The Role of Amyloid-Beta in the Late-Onset Post-Stroke Vascular Cognitive Impairment (I)

Project: A - Government Institutionb - Ministry of Science and Technology

Project Details

Description

There are around 10% stroke patients develop dementia within 3 months after the stroke and over 20% more stroke patients suffer from dementia in the subsequent 3 years. There are currently about 200,000 dementia patients in Taiwan and the number of dementia patients is increasing. Dementia not only is a simple aging process but also makes huge impacts on the health care and social safety systems. Comparing with patients without dementia, patients with dementia have more complications of diseases and higher cost of health care and more care-giver burden. Vascular cognitive impairment (VCI), including vascular dementia (VaD) and vascular mild cognitive impairment (VaMCI), following Alzheimer disease (AD), is the second leading cause of dementia. The molecular events, such as oxidative stress, inflammation, apoptosis and angiogenesis, have been understood in the acute ischemic stroke lesions but the late effects of stroke on late-onset VCI is not clear. In recent studies, simultaneous AD pathology, in terms of senile plaques or amyloid loads, and infarction are commonly found in either AD or VCI patients. The patho-mechanisms of VCI in late stage are speculated to include lacunal infarction in white matter, chronic inflammation and amyloid accumulation. However, the interaction between ischemic brain injury, cerebrovascular perfusion defects and inflammation, amyloid accumulation remain further investigation. In this study, we will collaborate with other medical centers, including NTUH, TSGH, SKMH, CMMH to establish an ischemic stroke cohort and study the risk factors or biomarkers/patho-mechanisms for developing VCI among them. This study will focus on the role of amyloid in the occurrence of VCI by use of novel assay for amyloid-beta concentration in blood, cerebro-vascular perfusion/auto-regulation and amyloid positron emission tomography (PET). We also will test or validate the findings of other sub-proposals, such as genomic effects, inflammasome, Toll-like receptor-related biomarkers, and platelet function. We also will study interaction between these biomarkers and their impacts on the clinical outcome, in terms of early or late VCI or non-VCI. Our work will include the below. Specific aim and Experiments 1 (year 1-2). To dissect all the possible risk factors of VCI in early-onset VCI, stroke without VCI (SW-VCI) and non-stroke controls (NSC), including neuro-image (MRI, PET), cerebro-vascular perfusion/auto-regulation, blood amyloid-beta. Specific aim and Experiments 2 (year 2-3). To dissect all the possible risk factors of VCI in late-onset VCI, stroke without VCI (SW-VCI) and non-stroke controls (NSC), including neuro-image (MRI, PET), cerebro-vascular perfusion/auto-regulation, blood amyloid-beta. Specific aim and Experiments 3 (year 1-3). To dissect all the possible risk factors and all biomarkers in this integrated proposal among early/late-onset VCI, stroke without VCI (SW-VCI) and non-stroke controls (NSC)
StatusFinished
Effective start/end date8/1/157/31/16

Keywords

  • Vascular cognitive impairment
  • amyloid-beta
  • perfusion/auto-regulation
  • Alzheimer disease