Alzheimer’s disease (AD) is a progressive neurodegenerative condition marked by a decline in cognitive functions with no validated disease modifying treatment. It is critical for timely treatment to detect AD in its earlier stage before clinical manifestation. Mild cognitive impairment (MCI) is an intermediate stage between cognitively normal older adults and AD. To predict conversion from MCI to probable AD, we applied a deep learning approach, multimodal recurrent neural network. We developed an integrative framework that combines not only cross-sectional neuroimaging biomarkers at baseline but also longitudinal cerebrospinal fluid (CSF) and cognitive performance biomarkers obtained from the Alzheimer’s Disease Neuroimaging Initiative cohort (ADNI). The proposed framework integrated longitudinal multi-domain data. Our results showed that 1) our prediction model for MCI conversion to AD yielded up to 75% accuracy (area under the curve (AUC) = 0.83) when using only single modality of data separately; and 2) our prediction model achieved the best performance with 81% accuracy (AUC = 0.86) when incorporating longitudinal multi-domain data. A multi-modal deep learning approach has potential to identify persons at risk of developing AD who might benefit most from a clinical trial or as a stratification approach within clinical trials.
Our aim was to examine whether the influence of apolipoprotein E4 (APOE4) genotype on cognitive decline differs in male and female across the Alzheimer's disease (AD) continuum. Among individuals with normal cognition (NC; n = 415), mild cognitive impairment (MCI; n = 870), and AD (n = 334), we investigated the longitudinal associations of APOE4 genotype and sex with cognitive decline over 13 years. Our cognitive outcomes were Rey Auditory Verbal Learning Test (RAVLT) total learning score and delayed recall and Mini-Mental State Examination (MMSE) score. There were significant effects of the APOE4×sex interaction on change in verbal memory in the MCI group, but not the NC or AD group. Specifically, among individuals with MCI, female APOE4 carriers had a steeper decline in RAVLT total learning score, but not delayed recall or MMSE score compared to all other groups (APOE4 + /Male, APOE4-/Female, APOE4-/Male). In conclusion, female APOE4 carriers have faster rates of memory decline than their male counterparts among MCI individuals.
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