Cerebral microvascular rarefaction, the reduction in number of functional or structural small blood vessels in the brain, is thought to play an important role in the early stages of microvascular related brain disorders. A better understanding of its underlying pathophysiological mechanisms, and methods to measure microvascular density in the human brain are needed to develop biomarkers for early diagnosis and to identify targets for disease modifying treatments. Therefore, we provide an overview of the assumed main pathophysiological processes underlying cerebral microvascular rarefaction and the evidence for rarefaction in several microvascular related brain disorders. A number of advanced physiological MRI techniques can be used to measure the pathological alterations associated with microvascular rarefaction. Although more research is needed to explore and validate these MRI techniques in microvascular rarefaction in brain disorders, they provide a set of promising future tools to assess various features relevant for rarefaction, such as cerebral blood flow and volume, vessel density and radius and blood-brain barrier leakage.

Background: Hypertension is the leading modifiable risk factor for cerebral small vessel diseases (SVDs). Yet, it is unknown whether antihypertensive drug classes differentially affect microvascular function in SVDs. Aims: To test whether amlodipine has a beneficial effect on microvascular function when compared to either losartan or atenolol, and whether losartan has a beneficial effect when compared to atenolol in patients with symptomatic SVDs. Design: TREAT-SVDs is an investigator-led, prospective, open-label, randomised crossover trial with blinded endpoint assessment (PROBE design) conducted at five study sites across Europe. Patients aged 18 years or older with symptomatic SVD who have an indication for antihypertensive treatment and are suffering from either sporadic SVD and a history of lacunar stroke or vascular cognitive impairment (group A) or CADASIL (group B) are randomly allocated 1:1:1 to one of three sequences of antihypertensive treatment. Patients stop their regular antihypertensive medication for a 2-week run-in period followed by 4-week periods of monotherapy with amlodipine, losartan and atenolol in random order as open-label medication in standard dose. Outcomes: The primary outcome measure is cerebrovascular reactivity (CVR) as determined by blood oxygen level dependent brain MRI signal response to hypercapnic challenge with change in CVR in normal appearing white matter as primary endpoint. Secondary outcome measures are mean systolic blood pressure (BP) and BP variability (BPv). Discussion: TREAT-SVDs will provide insights into the effects of different antihypertensive drugs on CVR, BP, and BPv in patients with symptomatic sporadic and hereditary SVDs. Funding: European Union’s Horizon 2020 programme. Trial registration: NCT03082014.

Background Cerebral small vessel disease (cSVD) is a late consequence of cerebral microvascular dysfunction (MVD). MVD is hard to measure in the brain due to its limited accessibility. Extracerebral MVD (eMVD) measures can give insights in the etiology of cerebral MVD, as MVD may be a systemic process. We aim to investigate whether a compound score consisting of several eMVD measures is associated with structural cSVD MRI markers. Methods Cross-sectional data of the population-based Maastricht Study was used (n = 1872, mean age 59 ± 8 years, 49% women). Measures of eMVD included flicker light-induced retinal arteriolar and venular dilation response (retina), albuminuria and glomerular filtration rate (kidney), heat-induced skin hyperemia (skin), and plasma biomarkers of endothelial dysfunction (sICAM-1, sVCAM-1, sE-selectin, and von Willebrand factor). These measures were standardized into z scores and summarized into a compound score. Linear and logistic regression analyses were used to investigate the associations between the compound score and white matter hyperintensity (WMH) volume, and the presence of lacunes and microbleeds, as measured by brain MRI. Results The eMVD compound score was associated with WMH volume independent of age, sex, and cardiovascular risk factors (St β 0.057 [95% CI 0.010–0.081], p value 0.01), but not with the presence of lacunes (OR 1.011 [95% CI 0.803–1.273], p value 0.92) or microbleeds (OR 1.055 [95% CI 0.896–1.242], p value 0.52). Conclusion A compound score of eMVD is associated with WMH volume. Further research is needed to expand the knowledge about the role of systemic MVD in the pathophysiology of cSVD.

INTRODUCTIONChronic cerebral hypoperfusion is one of the assumed pathophysiological mechanisms underlying vascular cognitive impairment (VCI). We investigated the association between baseline cerebral blood flow (CBF) and cognitive decline after 2 years in patients with VCI and reference participants.METHODSOne hundred eighty‐one participants (mean age 66.3 ± 7.4 years, 43.6% women) underwent arterial spin labeling (ASL) magnetic resonance imaging (MRI) and neuropsychological assessment at baseline and at 2‐year follow‐up. We determined the association between baseline global and lobar CBF and cognitive decline with multivariable regression analysis.RESULTSLower global CBF at baseline was associated with more global cognitive decline in VCI and reference participants. This association was most profound in the domain of attention/psychomotor speed. Lower temporal and frontal CBF at baseline were associated with more cognitive decline in memory.DISCUSSIONOur study supports the role of hypoperfusion in the pathophysiological and clinical progression of VCI.Highlights Impaired cerebral blood flow (CBF) at baseline is associated with faster cognitive decline in VCI and normal aging. Our results suggest that low CBF precedes and contributes to the development of vascular cognitive impairment. CBF determined by ASL might be used as a biomarker to monitor disease progression or treatment responses in VCI.

Since the introduction of non-invasive prenatal testing (NIPT) in Belgium in 2013, expectant parents have had access to a new efficient and reliable test for genetic abnormalities, including trisomy 13, 18 and 21. In 2017, the Belgian government decided to cover over 95% of the cost for all women who choose to take this test. In this context, a diagnosis of trisomy 21 (Down syndrome) presents an especially challenging decision for parents: it is impossible to tell the severity of impairment prenatally, and although several medical risks are involved in the condition, many individuals with Down syndrome live a long, happy, and relatively independent life (Shakespeare, 1998; Scott et. al., 2014). Expectant parents face a very difficult situation: how to decide whether or not to terminate a pregnancy? It appears that termination is becoming the routinized outcome of the clinical encounter during which a diagnosis is delivered.The intricacy of the matter, and the fact that many actors are involved, lead to the necessity of a transdisciplinary methodology when scrutinizing the future of prenatal counseling. However, medical professionals tend to approach Down syndrome from an exclusively medical perspective (Skirton and Barr, 2010), leaving aside the economic, social and psychological dimensions of living with Down syndrome. This may result in unbalanced information; some (perhaps precipitously) refer to this phenomenon as ‘nudging practices’ (Hippman et. al., 2012; Reid et. al., 2009). In order to address this imbalance, we adopt a stakeholder approach in this project: we consulted <target target-type="page-num" id="p-39"/>experts with diverse backgrounds and fields of expertise. Through this transdisciplinary approach, we hope to bring about a more transdisciplinary perspective directly within the offices of gynecologists and GPs. More specifically, we aim to find ways to provide GPs and gynecologists with direct access to information about the aforementioned dimensions of Down syndrome.The next step is to define a strategy to achieve this goal. Given the fact that medical professionals often lack both time and easy access to concise information about Down syndrome to present a nuanced perspective (Ahmed et. al., 2007), but are still the first in the prenatal screening process, the output of this project is the idea of an online tool in a succinct Q&A format. The goal of such a website would be to provide up-to-date, easily accessible and balanced information for general practitioners and gynecologists on multiple aspects of Down syndrome. This way, in anticipation of and directing explicitly towards further counseling by a multidisciplinary team, physicians can provide expectant parents with a more balanced, transdisciplinary view of Down syndrome, thereby enhancing their capability to make informed, autonomous and hence sustainable decisions about their pregnancies.