This paper is a proposal for an update on the characterization of cognitive impairments associated with sporadic cerebral small vessel disease (SVD). We pose a series of questions about the nature of SVD‐related cognitive impairments and provide answers based on a comprehensive review and meta‐analysis of published data from 69 studies. Although SVD is thought primarily to affect executive function and processing speed, we hypothesize that SVD affects all major domains of cognitive ability. We also identify low levels of education as a potentially modifiable risk factor for SVD‐related cognitive impairment. Therefore, we propose the use of comprehensive cognitive assessments and the measurement of educational level both in clinics and research settings, and suggest several recommendations for future research.

Background and Purpose: Cerebral small vessel disease—a major cause of stroke and dementia—is associated with cerebrovascular dysfunction. We investigated whether short-term isosorbide mononitrate (ISMN) and cilostazol, alone or in combination, improved magnetic resonance imaging–measured cerebrovascular function in patients with lacunar ischemic stroke. Methods: Participants were randomized to ISMN alone, cilostazol alone, both ISMN and cilostazol, or no medication. Participants underwent structural, cerebrovascular reactivity (to 6% carbon dioxide) and phase-contrast pulsatility magnetic resonance imaging at baseline and after 8 weeks of medication. Results: Of 27 participants (mean age, 68±7.7; 44% female), 22 completed cerebrovascular reactivity and pulsatility imaging with complete datasets. White matter cerebrovascular reactivity increased in the ISMN (β=0.021%/mm Hg [95% CI, 0.003–0.040]) and cilostazol (β=0.035%/mm Hg [95% CI, 0.014–0.056]) monotherapy groups and in those taking any versus no medication (β=0.021%/mm Hg [95% CI, 0.005–0.037]). Conclusions: While limited by small sample size, we demonstrate that measuring cerebrovascular function with magnetic resonance imaging is feasible in clinical trials and that ISMN and cilostazol may improve cerebrovascular function. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02481323. URL: www.isrctn.com ; Unique identifier: ISRCTN12580546. URL: www.clinicaltrialsregister.eu ; Unique identifier: EudraCT 2015-001953-33.

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Blood-brain barrier (BBB) is known to be impaired in cerebral small vessel disease (SVD), and is measurable by dynamic-contrast enhancement (DCE)-MRI. In a cohort of 69 patients (42 sporadic, 27 monogenic SVD), who underwent 3T MRI, including DCE and cerebrovascular reactivity (CVR) sequences, we assessed the relationship of BBB-leakage hotspots to SVD lesions (lacunes, white matter hyperintensities (WMH), and microbleeds). We defined as hotspots the regions with permeability surface area product highest decile on DCE-derived maps within the white matter. We assessed factors associated with the presence and number of hotspots corresponding to SVD lesions in multivariable regression models adjusted for age, WMH volume, number of lacunes, and SVD type. We identified hotspots at lacune edges in 29/46 (63%) patients with lacunes, within WMH in 26/60 (43%) and at the WMH edges in 34/60 (57%) patients with WMH, and microbleed edges in 4/11 (36%) patients with microbleeds. In adjusted analysis, lower WMH-CVR was associated with presence and number of hotspots at lacune edges, and higher WMH volume with hotspots within WMH and at WMH edges, independently of the SVD type. In conclusion, SVD lesions frequently collocate with high BBB-leakage in patients with sporadic and monogenic forms of SVD.