Patients with semantic dementia (SD) present with remarkably consistent atrophy of neurons in the anterior temporal lobe and behavioural impairments, such as graded loss of category knowledge. While relearning of lost knowledge has been shown in acute brain injuries such as stroke, it has not been widely supported in chronic cognitive diseases such as SD. Previous research has shown that deep linear artificial neural networks exhibit stages of semantic learning akin to humans. Here, we use a deep linear network to test the hypothesis that relearning during disease progression rather than particular atrophy cause the specific behavioural patterns associated with SD. After training the network to generate the common semantic features of various hierarchically organised objects, neurons are successively deleted to mimic atrophy while retraining the model. The model with relearning and deleted neurons reproduced errors specific to SD, including prototyping errors and cross-category confusions. This suggests that relearning is necessary for artificial neural networks to reproduce the behavioural patterns associated with SD in the absence of \textit{output} non-linearities. Our results support a theory of SD progression that results from continuous relearning of lost information. Future research should revisit the role of relearning as a contributing factor to cognitive diseases.

The differential diagnosis of neurodegenerative diseases, characterized by overlapping symptoms, may be challenging. Brain imaging coupled with artificial intelligence has been previously proposed for diagnostic support, but most of these methods have been trained to discriminate only isolated diseases from controls. Here, we develop a novel machine learning framework, named lifespan tree of brain anatomy, dedicated to the differential diagnosis between multiple diseases simultaneously. It integrates the modeling of volume changes for 124 brain structures during the lifespan with non-linear dimensionality reduction and synthetic sampling techniques to create easily interpretable representations of brain anatomy over the course of disease progression. As clinically relevant proof- of-concept applications, we constructed a cognitive lifespan tree of brain anatomy for the differential diagnosis of six causes of neurodegenerative dementia and a motor lifespan tree of brain anatomy for the differential diagnosis of four causes of parkinsonism using 37594 MRI as a training dataset. This original approach enhanced significantly the efficiency of differential diagnosis in the external validation cohort of 1754 cases, outperforming existing state-of-the art machine learning techniques. Lifespan tree holds promise as a valuable tool for differential diagnostic in relevant clinical conditions, especially for diseases still lacking effective biological markers.