression, anxiety, recent loss events, subjective social support, relationship status, general distress, and neuroticism) are associated with the incidence of any cancer (any, breast, lung, pro...
Background and Purpose: For prevention of cerebrovascular diseases at younger age, it is important to understand the risk factors occurring early in life. We investigated the relationship between mothersâ general health during pregnancy and the offspringâs risk of cerebrovascular disease in age of 15 to 52 years.
Methods: Within the population-...
Background:
Early identification of Alzheimer's disease (AD) may be extremely beneficial for delaying disease progression. Subjective cognitive decline (SCD) may be an early indicator of AD pathology. Not all individuals with SCD will eventually develop AD, making it critical to identify biomarkers during the SCD stage which indicate likely clinic...
Lacunes of presumed vascular origin are fluid-filled cavities of between 3 - 15 mm in diameter, visible on T1 and FLAIR brain MRI. Quantification of lacunes relies on manual annotation or semi-automatic / interactive approaches; and almost no automatic methods exist for this task. In this work, we present a two-stage approach to segment lacunes of...
Pathological tau is suggested to play a role in cognitive deterioration in the preclinical phase of Alzheimer’s disease. We investigated cross-sectional associations of tau burden with episodic and semantic memory performance in older adults without dementia. A systematic search in MEDLINE (via PubMed), PsychINFO, and Embase resulted in 24 eligible...
We aimed to evaluate the external performance of prediction models for all-cause dementia or AD in the general population, which can aid selection of high-risk individuals for clinical trials and prevention. We identified 17 out of 36 eligible published prognostic models for external validation in the population-based AGES-Reykjavik Study. Predicti...
Objective
To investigate the association of silent vascular lesions, imaging negative ischemia, and symptomatic cerebrovascular disease with long-term progression of brain atrophy and cerebrovascular lesions in patients with arterial disease.
Methods
Within the SMART-MR study, stroke status of participants at baseline was classified as no cerebrov...