TARDBP and Alzheimer disease: ADAD constitutes a unique training sample as the disease onset is at a relatively young age and the development of AD pathology and cognitive decline are not confounded by age-related comorbidities (eg, TDP-43, small-vessel disease).26 Because in ADAD the time course of the development of dementia symptoms is strongly genetically driven, EYO can be used as a surrogate marker of AD-related cognitive decline.27–29 Here, we first trained biomarker-based machine learning models for predicting EYO in ADAD.