Abstract
BackgroundSubcortical ischemic vascular dementia (SIVD) is very common among the older people, but has no approved treatment. Preclinical trials show that remote ischemic conditioning (RIC) reduces recurrence of ischemic stroke. We hypothesize that RIC may also be an effective therapy for patients with SIVD.MethodsThirty-seven consecutive SIVD cases were enrolled in this randomized control study. Eighteen RIC patients underwent five brief cycles of conditioning (bilateral upper limb compression at 200 mmHg) followed by reperfusion twice daily over 6 consecutive months. Nineteen control patients underwent the same process, but at a pressure of 60 mmHg which caused no restriction on the blood flow of the upper limb. The primary outcome measures were changes in neuropsychological assessments. The secondary outcomes included the changes in high-sensitive C-reactive protein (hs-CRP) concentration, white matter lesion volume (WMLV), diffusion tension imaging (DTI) metrics of white matter. All data were collected at baseline and follow-up.ResultsA significant treatment difference favoring RIC at 6 months was observed on performance of Hopkins Verbal Learning Test-Revised (HVLT-R), Controlled Oral Word Association Test (COWAT), Trail Making Test A and B (TMT-A & TMT-B), and Judgment of Line Orientation (JLO) (p < 0.05). The control group did not show much improvement after the treatment, and only with a slight change in HVLT-R and TMT-R (p < 0.05). Covariance analysis of efficacy between the two groups suggested that RIC patients performed better on JLO than control patients at the 6-month follow-up (RIC 23.10 vs. control 18.56; p = 0.013). Although DTI metrics were comparable, Hs-CRP levels and WMLV in RIC patients showed a declining trend.ConclusionsOver the 6-month treatment period, we found that RIC was safe and effective for improving cognitive function in SIVD patients.Trial registrationClinical Trial Registration (http://www.clinicaltrials.gov), Unique identifier: NCT 03022149; Retrospectively registered; Date of registration: January 16, 2017.
Highlights
Subcortical ischemic vascular dementia (SIVD) is very common among the older people, but has no approved treatment
Exclusion criteria included dementia diagnosed as other causes, such as Alzheimer’s disease and Lewy body dementia; the patients cannot complete neuropsychological testing, or experienced new strokes within 3 months before enrollment; small vessel disease due to inheritance or inflammation; schizophrenia or a score > 17 on the Hamilton Depression Scale (HAMD); cancer; clinically significant systemic diseases; peripheral vascular disease; use of donepezil and memantine that may affect cognitive functioning; Refusal to sign informed consent
As evidenced by the improvement in Judgment of Line Orientation (JLO) performance, our study indicates that remote ischemic conditioning (RIC) may improve visuospatial perception and spatial orientation ability in patients with SIVD
Summary
Subcortical ischemic vascular dementia (SIVD) is very common among the older people, but has no approved treatment. Preclinical trials show that remote ischemic conditioning (RIC) reduces recurrence of ischemic stroke. Vascular dementia is the second most common cause of dementia after Alzheimer’s disease, comprising around 15% of dementia cases [1]. Subcortical ischemic vascular dementia (SIVD) is a major cause of vascular dementia, which is clinically homogeneous and results from small vessel disease and hypoperfusion [2]. Unlike Alzheimer’s disease, no authorized treatments exist for SIVD to date. Transient limb ischemic conditioning, which could help to reduce proinflammatory cytokine synthesis and increase cerebral blood flow, has been suggested to be a protective treatment against recurrent stroke in cranial atherosclerotic stenosis [5, 6]
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