Alexis N. Simpkins, MD, PhD
Cerebral small vessel disease (sCVD) is an important cause of both vascular dementia and lacunar infarction. Accumulation of white matter lesions and lacunar infarcts from sCVD is associated with cognitive dysfunction, increased risk of stroke, and worsened neurologic outcome after stroke. Here the authors test the hypothesis that remote ischemic conditioning (RIC) can improve cognitive outcomes in patients with mild cognitive impairment and cSVD as a follow up to the pilot study in which they showed that cSVD can reduce white matter disease and increase mean velocity of the middle cerebral arteries.
This study was a 1-year, single-center, prospective, double-blinded, randomized, placebo controlled study of consented patients of Han Chinese decent between 45 and 80 years of age with mild cognitive impairment defined by a pre-treatment MMSE and MOCA score, sCVD as defined by the Standards for Reporting Vascular Changes on Neuroimaging criteria on pre-treatment brain MRI and automated measurements of white matter disease of MRI-fluid-attenuated inversion recovery sequences. Patients were excluded if they did not complete > 80 % of the therapy, had significant cardiac disease, medical illness, medical contraindication to having RIC performed, intracerebral hemorrhage, stroke within the past 6 months, or an alternate etiology of small vessel disease such as vasculitis, genetic disorder, > 50% stenosis of intracranial vessel, or atrial fibrillation. The difference between the RIC and placebo group was the pressure of the cuff inflation from the automated device (200 mmHg in RIC cycling for 5 cycles of inflation and deflating for 5 minutes vs. 50mmHg in control).
A total of 30 patients were included in the analysis with (RIC = 14, control = 16). While there were no differences in the burden of white matter disease between the RIC group and control at 1 year, the change in white matter disease within the RIC group was significantly reduced from baseline at 1 year. There was also an improvement in the visuospatial and executive functioning on the MoCA scoring in the RIC patients at one year. In addition, there was a reduction in pulsatile index in the MCA’s measured by TCD, total cholesterol, triglycerides, LDL, and homocysteine at 1 year in the RIC group at one year in comparison to baseline.
Some of the limitations of the study acknowledged by the authors include the small sample size. Also, cSVD is a chronic disease, and the length of this study was one year. In addition, this study was not a mechanistic study; thus, we cannot state which biological mediators may have been either up or downregulated by the RIC therapy and resulted in the effects on cSVD and cognition that were found.
This study addresses an area of significant need since the prevalence of sCVD and its sequela are likely to be more prevalent as the size of the elderly population increases. Although there are more questions to be answered, these findings show that reduction in white matter disease can improve some components of cognition in patients with cSVD. Further research is needed to determine if this intervention can be used in conjunction with medical therapy to reduce white matter disease burden and result in measurable improvement in the patient’s quality of life with long-term use.
Figure 2. A: The brain lesions showed on magnetic resonance imaging (MRI) mean (±SE) change from baseline of the intention-to-treatment population at 1 year. B: The MRI presentations (fluid-attenuated inversion recovery) of patient with cerebral small vessel disease (cSVD) pre- and post-RIC treatment: 1 Pre-treatment, the WMHs volume was 11.69 cm3; 2 post-treatment, the WMHs volume was 7.05 cm3.
Figure 3. The mean (±SE) changes of cognition from baseline of the intention-to-treatment population at 1 year.
