Research on the Early and Prognosis Diagnosis of Vascular Dementia

Around 10% of stroke survivors develop dementia within 3 months after stroke and over 20% more stroke patients have dementia in the subsequent 3 years. Previous studies documented a close relationship between stroke and Alzheimer's disease (AD). There are, however, no reliable biomarkers to detect cognitive dysfunction and dementia among stroke patients or to predict the risks of vascular dementia (VD) and AD among patients with stroke. There is a clear need to identify novel mediators of cognitive dysfunction in stroke patients to provide insights into the pathogenesis, to tailor clinical care based on risks, and to develop new therapeutic strategies. While the expression of messenger RNAs (mRNAs) and microRNAs (miRNAs) account for only \~1% of all transcribed species, up to 90% of the mammalian genome is transcribed as long non-coding RNAs (lncRNAs), a heterogeneous group of non-coding transcripts longer than 200 nucleotides. LncRNAs have been shown to be functional and involved in specific physiological and pathological processes through epigenetic, transcriptional and post-transcriptional mechanisms. While the roles of lncRNAs in human diseases including cancer and neurodegenerative disorders are beginning to emerge, it remains unclear how lncRNA regulation contributes to cognitive dysfunction and dementia in stroke patients. In this proposal, we seek to apply next-generation sequencing technology to investigate circulating lncRNA expression, as well as exosomal RNAs in the subjects with and without cognitive dysfunction or dementia. In addition, we will apply the near-infrared spectroscopy (NIRS) to evaluate cerebral blood flow, metabolism and oxygenation in these subjects. We will test the hypothesis that circulating lncRNA/exosomal RNA signature and NIRS imagaing can reflect the cognitive states in stroke patients. The accuracy, sensitivity and specificity of the lncRNA-exosomal RNA-NIRS-based cognitive dysfunction scoring system will then be tested in an independent, large validation cohort. Next, we propose to test the hypothesis that circulating lncRNAs/exosomal RNA and NIRS imaging can be novel prognostic biomarkers to predict cognitive dysfunction and dementia in stroke patients. These studies will also establish a set of novel, lncRNA-based diagnostic and prognostic biomarker in stroke patients to improve clinical preventive and therapeutic care.