In our aging society, diseases in the elderly come more and more into focus. An important issue in research is Mild Cognitive Impairment (MCI) and Alzheimer’s Disease (AD) with their causes, diagnosis, treatment, and disease prediction. In this work, the Brain Age Gape Estimation (BrainAGE) method was applied to examine the impact of the Apolipoprotein E (APOE) genotype on cognitive deterioration and MCI and AD development. We examined whether a combination of BrainAGE and APOE status could improve diagnostic accuracy and prediction of cognitive decline in MCI patients. We analyzed structural magnetic resonance images (MRIs) of 405 subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database with the BrainAGE framework. Hereby we tested for differences between carrier and non-carrier of APOE e4 within the diagnostic groups during follow-up time and for estimated longitudinal changes up to 1600 days after baseline. The influence of the APOE status on conversion from MCI to AD was analyzed within all allelic subgroups as well as for carriers and non-carriers, and for a special risk group of MCI patients. The BrainAGE method differed significantly between normal controls, stable MCI (sMCI) and progressive MCI (pMCI) as well as AD patients. Differences between APOE e4 carriers and non-carriers were seen with BrainAGE changing rates over time and for NO/sMCI vs. pMCI/AD. During baseline and follow-up, BrainAGE scores correlated significantly with cognitive scores for carriers and non-carriers throughout the whole sample, and for subgroups of pMCI and AD patients. Prediction of conversion was most accurate using the BrainAGE score compared to cognitive scores, even when the patient’s APOE status was unknown. Diagnosing AD and its preliminary phases, as well as predicting conversion from MCI to AD, the BrainAGE method is a useful and accurate tool even if there is information of the patient’s APOE status missing.
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