IntroductionCognitive impairment is the main clinical manifestation of cerebral small vessel disease (CSVD). However, the mechanism and structural damage in different domains of cognitive disorders are poorly understood. There is an urgent need to quantify the relation between diffusion tensor imaging (DTI) data and impaired cognitive testing in CSVD, which may help to find biomarkers for early diagnosis or treatment evaluation. We aim to summarise the understanding of association between DTI findings and domain-specific cognitive impairment.Methods and analysisPubMed, EMBASE, Web of science, Cochrane library, Chinese National Knowledge Infrastructure Databases, Wanfang, SinoMed and VIP will be searched, from 1 January 1994 to 1 August 2021. The ClinicalTrials.gov and Chictr.org.cn records will also be searched to identify further potential studies. The included studies should report fractional anisotropy and/or and mean diffusivity/apparent diffusion coefficient data for one or more individual regions of interest in DTI analysis. Meanwhile, cognitive testing scores are also needed. This systematic review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The quality of cohort or case–control studies will be evaluated by the Newcastle-Ottawa Scale, and the cross-section studies will be evaluated by Agency for Healthcare Research and Quality scale. Meta-analysis, subgroup and sensitivity analyses, and publication bias will be all performed with Stata.Ethics and disseminationPatients and the public will not be involved in this study. The existing data from published studies will be used. The findings from this research will be relevant information regarding the association of DTI metrics with cognitive disorder, which will be published in a peer-reviewed journal. If we need to amend this protocol, we will give the date of each amendment, describe the change and give the rationale. Changes will not be incorporated into the protocol.PROSPERO registration numberCRD42021226133.

Background: Vascular cognitive impairment (VCI) is one of the most common diseases among the elderly. However, few effective drugs have been approved for VCI. Traditional Chinese medicine (TCM) has been used in dementia for thousands of years. Currently, there is limited high-quality evidence for the efficacy of TCM, and the specific characteristics of its effects and the appropriate patient populations for TCM therapies remain unclear. Herein, we aim to explore the effectiveness and safety of TCM by conducting a longitudinal, patient-centered study. Methods: REgistry for Vascular cognitive Impairment trEatment With Traditional Chinese Medicine (REVIEW-TCM) is a prospective, observational disease registry study. 1000 VCI patients at the Hunan Hospital of Integrated Traditional Chinese and Western Medicine will be recruited based on the following criteria: aged 18 years or older, Montreal Cognitive Assessment (MoCA) score <26, and Hachinski Ischemic Score (HIS)≥7. There is no strict limit on the intervention, and different TCM formulas will be focused. Cognition, activity of daily living, quality of life, mental, psychology, ZHENG of TCM, and burden of caregiver will be evaluated at admission, and 6, 12, 18, and 24 months. Meanwhile, biological tests and neuroimaging examination will be applied to further explore the mechanism of TCM. Especially, a mixed-methods embedded design will be applied by adopting quantitative and qualitative studies to explore patients-reported outcomes of TCM. Finally, propensity score matching will be adopted to analyze the effectiveness of TCM. Discussion: To the best of our knowledge, the REVIEW-TCM study is the first comprehensive, prospective, mixed-methods, registry-based study to evaluate TCM treatment in VCI, which will analyze the effectiveness and safety of TCM in the real world and explore population characteristics and subtypes of VCI suitable for TCM. Study registration: This study was registered on www.chictr.org.cn (ChiCTR2200064756).

ObjectiveTo investigate the association between diffusion tensor imaging (DTI) findings and domain-specific cognitive impairment in cerebral small vessel disease (CSVD).MethodsDatabases such as PubMed, Excerpta Medical Database (EMBASE), Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure Databases (CNKI), Wanfang, Chinese Biomedical Literature Database (SinoMed), and Chongqing Chinese Science and Technology Periodical Database (VIP) were comprehensively retrieved for studies that reported correlation coefficients between cognition and DTI values. Random effects models and meta-regression were applied to account for heterogeneity among study results. Subgroup and publication bias analyses were performed using Stata software.ResultsSeventy-seven studies involving 6,558 participants were included in our meta-analysis. The diagnosis classification included CSVD, white matter hyperintensities (WMH), subcortical ischemic vascular disease, cerebral microbleeding, cerebral amyloid angiopathy (CAA), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and Fabry disease. The pooled estimates showed that the fractional anisotropy (FA)-overall exhibited a moderate correlation with general cognition, executive function, attention, construction, and motor performance (r = 0.451, 0.339, 0.410, and 0.319), and the mean diffusitivity/apparent diffusion coefficient (MD/ADC)-overall was moderately associated with general cognition, executive function, and memory (r = −0.388, −0.332, and −0.303, respectively; ps &lt; 0.05). Moreover, FA in cingulate gyrus (CG), cerebral peduncle (CP), corona radiata (CR), external capsule (EC), frontal lobe (FL), fornix (FOR), internal capsule (IC), and thalamic radiation (TR) was strongly correlated with general cognition (r = 0.591, 0.584, 0.543, 0.662, 0.614, 0.543, 0.597, and 0.571), and a strong correlation was found between MD/ADC and CG (r = −0.526), normal-appearing white matter (NAWM; r = −0.546), and whole brain white matter (WBWM; r = −0.505). FA in fronto-occipital fasciculus (FOF) (r = 0.523) and FL (r = 0.509) was strongly associated with executive function. Only MD/ADC of the corpus callosum (CC) was strongly associated with memory (r = −0.730). Besides, FA in CG (r = 0.532), CC (r = 0.538), and FL (r = 0.732) was strongly related to the attention domain. Finally, we found that the sample size, etiology, magnetic resonance imaging (MRI) magnet strength, study type, and study quality contributed to interstudy heterogeneity.ConclusionLower FA or higher MD/ADC values were related to more severe cognitive impairment. General cognition and executive function domains attracted the greatest interest. The FL was commonly examined and strongly associated with general cognition, executive function, and attention. The CC was strongly associated with memory and attention. The CG was strongly related to general cognition and attention. The CR, IC, and TR were also strongly related to general cognition. Indeed, these results should be validated in high-quality prospective studies with larger sample sizes.Systematic review registrationhttp://www.crd.york.ac.uk/PROSPERO, identifier: CRD42021226133.