A brain signature highly predictive of future progression to Alzheimer's dementia

Early prognosis of Alzheimer's dementia is hard. Mild cognitive impairment (MCI) typically precedes Alzheimer's dementia, yet only a fraction of MCI individuals will progress to dementia, even when screened using biomarkers. We propose here to identify a subset of individuals who share a common brain signature highly predictive of oncoming dementia. This signature was composed of brain atrophy and functional dysconnectivity and discovered using a machine learning model in patients suffering from dementia. The model recognized the same brain signature in MCI individuals, 90% of which progressed to dementia within three years. This result is a marked improvement on the state-of-theart in prognostic precision, while the brain signature still identified 47% of all MCI progressors. We thus discovered a sizable MCI subpopulation which represents an excellent recruitment target for clinical trials at the prodromal stage of Alzheimer's disease. Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. Acknowledgement_List.pdf Preprint submitted to March 5, 2018 1. Introduction Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder. The typical progression of late-onset, sporadic AD comprises a lengthy preclinical stage, a prodromal stage of mild cognitive impairment (MCI), and a final stage of dementia. Usually, by the time patients suffer from dementia, severe and irreversible neurodegeneration has already occurred.