Bias induced by ignoring double truncation inherent in autopsy-confirmed survival studies of neurodegenerative diseases.

Neurodegenerative diseases require an autopsy for confirmation of diagnosis. When death is the event of interest, studies based on autopsy-confirmed diagnoses result in right truncated survival times because individuals who live past the end of study date do not receive a pathological diagnosis and are therefore not included in the sample. Furthermore, many studies of neurodegenerative diseases recruit subjects only after the onset of the disease, which may result in left truncated survival times. Therefore, double truncation, the simultaneous presence of left and right truncation, is inherent in many autopsy-confirmed survival studies of neurodegenerative diseases. The main focus of this paper is to inform about the inherent double truncation in these studies and demonstrate how to properly estimate and compare survival distribution functions in this setting. We do so by conducting a case study of subjects with autopsy-confirmed Alzheimer's disease and frontotemporal lobar degeneration. This case study is supported by extensive simulation studies, which provide several new contributions to the literature on survival distribution estimation in the context of double truncation.