Background Cognitive reserve and physical exercise has been found to have positive function and brain effects in a number of neurodegenerative disorders. No study to date has examined whether these factors can beneficially modulate functional brain activity during the premanifest stages of Huntington’s disease (pre-HD).

Aims We examined the relationship between cognitive reserve, level of physical exercise and functional brain activity in pre-HD, compared with healthy controls, using functional MRI (fMRI) while individuals performed a visuospatial working memory task.

Methods Pre-HD (n=15; M=37.33; SD=10.82) and age- and gender-matched healthy controls (n=15; M=35.60; SD=10.69), completed the Cognitive Reserve Index Questionnaire (CRIq) and the International Physical Activity Questionnaire Long (IPAQ-L). Participants also performed an 18 min fMRI visuospatial working memory task with low (2 items), intermediate-1 (3 items), intermediate-2 (4 items), and high (5 items) memory loads.

Results Pearson’s correlation revealed that greater cognitive reserve (CRIq) was associated with decreased functional brain activity in the left posterior medial frontal cortex in pre-HD at intermediate-1 memory load (r=−0.52, p=0.045) and intermediate-2 memory load (r=−0.56, p=0.030), compared with healthy controls. Higher level of physical exercise (IPAQ-L) was also related to reduced functional brain activity in pre-HD, including in left (r=−0.52, p=0.050) and right (r=−0.65, p=0.009) anterior insula, left (r=−0.69, p=0.004) and right (r=−0.72, p=0.002) inferior frontal gyrus, left intraparietal sulcus (r=−0.64, p=0.01) and left dorsolateral prefrontal cortex (r=−0.57, p=0.03) at low memory load; and, right intraparietal sulcus (r=−0.61, p=0.015) at intermediate-1 memory load, compared with healthy controls.

Conclusions These findings demonstrate that cognitive reserve and level of physical exercise can modulate functional brain reorganisation in pre-HD.