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

Ellström, Katarina LU (2025) In Lund University, Faculty of Medicine Doctoral Dissertation Series
Abstract (Swedish)
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... (More)
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. (Less)
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author
supervisor
opponent
  • Associate Professor Fure, Brynjar, Örebro University, Sweden
organization
publishing date
type
Thesis
publication status
published
subject
keywords
cerebral small vessel disease, CSVD, hypertension, arterial stiffness, blood pressure, common carotid artery, Dopler ultrasound, chronic kidney disase, proteomics, biomarker, epidemiology, general population, Older adult, atrophy, microbleeds, white matter
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
issue
2025:103
pages
98 pages
publisher
Lund University, Faculty of Medicine
defense location
Aulan, Jan Waldenströms gata 1, Skånes Universitetssjukhus i Malmö
defense date
2025-10-17 09:00:00
ISSN
1652-8220
ISBN
978-91-8021-756-9
language
English
LU publication?
yes
id
995ef2cb-578a-4d98-ad09-2f65b6586454
date added to LUP
2025-09-26 19:55:29
date last changed
2025-09-29 10:25:45
@phdthesis{995ef2cb-578a-4d98-ad09-2f65b6586454,
  abstract     = {{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.}},
  author       = {{Ellström, Katarina}},
  isbn         = {{978-91-8021-756-9}},
  issn         = {{1652-8220}},
  keywords     = {{cerebral small vessel disease; CSVD; hypertension; arterial stiffness; blood pressure; common carotid artery; Dopler ultrasound; chronic kidney disase; proteomics; biomarker; epidemiology; general population; Older adult; atrophy; microbleeds; white matter}},
  language     = {{eng}},
  number       = {{2025:103}},
  publisher    = {{Lund University, Faculty of Medicine}},
  school       = {{Lund University}},
  series       = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
  title        = {{Assessment of Vascular Contributions to Cerebral Small Vessel Disease: Data from the general population study "Good Aging in Skåne"}},
  url          = {{https://lup.lub.lu.se/search/files/228529513/KatarinaEllstrom.pdf}},
  year         = {{2025}},
}