Background In Huntington’s disease (HD) cognitive decline can occur before unequivocal motor signs become apparent. Unfortunately, the exact progression of cognitive decline is unknown. As cognitive decline starts early in the course of the disease and shows a progressive nature cognition can be seen as a key target for symptomatic treatment.

Objective The main aim of this study is to evaluate the progression of cognitive decline across all HD stages, from pre-motormanifest to advanced HD.

Methods In the European REGISTRY study 2669 HD expansion gene carriers underwent annual cognitive assessment. General linear mixed models were used to model the cognitive decline for each cognitive task across all disease stages. Additionally, a model was established to evaluate the cognitive decline based on CAG length and age rather than disease stage.

Results All administered tasks are sensitive in discriminating between pre-motormanifest (close to estimated disease onset) and the subsequent motormanifest stages from 1 till stage 4. The first two cards of the Stroop discriminate from pre-motormanifest (far from estimated disease onset) through the latest stage 5.

The model with CAG length and age revealed that CAG length gives the best indication about the cognitive performance and the performance declines with older age.

Conclusion The in REGISTRY administered cognitive tasks are sensitive to discriminate between all stages of the disease. It seems that cognitive performance is the most dependent on CAG length and performance worsens over time.