Grant: Project Grant

Alzheimer's disease (AD) pathology may be present in the brain as many as 10-15 years before symptoms occur. As in most diseases, early treatment, before too much brain damage has been done, is likely to be more effective. However, accurately identifying people at risk of dementia due to AD early, before symptoms appear, is extremely difficult. We propose to study people with subjective cognitive decline - they have issues with memory or cognition, but not enough to be captured by standard cognitive tests. We will also study people with mild cognitive impairment - their memory issues can be measured with standard tests. Both groups have significantly increased risk of later dementia, making them very interesting to study for early AD. We have built a database of magnetic resonance images (MRI), cognitive and clinical data, with extensive follow up information from 7000+ subjects. We will use this data to develop and validate our DaMoCLES (Decline prediction using MRI, Cognition and LifEStyle) score. DaMoCLES will combine (1) results from sophisticated MRI analysis to detect patterns of brain atrophy typical of AD, (2) tests of cognition that can be completed quickly in the clinic, and (3) clinically available cardiovascular risk lifestyle factors known to be associated with cognitive decline. DaMoCLES is formulated to be a clinically useful tool to help determine which patients will develop cognitive decline. It will help clinicians to develop optimal patient-specific preventive treatment. In addition, the DaMoCLES score will enable enrichment of study populations in clinical trials, so that only people that are likely to decline are included in the trials, and any benefit of the drug will be easier to see. This makes clinical trials more powerful, allowing drugs to be properly tested with fewer participants over shorter durations, bringing new treatments to patients sooner.