Identification of plasma proteins relating to brain neurodegeneration and vascular pathology in cognitively normal individuals.

Introduction: This study aims to first discover plasma proteomic biomarkers relating to neurodegeneration (N) and vascular (V) damage in cognitively normal individuals and second to discover proteins mediating sex-related difference in N and V pathology.

Methods: Five thousand and thirty-two plasma proteins were measured in 1061 cognitively normal individuals (628 females and 433 males), nearly 90% of whom had magnetic resonance imaging measures of hippocampal volume (as N) and white matter hyperintensities (as V).

Results: Differential protein expression analysis and co-expression network analysis revealed different proteins and modules associated with N and V, respectively.

Early life predictors of late life cerebral small vessel disease in four prospective cohort studies.

Development of cerebral small vessel disease, a major cause of stroke and dementia, may be influenced by early life factors. It is unclear whether these relationships are independent of each other, of adult socio-economic status or of vascular risk factor exposures. We examined associations between factors from birth (ponderal index, birth weight), childhood (IQ, education, socio-economic status), adult small vessel disease, and brain volumes, using data from four prospective cohort studies: STratifying Resilience And Depression Longitudinally (STRADL) (n = 1080; mean age = 59 years); the Dutch Famine Birth Cohort (n = 118; mean age = 68 years); the Lothian Birth Cohort 1936 (LBC1936; n = 617; mean age = 73 years), and the Simpson's cohort (n = 110; mean age = 78 years).

Aspirin moderates the association between cardiovascular risk, brain white matter hyperintensity total lesion volume and processing speed in normal ageing.

Objectives: Cardiovascular risk is associated with cognitive decline and this effect is attributed to brain pathology, including white matter hyperintensity (WMH) burden. Low-dose aspirin is frequently recommended for reducing vascular events. We investigated the effect of taking aspirin on the association between cardiovascular risk, WMH burden and cognitive function.

Validation and comparison of two automated methods for quantifying brain white matter hyperintensities of presumed vascular origin.

Objectives: White matter hyperintensities (WMH) are a common imaging finding indicative of cerebral small vessel disease. Lesion segmentation algorithms have been developed to overcome issues arising from visual rating scales. In this study, we evaluated two automated methods and compared them to visual and manual segmentation to determine the most robust algorithm provided by the open-source Lesion Segmentation Toolbox (LST).