Dissociating cognitive compensation from cognitive deficit in neurodegenerative diseases: the model of premanifest Huntington’s disease mutation carriers

Abstract

Abstract Cognitive reserve is the ability to actively cope with brain deterioration and delay cognitive decline in neurodegenerative diseases. We combined computational modelling (drift diffusion models, DDMs) and neuroanatomical analysis using Huntington’s disease (HD) as a genetic model of neurodegenerative disease to study compensation in premanifest mutation carriers (preHDs). Twenty preHDs, 28 early-stage HD patients (earlyHDs), and 45 controls performed a discrimination task. We used DDMs to investigate underlying cognitive performances and explored the relationship with neuroanatomical substrates. Compared with controls, earlyHDs performed less and preHDs performed similarly. DDMs showed a progressive increase in the amount of evidence needed to take a decision from controls to preHDs and earlyHDs. This increase in response threshold predicted an increase in the rate of evidence accumulation. In preHDs, the higher rate was associated with left parietal and hippocampal hypertrophy, and showed an inversed U-shaped pattern over the course of disease progress, characteristic of compensation.