Associations of Cerebrovascular Regulation and Arterial Stiffness With Cerebral Small Vessel Disease: A Systematic Review and Meta‐Analysis

Abstract

Background Cerebral small vessel disease (cSVD) is a major contributing factor to ischemic stroke and dementia. However, the vascular pathologies of cSVD remain inconclusive. The aim of this systematic review and meta‐analysis was to characterize the associations between cSVD and cerebrovascular reactivity (CVR), cerebral autoregulation, and arterial stiffness (AS). Methods and Results MEDLINE, Web of Science, and Embase were searched from inception to September 2023 for studies reporting CVR, cerebral autoregulation, or AS in relation to radiological markers of cSVD. Data were extracted in predefined tables, reviewed, and meta‐analyses performed using inverse‐variance random effects models to determine pooled odds ratios (ORs). A total of 1611 studies were identified; 142 were included in the systematic review, of which 60 had data available for meta‐analyses. Systematic review revealed that CVR, cerebral autoregulation, and AS were consistently associated with cSVD (80.4%, 78.6%, and 85.4% of studies, respectively). Meta‐analysis in 7 studies (536 participants, 32.9% women) revealed a borderline association between impaired CVR and cSVD (OR, 2.26 [95% CI, 0.99–5.14]; P =0.05). In 37 studies (27 952 participants, 53.0% women) increased AS, per SD, was associated with cSVD (OR, 1.24 [95% CI, 1.15–1.33]; P <0.01). Meta‐regression adjusted for comorbidities accounted for one‐third of the AS model variance ( R 2 =29.4%, P moderators =0.02). Subgroup analysis of AS studies demonstrated an association with white matter hyperintensities (OR, 1.42 [95% CI, 1.18–1.70]; P <0.01). Conclusions The collective findings of the present systematic review and meta‐analyses suggest an association between cSVD and impaired CVR and elevated AS. However, longitudinal investigations into vascular stiffness and regulatory function as possible risk factors for cSVD remain warranted.

Sex-specific mechanisms of cerebral microvascular BKCadysfunction in a mouse model of Alzheimer’s disease

“…Paradoxically, we did not observe any significant changes in autoregulation. Although loss of autoregulation is observed in cerebral small vessel disease 45 and it was shown to occur in some rodent models of AD 46 , human studies have also failed to observe cerebral autoregulation impairments in AD patients 47 . The mechanistic explanation underlying these differences in autoregulation between AD models and humans remain unclear and require further exploration.…”

Leukoaraiosis: Epidemiology, Imaging, Risk Factors, and Management of Age-Related Cerebral White Matter Hyperintensities

“…180 Although the associations between LA and measures of cerebrovascular regulation and arterial stiffness have not been assessed independently, the significant associations between CSVD markers and increased arterial stiffness and impaired cerebrovascular reactivity seem to indicate that cerebrovascular regulation and arterial stiffness may have some role in the development or progression of LA. 180 Collectively, these findings suggest a strong association between arterial stiffness and LA. We believe that arterial stiffness should be considered a risk factor for LA and that it represents a potential mechanism of LA onset and progression.…”

“…Thus, arterial stiffness could be a crucial cause of rapid LA progression in older individuals. Recently, a systematic review and meta-analysis characterized the associations between CSVD markers (such as LA, lacunes, perivascular spaces, cerebral microbleeds, and recent small subcortical infarcts) and cerebrovascular reactivity, cerebral autoregulation, and arterial stiffness [ 180 ]. Although the associations between LA and measures of cerebrovascular regulation and arterial stiffness have not been assessed independently, the significant associations between CSVD markers and increased arterial stiffness and impaired cerebrovascular reactivity seem to indicate that cerebrovascular regulation and arterial stiffness may have some role in the development or progression of LA [ 180 ].…”