Perivascular spaces in the centrum semiovale at the beginning of the 8th decade of life: effect on cognition and associations with mineral deposition

Maria Del C Valdés Hernández,Mark E Bastin,Alan J Gow,Susana Muñoz Maniega,John M Starr,Lucia Ballerini,Ian J Deary,Andreas Glatz,Joanna M Wardlaw

doi:10.1007/s11682-019-00128-1

Maria Del C Valdés Hernández, Mark E Bastin + Show 7 more

Open Access

https://doi.org/10.1007/s11682-019-00128-1

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Abstract

Brain iron deposits (IDs) are indicative of microvessel dysfunction which may predispose to small vessel disease (SVD) brain damage and worsen cognition later in life. Visible perivascular spaces in the centrum semiovale (CSO-PVS) are SVD features linked with microvessel dysfunction. We examined possible associations of CSO-PVS volume and count with brain IDs and cognitive abilities in 700 community-dwelling individuals from the Lothian Birth Cohort 1936 who underwent detailed cognitive testing and multimodal brain MRI at mean age 72.7 years. Brain IDs were assessed automatically followed by manual editing. PVS were automatically assessed in the centrum semiovale and deep corona radiata supraventricular. General factors of overall cognitive function (g), processing speed (g-speed) and memory (g-memory) were used in the analyses. Median (IQR) volumes of IDs and CSO-PVS expressed as a percentage of intracranial volume were 0.0021 (0.011) and 0.22 (0.13)% respectively. Median count of CSO-PVS was 410 (IQR = 201). Total volumes of CSO-PVS and ID, adjusted for head size, were correlated (Spearman ρ = 0.13, p < 0.001). CSO-PVS volume, despite being correlated with all three cognitive measures, was only associated with g-memory (B = -114.5, SE = 48.35, p = 0.018) in general linear models, adjusting for age, sex, vascular risk factors, childhood intelligence and white matter hyperintensity volume. The interaction of CSO-PVS count with diabetes (B = -0.0019, SE = 0.00093, p = 0.041) and volume with age (B = 1.57, SE = 0.67, p = 0.019) were also associated with g-memory. Linear regression models did not replicate these associations. Therefore, it does not seem that CSO-PVS burden is directly associated with general cognitive ability in older age.

Highlights

It is known that minerals accumulate in several brain regions and cell types (Ward et al 2014)
In a large narrow-age cohort of community-dwelling septuagenarian, we investigate whether volumes of perivascular spaces (PVS) and iron deposits (IDs) are related to each other, and whether CSO-PVS volume and count are associated with poorer cognition than that expected for a given premorbid IQ
By seeking to answer these research questions, we explore the role of white matter hyperintensities (WMH) and vascular risk factors in CSO-PVS burden and how these in turn might affect cognition; seeking information that could explain the link between early life factors and greater small vessel disease (SVD) burden in later life

Summary

Introduction

It is known that minerals accumulate in several brain regions and cell types (Ward et al 2014). The mineral most commonly found in these aggregates is iron. It mainly accumulates gradually with age in areas associated with motor activity (Rouault 2013) (i.e. corpus striatus, substantia nigra and brainstem) via dysfunctional brain regulatory mechanisms (McCarthy and Kosman 2014), or as a residual from very small chronic haemorrhages, namely microbleeds, in abnormal blood vessels (i.e. capillaries) throughout the brain (Martinez-Ramirez et al 2014). Several MRI studies have reported associations of these three forms of mineral accumulations (Yates et al 2014) with cognitive decline (Valdés Hernández et al 2015; Sullivan et al 2009), neurodegeneration (Graham et al 2000; Thompson et al 2001; Ke and Qian 2003), and perivascular spaces (PVS) in the white matter (Charidimou et al 2014)

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