Assessment of Vascular Contributions to Cerebral Small Vessel Disease: Data from the general population study "Good Aging in Skåne"

Cerebral small vessel disease (CSVD) are highly age-related pathologies isualized by neuroimaging. CSVD can be silent lesions but are associated with cognitive decline, dementia, gait disorders, depression and stroke. A growing body of evidence links CSVD to systemic vascular processes, but the pathophysiology is not fully explained. The aim of this thesis is to investigate possible links between markers of vascular burden or hypertension-related organ dysfunction with CSVD or atrophy. The Swedish study Gott Åldrande i Skåne (Good Aging in Skåne, GÅS) is a longitudinal population study of older adults. In a sub-cohort aged 70-87 we performed carotid artery Doppler ultrasound and 3T magnetic resonance imaging (MRI). Markers of CSVD were assessed by visual rating scales and included: white matter hyperintensities (WMH), cerebral microbleeds (CMB), lacunar infarctions (LAC), and patterns of brain atrophy; medial temporal lobe (MTA), parietal (PAR), precuneal (PREC), central (CA) and global cortical (GCA). In paper I (n=344) we cross sectionally investigated the association of hypertension and blood pressure variables, with CMB and spatial distribution of CMB. Deep CMB had a stronger association with hypertension and blood pressure measurements than lobar CMB. In paper II (n=291) we cross sectionally investigated the association between common carotid artery (CCA) mean flow velocities and CSVD/atrophy. Peak systolic velocity (PSV) and end diastolic velocity (EDV) were assessed by Doppler ultrasound, and pulsatility index (PI) and resistivity index (RI) were calculated. Low EDV in CCA was associated with WMH, PAR, PREC and GCA. Low EDV and high PI and RI were associated with composite scores of CSVD burden. In paper III (n=390) we cross sectionally investigated the association between chronic kidney disease (CKD) and CSVD, specifically considering hypertension status. An association between CKD and the presence of CMB and cortical atrophy was observed only in the hypertensive cohort. In paper IV (n=401) we cross sectionally investigated the associations between 257 circulating plasma proteins investigated by proximity extension assay (PEA) by Olink Proteomics (CVD II, CVD III and inflammatory panels), and MRI manifestations. 18 proteins were significantly associated with markers of CSVD or atrophy. In conclusion, CSVD is common in the aging population. CSVD can be linked to hypertension, carotid artery flow parameters, and CKD, which are all closely related to vascular aging and arterial stiffness. Identified circulating proteins are markers of vascular burden, immune regulation, blood-brain barrier, apoptosis and tissue maintenance. The results of these studies emphasize the importance of a holistic approach to age related organ dysfunction, and careful management of vascular risk factors in the aging individual.