Association of cerebral small vessel disease burden with brain structure and cognitive and vascular risk trajectories in mid-to-late life

Abstract

We characterize the associations of total cerebral small vessel disease (SVD) burden with brain structure, trajectories of vascular risk factors, and cognitive functions in mid-to-late life. Participants were 623 community-dwelling adults from the Whitehall II Imaging Sub-study with multi-modal MRI (mean age 69.96, SD = 5.18, 79% men). We used linear mixed-effects models to investigate associations of SVD burden with up to 25-year retrospective trajectories of vascular risk and cognitive performance. General linear modelling was used to investigate concurrent associations with grey matter (GM) density and white matter (WM) microstructure, and whether these associations were modified by cognitive status (Montreal Cognitive Asessment [MoCA] scores of < 26 vs. ≥ 26). Severe SVD burden in older age was associated with higher mean arterial pressure throughout midlife (β = 3.36, 95% CI [0.42-6.30]), and faster cognitive decline in letter fluency (β = −0.07, 95% CI [−0.13–−0.01]), and verbal reasoning (β = −0.05, 95% CI [−0.11–−0.001]). Moreover, SVD burden was related to lower GM volumes in 9.7% of total GM, and widespread WM microstructural decline (FWE-corrected p < 0.05). The latter association was most pronounced in individuals who demonstrated cognitive impairments on MoCA (MoCA < 26; F3,608 = 2.14, p = 0.007). These findings highlight the importance of managing midlife vascular health to preserve brain structure and cognitive function in old age.

Neuroimaging biomarkers of small vessel disease in cerebral amyloid angiopathy‐related intracerebral hemorrhage

“…In CAA, a kind of SVD, the deposition of Aβ may impair the architecture and influence the vasomotor function of vessels, potentially leading to stroke or ICH. The total burden of SVD causes diffuse changes in brain microstructure, which impairs cognition, especially in mid‐to‐late life 16 . The SVD burden in individuals with CAA is often noticeable, as the CAA progresses, the key brain networks vital for rehabilitation, learning, and cognitive reserve are likely to disrupt.…”

“…The total burden of SVD causes diffuse changes in brain microstructure, which impairs cognition, especially in mid‐to‐late life. 16 The SVD burden in individuals with CAA is often noticeable, as the CAA progresses, the key brain networks vital for rehabilitation, learning, and cognitive reserve are likely to disrupt. Hence, the severity of neuroimaging abnormalities assessed by CT and MRI scans, such as WML, cortical cerebral microinfarcts 17 and brain atrophy, indicate the frailty of the underlying brain, which influences susceptibility to, and recovery from, ICH.…”

Implication of heart rate variability on cerebral small vessel disease: A potential therapeutic target

“…Thirdly, many risk factors and mechanisms which were reported to be associated with HRV, such as diabetes and inflammation, were deemed to exert interactive effects that enhance the link between HRV and CSVD 4,6,12,54 . Meanwhile, symptoms including postural hypotension, cognitive impairment, and sleep disorders were related to both HRV and CSVD 11,55–57 . Furthermore, heart rate control may also be a possible reason 12 .…”

“… 4 , 6 , 12 , 54 Meanwhile, symptoms including postural hypotension, cognitive impairment, and sleep disorders were related to both HRV and CSVD. 11 , 55 , 56 , 57 Furthermore, heart rate control may also be a possible reason. 12 Taken together, the complex series of cascading responses in the regulation of the ANS during CSVD requires further investigation.…”

Role of Vitamin D Deficiency in the Pathogenesis of Cardiovascular and Cerebrovascular Diseases

“…In addition to stroke, cerebrovascular diseases also manifest with cognitive impairment. The term vascular cognitive impairment (VCI) refers to diverse forms of cognitive disorders (ranging from mild cognitive impairment to vascular dementia), which associate with various cerebrovascular pathologies, ranging from cerebral small vessel disease [ 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 ] to large vessel atherosclerosis and stroke [ 152 , 153 , 154 , 155 ]. VCI is the second most common cause of age-related cognitive impairment and dementia after Alzheimer’s disease (AD).…”