An undesired outcome of an aging society is the increasing prevalence of age-associated diseases. Among these emerging challenges, inadequate treatment for dementia is one of the biggest unmet healthcare needs globally. Alzheimer’s disease (AD) and vascular dementia (VaD) are considered the two major age-related causes of dementia. We chose vascular cognitive impairment (VCI) in this proposal as VCI more accurately covers the full spectrum of symptoms and recognizes that the mechanisms involved are complex and heterogenous: not only systemic or local large or small cerebral vessel disease resulting in overt strokes or microinfarcts, microhemorrhages, and white matter injury, but also neurodegeneration and AD pathology.
Our Research Group, highly focused on VCI, involves multiple institutions and investigators from across Singapore, led by well-established and productive PIs, seeks to:
- Theme 1: undertake a multiple lifestyle interventional study to retard VCI-associated disease progression and to evaluate selected biomarkers for their predictive and surrogate outcome potential.
- Theme 2: assess longitudinal changes in brain structure, function and pathology using (MRI, PET, retinal) neuroimaging, as well as novel blood and genetic markers to determine their diagnostic and prognostic value as biomarkers.
- Theme 3: to link Themes 1 and 2 with health services research (HSR) on healthcare costs associated with VCI to facilitate clinical and policy decision making. Hence, we shall utilise basic, translational, clinical and implementation science approaches to improve the understanding of basic mechanisms underlying age-related VCI which will improve disease diagnosis, reduce incidence and progression through the development of new therapies and hence enhance quality of life.
Themes 1 and 2 will set up two projects that we hope will point to new approaches in VCI prevention: one through careful longitudinal multimodal phenotyping of individuals at risk for cognitive impairment and dementia focusing on vascular burden that may reveal new insights into underlying disease mechanisms with therapeutic implications, and the other through the multiple lifestyle intervention study SINGER. These two prospective studies paired with advanced machine learning approaches will lead to predictive biomarkers for VCI diagnosis, risk determination and prognosis, and treatment efficacy. If these projects are successful, we will have in the process, delivered a trial testing lifestyle intervention that are up to international standards. We consider the use of imaging markers as a secondary outcome to be not only novel, but also highly scientifically rigorous which may reduce sample sizes for future trials.
Theme 3 will develop macro (population level) and micro (individual level) system models to infer causal relationships between health states, interventions/policies, and outcomes in the context of delay and/or prevent vascular cognitive impairment allowing for the facilitation of clinical and policy decision and intervention strategies, which will make Singapore a global leader in vascular cognitive impairment. Thus, there is capacity for translation of findings to the following therapeutic fields:
- Neurodegenerative diseases: Alzheimer’s disease, Parkinson’s disease, Frontal Temporal Dementia, Retinal degeneration, mitochondrial diseases
- Vascular Disease: Acute Stroke Intervention and chronic stroke complications
- Psychiatry: Schizophrenia, Depression
- Neuroinflammatory: Multiple Sclerosis and related demyelinating diseases, neuro-infections, epilepsy
Please click on the respective themes to read more.
