Neurocognitive disorders (i.e. cognitive impairment and dementia) are a major health problem and significant contributor to death and dependence worldwide. Identifying neurocognitive disorders at the earliest, preclinical stages is of great public health interest as disease-modifying interventions are most likely to be effective at this phase. However, there are currently no valid, reliable and convenient diagnostic biomarkers to distinguish early neurocognitive disorders from benign symptoms. This is an important knowledge gap and a major limitation of current approaches to dementia prevention. The potential for blood biomarkers in this field is significant, with emerging research reporting that some novel blood-biomarkers may be comparable to cerebrospinal fluid markers in terms of diagnostic accuracy, but more pragmatic for population-level screening and risk stratification for primary prevention trials. During this fellowship I will undertake an innovative programme of research to develop blood-based biomarkers for the earliest, preclinical stages of neurocognitive disease using ‘gold standard’ neuroimaging outcome measures (ß-amyloid and tau on brain-PET) and structural MRI measures of early vascular brain injury. I will internally validate these biomarkers in the deeply phenotyped Framingham Heart Study followed by external validation, along with the development of a dementia risk prediction rule, in the globally diverse Prospective Urban and Rural Epidemiological study (representative of patients in primary care, the intended ‘context of use’).
The results of this research are expected to have an important public health impact including: 1) reliably identifying (and excluding) individuals with pre-clinical phases of neurocognitive disorders for primary prevention, 2) optimising participant selection in clinical trials, 3) informing a primary-care delivered population-level screening approach for neurocognitive disorders, and 4) helping to guide recommendations on prevention and treatment for patients attending Memory Disorders clinics. This research proposal will also facilitate my transition towards research independence and development as an emerging leader in neurocognitive disorders research.
